Programs Affecting Safety and Innovation in Pediatric Therapies

PROGRAMS AFFECTING SAFETY AND INNOVATION
IN PEDIATRIC THERAPIES
HEARING
BEFORE THE
SUBCOMMITTEE ON HEALTH
OF THE
COMMITTEE ON ENERGY AND

COMMERCE
HOUSE OF REPRESENTATIVES
ONE HUNDRED TENTH CONGRESS
FIRST SESSION
MAY 22, 2007
Serial No. 11049
(
Printed for the use of the Committee on Energy and Commerce
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COMMITTEE ON ENERGY AND COMMERCE

JOHN D. DINGELL,
HENRY A. WAXMAN, California
EDWARD J. MARKEY, Massachusetts
RICK BOUCHER, Virginia
EDOLPHUS TOWNS, New York
FRANK PALLONE, JR., New Jersey
BART GORDON, Tennessee
BOBBY L. RUSH, Illinois
ANNA G. ESHOO, California
BART STUPAK, Michigan
ELIOT L. ENGEL, New York
ALBERT R. WYNN, Maryland
GENE GREEN, Texas
DIANA DEGETTE, Colorado
Vice Chairman
LOIS CAPPS, California
MIKE DOYLE, Pennsylvania
JANE HARMAN, California
TOM ALLEN, Maine
JAN SCHAKOWSKY, Illinois
HILDA L. SOLIS, California
CHARLES A. GONZALEZ, Texas
JAY INSLEE, Washington
TAMMY BALDWIN, Wisconsin
MIKE ROSS, Arkansas
DARLENE HOOLEY, Oregon
ANTHONY D. WEINER, New York
JIM MATHESON, Utah
G.K. BUTTERFIELD, North Carolina
CHARLIE MELANCON, Louisiana
JOHN BARROW, Georgia
BARON P. HILL, Indiana
Michigan, Chairman
JOE BARTON, Texas
Ranking Member
RALPH M. HALL, Texas
J. DENNIS HASTERT, Illinois
FRED UPTON, Michigan
CLIFF STEARNS, Florida
NATHAN DEAL, Georgia
ED WHITFIELD, Kentucky
BARBARA CUBIN, Wyoming
JOHN SHIMKUS, Illinois
HEATHER WILSON, New Mexico
JOHN B. SHADEGG, Arizona
CHARLES W. CHIP PICKERING,
Mississippi
VITO FOSSELLA, New York
STEVE BUYER, Indiana
GEORGE RADANOVICH, California
JOSEPH R. PITTS, Pennsylvania
MARY BONO, California
GREG WALDEN, Oregon
LEE TERRY, Nebraska
MIKE FERGUSON, New Jersey
MIKE ROGERS, Michigan
SUE WILKINS MYRICK, North Carolina
JOHN SULLIVAN, Oklahoma
TIM MURPHY, Pennsylvania
MICHAEL C. BURGESS, Texas
MARSHA BLACKBURN, Tennessee
PROFESSIONAL STAFF
DENNIS B. FITZGIBBONS, Chief of Staff
GREGG A. ROTHSCHILD, Chief Counsel
SHARON E. DAVIS, Chief Clerk
BUD ALBRIGHT, Minority Staff Director
(II)
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SUBCOMMITTEE
FRANK PALLONE, JR.,
HENRY A. WAXMAN, California
EDOLPHUS TOWNS, New York
BART GORDON, Tennessee
ANNA G. ESHOO, California
GENE GREEN, Texas
Vice Chairman
DIANA DEGETTE, Colorado
LOIS CAPPS, California
TOM ALLEN, Maine
TAMMY BALDWIN, Wisconsin
ELIOT L. ENGEL, New York
JAN SCHAKOWSKY, Illinois
HILDA L. SOLIS, California
MIKE ROSS, Arkansas
DARLENE HOOLEY, Oregon
ANTHONY D. WEINER, New York
JIM MATHESON, Utah
JOHN D. DINGELL, Michigan (ex officio)
ON
HEALTH
New Jersey, Chairman

NATHAN DEAL, Georgia,
Ranking Member
RALPH M. HALL, Texas
BARBARA CUBIN, Wyoming
HEATHER WILSON, New Mexico
JOHN B. SHADEGG, Arizona
STEVE BUYER, Indiana
JOSEPH R. PITTS, Pennsylvania
MIKE FERGUSON, New Jersey
MIKE ROGERS, Michigan
SUE WILKINS MYRICK, North Carolina
JOHN SULLIVAN, Oklahoma
TIM MURPHY, Pennsylvania
MICHAEL C. BURGESS, Texas
MARSHA BLACKBURN, Tennessee
JOE BARTON, Texas (ex officio)
(III)
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CONTENTS
Page
Hon. Frank Pallone, Jr., a Representative in Congress from the State of

New Jersey, opening statement ..........................................................................
Hon. Nathan Deal, a Representative in Congress from the State of Georgia,
opening statement ................................................................................................
Hon. Henry A. Waxman, a Representative in Congress from the State of
California, opening statement .............................................................................
Hon. Michael C. Burgess, a Representative in Congress from the State of
Texas, opening statement ....................................................................................
Hon. Anna G. Eshoo, a Representative in Congress from the State of California, opening statement ........................................................................................
Hon. Marsha Blackburn, a Representative in Congress from the State of
Tennessee, opening statement ............................................................................
Hon. Gene Green, a Representative in Congress from the State of Texas,
Hon. Tim Murphy, a Representative in Congress from the Commonwealth
of Pennsylvania, opening statement ...................................................................
Hon. Lois Capps, a Representative in Congress from the State of California,
Hon. Darlene Hooley, a Representative in Congress from the State of Oregon,
Hon. Edolphus Towns, a Representative in Congress from the State of New
York, prepared statement ....................................................................................
Hon. Hilda L. Solis, a Representative in Congress from the State of California, prepared statement ......................................................................................
Hon. Barbara Cubin, a Representative in Congress from the State of Wyoming, prepared statement ...................................................................................
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WITNESSES
Rear Admiral Sandra L. Kweder, Deputy Director, Office of New Drugs,
Center for Drug Evaluation and Research, U.S. Food and Drug Administration ........................................................................................................................
Prepared statement ..........................................................................................
Donald Mattison, Chief, Obstetric and Pediatric Pharmacology Branch and
Human Development, National Institutes of Health ........................................
Lori Reilly, vice president, policy and research, Pharmaceutical Research
and Manufacturers of America ...........................................................................
Marcia Crosse, Director, Health Care Issues, U.S. Government Accountability
Office .....................................................................................................................
Richard L. Gorman, M.D., F.A.A.P., chair, AAP section of clinical pharmacology and therapeutics, American Academy of Pediatrics ...................................
Peter Lurie, M.D., M.P.H., deputy director, Public Citizens Health Research
Group ....................................................................................................................
Susan Belfiore, Princeton, NJ .................................................................................
Ed Rozynski, vice president, global government affairs, Stryker Corporation ...
Donald P. Lombardi, president and chief executive officer, Institute for Pediatric Innovation ....................................................................................................
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(V)
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PROGRAMS AFFECTING SAFETY AND

INNOVATION IN PEDIATRIC THERAPIES
TUESDAY, MAY 22, 2007
HOUSE OF REPRESENTATIVES,
SUBCOMMITTEE ON HEALTH,
COMMITTEE ON ENERGY AND COMMERCE,
Washington, DC.
The subcommittee met, pursuant to call, at 10:15 a.m., in room
2322 of the Rayburn House Office Building, Hon. Frank Pallone,
Jr. (chairman) presiding.
Members present: Representatives Waxman, Eshoo, Green,
Capps, Allen, Schakowsky, Hooley, Matheson, Deal, Murphy, Burgess, and Blackburn.
Also present: Representative Markey.
Staff present: Ryan Long, Nanden Kenkeremath, Chad Grant,
John Ford, Bobby Clark, Jack Maniko, Virgil Miller, and Melissa
Sidman.
OPENING STATEMENT OF HON. FRANK PALLONE, JR., A REPRESENTATIVE IN CONGRESS FROM THE STATE OF NEW JERSEY
Mr. PALLONE. We have no amplification, so we urge everyone to

speak loudly. There is no point speaking into the mic or turning
it on. It is not working. We will have no Web cast, so for those who
want to watch us from a distance, they are out of luck. We also
have no transcript. I apologize, we are going to have a transcript.
We are going to do the best we can. Thank you. It may not be a
full transcript because we may not be able to hear everything; but
yes, there will be a transcript, it just may not be complete. Other
than that, we are following normal procedures. And the air-conditioning works, too, just so you know. So I will recognize myself for
an opening statement initially.
Today the subcommittee is meeting to hear about programs affecting safety and innovation in pediatric therapies. Todays hearing is of critical importance because above all else, we must ensure
that the prescription medications and devices our children use are
in fact tested appropriately and deemed safe. I believe that we all
agree, regardless of our party affiliation, that we have an enormous
responsibility to our children to ensure that they have access to the
best possible medical treatment. And today we will hear about two
existing programs designed to facilitate better testing of drugs in
children. They are the Best Pharmaceuticals for Children and the
Pediatric Research Equity Act. Combined, these two programs are
often referred to a carrot-and-stick approach used by the FDA to
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encourage and direct drug manufacturers to test their products for
pediatric use. We will also discuss the need to encourage better research and development of medical devices for pediatric populations. Under BPCA, in exchange for completing a pediatric study
requested by the FDA, a drug manufacturer can receive a 6-month
extension of market exclusivity for the product that is studied. This
model has proven successful in providing new and valuable information about the appropriate pediatric use of many drugs. According to the GAO, who we will also hear from today, drug manufacturers agree to the pediatric studies requested by FDA for on-patent drugs 81 percent of the time. These studies have resulted in
important labeling changes that help providers and parents determine the best course of treatment for a child stricken by a particular illness or chronic condition.
In the past, I have raised concerns about the financial impact an
additional 6 months of market exclusivity has on American consumers. While the incentive under BPCA is clearly working to encourage companies to conduct the studies that FDA requests, at the
same time this type of patent extension serves as an obstacle that
blocks access to generic drugs for consumers, forcing them to pay
higher prices because lower-cost alternatives are kept off the market.
In looking over how the program has worked over the past 5
years, I am concerned about the amount of earnings drug manufacturers receive in exchange for completing these studies. The financial gain the drug makers receive from the market exclusivity
under BPCA usually far exceeds the costs incurred in completing
the pediatric trials requested by FDA. There may be a better way
to balance the need to provide incentives for drug manufacturers
who conduct pediatric studies and ensuring consumers have timely
access to lower-cost prescription drugs.
The Pharmaceutical and Research and Equity Act, or PREA, is
the other component of this approach, and gives FDA the regulatory authority to require certain pediatric assessments for a particular drug in which a drug maker is submitting an application.
The regulatory authority granted to FDA under PREA is linked to
the expiration of BPCA and thus will also expire at the end of this
fiscal year. This makes very little sense to me. Why should we put
a timetable on providing the FDA with the regulatory power to ensure drug companies conduct research necessary to ensure that our
children have access to safe and effective medicines? We dont place
such limits on FDA when it comes to conducting research on adult
populations, and so we shouldnt do it for our children, either.
Aside from drugs, we also have a responsibility to ensure that
children have access to appropriate medical devices. You know that
we had a hearing on PDUFA last week, but today we also want to
look at the childrens aspect. The problems that we face in encouraging pediatric studies of drugs are parallel to the problems that
we face in encouraging similar research in the device world. There
are few medical devices designed to be used in kids. Instead, doctors are often forced to jury-rig devices that are designed to treat
adults. We need legislation that will encourage device manufacturers to do their research and development necessary to provide our
children with devices that will fit their small and growing bodies.
