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21ST CENTURY CURES: EXAMINING WAYS TO 

COMBAT ANTIBIOTIC RESISTANCE AND FOSTER 

NEW DRUG DEVELOPMENT 

HEARING 

BEFORE THE

SUBCOMMITTEE ON HEALTH 

OF THE

COMMITTEE ON ENERGY AND 

COMMERCE 

HOUSE OF REPRESENTATIVES 

ONE HUNDRED THIRTEENTH CONGRESS 

SECOND SESSION 

SEPTEMBER 19, 2014 

Serial No. 113–178 

( 

Printed for the use of the Committee on Energy and Commerce 

energycommerce.house.gov 

(II) 

COMMITTEE ON ENERGY AND COMMERCE 

FRED UPTON, Michigan 

Chairman 

RALPH M. HALL, Texas 

JOE BARTON, Texas 

Chairman Emeritus 

ED WHITFIELD, Kentucky 

JOHN SHIMKUS, Illinois 

JOSEPH R. PITTS, Pennsylvania 

GREG WALDEN, Oregon 

LEE TERRY, Nebraska 

MIKE ROGERS, Michigan 

TIM MURPHY, Pennsylvania 

MICHAEL C. BURGESS, Texas 

MARSHA BLACKBURN, Tennessee 

Vice Chairman 

PHIL GINGREY, Georgia 

STEVE SCALISE, Louisiana 

ROBERT E. LATTA, Ohio 

CATHY MCMORRIS RODGERS, Washington 

GREGG HARPER, Mississippi 

LEONARD LANCE, New Jersey 

BILL CASSIDY, Louisiana 

BRETT GUTHRIE, Kentucky 

PETE OLSON, Texas 

DAVID B. MCKINLEY, West Virginia 

CORY GARDNER, Colorado 

MIKE POMPEO, Kansas 

ADAM KINZINGER, Illinois 

H. MORGAN GRIFFITH, Virginia 

GUS M. BILIRAKIS, Florida 

BILL JOHNSON, Missouri 

BILLY LONG, Missouri 

RENEE L. ELLMERS, North Carolina 

HENRY A. WAXMAN, California 

Ranking Member 

JOHN D. DINGELL, Michigan 

Chairman Emeritus 

FRANK PALLONE, JR., New Jersey 

BOBBY L. RUSH, Illinois 

ANNA G. ESHOO, California 

ELIOT L. ENGEL, New York 

GENE GREEN, Texas 

DIANA DEGETTE, Colorado 

LOIS CAPPS, California 

MICHAEL F. DOYLE, Pennsylvania 

JANICE D. SCHAKOWSKY, Illinois 

JIM MATHESON, Utah 

G.K. BUTTERFIELD, North Carolina 

JOHN BARROW, Georgia 

DORIS O. MATSUI, California 

DONNA M. CHRISTENSEN, Virgin Islands 

KATHY CASTOR, Florida 

JOHN P. SARBANES, Maryland 

JERRY MCNERNEY, California 

BRUCE L. BRALEY, Iowa 

PETER WELCH, Vermont 

BEN RAY LUJAN, New Mexico 

PAUL TONKO, New York 

JOHN A. YARMUTH, Kentucky7 

SUBCOMMITTEE ON HEALTH

JOSEPH R. PITTS, Pennsylvania 

Chairman 

MICHAEL C. BURGESS, Texas 

Vice Chairman 

ED WHITFIELD, Kentucky 

JOHN SHIMKUS, Illinois 

MIKE ROGERS, Michigan 

TIM MURPHY, Pennsylvania 

MARSHA BLACKBURN, Tennessee 

PHIL GINGREY, Georgia 

CATHY MCMORRIS RODGERS, Washington 

LEONARD LANCE, New Jersey 

BILL CASSIDY, Louisiana 

BRETT GUTHRIE, Kentucky 

H. MORGAN GRIFFITH, Virginia 

GUS M. BILIRAKIS, Florida 

RENEE L. ELLMERS, North Carolina 

JOE BARTON, Texas 

FRED UPTON, Michigan (ex officio) 

FRANK PALLONE, JR., New Jersey 

Ranking Member 

JOHN D. DINGELL, Michigan 

ELIOT L. ENGEL, New York 

LOIS CAPPS, California 

JANICE D. SCHAKOWSKY, Illinois 

JIM MATHESON, Utah 

GENE GREEN, Texas 

G.K. BUTTERFIELD, North Carolina 

JOHN BARROW, Georgia 

DONNA M. CHRISTENSEN, Virgin Islands 

KATHY CASTOR, Florida 

JOHN P. SARBANES, Maryland 

HENRY A. WAXMAN, California (ex officio) 

(III) 

C O N T E N T S 

Page 

Hon. Joseph R. Pitts, a Representative in Congress from the Commonwealth 

of Pennsylvania, opening statement ................................................................... 1 

Prepared statement .......................................................................................... 2 

Hon. Frank Pallone, Jr., a Representative in Congress from the State of 

New Jersey, opening statement .......................................................................... 3 

Hon. Phil Gingrey, a Representative in Congress from the State of Georgia, 

opening statement ................................................................................................ 5 

Hon. Henry A. Waxman, a Representative in Congress from the State of 

California, opening statement ............................................................................. 7 

Hon. Louise M. Slaughter, a Representative in Congress from the State 

of New York, prepared statement ....................................................................... 9 

Hon. Fred Upton, a Representative in Congress from the State of Michigan, 

prepared statement .............................................................................................. 146 

WITNESSES

Janet Woodcock, Director, Center for Drug Evaluation and Research, U.S. 

Food and Drug Administration ........................................................................... 10 

Prepared statement .......................................................................................... 12 

Answers to submitted questions ...................................................................... 162 

Kenneth J. Hillan, Chief Executive Officer, Achaogen, Inc. ................................ 43 

Prepared statement .......................................................................................... 47 

Answers to submitted questions ...................................................................... 179 

Barbara Murray, President, Infectious Disease Society of America ................... 55 

Prepared statement .......................................................................................... 57 

Answers to submitted questions ...................................................................... 184 

Adrian Thomas, Vice President, Global Market Access and Global Public 

Health, Janssen Global Services, LLC ............................................................... 76 

Prepared statement .......................................................................................... 79 

Answers to submitted questions ...................................................................... 193 

Kevin Outterson, Professor of Law, Boston University School of Law ............... 92 

Prepared statement .......................................................................................... 94 

Answers to submitted questions ...................................................................... 202 

Allan Coukell, Senior Director, Drugs and Medical Devices, The Pew Charitable Trusts .......................................................................................................... 112 

Prepared statement .......................................................................................... 114 

Answers to submitted questions ...................................................................... 209 

Dr. John H. Powers, Assistant Clinical Professor of Medicine, George Washington University School of Medicine ................................................................. 125 

Prepared statement .......................................................................................... 127 

Answers to submitted questions 1 ................................................................... 213 

SUBMITTED MATERIAL

Article entitled, ‘‘Andrew J. Moyer and Penicillin: Saving Lives on a Grand 

Scale,’’ in Moment of Indiana History, August 23, 2010, submitted by Mr. 

Burgess ................................................................................................................. 147 

Statement of the Flag & General Officers’ Network, Inc., submitted by Stephen Parente ........................................................................................................ 149 

Statement of Cubist Pharmaceuticals, submitted by Mr. Pitts ........................... 151 

Statement of California Healthcare Institute, submitted by Mr. Pitts ............... 159 

1 Dr. Powers did not respond to questions for the record. 

(1) 

21ST CENTURY CURES: EXAMINING WAYS TO 

COMBAT ANTIBIOTIC RESISTANCE AND 

FOSTER NEW DRUG DEVELOPMENT 

FRIDAY, SEPTEMBER 19, 2014 

HOUSE OF REPRESENTATIVES, 

SUBCOMMITTEE ON HEALTH, 

COMMITTEE ON ENERGY AND COMMERCE, 

Washington, DC. 

The subcommittee met, pursuant to call, at 9:00 a.m., in room 

2123, Rayburn House Office Building, Hon. Joseph R. Pitts (chairman of the subcommittee) presiding. 

Present: Representatives Pitts, Burgess, Shimkus, Gingrey, 

Lance, Bilirakis, Ellmers, Pallone, Green, and Waxman (ex officio). 

Also Present: Representative DeGette. 

Staff Present: Clay Alspach, Counsel, Health; Gary Andres, Staff 

Director; Sean Bonyun, Communications Director; Leighton Brown, 

Press Assistant; Noelle Clemente, Press Secretary; Paul Edattel, 

Professional Staff Member, Health; Sydne Harwick, Legislative 

Clerk; Robert Horne, Professional Staff Member, Health; Carly 

McWilliams, Professional Staff Member, Health; Tim Pataki, Professional Staff Member; Chris Sarley, Policy Coordinator, Environment and Economy; Heidi Stirrup, Health Policy Coordinator; Ziky 

Ababiya, Minority Staff Assistant; Eric Flamm, Minority FDA 

Detailee; Karen Nelson, Minority Deputy Committee Staff Director 

For Health; Rachel Sher, Minority Senior Counsel. 

OPENING STATEMENT OF HON. JOSEPH R. PITTS, A REPRESENTATIVE IN CONGRESS FROM THE COMMONWEALTH 

OF PENNSYLVANIA 

Mr. PITTS. The subcommittee will come to order. The chair will 

recognize himself for an opening statement. 

According to the World Health Organization’s Antimicrobial Resistance, Global Report on Surveillance 2014, antimicrobial resistance, AMR, is an increasingly serious threat to global public 

health. British Prime Minister David Cameron warned in July that 

if we do not confront the threat of antibiotic resistance, we could 

be ‘‘cast back into the dark ages of medicine where treatable infections and injuries will kill once again.’’ 

And just yesterday, the President announced an executive order 

focused on efforts his administration plans to take with regards to 

the antibiotic resistance issue. In 2012, this committee sought to 

help combat this global threat by passing the GAIN Act as part of 

the Food and Drug Administration Safety and Innovation Act of 

2 

2012. The GAIN Act was an important first step in the fight 

against antibiotic resistance and a great example of how bipartisan 

collaboration on this committee can save lives. And I want to commend the bipartisan authors that made GAIN possible, including 

Representatives Gingrey, Green, Shimkus, DeGette, Whitfield, and 

Eshoo for their leadership. 

I also want to commend the FDA for its role in making GAIN 

a success since its passage. But what is clear to many in this room 

is that GAIN did not fully fix the problem, and much more is needed if we are to incentivize the type of drug development needed to 

combat this global threat. 

And to that end, Congressmen Gingrey and Green have introduced another piece of legislation, the ADAPT Act, which would 

seek to address problems related to the FDA approval process of 

antibiotic drugs. It is one of a series of proposals that warrants serious consideration by this committee as part of our 21st Century 

Cures, and I want to thank them for their continued efforts in this 

space. 

I would like to thank all of our witnesses for being here today 

and yield the remainder of my time to the vice chair of the subcommittee, Dr. Burgess. 

[The prepared statement of Mr. Pitts follows:] 

PREPARED STATEMENT OF HON. JOSEPH R. PITTS

The Subcommittee will come to order. 

The Chair will recognize himself for an opening statement. 

According to the World Health Organization’s (WHO) Antimicrobial Resistance: 

Global Report on Surveillance 2014, ‘‘Antimicrobial resistance (AMR) is an increasingly serious threat to global public health.’’ 

British Prime Minister David Cameron warned in July that if we do not confront 

the threat of antibiotic resistance, we could be ‘‘cast back into the dark ages of medicine where treatable infections and injuries will kill once again.’’ 

And, just yesterday, the President announced an Executive Order focused on efforts his administration plans to take with regards to the antibiotic resistance issue. 

In 2012, this Committee sought to help combat this global threat by passing the 

GAIN Act as part of the Food and Drug Administration Safety and Innovation Act 

of 2012. 

The GAIN Act was an important first step in the fight against antibiotic resistance and a great example of how bipartisan collaboration on this committee can 

save lives. 

I want to commend the bipartisan authors that made GAIN possible including 

Reps. Gingrey, Green, Shimkus, DeGette, Whitfield and Eshoo for their leadership. 

I also want to commend the FDA for its role in making GAIN a success since its 

passage. 

But what is clear to many in this room is that GAIN didn’t fully fix the problem 

and much more is needed if we are to incentivize the type of drug development 

needed to combat this global threat. 

To that end, Congressmen Gingrey and Green have introduced another piece of 

legislation, the ADAPT Act, which would seek to address problems related to the 

FDA approval process of antibiotic drugs. 

It is one of a series of proposals that warrants serious consideration by this Committee as part of our 21st Century Cures and I want to thank them for their continued efforts in this space. 

I would like to thank all of our witnesses for being here today, and I yield the 

remainder of my time to Rep. ——————————————. 

Mr. BURGESS. Thank you, Mr. Chairman, and I certainly appreciate the fact we are having this hearing today. It is necessary as 

we proceed with the Cures initiative to talk about some of the 

things that are most important, some of the things that are relied 

3 

upon and familiar in our front line of our ability to fight infections 

and those are antibiotics. Antibiotic resistance, specifically resistant strains, is a growing problem. Equally troubling, despite widespread support, is the lack of a pipeline of new drugs that can improve on previous generations or fight drug resistance strains. A lot 

of facets to this issue, and there is no single silver bullet solution. 

But here is the deal, our drug arsenal is our drug arsenal. Today 

the committee continues to probe the various market reasons why 

we are not producing new antibiotics, and if the proper market incentives and regulatory pathways exist to encourage the development of new drugs. Very important strides that have been made 

in the FDA Safety and Innovation Act, most notably through the 

GAIN Act, but they were just the first steps. Part of the deal is 

once nature adapts, it is hard to force nature to unadapt. These resistant strains are out there, and they aren’t going away. Once this 

evolutionary leap has taken place, we are not going back, and that 

is why we need a continuous pipeline of new drugs. 

I would also just point out on a historical note, since the election 

in Scotland was yesterday, and Scotland is going to remain part of 

the British empire, and of course, it was a famous Scotsman, Sir 

Alexander Fleming who developed, or is credited with the discovery 

of penicillin, but Sir Alexander Fleming couldn’t produce a lot of 

penicillin, and it was Andrew Moyer from Indiana, who actually developed the deep fermentation process that allowed the penicillin 

to be mass produced and really made a significant difference in the 

lives of our soldiers returning—or the saving of lives of our soldiers 

returning from World War II, and parenthetically dropped the cost 

of a course of penicillin from $20, at that time was a significant 

amount of money, to less than 50 cents. 

So we know we can do this and we know we should do this, that 

is, we have done it before, so the forefront of innovation, and that 

is what the Cures Initiative is all about, and I think that is an important part of our discussion. I will submit this article on Andrew 

Boyer for the record. 

[The information appears at the conclusion of the hearing.] 

Mr. PITTS. Without objection, it will be entered into the record. 

The chair thanks the gentleman and now recognize the ranking 

member of the subcommittee, Mr. Pallone, 5 minutes for an opening statement. 

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

Mr. PALLONE. Thank you, Chairman Pitts. In 2006, in my State 

of New Jersey, a 17-year-old honor student named Rebecca Lohsen 

went to the hospital and within days died from a resistant strain 

of MRSA. Though her doctors were able to identify the infection 

and treat it with the available antibiotics, it failed to respond to 

treatment, advancing rapidly and cutting her life short. And stories 

like Rebecca’s are all too common and all the more frustrating 

given the remarkable advances in American medicine. 

The threat posed by antibiotic resistant bacteria or ‘‘super bugs’’ 

is growing, yet the supply of new antibiotic drugs is dwindling due 

to drug manufacturers’ declining interest and ability to produce 

4 

new drugs to meet this threat. In a CDC report released last year, 

they find that 2 million Americans are infected with antibiotic resistant bacteria each year, and unfortunately, 23,000 will eventually die as a consequence of their infections. Additionally, 5 to 10 

percent of patients in American hospitals will acquire an infection 

during the course of their treatment. And, though the majority of 

these infections can be treated, this complicates the recovery process and ultimately imposes greater costs on patients and the 

healthcare system. 

Due to the current state of the market, manufacturers are 

incentivized to focus their efforts elsewhere, at the expense of the 

research and development with new antibiotics to combat these 

rapidly evolving strains of bacteria. This reason is why Congress 

included many of the provisions of the GAIN Act in the FDASIA 

legislation, which was signed into law in 2012. The GAIN Act was 

an important step toward solving this problem. Through GAIN, we 

are supporting manufacturers in the development and introduction 

of new drugs largely through the use of marketing exclusivities. So 

far we have seen meaningful progress. 

Because of GAIN, FDA has approved a number of new drugs 

through the Qualified Infectious Disease Product designation. With 

priority review, these drugs are able to combat an imminent infectious disease threat and reach patients at an accelerated pace. 

However, we should also remember why other laws such as the 

Hatch-Waxman Act, are so successful. If Congress decides to intervene in the market, using the carrot of marketing and regulatory 

exclusivities, we should be sure that it achieves the necessary impact on the pipeline of new drugs to safeguard the public health. 

In pursuit of the greater good, government struck a balance between the interests of private industry in the public, and society 

reaped the benefits. And so that is why I have concerns about ideas 

such as transferable exclusivity, the practice of giving a specified 

period of exclusivity to a company to use on any product it wishes 

as a reward for developing a new antibiotic. This is a recipe for 

higher cost drugs with no direct connection to the cost to developing new antibiotics. 