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Again, I cant emphasize enough that testing of drugs and devices for pediatric use is essential. As a father of three young children, I know how critical it is that we ensure our children with access to the treatments and therapies they need to live happy and
healthy childhoods. I also want to say that I know how important
these issues are to members of this subcommittee on both sides of
the aisle. Ms. Eshoo, Mr. Waxman are the voices in the debate
about encouraging pediatric studies for prescription drugs. Mr.
Markey and Mr. Rogers have been strong advocates on the need for
medical devices to be made available for kids, and I am going to
work with all of you to ensure that we pass legislation that includes access to the medical treatment our Nations children need.
Again, I want to thank all of our witnesses for being here today
even though we are dealing with certain limitations here in terms
of the technology, and we are the technology committee. So I dont
really know what to tell you.
I will yield to our ranking member for 5 minutes. Thank you.
OPENING STATEMENT OF HON. NATHAN DEAL, A REPRESENTATIVE IN CONGRESS FROM THE STATE OF GEORGIA
Mr. DEAL. We are going to have to stop letting the Telecommunications Subcommittee use this room. Meeting medical needs of children in the innovative world of todays medications and medical devices presents a challenge because of their smaller share of the
market and the typical focus on adults in the testing of any new
product. The Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act were important steps toward promoting
research in pediatric education or medical therapies. I know our
witnesses will highlight that the effect of a medication on a child
is not necessarily the same as an adult, and further study is necessary to establish the safety and effectiveness of products for children.
Developing medical devices for use by children also creates a
unique challenge. As we evaluate the reauthorization of our current programs which focus on pediatric testing, I look forward to
the testimony of the witnesses about their successes but also ways
to improve these programs. I would also like to hear about what
should be done in other areas of pediatric devices.
I thank our witnesses for their attendance today, and I look forward to your testimony. I yield back my time.
Mr. PALLONE. Thank you. Mr. Waxman.
OPENING STATEMENT OF HON. HENRY A. WAXMAN, A REPRESENTATIVE IN CONGRESS FROM THE STATE OF CALIFORNIA
Mr. WAXMAN. Thank you very much, Mr. Chairman. When a

pharmaceutical company gets a drug approved, for the longest period of time they never bothered to check what the dosage would
be for children. And that frustrated parents and pediatricians because they didnt have that information. So originally we decided
to give an incentive for that test by giving the pharmaceutical company an additional 6 months of exclusivity over their drug. Then
Congress passed another law saying, well, at least when they come
in for their first approval, we ought to require them to do the tests
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for children, and that should be a condition for approval. So we had
both laws working now to make sure that we get the pediatric
tests.
The first law that requires that they test the drugs on children
before approval of the drug at all has been sunsetted, and we ought
to remove that sunset. It ought to be a permanent feature of our
law.
The second one which gives the exclusivity as a reward for these
tests should be extended, but I think we need to think through a
number of different issues. One, in many cases, 6 months is too
generous a reward. It, in some cases, over 100 times rewards the
company for the expenditure of money to do the test. And it is all
at the expense of consumers because the consumers have to wait
an additional 6 months after continuing to pay the high monopoly
price for the drug. I think that we need to evaluate how generous
we should be in rewarding the drug companies for doing something
that quite frankly they should be doing anyway. We also ought to
evaluate the way that FDA acts in providing this 6-month or any
type of exclusivity. The FDA has a very short period of time in
which to make a decision, and we ought to give them enough time
to decide whether the company has done work that merits a reward
of exclusivity.
Some of the tests that the companies have done to gain this exclusivity really arent all that targeted. They will do tests on a bigselling drug that really dont have the applicability for children, for
example, doing tests on an anti-depressant that might never be
used for children but by doing the test, they get a longer period of
time for that particular drug which may be a very big-selling drug.
So I think we need to calibrate the reward for the job that we
want done. We all want the tests to be accomplished for pediatric
doses of these drugs. We need now at this time of reauthorization
of the legislation to figure out the best way to accomplish those
goals without putting the consumers at an economic disadvantage.
Mr. PALLONE. Thank you, Mr. Waxman. Mr. Burgess.
OPENING STATEMENT OF HON. MICHAEL C. BURGESS, A
REPRESENTATIVE IN CONGRESS FROM THE STATE OF TEXAS
Mr. BURGESS. Thank you, Mr. Chairman, and to Ranking Member Deal for holding this hearing. As we talk about the reauthorization of PDUFA, we come to some significant issues relating to
their reauthorization with regard to the needs children. When it
comes to children, drugs can react differently than they might in
adults; and medical devices need to fit on their bodies that are still
growing and bodies that are active in ways that many of us could
no longer remember.
My old professor of pediatric surgery, Dr. Vangy Brooks down in
Houston, perhaps the patron saint of pediatric surgery, summed it
up best one morning to a group of us medical students when she
looked at us and said, you know what, kids are different. And indeed they are. I think we will hear that from several of our witnesses this morning that children are more than just little adults.
They react differently to devices and drugs, and our Federal regulations should be crafted in a way that is sensitive and provides appropriate safeguards to protect their health and ensure their safety
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for their unique situation where an implant may be placed into a
growing body and is active in ways that we can only vaguely remember.
At the same time, overregulation can have a negative effect in
the impact on the development and availability of drugs and devices for children, especially in the medical device realm in a pediatric environment where patient population can be small, both in
number and literally, companies have huge incentives to enter the
market. I believe that we need to expand on incentives that are
currently available under the law such as the Humanitarian Device
Exemption to encourage more companies to conduct research and
more development in this important field.
Now, we are going to be hearing from several witnesses this
morning, and I am especially glad to be hearing from Mr. Rozynski
from the Stryker Corporation. They have a big presence in my district down in Flower Mound, TX, but what really excites me is
some of the work in Dr. Rozynskis testimony that Stryker has
done absolutely changing the landscape of the treatment of pediatric bone cancer, changing the environment for diseases as diverse
as CLEP and cranial synostosis. The non-healthcare expenses related to moving a child or getting a child treated at the Center of
Excellence are big, but Stryker has stepped up to the plate and
said we will bear some of those expenses not covered by traditional
insurance. These are particularly exciting events that are occurring, and I certainly salute Stryker and their corporate benevolence
for looking and recognizing that this is important.
Additionally, we are going to hear from Dr. Gorman. His testimony will be illustrative of the clinical difficulties with treating
children with outsized tools and medications that react differently
in their bodies.
Over the past several years, I believe the drug and device industry, medicine, and its regulators have made important strides in
improving safety and efficacy of pediatric drugs and devices. As
this committee works on legislation relating to both, I hope this
hearing will be instructive and our legislation will be appropriately
inspired.
Thank you, Mr. Chairman. I will yield back.
Mr. PALLONE. Thank you. Ms. Eshoo.
OPENING STATEMENT OF HON. ANNA G. ESHOO, A REPRESENTATIVE IN CONGRESS FROM THE STATE OF CALIFORNIA
Ms. ESHOO. Good morning, Mr. Chairman, and thank you for
having this very important hearing. Despite our efforts, approximately 75 percent of drugs and a large majority of medical devices
used by children have not been tested specifically for that use. So
we have our work cut out for us. I think while the Congress has
taken very, very important steps to turn these statistics around,
understanding that children are not small adults. We recognized
this fact in 1997 with the initial authorization of Best Pharmaceuticals for Children Act. I am very proud to be the Democratic
sponsor of that, and again in 2003 with the enactment of Pediatric
Research Equity Act. And together, I think that these two laws
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have established what might be called a carrot-stick approach to
pediatric drug testing that has been I think very successful.
Now, we are on the threshold of reauthorizing them, and as we
reauthorize, we not only build on the successes of the past but I
think having learned some things that we need to add some important things that will hopefully, when the next reauthorization
comes around, that we can hail some more successes.
I think that the successes are evident because the laws have generated important, new information about safety and the efficacy of
drugs prescribed to children. Pediatricians now know more about
what therapies work and dont work in children. Unfortunately,
nearly two-thirds of drugs currently used in children are still not
labeled for their use. We need these two laws as I said renewed
and improved if we want progress to be continued.
In the coming days, I am going to be introducing legislation to
reauthorize both of these programs, and my legislation is going to
make permanent the FDAs authority to require pediatric studies.
This adjustment I think is consistent with FDAs permanent authority to require studies of adult formulations. I am also going to
incorporate many of the recommendations of the GAO, the American Academy of Pediatrics, and the Elizabeth Glaser Pediatric
AIDS Foundation; and I want to thank all of them, for all of these
organizations for helping in the development of the legislation.
Medical and surgical devices designed just for children also need
to be developed, but experience tells me that it wont happen without legislation. I think the Pediatric Medical Devices Safety Improvement Act is an important step in that direction. So I am confident that we are going to reauthorize, and I think passage of not
only the reauthorizations but the Pediatric Medical Device legislation is going to protect children, really our Nations most vulnerable citizens. They cant do these things for themselves.
I would also like to pay tribute to what Dr. Phil Pizzo, one time
was at NIH. He is a pediatrician by background, and today heads
up the Stanford Medical School; and he has been of great assistance to me, and I think without his steady, sure advice that we
wouldnt have had the previous legislation and hopefully really
sound legislation this time around.
Thank you, Mr. Chairman, and I look forward to working with
all the committee members on this. These are not partisan issues
by any stretch of the imagination. So I have confidence that we will
be a solid group here, reauthorize and reform at the same time.
Thank you. Thank you to our witnesses.
Mr. PALLONE. Thank you. The gentlewoman from Tennessee.
OPENING STATEMENT OF HON. MARSHA BLACKBURN, A REPRESENTATIVE IN CONGRESS FROM THE STATE OF TENNESSEE
Mrs. BLACKBURN. Thank you, Mr. Chairman, and I do thank you

and Ranking Member Deal for allowing us to engage in this discussion today with our witnesses, and we thank you for the time that
you are giving to us for our hearing today. We know from so many
different agencies and so many different participants that having
this current pediatric exclusivity program has done quite a bit to
spur some research and development and to generate some critical
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information about the use of medicines in pediatric patients. And
it is done more than probably any other Government initiative, and
so we are interested in how to best go about and how to best approach the reauthorization of the Best Pharmaceuticals for Children Act. And it does give us a unique opportunity, I think, to expand our knowledge about the safety, the effectiveness of the products that are used with our children and to certainly protect our
children as they are a part of our medical community.
Prior to passage of this legislation there was little incentive that
existed to conduct clinical trails on pediatric use of medicines developed primarily for the adult population. The success of the
BPCA has equipped doctors with accurate information about which
drugs and which doses work best for our children. The pediatric exclusivity provision of the BPCA provides a critical incentive for our
biopharmaceutical companies and for that research to invest in lifesaving drugs for our pediatric patients. This incentive has helped
these companies, many companies of all sizes, to develop innovative
medicines and protocols that would improve the lives of our children.
We are so fortunate in Tennessee to have some wonderful work
that is being done at St. Judes and also at Vanderbilt with our
children; and we have talked with these researchers and we talked
with some of these innovators and the scientists, and we know the
importance of this legislation to their work. We know also it is important to keep our attention to preserving their right to the intellectual property and the research that they do. And we will continue to focus on that.
It is good legislation. As we move forward, I hope that our focus
in our discussion will remain on how we preserve access to these
protocols and therapies and formulations for our children.
Thank you, Mr. Chairman. I yield back.
Mr. PALLONE. Thank you. Our vice chairman, Mr. Green.