Yet, there are some ideas that are worth further examination, 

such as the ADAPT Act introduced by Congressmen Green and 

Gingrey. That bill would establish a limited population approval 

pathway that would permit FDA to approve drugs based on smaller 

clinical trials. So Mr. Chairman, there are a number of angles the 

government and private industry can take to meet this problem 

head on. I think we all agree this is an issue which warrants further action, and I welcome the opportunity to hear from our witnesses today. A special welcome to Adrian Thomas from Johnson 

& Johnson, which is headquartered in my district. I am always 

pleased to see you represented in front of our committee. 

So I would like to yield the remainder of my time to Mr. Green. 

Mr. GREEN. Thank you, Ranking Member, for yielding. Few 

issues in the public health today are as grave and urgent as combating the growing threat antibiotic resistance. I am pleased to 

learn that yesterday the White House announced the President’s 

Executive order on the national Combating Antibiotic Resistance 

5 

Bacteria, CARB strategy. We need to control bacteria and carbs, I 

guess. 

Recently, both the World Health Organization and the United 

Kingdom joined the United States in recognizing antibiotic resistance as a global threat. Fighting antibiotic resistance is both a public health and a national security priority. It is a threat that I take 

seriously and believe Congress has a strong role in answering. The 

FDA has played a central role in this important effort, and I thank 

the agency for their work. We must all work together to ensure 

that we have effective antibiotics for the future. 

In 1929, Alexander Fleming invented the process for the first antibiotic wonder drug, penicillin. Such discoveries for the 21st century can happen as well if we encourage greater investment in the 

development of novel antibiotic drugs. Antibiotics have saved millions of lives by treating infections caused by bacteria and made 

through therapies like surgery, chemotherapy, and care for neonatal infants possible. By nature, bacteria evolve and become resistant over time. In addition, misuse and inadequate diagnosis 

have contributed to antibiotic resistance, and most antibiotics are 

now less effective or ineffective against infections. 

The consequences of antibiotic resistance must not be underestimated. With each day, many more patients will have few or no 

therapeutic options because of the resistance to available therapies. 

I thank the chair and ranking member for this hearing today. Antibiotic resistance and development must be a high priority for this 

committee and central to the way we treat and cure disease in the 

21st century. I look forward to the hearing, and again, I want to 

thank my colleague, Congressman Gingrey, for partnering both on 

the GAIN Act last Congress and also on the ADAPT Act this Congress, and I yield back my time. Thank you. 

Mr. PITTS. The chair thanks the gentleman and now recognizes 

the gentleman from Georgia, Dr. Gingrey, 5 minutes for an opening 

statement. 

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

Mr. GINGREY. Mr. Chairman, I want to thank you. I want to 

thank you for calling today’s hearing within the 21st Century 

Cures Initiative entitled, ‘‘Examining Ways to Combat Antibiotic 

Resistance and Foster New Drug Development.’’ Let me first commend Chairman Upton and our colleague from Colorado, Ms. 

DeGette, for spearheading this bipartisan endeavor that really 

looks at ways we can address emerging challenges in the 

healthcare industry. 

I have participated in a number of the hearings and roundtable 

discussions and have found each to be very beneficial to all the 

members of this subcommittee. Mr. Chairman, we all understand 

that antibiotic resistant pathogens are a growing concern not only 

across the country, but across the globe. According to the CDC in 

Atlanta, each year more than 2 million Americans get infections 

that are resistant to antibiotics, resulting in the deaths of some 

23,000 people and costing our healthcare system nearly $20 billion 

in direct cost, probably $35 billion more in indirect cost, lost time 

from work, et cetera. 

6 

This year alone, both the World Health Organization and the 

U.K. have acknowledged this looming threat. Just yesterday, the 

Obama administration took action on antibiotic resistance as well. 

Through the signed Executive order, the national strategy on Combating Antibiotic Resistant Bacteria and the President’s Council of 

Advisors on Science and Technology, referred to as PCAST, will be 

issuing a report, this is an issue that is now receiving global attention. Unfortunately, though, according to the FDA, new antibiotic 

approval has decreased by 70 percent since the mid 1980s. 

A combination of barriers, including, of course, the high cost of 

drug development and the small profit margins have helped to 

drive companies out of the anti-infectious space to markets where 

the return on investment is much higher. You think of your favorite drug, whether it is for arthritis or whatever, they simply can 

make a lot more money and there is a lot bigger market. These few 

incentives for companies to produce new antibiotics have yielded a 

stagnant research and development pipeline for antibiotics, and it 

is ill-equipped to keep up with the evolving bacterium. 

Mr. Chairman, I am glad that Congress has been a true leader 

in this arena. With the partnership of my colleague from Texas, 

Gene Green, as the other lead author/sponsor of the GAIN Act, we 

were able to find a path for this legislation to be signed into law, 

and it was, in July of 2012. As many of the witnesses’ testimonies 

state, the GAIN Act has been an important step to encourage new 

development of antibiotics by focusing on economic incentives to 

keep companies in the game, in the market. However, despite these 

advances, there is still more work that needs to be done. That is 

precisely why Mr. Green and I authored H.R. 3742, the ADAPT Act 

during this Congress. 

This legislation, a logical next step to the GAIN Act, develops a 

new pathway at the FDA for antibiotics aimed at treating merging 

threats in limited and high-need populations when they have no 

available option at their disposal. The ADAPT Act will also streamline the process by which the FDA updates break points information so doctors and medical researchers have the most up-to-date 

information in which to expedite the decisions in the drug approval 

process. 

Mr. Chairman, the model of the 21st Century Cures Initiative 

work on the GAIN Act and the ADAPT Act has been a true bipartisan product, and I commend Mr. Green for his continued efforts 

with me on both pieces of legislation. Earlier this morning, both of 

us spent an hour on Washington Journal discussing our efforts addressing drug resistant bacteria with a sense of comity befitting 

our committee, and I think Mr. Green and the moderator and hopefully all the viewers and listeners would agree with that. And with 

that in mind, I look forward to hearing from all of our witnesses 

today, the first and second panel. 

I had the pleasure yesterday of meeting with Dr. Barbara Murray, who will be on the second panel, the President of the Infectious Disease Society of America, and after hearing some of her anecdotal accounts of life-threatening infections with her own patients, I am even more motivated to continue the fight against drug 

resistant bacteria. 

7 

I will give a real quick anecdote, Mr. Chairman. I know I am 

running out of time, but my brother is 1 year older than me, and 

in 1941, he was sick as a gourd, home with pneumonia, and the 

family doctor came to the house and told my parents that he was 

going to die unless he gave him a shot of this new antibiotic called 

penicillin. And my brother James got that shot of penicillin and fortunately he lived. Now, there have been some days since then that 

I wish he hadn’t. He beat me up every day since then and still 

does, but that is my own little anecdote, Dr. Murray. 

Mr. Chairman, as we continue with the 21st Century Cures Initiative, we must work in a bipartisan manner to address this growing problem across our country. Ultimately, I believe that the 

ADAPT Act is the next step in the fight. It is my hope that we will 

mark up this legislation during the lame duck session later next 

month. Until then, I welcome the testimony that we will be hearing 

today to further educate members of the subcommittee on this critically important issue. 

Make no mistake, the cost of inaction in the fight against life 

threatening infections is grave, and the CDC has already provided 

us with the statistics to prove that. Today’s hearing will serve as 

a great way to raise awareness on this important issue. 

Mr. Chairman, thank you for allowing me the time normally reserved for Chairman Upton, and I look forward to continuing to 

work with all of my colleagues as this process moves forward. 

Thank you for the extra time and being a little soft on the gavel, 

Mr. Chairman, as I yield back. 

Mr. PITTS. The chair thanks the gentleman and thanks him for 

his leadership on this issue. 

Now recognizes the ranking member of the full committee, Mr. 

Waxman, for 5 minutes for opening statement. 

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

Mr. WAXMAN. Thank you very much, Mr. Chairman. We held 

hearings in this committee in 2010 on the problem of antibiotic resistance and the fact that it is a growing and dangerous threat to 

public health. It is certainly an issue that deserves the full and 

complete attention of this committee, so I am pleased you are holding this hearing. Our overarching goal should be to ensure that 

people continue to benefit from these life-saving treatments, both 

here and in the United States and around the globe. 

This is an inherently difficult goal to achieve. After all, when we 

use these antibiotics, it leads to the development of pathogens that 

can no longer be treated by those antibiotics. Rather than use it 

or lose it with antibiotics, it is use it and lose it. 

So we are at great risk of losing much of the progress that has 

been made in fighting infection and subsequent disease. Many 

Americans die or are infected each year from antibiotic resistant 

microbes. We pay a high price in other ways as well, additional 

hospital stays, hospital readmissions, increased doctor visits, all 

add unnecessarily to the Nation’s annual healthcare bill. It will 

take a multi-pronged approach to overcome this very serious problem. There is no question that our arsenal of effective antibiotics 

8 

is dangerously low today as a result of antibiotic resistance, so we 

need to replace ineffective antibiotics with new ones. 

In the 2012 FDA user fee legislation, we enacted a law designed 

to create incentives for companies to replace those antibiotics and 

develop new ones. That legislation included provisions from the 

what was called the Generating Antibiotic Incentives Now Act 

called the GAIN Act, and that granted a 5-year period of exclusive 

marketing for new antibiotics for serious and life-threatening diseases. 

I look forward to hearing today from our witnesses about what 

impact that legislation is having on investments in these drugs. 

Exclusivity rewards drug companies by allowing them to charge 

higher prices. As a result, it also imposes a significant burden on 

patients and on the healthcare system overall, so we need to approach this particular form of incentive with great caution. 

One bad idea, in my opinion, is the concept of transferable market exclusivity which is sometimes called the wildcard exclusivity. 

This form of exclusivity would give a company that developed a 

new antibiotic the ability to transfer a term of exclusivity to another drug, any other drug that they have, and this is a hugely 

costly idea that leads to unfair cross subsidies. If AstraZeneca were 

to develop a specified antibiotic, it could earn a term of exclusivity 

that it could transfer to Nexium, a treatment for heartburn which 

is the second highest grossing drug last year and earns over $6 billion. Even if the term of exclusivity were just 6 months, that would 

result in a reward of almost $3 billion. That means Nexium patients pay higher prices for longer even though they may never actually take the antibiotic itself. 

As we tackle the problem of antibiotic resistance, we need to ensure that whatever form the incentive takes, it bears some reasonable relationship to the amount of the investment the company is 

making. I hope we will discuss today another approach to getting 

new antibiotics on the market. That is what has been referred to 

as the ADAPT Act, or the Antibiotic Development to Advance Patient Treatment. That bill would establish a limited population approval pathway that would permit FDA to approve drugs based on 

smaller clinical trials. This is an idea worth examining. 

If we do create such a pathway, any drugs approved as a result 

would need to be clearly marked with a prominent symbol to alert 

providers and patients that the safety and effectiveness of these 

drugs has only been assessed on a limited population. Requiring a 

designation is integral to the idea of a limited population approval 

pathway because providers have to know that these drugs are to 

be used only when absolutely necessary. Otherwise, they will not 

only put patients at risk but will contribute to the more rapid development of antimicrobial resistance to the drugs. 

In addition to incentives for developing new antibiotics, we ought 

to find ways to cut back on the overuse and misuse of these drugs. 

Patients cannot expect to get them every time they come down 

with a cold, and physicians should only prescribe them when they 

are truly necessary. Perhaps most important, the indiscriminate 

administration of these drugs in animal agricultural operations 

needs to stop. We should mandate an end to this practice, but if 

we cannot take that step, we should at least have better data about 

9 

how and where antibiotics that are important for humans are being 

used in food animals. We know practically nothing about this situation. 

As a recent Reuters article points out, the data exists in the 

hands of major corporations producing these animals. I would like, 

Mr. Chairman, another 30 seconds. 

Mr. PITTS. Go ahead. 

Mr. WAXMAN. Like Perdue and Tysons, and I have a bill that 

would finally give the public access to this information, H.R. 820, 

the DATA Act. I hope this commonsense bill can be included in the 

21st Century Cures legislation. 

I thank the witnesses for being here today and for their testimony. And Mr. Chairman, I would like to ask unanimous consent 

that a statement prepared by Congresswoman Louise Slaughter be 

included in the record. She is talking in her statement about ways 

to combat antibiotic resistance and foster new drug development. 

Mr. PITTS. Without objection, so ordered. 

Mr. WAXMAN. Thank you, Mr. Chairman. 

[The prepared statement of Ms. Slaughter follows:] 

PREPARED STATEMENT OF HON. LOUISE M. SLAUGHTER

Mr. Chairman, thank you for the opportunity to submit remarks for the record 

this morning. I appreciate the attention being paid to the crisis of antibiotic resistance and the immediate need to address it. While I appreciate that the focus of today’s hearing is on the development of new antibiotics, I cannot let the opportunity 

pass to discuss the overuse of antibiotics in agriculture and the connection to the 

development of superbugs resistant even to some of our last line of defense antibiotics. 

Almost 70 years ago, Alexander Fleming first warned about the possibility of a 

post-antibiotic era, warning that—quote—‘‘the ignorant man may easily underdose 

himself and by exposing his microbes to non-lethal quantities of the drug make 

them resistant.’’ 

I’m not sure Dr. Fleming could have envisioned that the biggest threat to antibiotics in the future would come from factory farms—where 80 percent of the antibiotics in this country are used in animals that eventually end up on our dinner 

plate. His warning rings true today: the daily distribution of antibiotics in feed and 

water at sub-therapeutic levels is creating resistant superbugs, and destroying the 

effectiveness of these miracle drugs. 

According to a recent report from the World Health Organization, ‘‘Antibiotic resistance is now a bigger crisis than the AIDS epidemic,’’ and if we do not curb our 

antibiotic overuse, ‘‘a post-antibiotic era-in which common infections and minor injuries can kill-far from being an apocalyptic fantasy, is instead a very real possibility 

for the twenty-first century.’’ This would redefine modern medicine. Routine infections like strep throat could be fatal. A skinned knee that became infected could become fatal. Life-saving surgeries like open-heart surgery or organ transplants that 

require antibiotics to stave off infection would become too dangerous for doctors to 

consider. All of these medical advances would be thrown away because we are wasting these critical antibiotics on the farm. 

There are those who say there is not a connection between overuse of antibiotics 

on the farm and resistant diseases in humans. I struggle to understand their decision-making process when the National Antimicrobial Resistance Monitoring System 

(NARMS) reports that antibiotic resistant bacteria exist in 81% of ground turkey, 

69% of pork chops, 55% of ground beef, and 39% of chicken breasts, wings and 

thighs found in grocery stores. More than 27% of bacterial isolates found on retail 

chicken are resistant to more than five classes of antibiotics. 

Just this week, the top scientific minds in this country who make up the President’s Council of Advisors on Science and Technology released their report on antimicrobial resistance and confirmed what I and over 450 of the leading medial, scientific and consumer groups in the country who support my legislation have been 

shouting from the rooftops for years. Allow me to quote that report: 

‘‘Substantial evidence demonstrates that use of antibiotics in animal agriculture 

promotes the development of antibiotic-resistant microbes in animals and that retail 

10 

meat can be a source of microbes, including antibiotic-resistant microbes. Moreover, 

antibiotic resistance can spread between microbes (through the transfer of DNA elements, such as plasmids, between species) and antibiotic-resistant microbes can 

spread from animals to people who come into contact or close proximity with them. 

For example, poultry workers in Maryland and Virginia have been reported to be 

much more likely to be colonized by gentamicin-resistant E. coli and are at a higher 

risk of infection by multi-drug resistant E. coli than residents of the community surrounding the poultry operation. A survey of over 900 adults in Wisconsin and Minnesota found that drug-resistant E. coli bacteria isolates present in humans were 

similar to those in poultry meat, whereas drug-susceptible E. coli bacteria isolates 

were not. A study of veterans in rural Iowa reported that the frequency of resistant 

Staphylococcus aureus was 88% higher among veterans living within one mile of a 

high-density swine-feeding operation.’’ 

Despite the substantial evidence and despite the nightmare scenario of a post-antibiotic era, both our federal regulatory agencies and the Congress are still refusing 

to acknowledge the devastating role that antibiotic use in agriculture is having on 

the future of medicine in the United States. I am imploring you today, as you consider the future of antibiotic development in this country, that you also consider 

that the routine overuse of future antibiotics would result in the same conditions 

we face today. We must preserve those antibiotics critical to human health for use 

in treating disease—not for growth promotion or disease prevention. Antibiotics are 

for treatment of illness—period. 

My legislation—the Preservation of Antibiotics for Medical Treatment Act -would 

save eight critical classes of antibiotics for human use while still allowing the treatment of sick animals. I’ve carried this bill for seven years now, and I’m not going 

to rest until it becomes law. There are too many lives at stake to give up. We can 

and must preserve antibiotics—the future of modern medicine depends upon it. 

Thank you. 

Mr. PITTS. And I have a unanimous consent request. I would like 

to submit the following for today’s hearing record. First, a letter 

from the Flag and General Officers’ Network, an official 501(c)(19) 

War Veterans Organization representing three-quarters of all living U.S. Armed Forces Flag and General Officers. Secondly, a 

statement from Cubist Pharmaceuticals, a global pharmaceutical 

company headquartered in Lexington, Massachusetts. And thirdly, 

a statement from the California Healthcare Institute, CHI, their 

statewide public policy organization representing California’s leading biomedical innovators, over 275 research universities in private, non-profit institutes, venture capital firms, and medical device diagnostic biotechnology and pharmaceutical companies. Without objection, so ordered. 

[The information appears at the conclusion of the hearing.] 

Mr. PITTS. All members’ written opening statements will be made 

a part of the record. At this point, we have two panels to present 

testimony. On the first panel today, we have again Dr. Janet 

Woodcock, the director of the Center for Drug Evaluation and Research, U.S. Food and Drug Administration. Thank you very much, 

Dr. Woodcock, for coming. Your written testimony will be made a 

part of the record, and you will be given 5 minutes to summarize 

your testimony before questions. So at this point you are recognized 

for 5 minutes for your opening statement. 

STATEMENT OF JANET WOODCOCK, DIRECTOR, CENTER FOR 

DRUG EVALUATION AND RESEARCH, U.S. FOOD AND DRUG 

ADMINISTRATION 

Dr. WOODCOCK. Thank you, Mr. Chairman, and members of the 

committee for holding this hearing on this really important issue. 

There is broad agreement that antimicrobial resistance is a worldwide crisis that is going to require major efforts to combat. In 2012, 

11 

the Congress took a significant step in passing GAIN Act which we 

have been implementing. In Europe, the Innovative Medicines Initiative, which is a public/private partnership launched a major research effort on antimicrobial resistance. Yesterday, the Administration released a national strategy for combating antimicrobial resistance. A high level task force was established by Executive order 

to carry out and develop an action plan to carry out the goals. 

The strategy is a multi-sector effort to attack this problem in all 

its diverse forms by bolstering basic research, enhancing product 

development, improving the surveillance, which has already been 

alluded to, of resistance and use of antimicrobials, modifying the 

use of antibiotics in food animals, and strengthening international 

collaboration. 

PCAST, which is the President’s Council of Advisors on Science 

and Technology also released a scientific report and scientific recommendations yesterday. 

Over the past year, the Center for Drugs at FDA has been very 

busy on this issue. We have issued many new or revised guidances 

on antimicrobial drug development. We approved three drugs designated under the GAIN Act. We recently cosponsored a workshop 

on this topic with the National Institutes of Health. Of course, our 

fellow center, the Center for Biologics has been working on vaccines, another way of addressing this problem, and the Device Center working on testing methods. 

Despite all this progress, we must recognize that a robust pipeline of new investigational antimicrobials does not currently exist, 

nor is there a large number of drug discovery laboratories out there 

working to bring forth the next generation of candidate drugs. So, 

we don’t have a robust pipeline. The reason for this, apparently, is 

primarily the absence of commercial incentives to antimicrobial development. This problem must be solved one way or another if we 

are going to prevail in our fight against the ever-changing microbes. 

We don’t just need new treatments for resistant organisms, although we need those urgently, we need to keep introducing additional treatments against common conditions as well, since our existing armamentarium is inevitably going to weaken over time. We 

don’t just need to respond to the current crisis, we need a robust 

pipeline going forward. 

Because this is such a multidimensional problem, we all must 

work together to prevent the loss of these critical weapons against 

disease, so I am very happy to answer any questions. 

Mr. PITTS. The chair thanks the gentlelady. 

[The prepared statement of Dr. Woodcock follows:] 

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Mr. PITTS. I will begin the questioning and recognize myself 5 

minutes for that purpose. 

Dr. Woodcock, yesterday FDA Commissioner Hamburg posted a 

blog post titled, ‘‘FDA’s Take on the Executive Order and National 

Strategy to Combat Antibiotic Resistance Bacteria’’ where she 

wrote ‘‘Few issues in public health today are as critical and time 

urgent as combating the growing threat of antibiotic resistance. It 

is a high priority for FDA to work with our partners to find solutions for this serious public health problem.’’ 

Would you explain the urgency of this situation for public health 

and national security? 

Dr. WOODCOCK. Well, as many of the members have already stated—— 

Mr. PITTS. Press your—— 

Dr. WOODCOCK. Sorry. As many of the members have already 

stated, for public health, we are already seeing excess deaths, and 

we are seeing people who in fact cannot be treated with any existing therapy that we have, and I think the threat here to public 

health is that we can have emerging epidemics of these organisms 

that they will spread. Right now they are fairly limited and sporadic, but will spread, and we will be in a situation where we literally can’t treat an infection that is unfolding in a wider sense. 

In addition, each year we are seeing greater and greater resistance problems for ordinary microorganisms, and so doctors are having to turn to what we would call second or third line antimicrobial 

agents, agents we use to reserve for very selected situations. And 

as that occurs, more resistance to those will evolve, and so eventually we are going to be empty handed. 

Mr. PITTS. OK. In the case of antibiotics, even slight variations 

in the bacteria’s genetic makeup can be the difference between a 

drug working or not working. Understanding that bacterial resistance compounds this problem many times over, why is it important 

for our antibiotic drug pipeline that we have multiple drug options 

for the same class or family of drugs? 

Dr. WOODCOCK. Yes. Well, what we know is when we develop an 

antimicrobial it evolves over time after that antimicrobial is used, 

and after time, it may be that it can be effective against certain 

forms of an organism and not against other more resistant forms, 

and the mechanism of resistance is different. There are many different mechanisms of drug resistance. That is why having a large 

number of drugs in a class or even improvements in a class can be 

extremely helpful in this situation because you can match the antimicrobial to the organism you are trying to treat. 

Mr. PITTS. Do we have the type of drug redundancy highlighted 

above that we need to effectively combat this problem right now? 

Dr. WOODCOCK. We do not because that is sort of the cutoff line. 

The antimicrobials that are no longer useful against many infections is getting higher and higher every year, especially for certain 

types of bugs. 

Mr. PITTS. Do you believe that we need to further incentivize 

new drug and diagnostic development if we are to appropriately address the issue of antibiotic resistance, and if so, what would you 

recommend? 

29 

Dr. WOODCOCK. I do believe we must incentivize it because the 

current situation shows that the incentives have not been enough 

to stimulate development in this area. So for drug development, apparently, developing antimicrobials is still not attractive enough. It 

still doesn’t appear that it might not be a loss to business, that 

there isn’t an attractive enough business model to build those robust programs that are needed to both discover and then develop 

new classes of antimicrobials. 

For diagnostics, I will tell you that Louis Pasteur and Alexander 

Fleming would recognize the methods we use today because they 

invented them, and so there is a lot of room at the top for improvement. We are using genetic sequencing of human genome, which is 

huge compared to the microbial genome, but using clinical practice 

of advanced methods is not the norm, and that, improving 

diagnostics would tremendously simplify clinical trials and also 

treatment. 

Mr. PITTS. Now, we are talking about incentives here. Do you believe that such incentives could be used in other unmet need areas 

beyond just antibiotics? 

Dr. WOODCOCK. Well, of course, I believe that that is possible. 

However, as I think Mr. Waxman said, there are tradeoffs you 

have to balance. There are always tradeoffs in putting these incentives in place, and I, being a physician and a scientist, am not the 

most qualified person to make those tradeoffs. I think Congress 

really has to weigh those. 

I can tell you that the public health urgency for this problem is 

severe and will continue, and I think you’ll hear that from other 

experts as well. We are not over the hump here. We have not succeeded in developing a system that will continue to generate effective new antimicrobials. We don’t have that. We have sort of heroic 

efforts here and there. 

Mr. PITTS. Thank you, Dr. Woodcock. My time is expired. The 

chair recognizes the ranking member, Mr. Pallone, 5 minutes for 

questions. 

Mr. PALLONE. Thank you, Mr. Chairman. Both the Executive 

order issued yesterday and the report of the President’s Council of 

Advisors on Science and Technology emphasize the danger of antibiotic use in the agriculture industry. 

While it is clear we should do more to encourage greater research 

in development of new drugs, it also makes sense that we should 

be investing in efforts to limit the further spread of drug resistant 

bacteria strains and make the best use of existing drugs so they 

can remain effective for longer periods. 

So Dr. Woodcock, in your testimony, you point to FDA’s cooperative effort with CDC to promote greater stewardship, including the 

‘‘Get Smart’’ campaign. I would like you to elaborate on this partnership, and on FDA’s role in the initiatives laid out in yesterday’s 

Executive order. 

Dr. WOODCOCK. Well, obviously there needs to be better stewardship both in human and agricultural uses of antimicrobials, as has 

already been said. About half, CDC estimates, of antimicrobial outpatient prescriptions are not necessary, given the condition the patient has, and that leads, especially if people only take the drugs 

for a little bit, can lead to big problems, and also in the animal 

30 

world. Now, in the human area, FDA is collaborating with CDC on 

these efforts, but CDC is primarily the lead on improving better 

use in health care, and that is a multi-faceted effort. 

In the animal health space, FDA had put out a guidance to the 

Center for Veterinary Medicine calling on manufacturers to cease 

use of important human antimicrobials for growth promotion in 

food animals, and they have secured the cooperation of all the manufacturers who are engaged in that space, to my understanding, 

and then there will be a process whereby those indications are 

withdrawn. And then use in food animals would be required under 

the supervision of a veterinarian for a health condition in the animal, so that would be a great improvement. 

Also, as was discussed in the report yesterday, though, we need 

better surveillance and data to understand the link between antimicrobial use in animals, or humans, in the development of resistance. That is still rather poorly understood. 

Mr. PALLONE. All right. Thanks. I wanted to get FDA’s views on 

certain aspects of the ADAPT Act. As I understand the purpose of 

the bill, its goal is to facilitate FDA’s ability to approve new antibiotics that have been tested only in a limited population, and for 

which the need for the drug is critical. I know you already do approve drugs tested in limited populations, for example, drugs for 

rare diseases, so I would like you to explain if and why the existing 

accelerated approval mechanisms aren’t meeting the current need. 

I would also like you to address whether you believe the ADAPT 

Act as currently drafted provides the FDA with sufficient authority 

to ensure that ADAPT antimicrobials would be labeled in a way 

that clearly distinguishes them as different from other 

antimicrobials. 

It seems that if we are considering allowing drugs on the market 

tested only in very limited clinical trials, we need to be confident 

that providers and patients understand the care with which these 

drugs must be used. 

Dr. WOODCOCK. Yes. Well, we think the ADAPT Act has elements that we have been discussing for a long time. Let me explain 

some of the situation. We approve drugs for limited population all 

the time, orphan drugs, rare subsets, but generally speaking, the 

clinical community is not tempted to use those for somebody with 

a cold, right. It is for some rare enzyme deficiency or some cancer, 

rare cancer or whatever. With antimicrobials, the big problem is 

really the use outside of where it would really clinically be indicated, and one of the barriers for these highly resistant organisms 

is that their occurrence is sporadic. 

We are very lucky that there are not widespread outbreaks, 

right, but because there are not widespread outbreaks, it means 

the testing of the drugs in broad populations is difficult. Actually, 

that is good news because otherwise we would really be in trouble, 

all right, if there were large numbers of people suffering like this. 

So that means, by definition, if you are going to get these drugs 

on the market for these small populations of resistant organisms, 

you are going to have to have small trials, and you will have more 

uncertainty about the effects. So more uncertainty about the effects, and worries that the drug will be used in conditions where 

31 

it is not warranted, those are the two issues we are trying to address. 

In orphan conditions, yes, there is uncertainty about the effects, 

but the orphan community that uses these drugs, usually those are 

sub-specialists who are treating a very rare disease, and they have 

a very good understanding of what studies were done on the drug 

and so forth. It often may be the only drug ever studied for that 

condition. 

So our thoughts, and the Administration has not taken a position 

on this, but we have thought about this, that to offer very small 

development programs is a big incentive, but the quid pro quo really is to send a signal to the clinical community, some kind of signal, some kind of message that this is special. That there is more 

uncertainty and also use good stewardship with this particular 

product because using it in a lot of conditions where it is not warranted would also more rapidly increase the development of resistance. 

Mr. PALLONE. Thank you. 

Mr. PITTS. The chair now recognizes the gentleman from Georgia, 

Dr. Gingrey, 5 minutes for questions. 

Mr. GINGREY. Mr. Chairman, thank you for recognizing me. I 

know that the vice chairman of the subcommittee, my colleague, 

Dr. Burgess, was scheduled to go next, and Mike, thank you for letting me ask my questions now. 

Dr. Woodcock, thank you, too. As a witness, we have had you before our committee many times since I have been on the committee, 

and you are just always so straightforward and you explain things 

in a very clear way, and I mean that sincerely. You do a great job, 

and we appreciate that very much. 

I want to continue in the line of questioning that Mr. Pallone 

started, and again, I have limited time, so let me get right into 

that. Congressman Green and I had been working on this ADAPT 

Act, as you know, and it is legislation that supports the FDA’s 

flexibility to consider all forms of evidence in addition to data from 

clinical trials when considering novel antibiotics. 

How important do you believe adaptive and unique trial designs 

can play in encouraging new antibiotic drug development? And before you answer that part, and I am sure everybody in the hearing 

probably knows this, but in your typical phase 3 trials before a 

drug can get to market, you are going to have to have a population 

of 1,000 or more people that you are treating, and there are also 

other requirements that they can’t have had an antibiotic within 

24 hours of the start of the trial, or at one point it was 3 days, I 

think, and then we got it down to 24 hours. 

But you are going to have a limited population of people that 

have these diseases, and when they get to the hospital sick as 

heck, the first thing the doctor is going to do, the emergency room 

physician is going to hang some antibiotic, even if it is wrong, they 

are going to start treating them, and then, all of a sudden they are 

not eligible, and you have a limited number of people. If you wait 

till you get 1,000, it is too late. So if you will kind of take that a 

step further and discuss that for us. 

Dr. WOODCOCK. Thank you. And thank you, and Mr. Green, for 

your leadership on this. I think it is very important. 

32 

Yes, there is a range, and I think that is what people have to 

recognize. There is a range of development programs that are needed. For common conditions, outpatient pneumonia, we have a lot of 

drugs out there that still work. If we introduce new drugs, we want 

them to be just as good as the other drugs, and they are going to 

need larger development programs, and that is true for many. But 

for these very rare, fortunately, resistant organisms that are multidrug resistant, there is almost nothing to treat them. These cases 

are occurring sporadically here and there or in outbreaks in ICUs 

or something like that, and we have to think of different ways of 

evaluating new treatments. We can’t just set up a trial and wait 

for all this to happen and expect we will be able to enroll thousands of people. And it is true, in fact, if we enrolled thousands of 

people, it will have been too late, this would be a terrible thing. 

So it is true that all antimicrobial drug development is very difficult. In addition to the economic problems, there is this huge difficulty in doing trials, especially in people who are really sick. You 

can’t use a placebo, obviously. You don’t know, because of the problem with diagnostics, you may not know for a few days what organism they are infected with. So there are all these technical problems that make it very difficult to do antimicrobial drug development. 

So because we have a tremendous unmet medical need for people—where there is no treatment available, typically what we do 

in that case is we accept more uncertainty, and that means novel 

trials that we might do. 

Mr. GINGREY. Dr. Woodcock, speaking of that uncertainty, I 

think that is probably why, and I commend the President for this 

in his executive order of just yesterday, the $20 million award for 

the development of these point-of-care diagnostics so someone could 

take a pill or a piece of tape or something and put it inside their 

mouth. If it turns a certain color, you know what you are dealing 

with right there, and you don’t have to just shotgun approach. 

Dr. WOODCOCK. That is right. 

Mr. GINGREY. You can immediately go right to what you need, 

so I think it is a great thing. 

Dr. WOODCOCK. I agree. I mean, if we could bring diagnosis of 

infectious disease into the 21st century, we would have made a 

huge advance and really accelerated the development of therapy, so 

that is a good thing. 

Mr. GINGREY. Thank you very much, Mr. Chairman. I yield back, 

and thank you for your courtesy. 

Mr. PITTS. The chair thanks the gentleman. Now recognize the 

ranking member of the full committee, Mr. Waxman, 5 minutes for 

questions. 

Mr. WAXMAN. Thank you, Mr. Chairman. I also want to say to 

you, Dr. Woodcock, this may be the last hearing where you and I 

will have the opportunity to publicly talk like this, but you have 

done a wonderful job at the FDA, and your responses to questions 

from both sides of the aisle have been very, very thoughtful, and 

I want to commend you for the work you have been doing and 

thank you for it. 

I want to echo the comments by Mr. Pallone about the importance of strong labeling statement or logo in the context of the 

33 

ADAPT Act. I think it is essential that the drug bear a prominent 

statement describing the abbreviated pathway by which it came to 

market. Without this requirement, I am not sure that the whole 

thing would work. It would be much less likely to achieve its purpose of fostering and facilitating the development of critical new 

antibiotics for life-threatening resistant pathogens. And additionally, inappropriate or injudicious use of a drug developed through 

this pathway could result both in patient harm and in more rapid 

loss of the drug to antibiotic resistance, so I just wanted to underscore that point. 

I want to ask you about a concept that you mention in your testimony designed to spur development of new antibiotics. That is 

delinkage. As I understand it, under this model, the sale of antibiotics would be delinked from the returns on investment. After all, 

we don’t want to say that we want more antibiotics sold. We want 

to make sure that the antibiotics that are sold and used are antibiotics that are going to stay effective for as long as possible. 

So some other funding mechanism would be created besides the 

traditional way of selling more drugs to ensure that a company was 

able to make a profit from developing an antibiotic. As others have 

noted, the usual pharmaceutical business model doesn’t fit very 

well in the case of antibiotics. 

We need to, however, recognize companies need to be able to recoup their investment and make a reasonable profit. Others have 

raised the notion of a wild card exclusivity. I mention in my opening statement I think it is a very dangerous idea. We don’t want 

to force patients taking one type of drug to fund development of another, so ensuring that antibiotic developers still can make a profit 

without linking that profit to how much antibiotic is actually sold 

seems like a brilliant way to approach this problem. Could you 

elaborate on this, tell us more about what ideas you have along 

these lines? 