OPENING STATEMENT OF HON. GENE GREEN, A
REPRESENTATIVE IN CONGRESS FROM THE STATE OF TEXAS
Mr. GREEN. Thank you, Mr. Chairman, for holding this important hearing on pediatric therapies and our efforts to ensure their
safety and continued development. Most of the prescription drugs
we give children to cure their illnesses or treatment received are
actually drugs that are developed for adults and prescribed offlabel for children. While this is a common practice, it is clear that
children are simply not little adults. By treating children with
drugs that were developed for adults, we run the risk of exposing
them to ineffective drugs. Even worse is off-label use of drugs could
result in improper doses of drugs or adverse reaction for children
that would not necessarily appear in adults. Currently 75 percent
of drugs have not undergone studies in pediatric populations or
even pediatric party populations. Any one drug is too small for a
manufacturer to have the incentive to commit the resources or the
testing. To provide that incentive, we enacted the Best Pharmaceuticals for Children Act which would provide an additional 6
months of market exclusivity for market products when their sponsor agreed to perform pediatric studies on the drug. In some respects it has been a success. In the drugs granted pediatric exclu-
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sivity, 87 percent saw the changes to their label as a result of pediatric studies. These changes suggest that labels now provide physicians with better information, specific to the drugs indication for
children. On the flip side, however, there are one out of five manufacturers that received FDA requests for pediatric studies that declined to conduct the studies; and today, none of these drugs have
been studied for pediatric populations.
I look forward to hearing from our witnesses on how we can improve the Best Pharmaceuticals for Children Act and encourage
even better prescriptions from drug sponsors. Any discussion of the
Best Pharmaceuticals for Children Act should also be accompanied
by the discussion of the Pediatric Research Equity Act which for all
intents and purposes will expire at the end of this fiscal year along
with the Best Pharmaceuticals for Children Act. In this statute, we
give the Secretary the ability to require manufacturers to study
drug safety and the effectiveness of children. If the manufacturer
doesnt comply with the request, the Secretary can consider the
product misbranded. However, the Secretary doesnt have any enforcement action short ofmisbranded. I would like to learn what
additional authority Congress can give the FDA to better align the
research obligations and the appropriate enforcement effectiveness
with the end result of better information on the safety and effectiveness of drugs involving our children. And again, like everyone
else, I would like to thank our witnesses for being here today and
thank you for what you do every day regarding the health of our
children. I yield back.
Mr. PALLONE. Thank you. Mr. Murphy.
OPENING STATEMENT OF HON. TIM MURPHY, A REPRESENTATIVE IN CONGRESS FROM THE COMMONWEALTH OF PENNSYLVANIA
Mr. MURPHY. Thank you, Mr. Chairman. As we look at reauthorizing this bill, one of the things that I want to make sure that we
are working on here has to do with the issue of being very careful
that we are not taking away incentives in order to develop new
drugs. Any reauthorization that limits the money a company can
make and suddenly says you are making too much, we need to take
that away from you, concerns me if it ends up reducing money that
is used to develop new drugs. Let me give some examples.
When we look at a blockbuster drug that has emerged, we are
looking at something that is the outcome of years of testing in
which hundreds of millions of dollars may have been invested to
that end, including funding many dead-ends along the way. There
is also the issue about spin-off effects of profits that have funded
the research of the past in other diseases as well and can be used
for investments in researching other diseases in the future. But
even when there is a blockbuster drug that emerges and one that
may result in high profits, the risks do not end there. New problems may be found. For example, the news that came out about a
drug called Avandia used to treat Type II diabetes, has had a big
effect upon some of the profits and losses and stocks for
GlaxoSmithKline. And although the outcome of that is being disputed, regardless of that, still it does have an effect upon the stock.
It also has an effect then actually upon the profits and then the
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subsequent effects upon things with regard to lawsuits. So any
time we begin to look at such things such as profits, I hope we look
at what are some of the long-term effects on how to review that.
Another area I want to make sure with this that we dont harm
is the treatments and drugs that come for orphan diseases. There
is an NIH office for rare diseases, and this helps us with advances
in other areas so for those researching an area of a rare disease,
it oftentimes helps us come up with treatments for other more common diseases that we didnt specifically know about in the first
place. This is an area of such importance that in 1983 Congress
passed the Orphan Drug Act to provide financial incentives for
drug companies and biological manufacturers such as tax credits,
Government grants, other research assistance, and 7-year exclusivity on development. Because these extremely rare diseases were
ones that certainly didnt have the numbers to create profits big
enough or the money even to invest in some of the research, these
being infectious diseases, immune deficiency diseases, autoimmune
diseases, analogies that could be exaggerated if the immune systems are compromised.
Many of these areas are ones that I want to make sure we continue with this funding stream. So I hope whatever road we go
down is one we are very careful to make sure that funding is still
there in the future to come up with some of the medications we
need, particularly for rare childhood disorders, as we proceed forward.
Thank you, Mr. Chairman.
Mr. PALLONE. Thank you. Mrs. Capps.
OPENING STATEMENT OF HON. LOIS CAPPS, A REPRESENTATIVE IN CONGRESS FROM THE STATE OF CALIFORNIA
Mrs. CAPPS. Thank you, Mr. Chairman, and good morning to you
and to our witnesses for appearing with us today on this very important topic, pediatric therapies. I think it is so fitting we are
holding this hearing at the same time our Speaker, Nancy Pelosi,
is holding a national summit on Americas children. Unfortunately,
we cant be in both places at the same time, but several of us were
at the kickoff at 9 oclock; and the first panel I think is also very
appropriate, the panel under the topic the Science of Early Childhood
Mr. PALLONE. Wait a minute. Mrs. Capps, just hold on a second.
I am sorry. Go ahead.
Mrs. CAPPS. Well, I will leave thatmaybe that is the path
where we should be. But this is more directly attuned to a topic
of great importance to our committee, and if the Secretary had this
second on childrens health and I appreciate that and I think it is
a good sign of things to come.
As I mentioned in a hearing we had last week on a different
topic, I am very concerned by the fact that research tends to focus
on adult males while leaving out women and children; and we
know that there are biological and physiological differences that
need to be taken into account to best meet the needs of all men,
women, and children separately; and of course, when it comes to
testing medications and devices on children, we have to confront
many additional ethical issues and some economic issues for the
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lack of testing on children for one. The lack of proper testing on
children results in a lot of off-label prescribing and for a lack of access to potentially lifesaving treatment. As has been mentioned already, 75 percent of drugs have had no pediatric testing, yet we
know many of them are being prescribed for children. This puts all
of our children at risk.
So our task becomes answering the question of how do we ensure
safety. We have taken several steps to move forward in our quest
to incentivize both the development of drugs and biologics for use
in children. We also need to ensure that clinical testing in children
is carried out to the highest ethically accepted standard. And as we
move forward to find ways to improve existing frameworks developed through the Best Pharmaceuticals for Children Act and the
Pediatric Research Equity Act, we need to put in place incentives
for medical device manufacturers as well. And so I look forward to
hearing today from our witnesses on the current status of pediatric
development as well as testing and learning about areas that need
improvement. This is a work in progress. And most importantly I
believe we all need to be working to figure out how we can ensure
that both the Government and biotechnology industry keep children in mind as we move forward in developing and improving new
medications. Thank you. I yield back.
Mr. PALLONE. The gentleman from Utah.
Mr. Matheson. I will waive.
Mr. PALLONE. Ms. Hooley, the gentlewoman from Oregon.
Ms. HOOLEY. I guess it doesnt matter if I turn on the microphone?
Mr. PALLONE. It does not, although I should tell you we are trying to correct it, and we might have some luck. But right now, we
are operating without.
OPENING STATEMENT OF HON. DARLENE HOOLEY, A REPRESENTATIVE IN CONGRESS FROM THE STATE OF OREGON
Ms. HOOLEY. Well, first of all, Mr. Chairman, thank you; and I
want to thank the witnesses for being here today. Ensuring that
drugs and medical devices used by our children are safe and effective is a moral imperative for Congress and the FDA. The Best
Pharmaceuticals for Children Act and the Pediatric Research Equity Act have enabled us to make significant strides toward improving the safety of drugs prescribed for children. For example, labeling changes have been made to 87 percent of the drugs that are
used exclusively in pediatrics. That figure demonstrates a tremendous value in pediatric testing and the imperative for Congress to
take additional steps to push for increased clinical testing of drugs
prescribed for children. Because of the incentives provided under
BPCA, labeling changes have resulted in more appropriate dosing
for children and disclosure of previously unknown side-effects.
PREA has ensured appropriate pediatric testing can be required for
new drugs and BPCA has been successful in incentivizing studies
for on-patent drugs. Drug companies have conducted pediatric
studies under BPCA on over 80 percent of FDA requests for on-patent drugs. I love all these initials. They are so wonderful. However,
even with our successes, significant work remains to increase the
prevalence of pediatric testing. Only four or five of the 10 most
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commonly prescribed drugs for children have ever undergone pediatric testing. To increase pediatric testing, the FDAs very limited
success with getting off-patent drug sponsors to conduct pediatric
studies deserves more careful consideration. The National Institutes of Health has not funded studies on more than half of the offpatent drugs on which drug sponsors have declined FDA-requested
pediatric studies.
The FDA must also reduce the amount of time between completion of its scientific review and approval of necessary labeling
changes. Over 15 percent of drugs that require labeling changes
under BPCA took more than 1 year from completion of the review
process to a review of those labeling changes. The average time is
nearly 9 months. Delays in making labeling changes may mean
that children continue to receive inappropriate doses or that doctors remain unaware of potential serious side-effects for children.
I hope the FDA does better. I also hope the FDA and the committee
will look into the 2005 Institutes of Medicine Report on Pediatric
Medical Devices for Reform Recommendations. As a starting point,
the Center for Devices and Radiological Health should follow the
IOM recommendation to form a division with expertise on pediatric
devices. I look forward to discussing more of the IOMs recommendation on pediatric devices with the panelists during my
question time.
Finally, it is imperative that as we take steps to expand testing
of drugs and devices in pediatric populations that we do not
produce unintended consequences that discourage development of
products for children.
Thank you, Mr. Chairman. I yield back my time.
Mr. PALLONE. Thank you. We are going to take just a brief break
to see if we can test the equipment. It might be working again. OK.
Sounds like we are in order so we can use the equipment again
starting with Mr. Allen who is recognized for 5 minutes.
Mr. ALLEN. Mr. Chairman, I will waive my opening remarks and
submit it for the record.
Mr. PALLONE. OK. I think that ends all the opening statements.
Any other statements for the record will be accepted at this time.
[The prepared statements follow:]
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PREPARED STATEMENT
OF HON. HILDA L. SOLIS, A REPRESENTATIVE IN

FROM THE STATE OF CALIFORNIA
CONGRESS
Mr. Chairman, thank you for holding this hearing today to discuss safety and innovation in pediatric therapies. Children are sometimes forgotten and left out because some consider them a small, niche market.
While the FDAs mission is to protect and advance the publics health, we must
not forget that this must include children as well as adults. The FDA is also responsible for providing accurate, evidence-based information to the public so that individuals can make optimal health decisions. It is important to discuss and determine
how we can increase the number and types of safe and effective medical devices and
drugs designed for children. In order to do so, we must have accurate, scientific data
on the safety and effectiveness of drugs and devices for children.
Before the enactment of the Pediatric Research Equity Act, 75 percent of the prescriptions that pediatricians wrote were for medications that had been found appropriate only for adults, even though their labels provided suggested childrens dosages. As we know now, just because a drug has been proven safe and effective for
an adult does not mean that it is equally safe and effective in a child. We must adjust medications and devices for childrens small and rapidly growing bodies based
on science, not guesswork. Improper medical treatments such as overdosing and
underdosing can both lead to adverse health consequences. This is why medicines
that will be used by children should be found safe for children.