Dr. WOODCOCK. Well, yes, because right now we have incentives 

that actually weigh against our objectives. Our objectives are that 

we have the most judicious use of new antimicrobials possible, and 

yet the incentive, if you have spent $500 million developing the 

drug, you need to recoup that amount of money and a fair profit 

to stay in business and develop the next generation. And so these 

incentives are sideways to each other and countervailing, and so 

that is one idea that has been raised that we mentioned to delink 

the need to have a large volume of the antibiotic used which would 

then lead to faster development of resistance. So if that were 

delinked from the—— 

Mr. WAXMAN. Do you have ideas on how to do that? 

Dr. WOODCOCK. I, as I said, I am really not good at financial 

matters, and so I am sorry. 

Mr. WAXMAN. We could count on you for everything, economic advice as well as pharmaceutical and food and other things that FDA 

does. 

Well, let me talk to you about another issue and that is in stewardship, using antibiotics judiciously. It seems to me this is a critical component of any effort to address the antibiotic resistance 

problem. The just released report on Combating antibiotic resistance from the President’s Council of Advisors in Science and TechVerDate Nov 24 2008 11:12 Mar 03, 2016 Jkt 037690 PO 00000 Frm 00037 Fmt 6633 Sfmt 6633 F:\MY DOCS\HEARINGS 113\113-178 CHRIS
34 

nology, or the PCAST, stresses the importance of increasing the 

longevity of current antibiotics by improving the appropriate use of 

existing antibiotics and it discusses the need to look at both human 

use and animal use of existing antibiotics. 

We know there is a lot of inappropriate use of antibiotics, both 

on the human side and I believe on the animal side. The PCAST 

report describes the important role that diagnostics can play in reducing this type of inappropriate use. Do you agree that diagnostics 

are important for stewardship efforts? And you alluded to this earlier, but can you describe how the widespread adoption of diagnostic tests would help preserve existing antibiotics, and is FDA 

taking any actions to foster the development in the use of these 

tests? 

Dr. WOODCOCK. Well, I believe diagnosis should be the foundation of therapy, and unfortunately, in the infectious disease space, 

often you are treating well before you know or before you ever 

know what the person has, and this is a fundamental problem. 

Like I believe the advent of rapid strep testing has really reduced 

the use of drugs for presumptive strep that often is colds or something, upper respiratory infections of one sort of another. 

So if we could get more certainty into the diagnosis early, be able 

to reassure the doctor and the patient or family that, no, this is not 

a dreaded bacterial infection that needs an antimicrobial, we could 

go a long way, I think, to lowering this inappropriate use. So 

diagnostics are the key. It is just we are far away from that right 

now and need to stimulate that. 

Mr. WAXMAN. Give more incentives for that? 

Dr. WOODCOCK. I believe so, uh-huh. 

Mr. WAXMAN. Thank you. Thank you, Mr. Chairman. 

Mr. PITTS. The chair thanks the gentleman. Now recognizes the 

vice chair of the subcommittee, Dr. Burgess 5 minutes for questions. 

Mr. BURGESS. Thank you, Mr. Chairman. And Dr. Woodcock, 

again, welcome to our humble little subcommittee. Your last statement, diagnostics are the key, now, this is not part of this discussion today, but we have had discussions on diagnostics, and I realize it is not your part of FDA that is talking about increasing the 

regulation of testing, particularly laboratory diagnostic tests, or 

laboratory developed tests, rather, but that that factors into the 

equation. I mean, yes, we are talking about the length of drugs, of 

time it takes drugs to get through the pipeline, but if it also takes 

the testing longer to get through the pipeline, we are actually making things harder on ourselves, are we not? 

Dr. WOODCOCK. Yes. Well, recently, for example, we have had a 

workshop with Brookings on this issue of the co-development and 

the technical issues. On the final guidance that we put out recently 

on co-development and companion diagnostics said for life-threatening disease, we are going to go ahead and approve the drug even 

if the test isn’t fully baked yet. 

There are technical problems in getting these tests developed 

right now, and I think all of us believe that for many of the 

genomic tests, that next generation sequencing is really going to be 

a key and really rapidly improve this situation. So I have great 

hope that that will be coming soon because we are facing it now. 

35 

Every disease—say cystic fibrosis, for example, there are 150 different mutations in that gene, each of which may translate to a 

slightly different phenotype in prognosis, and that goes with cancer 

and many other diseases. We really need to rapidly get to a point 

where we have a true standard that we can all agree upon so that 

we know what we are dealing with, and that, yes, that will rapidly 

improve development of drugs for these serious conditions. 

Mr. BURGESS. Well, I share your enthusiasm for genomic testing. 

I am somewhat more pessimistic because it seems like I can remember Dr. Elias Zerhouni in my first term on this committee, 

which was many, many years ago talking about some of these same 

things and where it is sort of the Jetson’s flying car. We are still 

waiting for that to happen. 

On the issue, and at HHS, you did your study on antibiotic initiatives, the incentives for development of new drugs, vaccines, and 

rapid diagnostics for bacterial disease, and then talked about moving the needle in monetary terms for companies by a reduction of 

the time for clinical trials, correct? 

Dr. WOODCOCK. Yes. 

Mr. BURGESS. Is it really possible to move the needle on that? 

Dr. WOODCOCK. Well, I believe for the limited population antibiotic development use that is possible. That is only one factor, but 

if you have a very high bar to getting on the market, then you are 

going to need much stronger incentives. I believe for those very 

rare, right now, resistant organisms, we could have very small development programs and that there be a societal agreement that 

having a treatment available for those is better than having nothing. And so we could have very small development programs. 

We simply would like to have a signal then to say to the clinical 

community, ‘‘No, that this is different, OK. No, this didn’t have a 

huge development program. We are offering you a tool, but you 

ought to be aware and provide good stewardship of this tool.’’ So 

we do believe in most cases it is possible, and even for common diseases, we have worked with new guidances to try to lower the cost 

of a development program so that the pipeline can be, you know, 

more robust. 

Mr. BURGESS. On the issue of judicious use and stewardship, and 

I hear the birds that are set on that, but when you talk about 

using things outside their area of indication, we tend to think of 

the world in which we live, but I am from Texas, and just a little 

bit south of Texas there is a different world where there is not a 

prescription required and people can simply go to the farmacia and 

say I need this—— 

Dr. WOODCOCK. Right. 

Mr. BURGESS [continuing]. And the pharmacist may direct them 

to a particular drug or they may just simply come in with a recommendation from a family member and make that purchase. So 

it is obviously harder to control that within the jurisdiction of the 

United States when it is happening right outside; is that not correct? 

Dr. WOODCOCK. I totally agree. Everywhere is right outside with 

modern air travel, and so we are getting soldiers back from combat 

who have acquired very dire resistant infections. We have travelers 

who are coming back in the United States who have been in—there 

36 

are many countries where antimicrobials are used very freely and 

may be available to consumers without intermediaries. 

Mr. BURGESS. And it concerns me that we want to put the onus 

on the doctor treating the patient in an emergency room with a 

sick kid and a concerned family, and we are putting all the onus 

on our physician here when the greater wide world none of those 

constraints exist. I agree with labeling. I agree with making the indications well known, but I don’t think we should ever try to put 

the Federal Government in the position of second guessing the 

judgment of a physician. 

Dr. WOODCOCK. Well, we agree with that. Because treatment is 

empirical, we can’t indicat. It has to be suspected. You can’t say 

you can’t treat a patient because this wasn’t studied in clinical 

trials if there is nothing else available, or if clinicians, as you said, 

must use their best judgment when a patient presents before them. 

We agree with that. We want to give the best directions and information to the clinician so they are aware of not only what clinical 

situation they are dealing with but how much information pertains 

to the drug and what kind of drug it is. 

Mr. BURGESS. Thank you, Mr. Chairman. I will yield back. 

Mr. PITTS. The Chair thanks the gentleman. 

Now, recognize the gentleman from Texas, Mr. Green, 5 minutes 

for questions. 

Mr. GREEN. Thank you, Dr. Woodcock, for being here this morning. It is always a pleasure to have you before our subcommittee. 

I want to commend you and the FDA on the efforts on the GAIN 

Act. I know at least two drugs have been released, and I also want 

to thank you for your efforts on the ADAPT Act legislation I cosponsored with my colleague and good friend, Dr. Gingrey. 

When Dr. Hamburg participated in last week’s Cures round 

table, she spoke about the troubles with large clinical trial designs 

in the antibiotic space. 

Can you tell me your thoughts on how the unique nature and incentives, or even disincentives, inherent to the antibiotic space can 

sometimes make large clinical trials prohibitive? 

Dr. WOODCOCK. Certainly. Well, not only is it actually kind of 

hard to discover new antibiotics, it is expensive to develop them, 

and the reason is you have a—it is really what Dr. Burgess was 

talking about. You have a patient before you with pneumonia. They 

could have all sorts of different organisms causing the pneumonia, 

and without rapid diagnostics, you don’t know what is causing the 

pneumonia. 

And so when a physician is trying to use an investigational drug, 

you have a sick person in front of you, you have a prolonged consent process where you have to have informed consent; people are 

not going to wait, often, to go through that process to start a sick 

person on antibiotics. 

And so then we have the issue that the patients are pretreated 

with different therapies until they get into the clinical trial, and 

then you have all the heterogeneity, and then you have existing 

therapies. It is not ethical to have the comparison group have no 

treatment usually. And so you have to compare it. You have to do 

a comparative trial against existing therapy. Those are typically 

called non-inferiority trials because you may not expect to be better 

37 

than existing therapy; you simply want to show you’re statistically 

as good as. 

So those challenges tend to increase the number of people needed 

to be enrolled in a clinical trial to a very large number, and they 

are hard to get. They are hard to enroll because clinicians often 

don’t want to take sick people and go through all the paperwork 

to get them in a clinical trial. 

Mr. GREEN. OK. 

The ADAPT Act envisions a scenario where more adaptive clinical trials may be used to help drug developers seeking to create 

the next antibiotic effective against drug-resistant bacteria. 

Can you tell me your thoughts on how the pathway laid out in 

the ADAPT Act may benefit drug companies in pursuit of these 

new and novel antibiotics? 

Dr. WOODCOCK. Yes. Well, we envision that you can make trade 

offs based upon the medical need, and we do this in many cases. 

So if you have a tremendous medical need, people are going to die 

quickly, and you have nothing to treat them with, then you will accept a lot of uncertainty about the estimates around safety and effectiveness in exchange for something that may work for that patient. Right? And so that means you can have shorter, very small 

development programs, if the need is huge. 

On the other hand, if we are talking, for example, about another 

drug to treat pneumonia, which is a more common infection for 

which therapies are available, that situation would not be covered 

by the ADAPT Act. With ADAPT we are talking about rare resistant organisms where there are really very few treatment options 

available. And we actually think there are multiple development 

programs that could be done, depending on this level of need. 

In some cases, you may only have ten infections in the United 

States a year of this certain organism. In other cases, you may 

have hundreds. You could get a more robust program there, right? 

But then you are going to be exposing more people when you approve the drug because there are hundreds of people, maybe thousands of people, out there that have the condition. 

So you would basically match the development program and the 

medical need together and put that together, but then we would 

like to have a very strong signal or symbol or whatever, not of a 

fearful signal or whatever, but an informative signal to the clinician that the drug had gone through this kind of development 

pathway so they would understand that. 

Mr. GREEN. Thank you. 

And I hope with this hearing today and we will be able to move 

the ADAPT Act across the line in the future. 

In the coming weeks and months I expect to continue our dialog 

with interested parties and stakeholders, including our second 

panel today, on ways to strengthen this proposal and complete the 

next step in fighting our public health crisis. 

I want to thank you and your staff for your hours you have spent 

working with our offices during the August recess, and I know we 

can continue that effort because this is important. And again, 

thank you for being here. 

And I yield back my time, Mr. Chairman. 

Dr. WOODCOCK. And I thank you for your leadership. 

38 

Mr. PITTS. The chair thanks the gentleman. 

And now recognizes the gentleman from New Jersey, Mr. Lance, 

5 minutes for questions. 

Mr. LANCE. Thank you very much, Mr. Chairman. 

Good morning to you, Dr. Woodcock. 

Dr. WOODCOCK. Good morning. 

Mr. LANCE. As members of the committee, we have heard firsthand the urgent need for greater incentives to encourage new drug 

and diagnostic development in the antibiotic space. 

Some of the witnesses on the second panel have recommended a 

wide range of incentives that would encourage greater development. 

Do you believe that incentives we identify in the antibiotic space 

might also benefit other areas of unmet need such as rare diseases? 

Dr. WOODCOCK. Well, as I said earlier, I believe that there is a 

tradeoff between the incentives you offer. There is always some 

tradeoff there, and there are various orphan diseases for which 

there are many, for which no development is occurring. So I think 

you have to determine whether, those tradeoffs, those economic 

tradeoffs and I am not qualified to say what is the right course. I 

think that Congress makes those decisions. 

However, I can tell you that antimicrobial development is urgent 

and it is a public health issue. The orphan drugs, those people are 

suffering from those, have a tremendous need for therapies to be 

developed, and few are being developed. 

We are doing some things such as working with the National Organization for Rare Diseases to get better natural history studies 

that will incentivize development and make it easier to understand 

what is the course of this orphan disease so we understand what 

is needed to study it. However, there are still major financial obstacles. 

Mr. LANCE. Thank you. 

As you know, I chair the rare disease caucus on the Republican 

side, and I have in my office virtually every week parents of children who suffer from rare diseases where there are no medicines 

at all, and as a society, we have to do a better job, and I have read 

the testimony of those on the second panel, and I hope we can 

move forward. 

And you say you may not be qualified, but I think you are one 

of the great experts in the country on all of these issues, and we 

look forward to working with you in that area. 

Yesterday the President announced an executive order on a fiveyear plan to combat antibiotic resistance. What role, Dr. Woodcock, 

will the FDA play in helping to facilitate the President’s order? 

Dr. WOODCOCK. Yes. Well, we have been working with the planning group on this, and the FDA has a wide range of responsibilities, everything from animal health and those issues, the surveillance activities which are done of antimicrobial resistance, for 

which CDC is the primary lead, but FDA, for example, works with 

CDC and USDA on the National Antimicrobial Resistance Monitoring System, NARMS, which is mentioned in those reports which 

monitors antimicrobial resistant organisms in foods and so forth, 

and these things are intended to be strengthened. 

39 

In addition, we will work on redoubling our efforts to streamline 

antimicrobial development from a regulatory perspective, and obviously there is interest in better diagnostics which is put forth in 

that report. So we have multiple roles to play. 

Mr. LANCE. Thank you. 

And finally, Dr. Woodcock, may Bucknell win all of its games in 

football this autumn except, of course, against Lehigh. 

I yield back the balance of my time. 

Dr. WOODCOCK. Thank you. 

Mr. PITTS. The chair thanks the gentleman. 

Now recognize the gentleman from Illinois, Mr. Shimkus, 5 minutes for questions. 

Mr. SHIMKUS. Thank you, Mr. Chairman. 

And, Dr. Woodcock, it is good to see you back here again, but I 

think you are being too coy. The business model to whether it is 

going to be in diagnostics or testing is the same business decisions 

that we make in our home. It is simply about risk and reward, and 

so what is the reward that will encourage them to stay and what 

is the amount of risk, and I think you all are going to play a big 

role in that, and we would hope you will work with us to do that. 

I have been very excited about this debate of the diagnostic 

space, and in your opening statement, and I had to go onto the 

World Wide Web. All new technology allows us to do that without 

telling staff to go find it and then get it back to us. 

Fleming was born in 1881. Pasteur was born 1822. 

Dr. WOODCOCK. Right. 

Mr. SHIMKUS. Surely if they could recognize our testing procedures now, we have got work to do to ramp it up, I think, and that 

is the whole biosimilar debate and the genetic markings and all 

this other genome stuff that is going on. So I am very, very excited. 

Also I have been involved and helped along with following Dr. 

Gingrey’s lead. Appreciate the work he has done. And Gene Green, 

I look forward to working with Gene as we move forward in the 

next Congress, and we are having discussions to do that. 

So you hear the same questions right from us? And so I think 

what we really want to do, and we will hear it from the next panel, 

is let’s get a handle on this risk and reward, and I am not so adverse to incentivizing the private sector in something that they are 

moving on that is going process and helping them do that if then 

they are going to take and then go in places that no one else is 

going to go. 

So one of the first questions was, as you have seen of companies 

leave the field of antibiotics, are they small, medium, or large? How 

would you classify them? 

Dr. WOODCOCK. Well, I would say that the larger companies, 

most of them have left the area for better pastures, so to speak, 

where they see a business model that provides a return on investment, and similar with many of the medium companies. 

There are many small startups that are trying to get into the 

antimicrobial space and that is good news, but I must recognize 

they aren’t always as successful and they may only have one product that they are trying to develop. 

Mr. SHIMKUS. So, and we have talked a lot about the ADAPT Act 

today, and there has been some success in that process. 

40 

Do you think there are some additional things we can do to 

incentivize? What other things can we build on to encourage additional incentives for the ADAPT Act or other processes that we are 

talking about? 

Dr. WOODCOCK. Well, I think you have to think about what are 

the alternatives. All right? I know there is some government development—there are government awards. Those are usually under 

contract. They are for certain entities—molecular entities. 

So there are a few of those, but what are the other ideas to develop a robust—you need drug discovery effort, and that means scientists working full time in laboratories trying to figure out the 

new molecules. This is way before a drug gets tested in people, and 

it doesn’t really involve the FDA, and what I understand from the 

community, the discovery community, is actually antimicrobial discoveries are quite hard. 

And I didn’t know that until I talked to them, that they have 

screened large numbers of molecules and pathways and so forth, 

and it is harder, it is hard to find the next generation of products. 

And so that means a very robust scientific effort has to go on in 

the basic science of microbes and also in discovery of these new 

molecules, and to do that, somebody has to have the faith that they 

are going to make money from that 10, 15 years hence. OK? And 

they don’t have that faith right now, I can tell you. 

So I don’t think whatever has been done is enough. And because 

you have to consider, if it is not going to be commercial development, how is it going to happen? Where is it going to happen? 

Mr. SHIMKUS. And would help us as we go through this process, 

help this committee to identify ways that we can help incentivize? 

Dr. WOODCOCK. Absolutely. 

Mr. SHIMKUS. I mean, because you are talking with these folks. 

And we will too, but we will need a lot of ears on it. 

And I am going to end just with this, this labeling debate, the 

way I understand it. We went through this debate with the paper 

labelings and the information on pill bottles that no one reads. Everybody knows that. So labeling through the Web and labeling 

through—there has got to be a better way than just to keep putting 

stickers on pill bottles or things, because they are just overwhelmed, and I would like some simplicity in that. That is just a 

statement. 

Dr. WOODCOCK. Could I respond to that? 

Mr. SHIMKUS. Please do. 

Dr. WOODCOCK I think the FDA—CDER is working on developing a patient information leaflet. All right? A one-pager that you 

get either electronically or at the pharmacy that tells you—every 

other country has this kind of thing. OK? So it tells you how to 

take the drug, what it is for, and so forth. 

But then we have proposed and we are interested in going to an 

electronic physician label which is that thing that is folded up inside the pill box. We would like to move that to electronic with 

some paper options for those who are still electronically impaired, 

shall we say. 

But most of the world can easily get that information at Drugs@ 

FDA, and many other sites. 

Mr. SHIMKUS. Thank you. 

41 

Mr. PITTS. Chair thanks the gentleman. 

And now recognize the gentleman from Florida, Mr. Bilirakis, 5 

minutes for questions. 

Mr. BILIRAKIS. Thank you, Mr. Chairman. I appreciate it. 

And thank you for your testimony, Dr. Woodcock. We submitted 

some questions for the record in November, and to my knowledge, 

the committee hasn’t received many responses. So I want to ask 

you one question again. 

Can you tell me how many treatments were approved with novel 

biomarkers used for the first time within the last 5 years? Have 

any accelerated approvals occurred with a novel marker and a 

never before treated disease within the last 5 years? How many 

new biomarkers did the FDA accept for first time use in the last 

5 years? If you can provide that answer. 

Dr. WOODCOCK. Yes. We are working very hard on this. That was 

a very provocative question and, actually, we had a very long debate last week among our senior people on the definition of a biomarker, and which of these end points, such as FEV1, which is how 

fast you can breathe into one of those machines, is that a clinical 

end point or is that a biomarker? Clearly, in my opinion, it is a biomarker, but not everyone agreed with that. So we are working very 

diligently on that. 

The answer is yes. We approve a large number of drugs on biomarkers end points all the time. A very significant proportion of 

the drugs we approve are based on that, and we have approved 

novel ones in the last 5 years, but to get you the count has taken 

a little bit more effort because we had to resolve these definitional 

issues, disputes with that. 

Mr. BILIRAKIS. When do you think we might get some answers 

with regard to the count? 

Dr. WOODCOCK. I am not in control of that time frame, but I can 

tell you we are working very diligently, and I believe you will get 

this response. 

Mr. BILIRAKIS. OK. Well, continue to follow up. 

Dr. WOODCOCK. It was a good question. It really provoked some 

thought internally. 

Mr. BILIRAKIS. Thank you. There was approximately $450 million in direct funding in Fiscal 

Year 2014 to address the antibiotic crises. These funds were allocated across HHS, the VA, of course, DOD, and USDA. About 75 

percent was used for basic and applied research with the rest directed toward stewardship and surveillance. 

Currently how do these various agencies coordinate their efforts? 

Dr. WOODCOCK. Well, there has been a longstanding antimicrobial task force at the agency level across the government that 

was headed at HHS, and FDA has been a part of that. 

The Executive order conceives and directs formation of a higher 

level task force in the government that will direct the implementation of the strategy that was announced. 

But there has long been coordination across the government 

agencies, and I believe the PCAST report discusses that. 

Mr. BILIRAKIS. OK. On this how is the U.S. coordinating with the 

World Health Organization and other organizations as well as 

other countries working to combat antibiotic resistance? 

42 

Dr. WOODCOCK. Yes. We do have, we, the FDA, CDC, and many 

others have relationships withthe World Health organization, and 

I think the Executive order yesterday and the strategy conceives of 

much tighter collaboration with WHO in a very concerted way. 

Mr. BILIRAKIS. OK. Thank you very much. 

And I yield back, Mr. Chairman. Appreciate it. 

Dr. WOODCOCK. Thank you. 

Mr. PITTS. Chair thanks the gentleman, and now recognize the 

gentlelady from Colorado, Ms. DeGette, 5 minutes for question. 

Ms. DEGETTE. Thank you very much, Mr. Chairman. 

I think this has been an excellent discussion, and I just wanted 

to ask you to clarify one thing, Dr. Woodcock. 

Mr. Outterson on our next panel is going to talk about the report 

on initiatives by the Eastern Research Group, and what that report 

concludes is that shortening clinical trial time frames is an unlikely contributor to innovation. 

We have been hearing counter arguments to this that without 

something like the approach taken in the ADAPT Act that I am a 

cosponsor of, it just isn’t feasible to do clinical trials on drugs intended to treat the most serious and resistant pathogens. 

So from that perspective, ADAPT might be considered a necessity 

but not a sufficient condition for developing the most needed antibiotics, but also it would need to be paired with other incentives 

to spur investment in that area. 

So I am wondering if you can just spend a minute giving us your 

views on this issue because, really, it seems to go to the heart of 

whether we should even go forward with the ADAPT Act? 

Dr. WOODCOCK. Well, clearly there are multiple barriers to antimicrobial drug development for antimicrobial resistance. I do agree 

that the streamlining of clinical trials for testing drugs that treat 

resistant organisms will stimulate development in that area. Why? 

Partly because developers have told me that. 

But two, because we know from experience that if we have a 

clear path to market and people understand it, they are willing to 

put their money down, betting that they will have a molecule that 

can get approved. 

But this is clearly not sufficient. Number one, we are only talking about the most resistant organisms here and a small cadre of 

drugs to treat them. 

We also need a robust pipeline of discovery that will lead to new 

drug candidates for all different kinds of infections. 

So the limited population antibacterial drug idea and the streamlining of clinical trials, which wouldn’t just decrease the time 

frame, it would also decrease the cost and the number of people 

needed. So it would do a number of things. 

That is one thing that we can do at FDA that we think would 

be beneficial and would be beneficial for patients, but it is not 

going to fix this problem we have of investment. 

Ms. DEGETTE. Thank you. 

Mr. Chairman. I yield back. 

Mr. PITTS. I think that concludes this round of questioning. We 

will have follow-up questions, I am sure, from members. We will 

send them to you and ask that you please respond. 

43 

But, again, Dr. Woodcock, you are a terrific witness. Thank you 

for your being so forthright and clear in your answers. 

And we will now take a 3-minute recess as we set up for the second panel. 

Dr. WOODCOCK. Thank you. 

[Recess.] 

Mr. PITTS. The subcommittee will reconvene on our second panel. 

Today we have and I will introduce them in the order that they 

will make their presentations. 

First, Dr. Kenneth Hillan, Chief Executive Officer of Achaogen; 

Dr. Barbara Murray, President, Infectious Disease Society of America; third, Dr. Adrian Thomas, Vice President of the Global Market 

Access and Global Public Health, Janssen Global Services; and 

then Mr. Kevin Outterson, Professor of Law, Boston University 

School of Law; Mr. Allan Coukell, Senior Director, Drugs and Medical Devices of the Pew Charitable Trust; and Dr. John Powers, Assistant Clinical Professor of Medicine, George Washington University School of Medicine. 

Thank you all for coming. Your written statements will be made 

a part of the record. You will each have 5 minutes to summarize 

your testimony. 

And we will begin with Dr. Hillan. You are recognized 5 minutes 

to make your opening statement. 

STATEMENTS OF DR. KENNETH J. HILLAN, CHIEF EXECUTIVE 

OFFICER, ACHAOGEN, INC.; DR. BARBARA MURRAY, PRESIDENT, INFECTIOUS DISEASE SOCIETY OF AMERICA; DR. 

ADRIAN THOMAS, VICE PRESIDENT, GLOBAL MARKET ACCESS AND GLOBAL PUBLIC HEALTH, JANSSEN GLOBAL 

SERVICES, LLC; KEVIN OUTTERSON, PROFESSOR OF LAW, 

BOSTON UNIVERSITY SCHOOL OF LAW; ALLAN COUKELL, 

SENIOR DIRECTOR, DRUGS AND MEDICAL DEVICES, THE 

PEW CHARITABLE TRUSTS; AND DR. JOHN H. POWERS, ASSISTANT CLINICAL PROFESSOR OF MEDICINE, GEORGE 

WASHINGTON UNIVERSITY SCHOOL OF MEDICINE 

STATEMENT OF DR. KENNETH J. HILLAN 

Dr. HILLAN. Thank you. 

Good morning and thank you, Mr. Chairman and members of the 

committee for inviting me to testify today. 

It was also heartening to hear the recognition of the work of Alexander Fleming, my fellow countryman. Of course not only did he 

discover penicillin, but actually when he received his Nobel Prize, 

he also spoke of the danger of the ignorant man who may easily 

underdose himself by exposing the microbes to non-lethal doses, 

make them resistant. That was back in 1945. 

I am the chief executive officer of Achaogen, a company focussed 

on discovery, development, and commercialization of novel antibiotics for multi-drug resistant gram-negative infections. 

It is a small company with fewer than 50 full-time employees 

and is based in the San Francisco Bay area. We are a member of 

the Antimicrobial Innovation Alliance, a coalition created to address the unique challenges that we have heard about today. 

44 

As you have already heard, antibacterial resistance is one of the 

most significant medical challenges our country faces today, and at 

Achaogen, we are committed to trying to find solutions. 

Our lead product candidate, plazomicin, which has been engineered specifically for multi-drug resistance is currently being evaluated in phase 3 clinical trial in patients with bacterial infections 

caused by carbapenem resistant Enterobacteriaceae, and the 

carbapenems are considered to be our last line of antibiotic defense 

in settings where antibiotics are no longer active. 

The phase 3 trial utilizes a superiority designed to demonstrate 

a reduced number of deaths in patients treated with plazomicin 

based therapy versus the best available standard of care, which, 

unfortunately, is not very good today. 

We have also developed the diagnostic assay that has being used 

in the phase 3 trial to measure plazomicin blood levels to try to 

help to individualize dosing for patients which we believe will improve outcomes. 

The innovative design and incorporation of the diagnostic assay 

required close consultation and coordination with both the drug 

and diagnostic branches of the FDA, and we find our interactions 

with the agency to be extremely collaborative and believe this approach serves as a model for how the FDA can help to facilitate 

companies with development of antibiotics in settings of urgent 

unmet medical need. 

The plazomicin program is also benefited by receiving the first 

contract awarded through the Broad Spectrums Antibacterial program from the Biomedical Advanced Research and Development 

Authority, also known as BARDA, and this contract is designed to 

advance plazomicin through approval by the FDA and could provide over $100 million in total funding. 

However, even with plazomicin in a groundbreaking phase 3 

study, a great team back at Achaogen, and exciting early stage 

pipeline, a successful IPO, and significant government investors 

aboard, it has not been easy, and there remains significant barriers 

for companies developing antibiotics, and we can and must work together to address these obstacles so that effective antibiotics will 

always be available for patients. 

We would like to propose significant changes in four key areas. 

First, we believe new economic incentives are key. There is a 

need for reimbursement reform for antibiotics and for additional incentives, both push and pull mechanisms. The economics of developing new antibiotics is not currently attractive to the pharmaceutical industry, and many leading companies have exited from 

the antibiotic space. This has lead to a decline in the number of 

new antibiotic approvals, and has heralded the increase in antibiotic resistance. 

Commercial returns for an antibiotic are limited by the fact that 

generic antibiotics are cheap. New antibiotics are used sparingly to 

preserve their use. Reimbursement at hospitals is limited to a fixed 

payment system that is intended to cover the total cost of patient 

care, and because longer-term returns are eroded by the unavoidable development or resistance. 

45 

Furthermore, other therapeutic areas such as oncology or diabetes provide pharmaceutical companies with much more attractive 

opportunities for a return on their investment. 

We believe the DISARM Act sponsored by Congressman Pete 

Roskam and Danny Davis has been proposed for reimbursement for 

qualifying antimicrobial products in a hospital setting. We belive 

this would provide a powerful incentive as currently the payment 

to the hospital is the same regardless of the price of the antibiotic. 

So hospitals are incentivized to use the cheapest but not always the 

best and most effective antibiotic. By providing separate reimbursement for qualifying antibiotics, the DISARM Act would eliminate 

an important barrier to the use of more expensive antibiotics. 

Achaogen supports passage of the DISARM Act, and we would 

like to see reimbursement for qualifying antibiotics extended beyond Medicaid and Medicare patients to patients covered by private insurance. 

Second, the FDA needs authorization for greater flexibility for 

approval of antibiotics based on limited clinical data sets, and we 

have heard the rationale for that today. 

Plazomicin is following a streamlined development program with 

a single phase 3 trial. However, due to the need to power the study 

to demonstrate statistical significance for a mortality end point and 

the relative rarity of these infection times, the enrollment period 

for this study is expected to take 3 years. 

In contrast in Europe, recent EMA guidance extends more flexibility in the scenario of unmet clinical need and does not require 

inferential statistical testing for antibiotic approvals. 

In order for new drugs to be available ahead of the emergence 

of unacceptably large numbers of drug resistant infections, Congress must enact legislation that authorizes the FDA to approve 

new antibiotics for limited patient populations based on smaller 

clinical trial data sets, but where the totality of the available evidence supports a favorable benefit risk profile for the antibiotic 

while acknowledging and reflecting the greater uncertainty associated with limited testing in the product label. 

Achaogen supports passage of the ADAPT Act to provide the 

FDA with the increased flexibility that we believe it needs. 

Third, there is a need for more rapid point of care diagnostic 

tests and a more streamlined approval path for diagnostics. For serious infections, a delay in the administration of the right antibiotic 

by just one hour significantly increases patient mortality. Traditional diagnostic tests, as we have heard, from the days of Louis 

Pasteur may take 72 hours to complete, and we believe the Federal 

Government could make a significant impact by providing support 

and incentives for the development of rapid and cost effective point 

of care diagnostics that advance antibiotics stewardship and clinical care. 

There is also an opportunity to streamline the regulatory process 

for development and approval of companion diagnostics tests. 

There is a need for an expedited and iterative approach to diagnostic development and approval through regulations that are anchored in consideration of the urgency of the unmet medical need 

and the overall benefit/risk for patients. 

46 

The regulation should provide the FDA with flexibility to streamline the required analytical studies as well as a testing related to 

quality manufacturing software and documentation for the diagnostic device. 

And, fourth and finally, we need sustained funding for antibiotic 

research and development. We must be prepared to take a longterm perspective in order to fully realize the public health benefits 

that will be derived from increasing funding for antibiotic research 

and development. 

The funding that Achaogen has received from BARDA, NIAID, 

and the Department of Defense have been essential, and we believe 

it illustrates how public/private partnerships can successfully advance antibacterial research and development. 

We support increased funding on an ongoing and predictable 

basis for BARDA’s broad spectrum antibacterial program and the 

expansion of BARDA’s mission to allow investment and programs 

designed to address the public health threat posed by antibacterial 

resistance. 

We also support continued funding through NIH devoted to antibacterial discovery and development. 

We appreciate the opportunity to contribute to the discussion 

today, and strongly encourage Congress to take additional measures to mitigate the very significant public health threat posed by 

multi-drug resistant gram-negative bacteria. 

Mr. PITTS. Chair thanks the gentleman. 

[The prepared statement of Dr. Hillan follows:] 

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93933.032
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93933.035
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93933.036
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Mr. PITTS. And now recognizes Dr. Murray 5 minutes for an 

opening statement. 

STATEMENT OF DR. BARBARA MURRAY 

Dr. MURRAY. Thank you very much, Mr. Chairman. 

Thank you for inviting me to testify on behalf the Infectious Diseases Society of America, IDSA, on the public health crisis of antibiotic resistance and the urgent need for new antibiotics in 

diagnostics. 

IDSA is grateful for this subcommittee’s continued leadership on 

these critical issues. 

Physicians are seeing more and more patients with very serious 

infections that are resistant to all or almost all antibiotics. For example, I recently saw a young woman with severe lupus, an autoimmune disease, who developed a very painful bile duct infection 

that persisted despite multiple antibiotics, endoscopies and surgical 

interventions. The infecting bacterium invaded her blood stream 

and it developed resistance to every antibiotic available, including 

colistin, a toxic antibiotic usually of last resort. Finally, all we 

could do was send her to hospice for palliative comfort care while 

she waited for the infection to claim her life after a very prolonged 

and expensive stay in the hospital. 