Just as there are difference between children and adults, there are also differences among children of color. For example, the incidence of diabetes disproportionately affects Latino and Black children. We should maximize the effectiveness
of drugs for the entire population. This means that when determining effectiveness
and safety, we must ensure that the process includes the diverse group of children
who represent the racial and ethnic groups that will likely receive the drug. I hope
that FDA can now efficiently identify the participation rates of children of color
under the pediatric exclusivity provision and that drug sponsors are required to use
standard definitions for race and ethnicity.
Accurate data collection is essential in determining how children from different
racial and ethnic react to specific drugs. We must enable providers and families to
make the best possible decision about using medicines to improve their health.
I hope we can work together in a timely manner to ensure that our children have
improved access to life-saving drugs and devices.
PREPARED STATEMENT
OF
HON. BARBARA CUBIN, A REPRESENTATIVE IN

FROM THE STATE OF WYOMING
CONGRESS
As the mother of two boys, I have made my fair share of trips to the doctors office, not to mention the occasional emergency room visit. No parent wants to find
out that their child is sick. But when it does happen, you hope that your physician
has the knowledge and resources necessary to treat the problem.
In modern medical practice, pharmaceutical drugs have played an increased role
in preventing, treating and curing disease. Yet federal drug safety policy fell behind
in labeling these products for pediatric use. As few as 10 years ago, roughly 80 percent of medication labels in the Physicians Desk Reference were not labeled for children.
Biologically, children are not simply miniature adults. Off-label drug prescribing
can result in a child receiving too much of a drug, or not enough for it to be effective. There can also be side effects unique to children, including effects on growth
and development.
In 1997, Congress recognized this problem and granted a 6-month market exclusivity period to drug manufacturers who conduct the pediatric studies necessary for
pediatric labeling. In 2002, this incentive was reauthorized in the Best Pharmaceutical for Children Act, or BPCA.
BPCA is arguably the most successful pediatric initiative the FDA has embarked
upon. In conjunction with the FDA authorities granted in the Pediatric Research
Equity Act, or PREA, the FDA has successfully spurred industry participation in the
riskier pediatric labeling arena.
Because of this robust carrot and stick approach, I am please to report that my
two grandchildren will have more access to pediatric specific labeling than I or their
parents ever did. Today there is a pediatric study infrastructure that before was
nonexistent.
I am confident that much of todays testimony will reaffirm the success of this approach. In reauthorizing BPCA and PREA, this committee ought to recognize the
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important role of both voluntary market incentives and the FDAs authority to impose mandated studies in certain circumstances.
We still have a long way to go in fitting our treatments for pediatric settings.
Nearly two-thirds of drugs used on children are still not labeled for children. We
can, and should, do better than this. I am hopeful our panelists here today can
share their suggestions for how Congress can best support our pediatric study infrastructure.
Let me turn to our first panel today.

First of all, welcome to all of you. Let me introduce each of you.
We have, beginning on my left, Dr. Joanne Less who is Acting Director of the Office of Combination Products for the U.S. Food and
Drug Administration; and then we have Dr. Sandra Kweder, Deputy Director, Office of New Drugs, Center of Drug Evaluation and
Research at the FDA; and then last is Dr. Donald Mattison who
is Chief Obstetric and Pediatric Pharmacology Branch of the National Institute of Child Health and Human Development at the
National Institute of Health. Thank you all for being here.
We start with 5-minute opening statements from each of you.
Your statements become part of the hearing record, and each witness, each of you in the discretion of the committee, may submit
additional brief or pertinent statements in writing afterwards if
you like; and I will start with Admiral Kweder.
STATEMENT OF REAR ADMIRAL SANDRA L. KWEDER, M.D.,
DEPUTY DIRECTOR, OFFICE OF NEW DRUGS, CENTER FOR
DRUG EVALUATION AND RESEARCH, U.S. FOOD AND DRUG
ADMINISTRATION
Dr. KWEDER. Good morning, Mr. Chairman, and members of the

committee. I am Rear Admiral Sandra Kweder. I am a physician
and the Deputy Director of the Office of New Drugs in the Center
for Drug Evaluation and Research of the FDA. Dr. Joanne Less,
the Acting Director of the Office of Combination Products, is accompanying me. She is here to respond to questions that you might
have regarding pediatric devices. I am here today to share with you
the real success of the pediatric exclusivity provisions that you
have authorized and the Pediatric Research Equity Act. There is no
question that they have expanded access to important therapeutics
for children and importantly promoted safety and innovation in
drug development for children.
Before the enactment of the exclusivity incentive program that
began in 1997, about 80 percent of medications in the Physicians
Desk Reference, a big compendium, did not have any pediatric use
information; and only about 20 to 30 percent of drugs approved by
FDA were labeled for pediatric use. Most drugs used for children
were considered to be used off-label; in other words, there was no
data to establish the correct dose in children or to confirm their
safety profile or if they even were effective in children, the pediatric population. In 1997 you provided marketing incentives to
manufacturers who voluntarily conduct studies of drugs in children. This law provides 6 months of additional market exclusivity
for a drug in return for conducting pediatric studies in response to
a very specific written request issued by FDA. The incentive had
become the most successful pediatric initiative that we at FDA
have ever participated in.
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In 2002, the pediatric exclusivity incentive was reauthorized as
this BPCA, the Best Pharmaceuticals for Children Act. This statute
added provision for safety evaluation of products once they had received exclusivity, public dissemination of study information, and
additional mechanisms for the study of drugs in children. Shortly
thereafter, Congress passed another important law to work in concert with BPCA, the Pediatric Research Equity Act. PREA provides
FDA authority to require pediatric studies under certain conditions. Since 1997, the exclusivity program has generated labeling
changes for 128 products. These labeling changes have significantly
increased the information available to healthcare professionals to
use in the treatment of pediatric patients. Eighty-three products
have updated new information expanding the use of the product to
a broader pediatric population and labeling. Twenty-five have had
dosing adjustments, important for clinicians, put in labels for pediatrics, and 28 products had information added to labeling indicating that the products were found not to be safe or effective in children. Thirty-seven had newer enhanced pediatric safety information added to labeling. This exclusivity, or BPCA, process can be
initiated in two ways. FDA can determine if there is a public
health need for additional pediatric studies for a drug and issue a
written request on our own. Alternatively, a sponsor can initiate
the process by submitting a proposal for a written request to us.
However, even if the sponsor issues such a proposal, we will not
issue a written request unless we perceive there to be an important
public health need for those studies to be conducted.
Under BPCA, two review processes occur in parallel once we
have data. One is the exclusivity review to determine whether the
studies that the company actually did fairly respond to the terms
we set forth in the written request that would therefore qualify the
product for exclusivity. There is a separate process, a scientific review, to determine whether the NDA or supplement should be approved. And those two processes occur on different timelines. The
scientific review is subject, however, to the same intense scientific
rigor and administrative terms and conditions that we provide to
any application that comes before the agency, and as part of that,
we will decide whether changes to a product label are warranted
at that time. Importantly, FDA includes both positive information
and negative information from study reports done on pediatric
studies in labeling because both types of information inform practitioners.
BPCA did several other important things that really have taught
us a lot about the study of drugs in children and monitoring the
safety of drugs in general. First, it authorized us to establish a Pediatric Advisory Committee that also provides for post-marketing
safety review on a regular schedule by that committee of information on adverse events for all pediatric products granted exclusivity. It also created our Office of Pediatric Therapeutics as part of
the Office of the Commissioner. This office provides scientific expertise and important ethics advice as we work with companies to
guide pediatric product development. In contrast to BPCA which
provides this voluntary mechanism for attaining needed studies on
approved or unapproved indications of a drug, PREA, Pediatric Research Equity Act requires pediatric assessment of certain products
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but only for the indications that are approved in adults. It is an
important distinction, only for the indications that the sponsor is
seeking adult approval for. FDA can defer or waive those pediatric
assessments under certain circumstances. In contrast to BPCA
though, PREA applies not just to NDAs or drugs, PREA also applies to biological products and biologic license applications. There
have been about 40 labeling changes involving pediatric studies
that are linked specifically to PREA.
Despite the success of the statutes, there are unquestionably a
large number of drug and biological products that remain inadequately studied for children. BPCA and PREA have acted in concert to provide important safety, efficacy, and dosing information
on pediatrics. We at FDA want to build on these improvements
with more studies to produce new labeling information that is a
value to the children in this country as well as physicians taking
care of them.
We welcome the opportunity to work with you to ensure that the
benefits of the incentive program continue in conjunction with our
need for our continued authority to mandate studies. We are just
getting on a roll, and Dr. Less and I will be happy to answer any
questions.
[The prepared statement of Dr. Kweder follows:]
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Mr. PALLONE. Thank you, Dr. Kweder. Dr. Mattison.
STATEMENT OF DONALD MATTISON, M.D., CHIEF, OBSTETRIC
AND PEDIATRIC PHARMACOLOGY BRANCH AND HUMAN DEVELOPMENT, NATIONAL INSTITUTES OF HEALTH
Dr. MATTISON. Good morning, Mr. Chairman. I am Donald

Mattison, Chief of the Obstetric and Pediatric Pharmacology Research Branch at the National Institute of Child Health and
Human Development, the National Institutes of Health. We appreciate the opportunity to appear before you and the rest of the committee to discuss NIHs research activities in relation to implementation of the pediatric drug testing program under the Best Pharmaceuticals for Children Act.
The BPCA legislation was enacted in 2002 to address the growing recognition that the great majority of pharmaceutical products
prescribed for children have never been tested for pediatric use.
Healthcare professionals were forced to depend upon experience
and their best judgment in prescribing medications for their pediatric patients. However, without a strong evidentiary base, it becomes difficult for practitioners to work with children of various
ages who are at various developmental stages to estimate what the
correct dose should be. Since children metabolize or respond to a
drug differently from an adult, that drugs effect may be variable
with too high a dose producing toxicity, too low a dose being ineffective to treat the childs disease.
Under current law, the NIH is directed to conduct research-related activities in three general categories, identifying and prioritizing
drugs needing study in children, developing new study requests in
collaboration with the Food and Drug Administration and other pediatric experts, and supporting studies on priority drugs after manufacturers decline to do so. In most cases, the drugs under consideration for study by the NIH are for off-patent or older medications
to which no marketing exclusivity can be granted. In some instances, these medicines have been used for over 30 years and yet,
those same efficacy and safety information have not been compiled
for children.
This is a challenging area of research. The available data are
mostly on adults. Some of the conditions that these drugs are used
to treat are relatively rare, and effects on childrens growth and development have largely been unrecognized and certainly cant be
studied in adults. In addition, human subjects concerns with a critical focus on balancing risks versus benefits are of particular importance in pediatric research. Moreover, long-term follow-up of the
possible effects on growth and development can be important but
costly aspects of pediatric clinical trials. To conduct these studies
and obtain generalizable data, we often need to enroll a larger
number of pediatric patients than have previously been studied. In
order to prioritize the drugs needing studies, NICHD has developed
an annual cycle of data gathering, expert consultation, and critical
analysis. The purpose of the process is to distill from the total
number of off-patent drugs to a manageable number, five to 10, for
study the following year. We look at whether dosing, safety, and efficacy data are already available from a reputable source and
whether additional data are needed, whether new studies will
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produce health benefits for children, and the balance between how
frequently the condition is to be treated and the severity of the condition, whether there is a need to reformulate the drug so that children will be able to use it. As an example, a drug that only comes
in tablet form cannot be readily taken by a young child with cerebral palsy. Together with other NIH institutes and centers, the
FDA and other pediatric experts, NICHD has made significant
progress on this front as required by BPCA by developing and publishing an annual list of approved drugs in need of further study
in pediatric populations. As of December 2006, 106 total drugs have
been addressed and discussed in scientific forums to decide if they
should be listed or whether we need further review of medical literature or outside consultation. From this group of drugs, approximately 60 drug indication pairs have been listed as off-patent priority drugs, drugs that require further pediatric studies. I have
provided a list of those drugs to the committee in table 1.