A colleague of mine recently took care of a very active patient in 

his sixties following a prosthetic knee replacement, he developed a 

serious pseudomonas infection that, despite removal of the implanted joint and multiple antibiotics, could not be controlled and 

he had to have an above-the-knee amputation. 

This summer I cared for two diabetic women with urinary tract 

infections, or UTI, who had to be admitted to the hospital, not because they were so seriously ill, but for IV therapy because their 

infecting organism was resistant to all oral antibiotics. 

For anyone who has had a UTI, which is going to be most of the 

women in this room and some of the men, having to be hospitalized 

for such a common infection is inconvenient, decreases productivity, 

and markedly increases our health care costs. 

Antibiotic R&D, as you have heard, faces significant barriers. 

Discovery is hard. Scientific challenges lead to very high development costs. Economically, antibiotics have a very poor return on investment because they are typically priced low, used for a short duration, and held in reserve by us to try to control antibiotic resistance. 

IDSA thanks the subcommittee, and especially Representatives 

Gingrey and Green, for its leadership in enacting the GAIN Act in 

2012, which is beginning to address some of the economic barriers. 

We hope you can now build on these efforts and address current 

regulatory barriers. 

Specifically, extensively resistant bacteria currently infect relatively small numbers of patients, making it virtually impossible, 

as you have heard, to populate traditional, i.e., large clinical trials, 

but we need to develop new drugs before there is an epidemic. 

Think of how our fear for Ebola would be much less if there were 

already effective therapies. 

56 

Representatives Gingrey and Green introduced the ADAPT Act, 

which would address this regulatory conundrum by allowing FDA 

to approve certain antibiotics with smaller trials. This approach 

would only be for antibiotics to treat serious infections where there 

is an unmet medical need. ADAPT would make trials of highly resistant bacteria feasible, possibly less costly, and it would allow 

FDA to assess the risk of a new antibiotic relative to its potential 

benefit to this limited population. 

IDSA is deeply concerned that without ADAPT many of the most 

urgently needed antibiotics would not be brought to the market. 

The strategy of a limited population approval pathway was also 

suggested in the PCAST report that you heard yesterday. 

ADAPT includes safeguards to help ensure that these drugs are 

used appropriately. It also contains multiple important provisions 

to ensure that susceptibility tests, interpretive criteria, or break 

points, which predict whether a patient will have a good response 

to an antibiotic, are quickly updated and made publicly available. 

Up-to-date information is crucial for clinical care and to ensure 

that antibiotics are not misused or overused. 

IDSA urges the subcommittee to mark up the ADAPT Act swiftly. 

As also mentioned in the PCAST and earlier today, additional 

economic incentives are required, such as public/private partnerships; support for Federal agencies that invest in antibiotic researched; improved reimbursements and/or tax credits. 

Ernst & Young estimated that an IDSA tax proposal targeting 

R&D for these needed antibiotics would result in an additional five 

to seven new antibiotics in the pipeline every year. 

While new antibiotics are critical, IDSA is also committed to a 

multi-prong response to antibiotic resistance, including a well-coordinated Federal leadership, as mentioned in the PCAST report; 

sustained involvement of nongovernment stakeholders; antibiotic 

stewardship programs in every health care facility; enhanced surveillance of antibiotic use and resistance patterns; and research on 

novel strategies to prevent and control antibiotic-resistance organisms. These steps are critical to protect patients, the public 

health, and the Federal investment in new antibiotics. 

Lastly, again, as you have heard, it is extremely important to 

promote the development and clinical integration of new 

diagnostics. Rapid point-of-care diagnostics can reduce inappropriate antibiotic use which drives resistance by lessening the need 

for empiric or shotgun therapy. 

IDSA recommends increased investments in diagnostics research, 

regulatory approval pathways, strengthening in reimbursement, 

and supporting outcomes research to demonstrate the impact of 

diagnostics on patient care. 

Thank you again for allowing me to testify here and for your continuing efforts in this very important area. 

Mr. PITTS. Chair thanks the gentlelady. 

[The prepared statement of Dr. Murray follows:] 

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Mr. PITTS. Now recognizes Dr. Thomas. Five minutes for questions. 

STATEMENT OF DR. ADRIAN THOMAS 

Dr. THOMAS. Thank you, Chairman Pitts and members of this 

committee for this opportunity to come before you today. 

I am Dr. Adrian Thomas, vice president at Global Market Access 

and head of the Global Health function at Janssen which is the 

pharmaceutical business of Johnson & Johnson. 

On behalf of Johnson & Johnson, I applaud you for organizing 

this hearing and commend all the leaders in this room for giving 

voice to the dire situation of antibiotic resistance. 

We also recognize this committee’s and Congress’ leadership, as 

well as the leadership of President Obama on this important issue, 

and we offer our support for the national strategy announced yesterday. 

Today I bring the lens of a private sector physician through more 

than 30 years’ experience in public health from my early career in 

the Australia’s Flying Doctor Service to my current role overseeing 

Janssen’s portfolio of production and services for diseases of high 

public health impact, which include HIV, tuberculosis, and also 

more recently, Ebola. 

I am a clinical pharmacologist and physician by training, with 

additional expertise in a variety of areas in the health care industry. The majority of my 17 years in the private sector has been 

with Johnson & Johnson. 

As many of you know, Johnson & Johnson is the world’s largest 

and most broadly based health care company, with a portfolio that 

also includes diagnostics and devices as well as the consumer products. 

We are an innovation-based business, and it is critical, as you 

think about this issue, that we address incentives that apply and 

are relevant to many different stakeholders in the area of innovation, not just large companies, but discovery, academic research, 

biotechs and start-up in the public sector. 

Our place in and reach across the health care innovation ecosystem allows us unique visibility into both the number and the 

status of projects underway across areas of unmet need, including 

antibiotics. It also leads me to comment that as we consider incentives for antimicrobial resistance, we should also consider incentives in vaccines and other preventive mechanisms and diagnostics 

if we are truly going to make progress against this terrible issue. 

Our work also brings us into proximity with patients facing lifethreatening illnesses, including patients with these infectious diseases. Their stories affirm what we have heard day; that we must 

do more to meet their needs. 

First and foremost, we must work together and think differently 

to bring forward new therapies. We have heard in some detail 

today that despite the need in recent efforts to improve it, including legislative efforts, the innovation climate for antibiotics and 

other antimicrobial R&D remain suboptimal. That is, in large part, 

because the basic science with this field continues to be very difficult with high rates of failure. If failure is no longer an option 

77 

given this critical and growing global health security, I would term 

it, crisis, then we need to take different measures. 

We can learn lessons and warnings from the Ebola crisis, which 

was also neglected, and which now we have companies scrambling, 

including our own, to try and provide new vaccines within 

unfeasibly short time frames and unfunded mechanisms. 

While strategies for better stewardship of antibiotics on the market are vital in the fight against resistance, current conditions demand that we need a new framework for innovation in antibiotics 

R&D. We have to track the world’s best and brightest to this challenge, including the private sector. 

As is done in other areas, the U.S. can and should lead the world 

in creating enabling conditions. We cannot wait for the European’s 

Medicines Initiative to solve the problems for us. 

It is our hope that this committee and the Congress will give serious consideration to new legislative proposals. Beyond this, we 

believe there remains the need to put forward a comprehensive set 

of both push and pull incentive options specific to antibiotics that 

address the need for R&D across a wide range of stakeholders. 

We must create a broad set of highly attractive although financially manageable incentives to engage the many different biomedical innovator companies large and small in this work, including academic networks. 

The policies can and should be able to take into consideration a 

holistic view of the costs and risks of this, and also the costs and 

risks of developing, introducing, and supporting these products 

worldwide. And how those risks are different for different stakeholders and the incentives must address, therefore, those different 

stakeholder perspectives. 

I would like to talk a little bit about transferable market exclusivity. We have heard different perspectives on this topic. As our 

company has undertaken its own in-depth analysis of different incentive proposals for antibiotic R&D, it is apparent that many existing proposals only offer marginal valuations. 

In addition to being a physician, I serve on the investment committee of our pharmaceutical business. I balance the difficult 

choices we have to make about, is Ebola, is multi-drug resistant tuberculosis, is diabetes, is cancer a more important public health 

question, and is it also financially feasible for us to balance our research efforts in this area. 

Spending almost $5 billion annually in research in pharmaceuticals, these decisions are not easy, and often have timeframes 

of 10 to 15 years. 

Thinking about transferable market exclusivity, the notion of an 

exclusivity that can be applied towards another product not only 

gives certainty the investments be made in very high-risk areas, 

but also disincentivize activities that might otherwise undermine 

both the public health stewardship and the protection of these 

products and assets need to offer against emerging and developing 

antibiotic resistance to encouraging appropriate use. 

The bottom line to our proposal is we believe we have to have 

more shots on goal, more basic research, more discovery, more 

biotech start-ups, more academic partnerships, more companies investing, and the in-house facilities to recognize and take up new 

78 

assets, and to conduct the expensive research necessary to deliver 

and develop these products to the marketplace. 

In conclusion, we welcome the changes in public policy to stimulate new antibiotic R&D, and thank you very much for your time 

today. 

Mr. PITTS. Chair thanks the gentleman. 

[The prepared statement of Dr. Thomas follows:] 

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Mr. PITTS. And now recognizes Mr. Outterson. Five minutes for 

an opening statement. 

STATEMENT OF KEVIN OUTTERSON 

Mr. OUTTERSON. Good morning, Mr. Chairman, and thank you, 

for inviting me to testify today. 

I am a professor at Boston University. I also serve on the Centers for Disease Control and Prevention Antimicrobial Resistance 

Working Group, and at the Royal Institute for International Affairs 

in London as a visiting fellow at Chatham House. 

My remarks today are my own, but at Chatham House, the work 

that we have been doing for the past year is focussed onto linkage. 

I think today we need to focus and act decisively because the 

business model for antibiotics is broken. Not only for antibiotics but 

for other things that treat and prevent infectious diseases such as 

diagnostics, vaccines, infection controls, and related devices. 

And so I have a couple of slides here to look at the business 

model, and the slides are based on the study that was done by the 

Eastern Research Group of which I was a part, I am a co-author 

of that study, for the department of Health and Human Services. 

This first slide no one in the committee needs to see this, honestly. We know that this a huge problem. The actual number of 

deaths in the CDC threat assessment was 37,000 per year because 

they included Clostridium difficile. It is a huge problem. 

So let’s look at the business model, and we are looking at the net 

present value from a private perspective. This is a company looking 

to make a decision about whether to invest in a molecule at an 

early stage. And this is a typical decision tree which tries to analyze for the company what is the chance of failure at each stage 

and how much it will cost to advance the molecule through. 

Every company uses a model like this. Everyone might use 

slightly different assumptions or numbers in it, but this is a typical 

thing done in the industry. In fact, there is in England right now 

at the Office of Health Economics using AstraZeneca data there is 

another study almost completed which comes out with I must, sad 

to say, much gloomier numbers than what we present here today. 

So the business model is broken. The first thing we looked at, the 

FDA and Health and Human Services asked us to look at six bacterial indications, and it is hard to read, and I am sorry for that, 

but what you need to see is that the companies were hoping for 

$100 million net present value. That was the money that they 

would get in return. 

And you see here on the arrow bars and on the colored things 

that for several of these indications they have a negative net 

present value. They are actually going to lose money after they 

build a factory to make this drug. And for others there was a positive one but nowhere here the $100 million threshold that was necessary for companies to move forward. 

The red arrow bars, the little light thing, is the 90 percent confidence interval. For every single indication, the confidence interval 

included a negative number. So it is really difficult for companies 

to commit to research programs in that sort of space. 

The second thing we were asked to look the is the social net 

present value. How valuable are these drugs to society. Now, we 

93 

didn’t have speculative numbers here. We didn’t look at the effect 

on reducing resistance. We didn’t model how it would keep us all 

working. You know, the kind of ancillary effects. We just looked at 

the direct cost for society. And yet the numbers we came up with 

were huge. These numbers are in the billions, and the arrow bar 

ranges are huge. So the social net present value for many of these 

drugs was two orders of magnitude higher. Several billion dollars 

for several of these drugs. 

In other words, society would be getting a tremendous bargain 

if it was able to procure one of these drugs for even a fraction of 

that amount. 

As a comparison, I compared for each of the six indications the 

social and the private, and if you look real carefully, you can’t even 

see the private on the same scale because it is in blue. It is so 

small it is almost impossible to see. There is a huge gap here. 

So I did just one and tried to stretch it out across the slide, and 

you can barely see the blue for HABP/VABP. OK? And so what I 

did here is I truncated everything at 100 million. Those red bars 

really would go up another 15 feet on the wall if I allowed them, 

and that is the gap between the social and private value. It is another way of saying we are tremendously under reimbursing for 

antibiotics. 

We also looked a incentives, and given that I have 30 seconds, 

I will get down to the key chart in which we modeled which incentives could we change in order to solve this $100 million benchmark. We looked at every incentive ever published, I promise you, 

and then put them in the different categories and fed them into 

some model. 

The short answer is that if you do something that affects the cost 

of capital, it has to be fairly significant in order for it to work. So 

if we had tax credits or BARDA funding, it better be significant in 

order to kick in; something on the range of a billion dollars per 

molecule we would want coming out the other side. So we are not 

talking small change. It is large. 

Yesterday’s proposal from the president $800 million under 

BARDA, they are hoping for one drug per year out of that. I think 

it is a reasonable number. 

Things that don’t seem to work based on the model. We even had 

unlimited perpetual forever patents. It still didn’t get the companies anywhere near the $100 million threshold. 

Similarly, to reduce clinical trial times, you would have to reduce 

it by 75 percent. So ADAPT could be very useful to bring a new 

drug to market for the people who need it today, but it should not 

be viewed as a powerful economic incentive for a company early in 

the stages to decide now is the moment to green light this drug. 

It doesn’t have that sort of effect. What the companies need is 

money, not the promises of earlier approval. 

Thank you. 

Mr. PITTS. The chair thanks the gentleman. 

[The prepared statement of Mr. Outterson follows:] 

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Mr. PITTS. Now recognizes Mr. Coukell 5 minutes for open statement. 

STATEMENT OF ALLAN COUKELL 

Mr. COUKELL. Mr. Chairman, I would like to thank you and the 

ranking member and the members of the committee for the opportunity to be here today. 

My name is Allan Coukell. I direct drug, medical device, and food 

programs at the Pew Charitable Trusts. We are independent research and policy organization with a longstanding focus on the urgent need for new antibiotics. 

As you have already heard, the dwindling pipeline of antibiotics 

is a potential public health crisis. Every one of us will need one of 

these drugs in our lifetime, and most of us already probably know 

somebody who has had a resistant infection. 

Children and seniors are particularly vulnerable, as are members 

of the military. One-third of those injured in Iraq and Afghanistan 

came back with an infection, some of them resistant to almost all 

existing drugs, and among the broader population, 23,000 Americans die every year from resistant infection. 

So a comprehensive response requires infection prevention and 

surveillance in reducing unnecessary use and better diagnostics. 

But my focus today is steps to reinvigorate the drug pipeline. 

And the state of the pipeline is not good. A Pew analysis included 

in my written statement finds 38 drugs, antibiotics, now in clinical 

testing. Five of them in advanced development have some potential 

to treat Gram-negatives, which are probably the most serious immediate threats. That may sound encouraging, but let’s recognize 

just based on general trends that 80 percent of those won’t reach 

market. They will fail because of reasons of toxicity or lack of effectiveness. 

What is more, very few of the drugs now in development actually 

have novel mechanisms of action that would significantly delay the 

onset of resistance. 

So what can be done? By passing the GAIN Act two years ago, 

this committee has already taken a leadership role. GAIN, introduced by Dr. Gingrey, Mrs. DeGette, and Mr. Green extends market exclusivity for certain antibiotics. This gives companies a better 

chance of a positive return in investment. GAIN also ensures swift 

FDA review of these drugs. 

That was an important first step, and more is needed, especially 

for the infections that are hardest to treat, and as has been mentioned, trials of antibiotics are hard because only a small proportion of the population with, say, pneumonia has a resistant bug at 

any given time. 

So to help address these challenges, Dr. Gingrey and Mr. Green 

and a long list of bipartisan cosponsors have introduced the 

ADAPT Act. ADAPT would create a new FDA approval pathway for 

antibiotics to treat patients with few or no other treatment options. 

This approach, which is also called LPAD, for Limited Population 

Antibacterial Drug, meets both a public health goal and helps 

streamline development. 

So let me make it concrete with two different scenarios. Imagine 

drug A which is approved for a range of bacterial pneumonias, 

113 

some easily treated, some resistant. When FDA approves drug A, 

it has to consider the universe of people who might get it. Some 

of them have lots of treatment options and won’t be willing to accept greater uncertainty. 

Now take a second drug, drug B, which is an LPAD drug only 

for life-threatening pneumonias caused by a resistant organism. 

The patient with this infection may well die if he doesn’t take drug 

B. So the potential benefit may be greater against the uncertainty. 

And the FDA, in making a benefit/risk calculation only for patients like our patient, can accept less data in approving the drug. 

That reduces development costs. 

To be clear, this does not change the standard of approval. It 

merely targets a specific population that is different from the general population. 

For LPAD to work as intended, health care providers have to 

know and understand that the drug is approved for the limited 

population based on limited data. The drug’s special status has to 

be clearly communicated through drug labeling and any marketing 

materials. 

To vet this concept, Pew has worked with the Infectious Disease 

Society, antibiotic stewardship personnel, drug companies, health 

insurers, the FDA, and others, and this legislation has the support 

of numerous and diverse stakeholders, and yesterday PCAST, the 

President’s Council of Advisors on Science and Technology, also 

called for such legislation. 

This committee has long understood the threat of antibiotic resistance and has done much to bring it to the national stage, and 

we appreciate your leadership and continued commitment. 

Let me conclude with the observation that we face many intractable problems in many diseases that seem intractable. This is not 

one of them. Bacterial infection is a solvable problem. Penicillin 

and the heyday of the drugs that followed effectively conquered 

bacterial illness for a time, and we can get back there if we commit 

and ensure that we do it again. 

I thank you and I welcome your questions. 

Mr. PITTS. The Chair thanks the gentleman. 

[The prepared statement of Mr. Coukell follows:] 

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Mr. PITTS. Now recognizes Dr. Powers 5 minutes for an opening 

statement. 

STATEMENT OF DR. JOHN H. POWERS 

Dr. POWERS. Thank you very much, Mr. Chairman. Thank you 

for inviting me to testify. 

I am a practicing infectious diseases and internal medicine physician, and a medical researcher who actively cares for patients. I 

was a scientist at FDA for almost a decade and the co-chair of the 

Inter-agency Task Force on Antimicrobial Resistance, and I am a 

member of the WHO Advisory Group on Antimicrobial Resistance. 

I am speaking today on behalf of the National Physicians Alliance. NPA is a professional home to physicians in more than 40 

medical specialties. We share a commitment to patient-centered 

health care, evidence-based health policy, and professional integrity. NPA does not accept pharmaceutical company funding. We believe in the advancement of knowledge through research that is 

free of financial conflicts of interest, transparent, and peer reviewed. NPA’s FDA Task Force was established to support our 

work in defense of a strong scientifically rigorous FDA. 

As members of this committee have pointed out, studies of infectious diseases in the early 1900s, at a time when there were no effective therapies, were the first to use the modern methods of adequate and well-controlled trials that are a part of law today. Investigators and then members of Congress realized that appropriate 

study methods are critical in order to separate the harmful from 

the helpful for patients. 

The problems of antibiotic resistance and the scientific and regulatory responses to it are also not new. Dr. Scott Podolsky in his 

recent book, The Antibiotic Era, recounts that during the rise of resistance the common staphylococcal infections in the 1950s, drug 

companies marketed numerous ineffective antibiotics based on supposed superiority in the test tube. 

Dr. Maxwell Finland, the first president of the Infectious Diseases Society of America, with 19 other prominent infectious disease clinicians, pointed out the need for adequate and well-controlled studies in patients. He said, ‘‘Properly conducted clinical 

studies may support the claims and justify the enthusiasm for 

these antimicrobial agents, but it is incumbent upon those of us 

who are intimately concerned with the welfare of our patients to 

wait until such data are presented before we accept and acclaim 

any new agents or recommend them for general use.’’ 

In 1962, Dr. Finland made these same points at the Senate hearings that resulted in adding the requirement for effectiveness for 

new drugs based on substantial evidence from adequate and wellcontrolled studies showing that, like with other drugs, antibiotic effectiveness cannot be assumed based on test tube tests, animal 

studies, or mathematical modeling, but can only be verified by 

studies that ask the right questions with the right outcomes in the 

patient who might benefit from experimental drugs. 

The problem of antibiotic resistance today is the same as it was 

in years past. The unmet medical need exists in those patients who 

have no effective therapies. The need for treatments with improved 

126 

effectiveness compared to older treatments on the outcomes of decreasing death or irreversible disability, not alternative outcomes. 

The program described by Dr. Hillan exactly focuses on this population and these outcomes. 

Drugs marketed as life saving should actually be shown to save 

lives in adequate and well-controlled studies using appropriate 

diagnostics such as those we have discussed this morning and advocated in yesterday’s PCAST report to select the patients who 

would receive added benefit from those drugs. And susceptibility 

criteria should be based on patient outcomes, not mathematical 

modeling from sources without conflicts of interest. 

Drugs that are highly effective need few patients to show those 

effects in adequate and well-controlled studies. Therefore, the sample size of a study is related to how effective the drug actually is. 

It is ethically questionable to expose our patients who have any 

current effective and safe options to less effective treatments in 

order to have a robust pipeline or as an economic stimulus to companies. It is scientifically invalid to test drugs in patients with disease due to susceptible organisms and then assume effectiveness in 

older sicker patients with disease due to resistant pathogens based 

on assumptions from modeling and individual and anecdotes. 

Recent clinical trials of new antibiotics carry warnings on FDA 

Web site of increased death compared to older effective drugs despite promising test tube tests, animal models, and mathematical 

modeling. A recent study by AHRQ showed a lack of evidence that 

this kind of mathematical modeling has been shown to result in 

better patient outcomes. This shows that now, as in past years, 

preliminary information is not a substitute for clinical studies in 

patients. 

Patients who wish to take an informed risk should have access 

to these drugs through requirements for expanded access under existing FDA programs for patients who do not qualify for ongoing 

clinical research studies, as was done in the early years of the HIV 

epidemic to allow access to new therapies while the drugs are continued to be evaluated in adequate and well-controlled studies prior 

to widespread marketing. 

FDA labeling should accurately reflect the benefits, the types of 

patients who benefit, how clinicians should select those patients, 

and the information used as the basis for approval. Telling clinicians a drug has not been studied properly does not help clinicians 

prescribe new drugs appropriately. 

Our written testimony provides NPA’s plan for a comprehensive 

approach to development, disease prevention, stewardship, diagnosis and reimbursement strategies for improved therapies of infectious diseases in line with the recommendations from the president’s PCAST report released yesterday. 

Dr. Finland sums up the issues we discuss today and that we as 

physicians still agree with today when he said, ‘‘Clinical investigators and authors of medical and scientific publications have the 

duty to protect the medical profession and the public against the 

abuse of preliminary scientific information and against the improper and premature exploitation of conclusions based on inadequate data.’’ 

Thank you very much for the opportunity to testify. 

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[The prepared statement of Dr. Powers follows:] 


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Mr. PITTS. The chair thanks the gentleman, thanks to all of the 

presenters for their testimony. We will begin questioning, and I 

will recognize myself 5 minutes for that purpose. 

Dr. Thomas, you mentioned in your testimony that a multipronged strategy is needed that includes both stewardship and antibiotic innovation incentives. If you think about the path to cures 

as being three phases, discovery, development, and delivery, do you 

believe that we need incentives in all three phases to have an effective incentive strategy? 

Dr. THOMAS. Thank you for the question, Mr. Chairman. Yes, I 

do, because I think often the players or the stakeholders who are 

conducting that research at those different stages are different. 

And what incentivizes academic or biotech startup might be different from what incentivizes a multi-national corporation like 

Johnson & Johnson, might be different from organizations that are 

involved in healthcare delivery. 

So one incentive is not going to—as we have seen, frankly, since 

we have had incentives introduced, we still have an empty pipeline 

of incentive is not going to solve this problem. It may well be that 

large grants or so-called prizes would attract academic researchers 

and startups. A very different incentive needs to encourage venture 

capitalism to go and back startup companies with a much higher 

level of risk. And for a company like Johnson & Johnson, we look 

at a portfolio of investment opportunities, need to understand 

which of those is both most important medically and to human impact but also which is most viably able to be conducted, and finally, 

which enables us to balance our risk and our return. 

Mr. PITTS. All right. Let’s look at each phase. First of all, what 

types of discovery or R&D incentives do you believe would encourage companies to develop new and novel antibiotics? 

Dr. THOMAS. I think we need to look at the discovery incentives 

not just for antibiotics, but also for antibiotics in adjacent technologies. Here it is absolutely critical that we focus on point of care 

diagnostics, biomarkers, new capabilities of being able to diagnose, 

and also to advance clinical research in this field. For this sort of 

endeavor, this is where large grants, funding, prizes would make 

the most sense, tax credits, because they will encourage broadbased academic research as well as broad-based technology company research that is often shorter in duration and is able to be 

managed in a different way. 

As we think about the incentives for development, development 

in the pharmaceutical process is the most expensive piece. We recently brought a new product called SIRTURO, which is indicated 

for multi-drug resistant tuberculosis. With 13 years of R&D and 

early development, we had proof of concept that was compelling, 

and through the leadership of agencies like the FDA and the European Medicines Agency and the World Health Organization had a 

conditional approval on early phase 2 results. 

We still have more than 15 years of clinical trials evidence generation showing safety and effectiveness in children, showing safety 

and effectiveness versus other drugs in real-world use in the field 

and proving out the hope that we saw in the phase 2 studies. Having spent well over $200 million to date with no commercial return 

foreseeable for this product, and nor necessarily should there be, 

137 

we are now looking at a further 15 years of investment and many 

hundreds of millions more. 

Tax credits are not enough to spur that sort of effort on a broad 

base across the industry. And I think for drug developers, we need 

to make sure that there is a very definite incentive for 2 things: 

One is, how can they justify maintaining the infrastructure inhouse, the competency to understand what is a good asset and how 

to develop it, whether or not they have one of those assets themselves, and that is critical because lightning doesn’t always strike 

in New Brunswick where our headquarters is. Lightening for innovation strikes all over the world, and we have to be able to understand when it hits, what that technology is worth. 

The second thing is we have to be able to encourage companies 

to actually invest in the long-range risks associated with the large 

dollars for drug development, and the way to do this is not to hope 

that they have a certain expertise in one drug. The way to do this 

is to say we want as many shots on goal as possible by as many 

large players as possible so that we can see a sustainable and continual pipeline to evolve, and for this activity, this is where the 

concept of tradeable vouchers or exclusivity additions comes in because what you are not doing is incentivizing people to go down a 

loss-making path. You are saying we understand that you have to 

go down a profit-making path in some of your business and we will 

trade off against these activities. 

Finally in the area of the delivery side, this is really problematic. 

By the nature of the sort of research we conduct to get products 

approved for antimicrobial resistance, we are looking at non-inferiority studies. From a payment perspective, that usually means in 

most countries in the world that you get price parity. Despite the 

fact that your price parity with what is on the market was for costs 

that were achieved many, many years ago and may not no longer 

be relevant, and that is why the ENPVs you heard about before are 

usually negative, so the notion of a price premium or reimbursement incentives are certainly attractive in that area. 

I would posit, however, and use as an example our own experience in multi-drug resistant tuberculosis, when you are talking 

about highly resistant bugs, highly transmissible bugs, you want 

the drugs used only in the people who need them, only for the bugs 

that need them, and by people who understand how to treat and 

use those products in an appropriate way. That is not really a very 

strong economic model for understanding how your product, even 

with a reimbursement incentive, is actually going to be successful. 

In fact, it is probably a negative commercial model in most areas. 

Mr. PITTS. The chair thanks the gentleman. Now recognize the 

ranking member of the full committee, Mr. Waxman 5 minutes for 

questions. 

Mr. WAXMAN. Thank you, Mr. Chairman. Last Congress we 

passed the GAIN Act to provide new incentives for the development 

of important antibiotics, and under that Act, antimicrobials and 

antifungals intended to treat serious or life-threatening infections 

can be designated as qualified infectious disease products, or 

QIDPs. We receive a priority review, that is helpful. If they are approved, they get an additional 5 years of protection from generic 

competition. That is a strong incentive. FDA has already granted 

138 

QIDP designations to almost three dozen different antibiotics, so 

companies clearly are interested in this program. 

A major impetus for the GAIN Act and for today’s hearing is a 

need for new antibiotics to treat the growing number of life-threatening pathogens that are resistant to all or virtually all antibiotics. 

However, in your testimony, Mr. Outterson, you note that there is 

nothing in the law that requires QIDP designations be only given 

to antibiotics intended to treat resistant pathogens. As a result, 

you assert that essentially every antibiotic ever approved by the 

FDA would qualify as a QIDP. 

Some of us, during the FDA Safety and Innovation Act negotiations tried to limit it, that designation to those antibiotics that 

would fulfill an unmet medical need. However, we were unsuccessful. 

Can you tell us how many, or what percentage of the QIDPs are 

for antimicrobials intended to treat highly resistant pathogens, and 

are their public health impacts we should be concerned about as a 

result of the lost failure to prioritize drugs for resistant pathogens, 

and how could we better incentivize the development of the drugs 

we most need? 

Mr. OUTTERSON. Thank you for your question. The definition of 

Qualified Infectious Disease Product is built on a previous definition of a qualified pathogen. And that list does not require any of 

the pathogens to be resistant. It includes most species known to 

cause any disease in humans. So, because it is difficult sometimes 

in these trials to run them where it historically hasn’t been done, 

to run them on people only with resistant pathogens. So you are 

correct in saying that the qualified infectious disease product will 

apply probably to every antibiotic that will be approved in this next 

decade or two, which is a question about whether the incentives 

are properly targeted. 

On the incentives themselves, when I talk to companies privately, large companies as well as small, they all say that the incentives in GAIN were in the correct direction, but there is a quiet 

walk when what we should be doing is running, that the economic 

value to them, of these incentives is really very small. They will 

take them and register, but it is 1 percent of the way to where we 

need to go to change the economic model. It is a small change, and 

we should be doing something else. 

Mr. WAXMAN. So tell us how to change this economic model. You 

talked about that in your presentation. How much do we have to 

keep giving in order to give the right incentives? And we ought to 

know how much this is going to cost the American people and 

whether it going to be successful. 

Mr. OUTTERSON. To use the three stages that the chairman mentioned. On the discover side, our NIH budgets need to be dramatically increased. We need basic science. 

Mr. WAXMAN. Yes. 

Mr. OUTTERSON. It was the PCAST report yesterday. 

Mr. WAXMAN. And we have been cutting back on that. 

Mr. OUTTERSON. It has been flatlined or slightly negative for the 

past half decade to the best of my knowledge on antibacterial research in the NIH. The second piece on developing, I think tax 

credits are a piece of that. I think BARDA is a huge piece of that. 

139 

Some of the best gram negative molecules in development now 

have a lot of money in them from BARDA. 

Mr. WAXMAN. We have given tax credits. We want to shorten the 

time at FDA to get this review done as quickly as possible to get 

the drug out there. We want to help companies decide its in their 

economic interest to do this. What do we need to do? 

Mr. OUTTERSON. The last piece is when it is delivered to the public, and I would agree with Dr. Thomas that there is a reimbursement problem, but I don’t particularly like the solution. At the 

Chatham House work, we are looking at the linkage, which is just 

saying the companies will be generously rewarded but on something that has nothing to do with volume. I think everyone here would agree we don’t want to put $100,000 

price on a drug and give a company a reason to over-promote it. 

And so there needs to be significant price-type or BARDA granttype rewards for companies, possibly based on an insurance model, 

which is what GlaxoSmithKline has suggested, to give significant 

rewards to the companies after they have delivered a drug to the 

market. 

Mr. WAXMAN. Well, I would suggest that we may be better off 

putting much more money into biomedical research at NIH and 

throughout universities around the country because they don’t have 

the profit motive and what they do helps the companies because 

that science is then used for these products. 

But if the companies are having too difficult a time without 

enough incentives to make a lot of money, well, let’s make sure 

that we get the work being done at the public expense because otherwise, we are going to pay a lot of money and we may not see the 

results that we need. You agree? 

Mr. OUTTERSON. I completely agree. If we do not have enough 

basic science, the pipeline that flows to venture capital and then 

to the larger companies runs dry. 

Mr. WAXMAN. Thank you. Thank you, Mr. Chairman. 

Mr. PITTS. The chair thanks the gentleman. Now recognizes the 

gentleman from Georgia, Dr. Gingrey, 5 minutes for questions. 

Mr. GINGREY. That was a very interesting line of questioning 

from the distinguished ranking member of the committee, and Mr. 

Outterson, your response was not unexpected. But there is something to say for the profit motive as well. You give more and more 

and more money, taxpayer money to NIH or wherever basic research is being done, and you don’t have this profit motive that you 

are talking about and the wrong incentive, misguided incentive, 

but if you don’t have somebody with the profit motive, a company, 

a pharmaceutical company, big or small, you can sit there doing 

basic research for 100 years, and maybe some brilliant scientist, 

many of them could be very comfortable in their labs and enjoy 

that to a fare thee well. I think I would. But you never really get 

to where you need to be in regard to drugs that treat patients that 

cure these terrible bugs that are killing them. 

So I am going to shift my question to Dr. Murray as President 

of the American Society of Infectious Diseases to basically ask you 

the same question, Dr. Murray. The business model for antibiotics, 

diagnostics, and vaccines is broken. I think we will all sort of agree 

with that. That is what we have learned this morning in this rathVerDate Nov 24 2008 11:12 Mar 03, 2016 Jkt 037690 PO 00000 Frm 00143 Fmt 6633 Sfmt 6633 F:\MY DOCS\HEARINGS 113\113-178 CHRIS
140 

er long two-panel hearing, but it has been good, but it a broken 

model. What specific steps, Dr. Murray, do you think Congress 

should take to address this crisis? Do you agree with Mr. 

Outterson? Do you agree with Mr. Waxman? What do you think? 

Dr. MURRAY. Well, I could take Dr. Woodcock’s approach and say 

I am not an economist, but I will try to address it. I think basic 

research input is an important component. I am biased. I do basic 

research in my laboratory, but I agree also there has to be a reward at the end, and the suggestions I have heard from others, and 

they are not my own, include taking certain drugs out of the DRG 

so that they are not part of the total hospital budget, which means 

everybody is trying to attack on antibiotics as one place to decrease 

cost. 