From the list of prioritized drugs, the FDA, in consultation with
the NIH, develops and issues written requests to the drug manufacturers. To date, 16 written requests have been developed and
forwarded to the manufacturers by the FDA. All but one of those
written requests have been declined by the manufacturer, and
those drugs have been referred to the NIH for study. Since receiving the 16 written requests, we have implemented, as shown on
table 2, 13 drug studies that we are currently conducting and funding with support from other NIH institutes and centers that have
significant pediatric research programs.
BPCA implementation is a trans-NIH collaboration with 19 NIH
institutes and centers investing more than $25 million annually.
While many of the projects first funded after the enactment of the
BPCA are in their final years of funding and results are expected
in the next few years, we have learned a great deal of pediatric
pharmacology and reach out regularly to the field to further understand the needs of clinicians who treat children. For example, research findings suggest the need for testing a variety of drugs and
other approaches to address the increasing problem of obesity-related hypertension in adolescents and improving the health of
these young people. We have also organized and invited experts to
numerous workshops on a myriad of issues that surround pediatric
studies, including formulations for use at different stages of development, the design requirements and ethics of clinical trials in this
special population.
Some of what we have learned has been unexpected. Information
on a number of drugs which we thought initially would require
only late phase III or phase IV clinical trials in children to provide
the data we were seeking, proved completely inadequate; and we
were forced to revise our plans and fund more preliminary studies
on safety and efficacy. A number of those studies are underway.
In summary, significant progress has been made to establish the
infrastructure and support for pediatric drug studies that can provide critical information regarding the safe and effective use of
these medications in children. We look forward to continuing to
work with this important committee and would be happy to answer
any questions you and other members of the committee might
have. Thank you.
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[The prepared statement of Dr. Mattison follows:]
STATEMENT
OF
DONALD MATTISON, MD
Good morning, Mr. Chairman. I am Donald Mattison, chief of the Obstetric and
Pediatric Pharmacology Research Branch at the National Institute of Child Health
and Human Development (NICHD), National Institutes of Health (NIH). We appreciate the opportunity to appear before you and the rest of the Committee to discuss
NIHs research activities in relation to implementation of the pediatric drug testing
program under the Best Pharmaceuticals for Children Act (BPCA).
The BPCA legislation was enacted in 2002 to address the growing recognition that
the great majority of pharmaceutical drugs prescribed for children had never been
tested for pediatric use. Health care professionals were forced to depend upon experience and their best judgment in prescribing medications for their pediatric patients. However, without a strong evidentiary base, it becomes difficult for practitioners who work with children of various ages who are at a range of developmental
stages to estimate what the correct dose may be. Since children may metabolize or
respond to a drug differently from an adult, that drugs effects may be variable
too high a dose for a given child poses risks of toxicity, too low a dose may be ineffective.
Under current law, the NIH is directed to conduct research-related activities in
three general categories: identifying and prioritizing those drugs needing study in
children, developing new study requests in collaboration with the Food and Drug
Administration (FDA) and other pediatric experts, and supporting studies on priority drugs after manufacturers decline to do so. In most cases, the drugs under consideration for study by the NIH are for off-patent or older medications for which no
marketing exclusivity can be granted. In some instances, these medications have
been in use for over thirty years, and yet relative dosing, efficacy and safety data
have yet to be compiled for children.
This is a challenging area of research. The available data are mostly on adults;
some of the conditions these drugs are used to treat are relatively rare; effects on
childrens growth and development have been largely unrecognized and certainly
cannot be studied in adults. In addition, human subjects concerns, with a critical
focus on balancing risks versus benefits, are of particular importance in pediatric
research. Moreover, long-term follow-up of the possible effects on growth and development can be an important, but costly, aspect of pediatric clinical trials. To conduct
these studies and obtain generalizable data, we often need to enroll larger numbers
of pediatric patients than have been previously studied.
In order to prioritize the drugs needing study, NICHD has developed an annual
cycle of data gathering, expert consultation and critical analysis. The purpose of the
process is to distill, from the total number of off-patent drugs (approximately 200)
to a manageable number (five to ten) for study in the following year. We look at
whether dosing, safety and efficacy data are already available from a reputable
source and whether additional data are needed, whether new studies will produce
health benefits for some subpopulation of children, the balance between how frequently the condition to be treated may occur and the severity of the condition, and
whether there is a need to reformulate a drug so that children will be able to use
it. For example, a drug that only comes in tablet form cannot readily be taken by
an infant or by a young child with cerebral palsy.
Together with other NIH Institutes and Centers, the FDA, and other pediatric experts, the NICHD has made significant progress on this frontas required by the
BPCAby developing and publishing an annual list of approved drugs in need of
further study in the pediatric population. As of December 2006, 106 total drugs have
been discussed in a scientific forum to decide if they should be listed, or whether
we need further review of the medical literature or outside consultation. From this
group of drugs, approximately 60 drug/indication pairs have been listed as off-patent
priority drugs that require further pediatric studies. These annual lists have been
provided to the committee in Table 1.
From each list of prioritized drugs, the FDA, in consultation with the NIH, develops and issues a series of Written Requests to the drugs manufacturers; to date,
all but one has been declined by the manufacturer, and the drugs have been referred to the NIH for study. Table 2 shows the 13 drug studies the NIH is currently
funding and the status of each. We could not be conducting this work without the
scientific expertise and financial support from the other NIH Institutes and Centers
that have significant pediatric research portfolios. BPCA implementation is a major
trans-NIH collaboration, as 19 NIH Institutes and Centers are investing more than
$25 million annually.
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While many of the projects first funded after the enactment of the BPCA are in
their final year(s) of funding and results are expected in the next few years, since
the enactment of BPCA, we have learned a great deal about the field of pediatric
pharmacology and reach out regularly to the field to better understand the needs
of the clinicians who treat children. For example, research findings suggest a need
for testing a variety of drugs and other approaches to address the increasing problem of obesity-related hypertension in adolescents (high blood pressure related to
weight gain), and improving the health of these young people. We also have organized and invited experts to numerous workshops on the myriad of issues that surround pediatric studies, including formulations for use at different stages of development, the design requirements and ethics of clinical trials in this special population.
Some of what we learned was unexpected. Information on a number of drugs,
which we initially thought would require only Phase III or IV clinical trials in children to provide the data we were seeking, proved to be completely inadequate, and
we were forced to revise our plans and fund more preliminary studies on safety and
efficacy. A number of those studies are now underway.
In summary, significant progress has been made to establish the infrastructure
and support for pediatric drug studies that can provide critical information regarding the safe use of these medications in children. We look forward to continuing this
important work, and I would be happy to answer any questions you or the other
members of the committee may have.
TABLE 1
2003:
Ampicillin/Sulbactam: treatment of pediatric infections
Azithromycin:
Prevention of bronchopulmonary dysplasia in infants with Ureaplasma
urealyticum
Prevention and treatment of Chlamydia conjunctivitis and pneumonia
Baclofen: treatment of spasticity in children with cerebral palsy
Bumetanide: treatment of pediatric hypertension
Diazoxide: treatment of hypoglycemia in children
Dobutamine: treatment of hypotension and low cardiac output in children
Dopamine: treatment of hypotension and low cardiac output in children
Furosemide: treatment of pediatric hypertension
Heparin: prevent blood clotting in children
Isofluorane: produce general anesthesia in children
Lindane: treatment of lice and scabies in children
Lithium: treatment of mania in children with bipolar disorder
Lorazepam:
Treatment of status epilepticus in children
Provide sedation for children in intensive care being treated with a respirator
Meropenem: treatment of pediatric infections
Metoclopramide: treatment of children with Gastroesophageal reflux
Piperacillin/Tazobactam: treatment of pediatric infections
Promethazine: treatment of nausea and vomiting in children
Rifampin:
Treatment of Methicillin resistant Staphylococcus aureus endocarditis in children
Treatment of central nervous system shunt infections in children
Sodium Nitroprusside: produce hypotension in children undergoing surgery to reduce blood loss
Spironolactone: treatment of pediatric hypertension
2004:
Ampicillin: treatment of pediatric infections
Dactinomycin: treatment of pediatric cancer
Ketamine: sedation of children for short procedures
Metolazone: treatment of pediatric hypertension
Vincristine: treatment of pediatric cancer
2005:
Acyclovir: treatment of pediatric infections with herpes
Clonidine:
Treatment of autism in children
Treatment of ADHD in children
Cyclosporine: prevention of organ transplant rejection in children
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Ethambutol: treatment of children with tuberculosis infections
Flecanide: treatment of cardiac arrhythmias in children
Griseofulvin: treatment of Tinea capitis infections in children
Hydrochlorothiazide: treatment of pediatric hypertension
Hydrocortisone valerate: treatment of inflammatory skin conditions in children
Hydroxychloroquine: treatment of connective tissue disorders in children
Ivermectin: treatment of scabies infection in children
Methadone: treatment of neonates undergoing opioid withdrawal
Sevelamer: treatment of hyperphosphatemia in children with chronic renal failure
Morphine: treatment of pain in pediatric patients
2006:
Albendazole: treatment of children with parasitic infections
Amantidine: treatment of children with influenza
Daunomycin: treatment of children with cancer
Guanfacine: treatment of children with ADHD
Methotrexate: treatment of children with cancer
Mebendazole: treatment of children with parasitic infections
Pralidoxime: treatment of children with organophosphate poisoning
Rimantadine: treatment of children with influenza
Hydroxyurea: treatment of children with sickle cell disease to prevent painful
blood sickling crisis
Methylphenidate: characterize safety in this drug used to treat children with
ADHD
Table 2
The following pediatric drug studies currently are being supported with NIH funding:
LorazepamPhase I, Phase II and Phase III clinical studies to support treatment for status epilepticus (NINDS)
LorazepamPhase I, Phase II and Phase III clinical studies to support sedation of children on respirators in an intensive care unit
NitroprussidePhase I, Phase II and Phase III clinical studies to understand
use to reduce blood pressure during surgery to reduce blood loss
Lithium Phase I, Phase II and Phase III clinical studies to define treatment
of mania in children with bipolar disorder (NIMH)
BaclofenPhase I, Phase II and Phase III clinical studies to understand oral
treatment of spasticity, most commonly from cerebral palsy
VincristinePhase I, Phase II and Phase III clinical studies to enhance treatment for malignancies in children (NCI)
DactinomycinPhase I, Phase II and Phase III clinical studies to enhance
treatment for malignancies in children (NCI)
DaunomycinPharmacokinetics, safety, efficacy of daunomycin to treat childhood cancers and relationship to body weight (NCI)
MethotrexatePhase II and Phase III clinical studies to improve treatment
outcomes for pediatric patients with high risk acute lymphoblastic leukemia (NCI)
KetaminePreclinical studies to evaluate the scientific and safety concerns
about the use as an anesthetic in children
HydroxyureaPreclinical, Phase I, Phase II and Phase III clinical studies to
improve treatment of children with sickle cell disease (NHLBI)
MethylphenidatePreclinical and clinical evaluation of pharmacokinetics and
safety to understand reports of cytogenetic toxicity (NIEHS)
Morphinepreclinical basic science evaluations of the developmental expression of opioid receptors to better understand management of pain in children of different developmental stages and safety issues in treating pain in neonates
Mr. PALLONE. Thank you, Dr. Mattison. We will move to questions now, and I will start by recognizing myself for 5 minutes.