That or the other model is buying up a number of doses at the 

end of a product, so they are bought up. I think perhaps that is 

what you meant by the insurance model. So you hope you never 

have to use them. They would be there but it guarantees the industry some return on their dollar. So those are the two—in addition 

to, of course, in the development phase, the tax credits, but the end 

product, I have heard it for many years, there has to be—they answer to taxpayers. I mean, I am sorry, they answer to stockholders. 

They don’t answer to taxpayers, and so the companies cannot just 

be motivated by the greater good. 

Mr. GINGREY. It is kind of like when we talk on this committee 

about energy and the energy policy that we should have, and all 

of the above policy is the one that I like the best, and I think really 

in regard to this, too, because I mean, as Mr. Waxman said, you 

are talking about tax credits, you are talking about what you just 

said, Dr. Murray, of buying back a certain volume that is not used 

because you don’t want to just incentivize based on sales, and more 

grants to the NIH. All of the above, really. I think that is the way 

we ought to look at it. 

I have got a little less than a minute left, and I want to shift to 

Dr. Hillan. You mention in your testimony that half of the investment cost necessary to support your drug, SIRTURO; is that correct? 

Dr. HILLAN. Plazomicin. 

Mr. GINGREY. Yes. 

Dr. HILLAN. Plazomicin. 

Mr. GINGREY. Will be required. Half of the investment cost necessary to support it, that drug, will be required after the point of 

the United States regulatory approval. What drives the cost of 

these investments post-FDA approval? What is the big cost driver? 

Dr. HILLAN. Sure. So I’m not sure if it was me, but I am certainly 

happy to answer that. There is an ongoing process after a drug is 

approved so that you actually understand the safety and effectiveness of the use of the product in the real world. There are additional pediatric studies which are very important. How do you—we 

believe our drug will be dosed in small—— 

Mr. GINGREY. Well, let me shift. Just I have got no time left, but 

Mr. Chairman, if you will bear with me because I really—and 

thank you, Dr. Hillan, and I really want to address this question 

to Dr. Thomas, so if you could quickly respond. Mr. Chairman, if 

you will bear with me. 

141 

Dr. THOMAS. Sure. And thank you for the question. Getting regulatory approval is really the start of a long process of paying for 

regulatory approval all over the world in a sequential basis for 

maybe over 100 countries. There is completion of commitments and 

unknown questions about safety. There is, as I said, 15 years of pediatric research, so with antibiotics that sometimes have toxicity 

starting at a 15-year-old and proving that, then a 10, a 12 and a 

2 and so on. There is drug safety reporting requirements that when 

you have a commercial product, these are all costs of doing business, but when you have a product where the aim is not to use it 

unless you absolutely have to, it is just a tremendous overhead that 

you can’t really discount any other way. It is the right thing to do 

and it is the way that we do it today, but it has caused a significant overhead. 

Mr. GINGREY. And I thank both of you for your response to that 

question. Thank you very much. Mr. Chairman, I yield back. 

Mr. PITTS. The chair thanks the gentleman. Now recognize the 

ranking member, Mr. Pallone, 5 minutes for questions. 

Mr. WAXMAN. Mr. Pallone, would you yield to me 1 minute? 

Mr. PALLONE. Yes, surely. 

Mr. WAXMAN. I thank you for yielding. I don’t think Mr. 

Outterson or I thought or would want anybody to believe that we 

thought you don’t need a profit and you don’t need the private enterprise, and I argue we need to put much more in the research 

side of it, but we do need a business model that says to a company 

if you do this work, you are going to make a profit. You have got 

to make a profit; otherwise, they are not going to do it, and to 

make a profit, we don’t want to just sell more antibiotics. We want 

to make sure they get a profit so that we want to guarantee we 

could take their investment, guarantee a certain percentage, and 

say that is how much the government will pay you. That is one 

idea. 

I don’t know if it is the only idea, but it is obviously a different 

kind of incentive that we have in other areas. So I thought Dr. 

Gingrey was right when he said all of the above. We got to do 

whatever we can, and I believe a lot more in public investment because the pharmaceutical engineers are not going to make a lot of 

investment in this area when their research investments can result 

in a blockbuster drug, but this is a social need, and they have got 

to do what we need them to do, but they are not going to do it 

without making a profit. So thank you for giving me that 

chance—— 

Mr. PALLONE. Sure. 

Mr. WAXMAN [continuing]. To add that additional thought. 

Mr. PALLONE. Thank you. Thank you, Mr. Waxman. I wanted to 

ask Dr. Murray and Mr. Coukell. I know that IDSA and Pew have 

worked very closely with the sponsors of the ADAPT Act, and they 

are strong supporters of it, I would like to get your views on a few 

aspects of this legislation. First, I am concerned that as currently 

drafted, FDA may not have adequate authority to require that an 

ADAPT antibiotic be labeled in a way that calls attention to the 

fact that it is intended only for special populations. I don’t think 

putting such a statement in the prescribing information is adequate, and I am concerned that if such drugs are used more widely 

142 

than appropriate, that we could end up both harming patients and 

losing the effectiveness of the drug to antibiotic resistance. 

So what are your views about the adequacy of the current labeling language in the bill? Do you agree that it is critical that there 

be a strong and prominent labeling statement to signal to providers 

that they should use the drug only in circumscribed situations? 

And I guess we could start with Dr. Murray and then go to Mr. 

Coukell. 

Dr. MURRAY. Well, I think it is important to have some label 

there. In a practical sense, what we do in the hospital to prevent 

overuse of certain drugs, is we already have stewardship in place 

in our county hospital, certain antibiotics, be they for cost, toxicity, 

or whatever reason, have to go through an infectious disease approval. That is already in place. 

Another thing we sometimes do is we don’t report on the chart 

of the report that goes to the patient’s chart, the susceptibility to 

certain antibiotics. If you are in infectious diseases or smart 

enough to know what is going on, you know to call the laboratory 

and ask for that susceptibility so the doctors that are actually caring for these multi-drug resistant infections know to do that. Usually it is done because there are certain combinations that even 

though the antibiotic is susceptible, you wouldn’t use it alone. 

The third way with the electronic records that might be possible 

that I was thinking about last night is that when this drug is written for, there is an automatic pop-up. We have all sorts of automatic pop-ups now, and an automatic pop-up could say this has 

been approved in a limited population. I think in many ways— 

there may not be as much of a problem as people are imagining. 

These infections occur in certain settings, usually in intensive care 

units, they are complicated. Infectious disease physicians are usually involved in these patients. 

For someone to try to use this drug or a special drug that has 

been approved in this fashion for an ordinaryE. coli infection, there 

is not a need to do that. The companies are not going to be able 

to be out there marketing for that purpose. FDA will be overseeing 

what goes into the promotional materials, so I am not sure the ordinary physician—certainly the one out in the community is never 

going to even think about using it. These are IV drugs by and 

large. So I think there is some inherent safeguard. 

Mr. PALLONE. OK. Mr. Coukell, do you want to respond? 

Mr. COUKELL. Thank you for that question, and let me build on 

what Dr. Murray has said that we have worked very closely on this 

bill, and we think this is the one place that we really would like 

the see some improvements. And as I said in my testimony, it is 

so important that we convey to the provider community the special 

status and nature of these drugs, and let’s recognize that the labeling is not just effective when somebody goes and looks at the fine 

print, but the labeling is the start of the process of how information 

about the drug is promulgated into the community through the 

medical record, through the marketing materials, and so on. 

We have called for a logo to distinguish these drugs. There may 

be other ways, as long as it is communicated very clearly that 

these drugs are different, and that is part of what Congress is 

doing, too, by creating this designation. 

143 

Mr. PALLONE. All right. Thanks a lot. 

Mr. COUKELL. One more point. 

Mr. PALLONE. Sure. 

Mr. COUKELL. The other thing that is in the bill that we think 

is important is the need to monitor how the drugs are used when 

they are out there so that we have some feedback and we know 

that the indication is working as intended. 

Mr. PALLONE. All right. Thanks. 

Mr. PITTS. The chair thanks the gentleman. Now recognize the 

gentleman from Illinois, Mr. Shimkus, 5 minutes for questions. 

Mr. SHIMKUS. Thank you, Mr. Chairman. This has been a tremendous hearing, and I am glad I stayed. I think you see the importance that this subcommittee puts on these issues. You-all on 

the panel, turn around and just turn around and see Dr. Woodcock 

is right there. Wave to her. And I want to make sure everyone 

knows she stayed, and I applaud her for doing that. So this is kind 

of a silly question but it is really, would you consider you-all 

Facebook friends with the FDA or in a relationship? Anyone want 

to answer? Are you friends or you not even—had a friend notification out there and they didn’t even accept. 

Dr. HILLAN. Maybe I could speak to that because obviously it is 

important that the pharmaceutical industry is regulated by the 

FDA both in terms of drugs and also in diagnostics, so I don’t know 

we would call ourselves friends, but we are certainly, I would say, 

professional colleagues that work together. 

Mr. SHIMKUS. Yes. 

Dr. HILLAN. We have had—— 

Mr. SHIMKUS. Well, the point is this only gets solved with the 

people in this room. It gets solved with you at the panel, it gets 

solved with the FDA, and it gets solved with the public policy folks 

here, and so we have to have that communication. We have to be 

in a relationship, and that is what I am taking from this because 

a lot of ideas. And I couldn’t believe it. I was also looking at stuff. 

The Pentagon was—the groundbreaking was September 11, 1941. 

The dedication was January 15, 1943. So in this issue, these are 

timelines. Thirteen years to get to one point; 15 years still down 

the road. We have got to switch those timelines, and there are people who are willing to accept some risk. And besides, we have 

heard numerous testimonies on this 21st Century Cures debate 

and how do we do that effectively. 

The question I have by listening to the testimony is government 

is historically bureaucratic and not flexible and we are very rigid, 

but in this process, you are the experts, you are the doctors, you 

are the scientists and stuff, how do we write into legislation the 

flexibility to incentivize while protecting public health? And can we 

do that? And then that is what we are going to move on legislatively, but am I right in that analysis and do you think we can get 

there? And I only have 2 minutes left, so why don’t we just go 

down and let everybody weigh into that if you would like. 

Dr. HILLAN. So, it obviously has to be done appropriately, but 

much of this is about building trust. We are working towards the 

same goal of bringing forward new antibiotics to patients. We have 

interacted with the FDA, and I can tell you the FDA has really facilitated the development of plazomicin. They came up with really 

144 

good ideas, totally appropriate ideas actually the company hadn’t 

thought about. BARDA has been incredibly supportive and brings 

technical expertise to the table as well, so we can work effectively 

together and we are all working towards the same goal. So I would 

hope that we can continue to do that in the future, and it does need 

to be flexible. We need to trust people to use good judgment so that 

we can all look after patients. 

Dr. MURRAY. I think one of the benefits of the PCAST report and 

the new structure that there will be, will include external stakeholders, be included, and I certainly agree with that, and external 

to the government, and I think their input is needed, and that may 

help keep driving the process. 

Dr. THOMAS. I think it is absolutely possible to write legislation 

that is flexible and also impactful. I also like to say that we want 

to be part of that discussion. We believe it does take a different 

way of thinking, and we have to be willing to test things that may 

not necessarily seem so palatable. I just want to finish with saying 

it is no accident that breast cancer is almost a curable disease 

today. It is no accident that many bone marrow tumors are curable 

of chronic diseases today. It is no accident that people can live with 

diabetes. It is because the incentives for everyone are to innovate 

in those areas. So if you don’t want this to be an accident, we need 

to design the right incentives. 

Mr. OUTTERSON. We need billion-dollar incentives hanging out 

there for companies, big incentives, not little. It is hard to write 

what you will need in 10 years, though, into legislation when we 

don’t know what the diseases will exactly look like. 

BARDA is a wonderful model. One of the most encouraging 

things I took from yesterday from PCAST was significant additional funding being proposed for BARDA because they can contract, given flexibility, based on what is happening now. The only 

other person who is not in this room are the pairs, so I would like 

to see Blue Cross and Blue Shield, insurance companies, Medicare, 

this is a pay-for-performance, pay-for-value issue. Let’s pay more to 

keep it valuable. 

Mr. COUKELL. There is no single solution here. There are things 

that Congress can do now and do quickly and should do. There are 

places where there needs to be continued collaboration. I think we 

have seen that with FDA and companies and stakeholders, and 

PCAST called for more of it. There are more important basic 

science questions that are not industry questions, are academic 

questions, but questions that will be solved when we have them effectively working together not just with more money but with 

smarter science, so there is no one-size solution here, but there are 

things we can do now quickly to move this along. 

Dr. POWERS. I think we talked a lot today about the history of 

resistance and how we got to this point, and actually there is already tremendous flexibility built into FDA’s regulations already. 

When FDA came out with the regulations in 1970 on what an adequate study was, the pharmaceutical companies immediately sued. 

And when it went to the courts, the courts actually found that the 

regulations allowed tremendous flexibility for FDA and how the 

studies can be designed. 

145 

I think what we were trying to say this morning, and Dr. 

Outterson brought this point up several times, is that these studies 

should actually show added value for patients, that really what we 

are trying to say is if we are going to give perks for companies, it 

ought to be perks for performance, not perks for potential, that the 

studies should actually show, as Dr. Hillan pointed out and how 

his study is designed, that the drugs actually save lives in the people that we need to use them in. 

Mr. SHIMKUS. Thank you, Mr.—and thank you—a minute ago— 

I want to end on this or not—— 

Dr. MURRAY. Could I add one additional comment? Would that 

be—— 

Mr. PITTS. Yes, you may. 

Dr. MURRAY. Thank you very much. I want to get back to the 

point of BARDA being a good model, and that is a wonderful 

model. NIAID could serve the parallel role of helping to develop 

drugs for—thanks. That BARDA is not directly applicable to, and 

they already do have an antibiotic resistance leadership group 

whose path is to help design trials for antibiotic resistance organisms, but I think the BARDA model is a good one. It does not necessarily have to be BARDA that would carry it out. 

Mr. SHIMKUS. And I appreciate that. The last comment. I just 

will say that these companies, I really—and Mr. Waxman just 

raises my ire every now and then, too. Because it is not perks. 

These guys raise capital, assume risk to try to save lives, employ 

thousands of people, and pay taxes, so they are the ones who are 

raising the capital and assuming a risk. So, if we go down the route 

of trying to beat up corporate America in this process, we are not 

going to be friends. We will be defriended and we can’t. We got to 

be all in this together, and with that, I yield back my time. 

Mr. PITTS. The chair thanks the gentleman. The gentleman from 

Georgia wanted to make a point of clarification. 

Mr. GINGREY. Mr. Chairman, thank you, and I don’t disagree. In 

fact, I do agree with the comments from my colleague, the gentleman from Illinois, Mr. Shimkus, in what he just said. But I also 

want to, Dr. Powers, let you know that the concerns that you express in your testimony are not lost on me at all, and I don’t think 

other members of the committee, and also, the ranking member of 

this health subcommittee, Mr. Pallone, and his concerns about labeling, and that is not lost on me either. And staff is working almost as we speak on that issue, Frank, to try to get that right and 

to lay those concerns. 

Mr. Chairman, this has been fabulous. You-all are great, both 

panels. Dr. Woodcock, we are so grateful to you, and I, like the 

other members that stayed over, and didn’t get an early flight back 

to Atlanta, I am grateful that I stayed because this has been most, 

most informative, and we are deeply appreciative. Thank you very 

much, and I yield back. 

Mr. PITTS. The chair thanks the gentleman, and I would like to 

say it is good to hear of the collaboration that is occurring between 

the public and private sectors, and that is so important. And I 

might mention, Dr. Woodcock has been before this committee many 

times, and she is one administrator that always stays through the 

146 

whole hearing, and you should be commended for that, and we 

thank you for your responsiveness. 

Now, other members will have questions, and we will have follow-up questions. We will send those to you. We ask that you 

please respond promptly. I remind members that they have 10 

business days to submit questions for the record. That means they 

should submit their questions by the close of business on Friday, 

October 3rd. Very good hearing, exciting, very informative. Thank 

you very much for your participation. Without objection, this subcommittee is adjourned. 

[Whereupon, at 11:35 a.m., the subcommittee was adjourned.] 

[Material submitted for inclusion in the record follows:] 

PREPARED STATEMENT OF HON. FRED UPTON

Today’s hearing is an important opportunity to review the growing threat of antibiotic resistant infection—a global health crisis. To quote the CDC: ‘‘The loss of effective antibiotic treatments will not only cripple the ability to fight routine infectious diseases but will also undermine treatment of infectious complications in patients with other diseases.’’ This public health crisis is an important topic for us to 

explore as we continue our work on the bipartisan 21st Century Cures initiative and 

work to bring more effective treatments to patients more quickly. 

Make no mistake: we are losing effective antibiotic treatments because the pace 

of new and novel drug development has not kept up with these organisms’ ability 

to build resistance to the treatments available today. 

Passage of the GAIN Act in the 112th Congress as part of our efforts to reauthorize the FDA User Fee legislation was an important step in incentivizing antibiotic 

drug development, but much work remains to be done. 

Committee members Congressmen Gingrey and Green have put forward one such 

idea—the Adapt Act—and I want to commend them for their continued leadership 

in addressing these important issues. 

The President’s own Council on Science and Technology (or PCAST) just yesterday 

released a call to action on the issue of antibiotic resistance. This plan included a 

number of initiatives it intends to undertake over the next 5 years, including incentives for the development new drugs and diagnostic tests. We will continue to engage on this issue as part of our bipartisan 21st Century Cures agenda. 

Today’s witnesses will provide important perspectives on the types of incentives 

to help drive the types of new drug development necessary to meet this growing 

threat and whether such incentives might also address other areas of unmet need. 

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