I wanted to talk about the pediatric exclusivity. Dr. Kweder, as
you are aware, there is some concern within Congress that there
are economic incentives associated with BPCA that encourage drug
sponsors to provide pediatric studies on those drugs that are most
widely used in adult populations, the so-called blockbuster drugs.
Furthermore, according to an article that appeared in the Journal
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of the American Medical Association, the value of the patent extensions under BPCA was often greater than the costs of conducting
the pediatric studies requested by the FDA. Some of these drugs
received as much as $508 million return because of the 6-month extension. The Senate, dare I mention the other body, included in
their bill recently reauthorizing BPCA and PREA a provision that
scaled back at the amount of exclusivity a company could get based
on its earnings. For drugs whose annual earnings exceed $1 billion,
they would get 3 additional months of exclusivity for conducting pediatric trials requested by FDA. I just want to know if that is
something the administration supports and why or why not.
Dr. KWEDER. I can comment generally on this. I am well-aware
of the article that really set out to look at the cost of doing the
trials themselves versus the exclusivity. What that study could not
do and one of the things that we are faced with doing is before we
issue such a request, we look very carefully to ensure that any
written request that we issue, any specific request for a trial or set
of trials, it is often more than one, that would lead to exclusivity
is something that will have a meaningful public health benefit for
children. The questions that will be answered in those trials will
result in something meaningful to the public health. Unfortunately
it is really difficult to assign a dollar amount to bump the public
health benefit; and that is what we are faced with. Remember that
in some cases, these are going to be for products that are manufactured by large companies that have wide use in adults and are
being used for a number of different things that are different from
adults than for pediatric patients. In other cases we are dealing
with a company that has one drug that has a very small niche but
we see an important pediatric need.
We have not been in a position where we have had to make those
determinations of what is the sponsor likely to get out of this.
Mr. PALLONE. You seem to be telling me that your decisions do
not in anyway reflect whether
Dr. KWEDER. Our decisions do not take into account how much
money they make today or are likely to make in the future. If you
were to decide that was something we needed to do, we would certainly have to work to obtain some expertise in helping us make
those assessments. Our concern is that that may end up delaying
the process in some ways.
Mr. PALLONE. All right. So you dont really want to link your decision to the money, but then you are really not taking a position
on the 3 months it seems to me, right?
Dr. KWEDER. No, I am not taking a position. I will say to give
you a flavor of how seriously we take this public health benefit, if
you look at the numbersI mentioned that sometimes a company
can initiate a request. We have had well over 500 of those come
from companies.
Mr. PALLONE. OK.
Dr. KWEDER. We have only issued like 350, 375, but for over 700
studies, which tells you that we dont take the companys initial request at face value. We are really looking harder. They complain
because our requirements are too tough.
Mr. PALLONE. OK. That is fair. Let me get to my next question.
As I understand it, there are different labeling requirements that
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apply when a drug maker applies to FDA for approval to list a pediatric indication of a new drug versus when a manufacturer received exclusivity after conducting appropriate studies. Under the
first case, pediatric use information is included in the labeling only
if FDA approved the pediatric indication. If FDA turned down or
the manufacturer withdrew a request for an indication, not only
does pediatric use information not appear in the products labeling
the fact that the manufacturer had made an unsuccessful attempt
and the research findings that blocked the approvalneither are
noted in the label, nor made public in other ways. But under exclusivity rules, information goes on the label regardless of whether or
not a drug is found to be appropriate for pediatric use. I am concerned by this disconnect. Shouldnt information regarding pediatric use be made available to the public regardless of whether we
learn about it when a drug manufacturer applies for a pediatric indication or through the exclusivity rules? Wouldnt it be helpful for
physicians or parents to know whether or not a drug maker applied
to have their drug approved for pediatric indications and was denied and would the administration be supportive of changing the
rules to accomplish that?
Dr. KWEDER. Let me say that we take the need for inclusion of
information about use of a product in pediatrics very seriously, and
where we have data that specifically suggests that there may be a
risk in pediatrics or that a drug may not be effective in pediatric
population, we will include that in the label, regardless of whether
the request came to us under an exclusivity, through an exclusivity
study, or as part of our general application. We are increasingly
pushing the envelope on that and ensuring that the public has that
information. That is for approved drugs.
Mr. PALLONE. Right.
Dr. KWEDER. Now, the difference under BPCA is that even if an
application is not approved under BPCA, a study summary does
appear on the web that lets people know about that oftentimes before we even get into the label. But we are increasingly successful
in including all that important information for practitioners in
product labels and the public in product labels.
Mr. PALLONE. But then if we change the law to make the information more available or to require it and to eliminate this disconnect, you dont have a problem with that?
Dr. KWEDER. We are strongly in favor of transparency.
Mr. PALLONE. OK. All right. Thanks a lot. Mr. Deal.
Mr. DEAL. When a manufacturer initiates the request, you dont
take them up on the offer
Dr. KWEDER. Sometimes we do but we usually modify a lot.
Mr. DEAL. Let us assume you dont take them up at all. Do you
have any idea how many of them go forward on their own initiative
at that point to do pediatric testing?
Dr. KWEDER. I do not have the answer to that question off the
top of my head. That is information I can get you and follow up
unless one of my colleagues knows. No, they dont know specifically. Very few. I would say, Mr. Deal, my best estimate is that
very few, very, very few.
Mr. DEAL. So the exclusivity is a real useful tool?
Dr. KWEDER. It is an extraordinarily useful tool for us, yes.
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Mr. DEAL. Dr. Mattison, let me ask you with regard to your offpatent further investigations, who makes the determination to select those drugs? Is there a scientific panel, is there public input
into that process? How do you go about selecting those drugs?
Dr. MATTISON. We have established a process by which we work
with the FDA to identify the drugs that are considered to be offpatent; and then on an annual basis, we have pulled together 30
to 50 experts in pediatrics to help us discuss the drugs that we
think have the greatest potential for improving public health benefit, in children or have the widest gap between what we know and
what we would like to know in terms of the use of those drugs in
children. We rely very, very heavily in the set of activities that lead
up to selecting drugs on input from experts from around the United
States in pediatrics, our colleagues in the various institutes and
centers of the NIH that participate in BPCA, as well as our colleagues at the FDA. So this is a very open, deliberative process
that we believe helps us identify those drugs for which testing will
have a substantial impact on childrens health.
Mr. DEAL. With regard to those tests, are most of those tests conducted within the institute or are they contracted out through
grant programs? How do you conduct them?
Dr. MATTISON. The tests are all financed by the institutes but
conducted outside of the NIH through grants and contracts, and
the choice of the mechanism that we use depends upon the nature
of the study that we are interested in performing. For large clinical
trials, we have used a contract as a way of assuring that the various institutions that participate understand what we specifically
need from the clinical trial to improve how the drug is used or
thought about in children. In some instances we have been surprised by the lack of even basic science knowledge about the drugs,
and in that case we have used grants as the mechanism to build
the scientific understanding that we need before we can actually
design the clinical trail.
Mr. DEAL. Let us take a situation in which you have done one
of these tests to further determine the applicability of a drug for
pediatric usage that was not initially approved by FDA. Do you
find at that point that the manufacturers of those drugs take your
information and then go back to FDA for relabeling or new applications? What is the process that follows your research?
Dr. MATTISON. When the research is completed and the data has
been analyzed from the clinical trials, that data is made publicly
available as a part of the FDA docket system so that any investigator from around the United States or anywhere around the world
could actually take a look at the outcomes of those clinical trials
and determine whether or not they thought it was appropriate to
use that drug in children. As I understand the current BPCA law,
the manufacturers cant get additional exclusivity. We havent encountered the issue of the manufacturers asking to use the data,
but we make the data publicly available to anyone that would like
to take a look at it.
Mr. DEAL. But it would seem to me to logically close the loop,
they would go back to FDA and apply for new application for usage
for pediatric purposes. Is that what happens, Dr. Kweder?
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Dr. KWEDER. Yes, if it were important information to come from
any of those studies, we absolutely would ensure that it made it
to product labeling. Oftentimes you are dealing with a generic
product that has multiple manufacturers, for example; but we
would make sure that those data were widely available in a package insert.
Mr. DEAL. But is there enough interest on the part of either the
initial innovator product or the follow-on generics? Do they have
enough interest in this to initiate it?
Dr. KWEDER. Seek to initiate it? I think it is quite variable, particularly if there is a safety issue. They will usually see that it is
in their best interest to include that information in their labeling,
but we have managed to find ways to require them to include that
information.
Mr. DEAL. OK. Thank you.
Mr. PALLONE. Mr. Waxman.
Mr. WAXMAN. Thank you very much, Mr. Chairman. When we
give the exclusivity, we are giving what could be a very rich reward, and it seems to me that we want to make sure that we are
getting something well worthwhile in return. There are many
drugs with annual U.S. sales in the billions, so when we are talking about an extra 6 months of exclusivity paid for by the uninsured, the Federal Government, businesses, and insurers in the
form of higher monopoly drug prices, we want to see if that price
tag was worth it.
Dr. Kweder, in your testimony you said that since BPCAs inception in 1997, FDA has made 150 exclusivity determinations and
has awarded exclusivity in 136 of those cases. Your testimony also
describes the process by which FDA makes the decision to award
exclusivity. Essentially you base that decision on a brief and cursory review of the submitted studies, looking only at whether they
fairly respond to the terms of the written request. That decision is
not based upon the latter and more thorough scientific review of
the studies which forms the basis for your decisions about what
FDA will actually do with the information contained in the studies.
You obviously award exclusivity in most cases based on the first
preliminary review, so I assume it is only companies who fail egregiously to comply with the terms of the written request that are denied exclusivity. Can you briefly give a couple of examples of cases
in which FDA denied exclusivity?
Dr. KWEDER. One thing that I think is important to understand
is the reason that we make that determination of exclusivity in advance of the scientific review is that BPCA requires to us to render
a decision on exclusivity at 90 days after the application is submitted. 90 days. For a priority review, scientific review, under our current user fee legislation, we have 6 months to complete our review.
And sometimes the decision aboutmany times the exclusivity determination is relatively easy to make where you can quickly get
a good sense of the data in the application, but the types ofand
some of the cases where we denied exclusivity is because it is very
clear on its face that we asked for a study of a certain size and the
company came in with a study a fraction of the size that we had
already made very clear in our written request, would never be
able to provide us meaningful information. That is common.
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The more difficult areas where we struggle with the 90 days versus the 6 months is where we are trying to make an assessment
about the quality in the way the study was conducted. It is extremely difficult to do that within 90 days in many cases. It may
require us to do an inspection of one of the clinical trial sites to
really delve into more detail or obtain more data from the sponsor
of the application. We have had one situation I can think of where
we did deny exclusivity for that reason. It was difficult for us to
get to that determination in 90 days, but we were able to do it because we thought that the study was very poorly conducted.
Mr. WAXMAN. You describe instances in which you would have
reversed your decision to avoid exclusivity after having conducted
the more extensive scientific review of the studies. GAOs report
describes an instance in which FDA awarded exclusivity only to
later find the children participating in the study had not actually
received the treatments as the drug sponsor had claimed in the description of the study.
Dr. KWEDER. Yes, I was trying to remember what the drug was.
There was one asthma drug for example where we did award exclusivity. A study appeared to have been conducted well, the size was
OK, the population was right. They seemed to have done all the
things that we asked for.
Mr. WAXMAN. But rather than talking about one alone because
I see my time is running out, are there instances in which you
would have reversed your decision
Dr. KWEDER. Yes, this is one. Yes, this is definitely one, yes, because when we got into the data in more detail we found significant problems with the findings of the data that indicated the
study had been not conducted well.
Mr. WAXMAN. OK. I want to ask Dr. Mattison, the GAO report
lists some of the studies that NIH is currently conducting and the
spending NIH anticipates on those studies. Most of the studies listed were under $10 million, and several were in the $1 to $2 million
range. Is it fair to say that those amounts are typical costs for pediatric studies both for NIH and companies that undertake this research?
Dr. MATTISON. Those are the costs that we have been able to negotiate with the various investigators, depending upon the nature
of the study. I cant comment on how companies would negotiate
with investigators to conduct their studies.
Mr. WAXMAN. They wouldnt do anything all that much different,
would they?
Dr. MATTISON. They would be doing similar ones, that is correct.
Mr. WAXMAN. OK. Thank you. Thank you, Mr. Chairman. I see
my time is expired.
Mr. PALLONE. Mr. Burgess.
Mr. BURGESS. Thank you. Dr. Mattison, in your written and your
oral testimony, you state that some of what we learned was unexpected, information on a number of drugs which we initially
thought would require only phase III or phase IV proved to be completely inadequate. We were forced to revise our plans and add a
few more preliminary studies. So in some instances you would have
to go back and essentially recreate the entire phase I, phase II,
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phase III, phase IV study for a particular drug? How does the NIH
fund that?
Dr. MATTISON. The funding for all of the studies that we have
conducted under BPCA has come from a series of contributions
from the 19 institutes and centers that partner with us in the
BPCA-related activity. Their partnership was determined based on
the size of their pediatric research portfolios. So it is a group of
contributions that have come from the various institutes and centers.
Mr. BURGESS. Are there examples from what you provided in
table 1 of some of those compounds where you had to literally go
back to the beginning and recapitulate the entire study?
Dr. MATTISON. That is correct, and I can give you several examples. In one instance, we have had extensive meetings with pediatric cardiologists, both in the United States and around the world
about two commonly used drugs used in the neonatal intensive
care unit, dopamine and dobutamine, drugs that are used variously
to increase blood pressure or increase profusion through organs;
and based on extensive discussions with these pediatric cardiologists, we have been unable to arrive at a scientifically credible clinical trial design. So we have decided that we needed to go back and
better understand how those drugs work in the newborn. We do
have a pretty good understanding of how those drugs work in
adults, but that understanding hasnt translated to an improved
understanding.
Another example is morphine, a drug that has been used extensively and is off-patent, 30, 40, 50, 75 years, very, very extensively
used. We have data suggesting that morphine alters the way the
childrens brains respond to trauma during development, and so we
have elected to try to understand better the expression of receptors
for that drug, rather than to embark on the clinical trials.
Mr. BURGESS. Is any of the body of evidence that has been collected over the last say 70 years in the instance of morphine, is any
of that useful to you or do you simply have to start anew?
Dr. MATTISON. Well, it is very useful because we are beginning
to understand the receptors that morphine interacts with in terms
of producing its effect. What it doesnt help us with is understanding how those receptors are expressed across the course of development in children and whether they are expressed the same way
centrally in the brain or in the central part of the body or peripherally.
Mr. BURGESS. That is a fascinating subject. I would actually like
to talk to you about that in greater detail, but I dont have time.
Dr. Kweder, in your testimony, you talked about the PREA process. You mentioned just almost in passing that some of these
things would apply to biologics also. Now, it is not really part of
this hearing but we are at some point going to be asked to issue
guidelines on what are so-called biosimilar products or follow-on
biologics and is it your feeling that these two would have to, these
follow-on or biosimilar products, would need to be exposed to the
same types of rigorous study, in some instances even going back to
the beginning for biologists in use in children?
Dr. KWEDER. You are asking me several things. Let me just say
it is a bit of a frustration for us that we cant utilize BPCA and
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biologic therapeutics. As clinicians, doctors dont make a distinction
in their treatment needs based on whether it is a biological or a
small molecule drug. That is an invisible distinction in the practice
of medicine. And so to the practicing clinician, the distinction we
have to make is a bit artificial. There are many biological products
that we regulate that have potentially very important uses in children.
Mr. BURGESS. But does the concept of having to approve and provide the certification of safety for a follow-on biologic for use in the
pediatric population, is this of necessity going to take you back further in that research timeline?
Dr. KWEDER. I am not sure it necessarily will. I mean, these
would be basically like generic, what we consider generic products.
We dont have these requirements necessarily for generics. We can
utilize BPCA if we elect to but
Mr. BURGESS. If we go to Dr. Mattison, the list in table 1, I
mean, it is basically all generics.
Dr. KWEDER. Right, because they are old products, off-patent.
Mr. BURGESS. Correct.
Dr. KWEDER. Right.
Mr. BURGESS. And he has found that it was necessary to get back
to step one.
Dr. KWEDER. And we may indeed have to. We may certainly have
to go back to some very basic science in studying these biological
products in children simply because of the way that they act, their
mechanisms of action.
Mr. BURGESS. All right. Thank you, Mr. Chairman.
Mr. PALLONE. Thank you. Ms. Eshoo.
Ms. ESHOO. Thank you for recognizing me, Mr. Chairman. As we
are asking questions and reviewing the potential for changes to the
reauthorizations of this bill, I couldnt help but think that elsewhere in the capitol there is a national summit on Americas children taking place which is I think the first time in at least a decade that the intelligencia of our country have gathered relative to
Americas children, and I cant help but think that what we are
doing here obviously is for them as well. So I think that this is a
good day here in the Congress.
Dr. Kweder, I wanted to go back to the exchange that you had
with Mr. Waxman when you spoke about the 90 days. In your view,
does that need to be adjusted? Do you need more than 90 days?
Dr. KWEDER. In some cases we would have been very happy to
have more than 90 days to make that determination.
Ms. ESHOO. Is it important enough to change it when you say
some?
Dr. KWEDER. Yes.
Ms. ESHOO. OK. I think that you both agree that FDAs authority
to require pediatric studies should be permanent in PREA? Do you?
I am making that assumption. I dont know whether you agree.
Dr. KWEDER. I cant imagine that we would have any objection
but that is certainly up to you.
Ms. ESHOO. Well, that sounds kind of medium-rare to me. Well,
I understand who the legislators are but we have the experts here
to help guide us in making policy.
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Dr. KWEDER. May I add to that? We are as I have said in my
oral testimony, we are just beginning and it is positive to really
fully utilize these tools, and we think that they offer enormous potential and look forward to their continuation.
Ms. ESHOO. I think that there were some questions earlier on the
Senate blockbuster provision or an extension of the current 6month exclusivity. Would you like to comment on that, Dr.
Mattison?
Dr. MATTISON. Not from the NIHs perspective, no.
Ms. ESHOO. Not from the NIHs? And Dr. Kweder, you dont have
anything further to comment on?
Dr. KWEDER. My comment is that this program has worked extraordinarily well. The opportunity to offer exclusivity in exchange
for something that we determine, and we are very particular about
this, will have a meaningful public health benefit to pediatrics has
been probably what has been the most useful tool that we have had
to encourage pediatric drug development, ever. We have been able
to utilize the exclusivity provision not just to get information about
drug A in a particular narrow indication but as Dr. Mattison has
implied, we have utilized it to build a field of pediatric research
and answer broader questions that will ultimately apply to more
than one product.
Ms. ESHOO. Well, I worked very hard on that part of the legislation to motivate the outcomes that we were looking for so what you
are saying is reinforcing it. On labeling, are there any instances
where as a result of pediatric studies FDA has requested labeling
changes be made to a product and where the drug sponsor has not
complied and if so, how did you handle these situations?
Dr. KWEDER. We have been very successful in getting pediatric
labeling changes. Some of them have taken longer than we would
have liked. Some cases it is because we need more information, but
the legislation does provide for us if we are having difficulty getting something in labeling to take it to the Pediatric Advisory Committee. We have not had to take anything.
Ms. ESHOO. Do you need any additional authority in that
Dr. KWEDER. We have been successful to date.
Ms. ESHOO. So you are saying you dont need any additional authority? Are there any instances, this is on pediatric formulations,
where pediatric formulations such as syrup or where a chewable
tablet has been developed but not marketed?
Dr. KWEDER. One of the big problems that we have is sometimes
there have been examples where a product has been developed for
use in a clinical trial, a very small batch that you use on a few patients. But the problem has come where when you try to scale up
manufacturing to make something widely available on the market,
everything changes. That is a common problem in manufacturing
and that is why the biggest I would say for in pediatric formulations as well as the experiment to development.
Ms. ESHOO. That is the debate on biosimilars but I didnt realize
that it applied here.
Dr. KWEDER. Yes, it does in formulation development, yes.
Ms. ESHOO. Do you have any specific suggestions about how Congress can improve pediatric labeling?
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Dr. KWEDER. Pediatric labeling? I think by some of the things in
the BPCA that will allow us to link exclusivity to the scientific review process will result in better decisions on exclusivity and better
decisions on labeling. I think otherwise we feel like we have most
of the tools we need in pediatrics.
Ms. ESHOO. Thank you, Mr. Chairman. Thank you to the witnesses for your good work and your testimony.
Mr. PALLONE. Thank you. Mr. Murphy.
Mr. MURPHY. Thank you, Mr. Chairman. I would like to thank
the panel. This is very enlightening. I want to further delve into
something here that in terms ofDr. Kweder, you are saying the
program is working pretty well. My understanding is about 80 percent of the time the labeling of the drugs were changed to reflect
the pediatric information obtained from this research. Does that
number sound about correct?
Dr. KWEDER. That sounds about right.
Mr. MURPHY. OK. But among these drugs that show labeling
changes, what percentage of the overall drugs the FDA has asked
manufacturers to study does that reflect? So in other words, you
may come up with 100 drugs. What percentage of those do the
manufacturers really choose to study, to go into further?
Dr. KWEDER. I am not sure I am really understanding the question. I am sorry to be dense.
Mr. MURPHY. Let me explain then.
Dr. KWEDER. Yes.
Mr. MURPHY. Let us say you lay out 100 drugs that you would
like some pediatric studies done on.
Dr. KWEDER. OK.
Mr. MURPHY. Do they do every one of those or do the companies
decline sometimes?
Dr. KWEDER. Actually, we usually issue the written requests.
Under the written requests we may ask for more studies than one,
in fact, often we do.
Mr. MURPHY. What percent of the time will they do those?
Dr. KWEDER. Most of the time we have had overall, since the beginning of exclusivity which was actually 1997, we have had 41
companies decline to
Mr. MURPHY. Why? Why did they decline?
Dr. KWEDER. They declined for a variety of reasons, sometimes
because they are off-patent and they dont see a benefit.
Mr. MURPHY. What kind of benefit dont they see?
Dr. KWEDER. They see the pediatric market is too small to make
it worth their while. They see that in order to address the written
request, we have to ask for some of the basic scientific information
that Dr. Mattison is referring to. They dont have the tools to address that.
Mr. MURPHY. So let me just continue on this. They say the pediatric population may be too small?
Dr. KWEDER. The pediatric population may be too small.
Mr. MURPHY. Too small for them to recover whatever investment
and make the research based upon the 6-month exclusivity?
Dr. KWEDER. Yes, even with the 6-month exclusivity.
Mr. MURPHY. The 6-month thing doesnt give them enough?
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Dr. KWEDER. It is not enough. And sometimes I dont have any
exclusivity to attach to but we will ask them to do the study anyway. But there is no incentive. They are not going to do it.
Mr. MURPHY. And I want to clarify this because it is important.
There are different kinds of populations of diseases, some are very
common, unfortunately common and so companies may feel they
can recoup their loss.
Dr. KWEDER. Right.
Mr. MURPHY. I am particularly concerned about some of the rare
diseases of some children that I have treated myself and saw that
no one was investing in some of these orphan diseases.
Dr. KWEDER. Right.
Mr. MURPHY. And are those the kind of things sometimes the
companies say is just not worth their
Dr. KWEDER. Yes.
Mr. MURPHY. I am really interested in any recommendations you
have on how we correct this. Does the 6-month number work, and
I dont know if all diseases should be treated equally here, and if
some are more rare and have some awful tragic consequence but
if we could somehow encourage companies to do some of the pediatric research on these, should we have different levels here? Some
have 6 months, some have longer, so that they can look in terms
of making the investments in some of these rarer diseases?
Dr. KWEDER. That is an interesting question. I am trying to remember. BPCA does apply to orphan products, but whether or not
additional exclusivity would give companies the incentive to further
their exploration of some of those even more orphaned pediatric indications as we dosome examples are things like juvenile rheumatoid arthritis, very, very rare. Doing pediatric studies is extremely difficult for a lot of these companies.
Mr. MURPHY. Yes.
Dr. KWEDER. If you are a large company particularly and you
have some experience in doing trials in children, you have a setup system and you know how to do these, it is a very, very different kettle of fish than if you are a company that has just done
adult studies, it takes an entirely different kind of expertise, entirely different network, and they just feel like they dont have the
resources and the energy to even begin.
Mr. MURPHY. Exactly. Thank you so much for your comments on
that because in my years of treating patients and psychologists, I
remember one young man who was diagnosed with adrenal
leukodystrophy, fairly rare, so much so that as I was identifying
some of these symptoms, we had to search around for people who
really knew these and treated these people.
Dr. KWEDER. Right.
Mr. MURPHY. And it was so tragic to watch this boy wither away
because his body was basically eating away at itself in its own proteins and watch what happened as his own neurological development eroded. And yet I saw people were not really investing in
treatments for someone like that. How many more diseases are
there are like that? I hope that one of the things you might be able
to provide this committee and send to the Chairman might be some
ideas of how we deal with some other diseases because there are
parents out there who feel that no one is paying attention to their
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children and to treat all diseases as equal. I dont think it is fair
to them, and I hope you canI dont expect you to do it now but
I hope that is something you can make some recommendations to
the Chairman on.
Dr. KWEDER. No. Thank you.
Mr. MURPHY. Thank you, Mr. Chairman.
Mr. PALLONE. And we would certainly welcome those recommendations in writing. Thank you. Mrs. Capps.
Mrs. CAPPS. I also particularly appreciated this last exchange of
questioning. It is has been lurking in the back of my mind, orphan
diseases, adults or children but children in general are not a lucrative population for the topic that we are discussing today. How we
can provide those services so that all patients can feel safe and confident that there is somebody looking out should something develop. I had two different questions to ask you since we have kind
of jumped around here, Dr. Kweder. One is in the Best Pharmaceuticals for Children Act, HHS was required to issue a rule regarding the availability of a toll-free number which patients and
providers could use to report adverse effects, and this rule was supposed to be proposed within 1-year of enactment. It is 3 years later,
and I want to ask about that rule. Has it been released?
Dr. KWEDER. I am looking at my regulatory counsel here who is
telling me that the answer is no.
Mrs. CAPPS. Well, you know what I am going to ask you next.
When and why not?
Dr. KWEDER. We do have on all product labels, on all product labels, and we do require that the FDA MedWatch 1800 number
and Web site address be listed where anyone, healthcare provider
or consumer, is encouraged to report any adverse effect related to
any medicine. When one reports, one of the questions that is asked
is what is the age of the patient, and so we are able to collect extensive amount of adverse event information through that system.
We worked very hard over the years, now independent of this, to
try and have one channel for communication to FDA so that people
dont have to figure out, oh, did I call the right number? But that
is one of the ways that FDA gets its information. One of the things
that we have had to do in thinking about putting together this rule
under BPCA is work through some consumer groups and do some
testing to determine whether or not having a second number or
second pathway is going to confuse things rather than help. And
we are in the process of completing some of those studies.
Mrs. CAPPS. In this case it would be parents most likely who
would be reporting because of the
Dr. KWEDER. That is right. And that is typically how we get the
information, even through our MedWatch system about children
fromthe children dont report them themselves obviously, the
parents do.
Mrs. CAPPS. And I think again with all the questions that have
come up with what we are talking about, this is so important for
us to know, for you all to know, and the public to feel confident
that this unique population, always changing, developing, is going
to be acknowledged in terms of any kind of effect, good, bad, or
Dr. KWEDER. Right. And this kind of information is exactly the
kind of information that we ask our Pediatric Advisory Committee
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to review at the 1-year mark, information about both adults and
children, after exclusivity is granted.
Mrs. CAPPS. Now, a different topic but also based on child development. Children, because they are constantly growing and developing, it is even more important I believe that ongoing clinical
studies are part of that process to determine the long-term safety
and efficacy of either a device or a pharmaceutical. But currently
there is a 3-year limit on FDA mandated post-market studies on
medical devices. An Institute of Medicine report released in 2005
recommends that this 3-year limit be lifted because it restricts the
FDA from mandating appropriate studies involving devices effects
on children growth and development. I wonder if you agree with
this conclusion and the suggestion that this limit should happen,
be lifted. And Dr. Less? OK.
Ms. LESS. Congresswoman Capps, thank you very much. Before
I answer your question, let me just say thank you to Chairman
Pallone and the members of the subcommittee for inviting us today
to speak with you on this important issue, both post-market safety
of pediatric medical devices as well as facilitating the development
of new devices. We welcome this opportunity and look forward to
working with you this very important issue.
With regard to section 522, currently it is limited to 3 years, and
we agree with the IOM that in some cases, especially in the cases
of implants, it would be important to be able to go longer than the
3 years. Right now, if we want to go longer we have to work with
the manufacturer and get their agreement in order to do so. We
have not had that problem or we think that because manufacturers
are paying much more attention and recognize the importance of
collecting this information, it hasnt been an issue. But we would
not be opposed to having that additional authority.
Mrs. CAPPS. Good. I was just thinking of an important or some
device for a 2-year-old would notat 3 years, they are still very
much in the process of developing. So I would hope that this advise
be taken seriously in the reauthorization.
Ms. LESS. Thank you.
Mr. PALLONE. Thank you. Mr. Green.
Mr. GREEN. Dr. Mattison, would you like to explore the requirements of NIH and the resources it receives to study the drugs both
on-patient and off-patient, and can you compare the process and resources NIH receives distinguishing between the off-patent and onpatent drugs, resources comparison.
Dr. MATTISON. The funding that we use to support the studies
that we do on the drugs comes from contributions from the 19 institutes and centers that are participating with us in the BPCA activities, and those cover the studies that we need to conduct both
on- and off-patent drugs. We also receive contributions from the
foundation for the NIH to help defray the cost of the on-patent
drug studies that we are engaged in, but those contributions are
substantially less than the cost of the studies themselves.
Mr. GREEN. Do you have any comparison of the process or resources it receives? That is the only funding you receive?
Dr. MATTISON. I am sorry. I am not sure I understand it, but the
funding from the institutes has been a set contribution from each
of them since 2004. Again, through the foundation for the NIH,
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they have provided us what they felt was appropriate based on the
resources that they have collected. I am sorry if I am not answering you.
Mr. GREEN. Are there any private contributions?
Dr. MATTISON. There are private contributions that come to the
foundation for the NIH. I cant answer the question about who has
contributed those.
Mr. GREEN. OK. Recently a published GAO report on studies conducted under the BPCA had noted that the process for approving
labeling changes is often lengthy for drugs that have labeling
changes after being granted exclusivity. The report states that it
took between 238 and 1,055 days for information to be reviewed
and labeling changes to be approved for approximately 40 percent
of the drugs granted exclusivity, with seven of these taking more
than a year. Drug studies under the BPCA are used for a number
of life-threatening diseases. Would you agree that the amount of
time consumed for labeling changes to occur poses a dangerous
public health concern for some children and why is it taking so
long for labeling changes to occur? Is it lack of resources?
Dr. MATTISON. That I think is a question for the FDA.
Dr. KWEDER. I would be happy to answer that question. When
we make an approval for labeling changes, it is usually based on
a scientific review which as I mentioned before is on a different
time clock than the exclusivity determination. So the exclusivity
determination precedes the ultimate decision on how and whether
to label a product. Decisions about labeling ultimately depend on
the scientific data available that underlie those changes. For a priority application, we would usually render a decision on that scientific application at 6 months, others are a 10-month clock. It is
not unusual for us to have to go back and ask for more information
and another round of review before we can have the confidence
that we need in the labeling that we want to make. We have become I would say since we started these programs a few years ago
much better at getting those out there more quickly and making
cuts on labeling changes that we can make early while we wait for
additional data to supplement the labeling later. But there will always be a situation where we are stuck with needing more information before we can make a confident change to a label.
Mr. GREEN. But it is not from lack of resources?
Dr. KWEDER. No.
Mr. GREEN. What about with disagreements with manufacturers
on labeling?
Dr. KWEDER. Again, that is an area where we have been really
pushing the envelope to getting these things into the label. We feel
very strongly that information about pediatric use of products
needs to be available to practicing clinicians. Our best tool for that
is the labeling. We do have a provision in the statutes that allows
us to take a labeling dispute with a company to the Pediatric Advisory Committee. We have not had to utilize that to date.
Mr. GREEN. So you are saying that the numbers I gave, you
know, the 238 to 1,055 days, it is much better in the last few
years?
Dr. KWEDER. Yes, yes. Absolutely.
Mr. GREEN. OK. Thank you, Mr. Chairman.
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Mr. PALLONE. Thank you. The gentlewoman from Illinois?
Ms. SCHAKOWSKY. Thank you, Mr. Chairman. I am picking up a
little bit on what Mr. Waxman had raised about the cost of actually
doing the pediatric studies versus the amount of money that the
pharmaceutical companies make with this exclusivity provision.
The Wall Street Journal estimated that pediatric studies have
grown from $200,000 to $3 million each. Does that sound right or
is that $200,000 maybe a little low?
Dr. MATTISON. $200,000 is awfully low.
Ms. SCHAKOWSKY. OK.
Dr. MATTISON. The studies that we are conducting, depending
upon the severity of the disease and the children that are enrolled
in the study, they typically cost in the $10 to $15 million range.
Ms. SCHAKOWSKY. OK. And yet, 6 months of additional exclusivity was worth nearly $8 billion for Prozac and $575 million for
Claritin. So regardless, $10 or $15 million, it is a lot of money, potentially a lot of money in exclusivity. My staff is telling me that
the FDA has estimated that consumers will pay nearly $14 billion
in higher prescription drug costs over the next 20 years if the current pediatric exclusivity program is reauthorized. You look quizzical. Is that
Dr. KWEDER. That is not a statistic I am familiar with.
Ms. SCHAKOWSKY. OK. Maybe my staff will write me a note while
I am asking the rest of the questions. And I am concerned though
that these high prices and the differential is so high, is virtually
borne by senior citizens who are the highest consumers of and have
a disproportionate share of prescription drug use and the uninsured who have to pay the full cost. And I am concerned that under
the current system of granting additional exclusivity, there really
is little incentive for companies to test drugs other than the blockbusters.
For example, I have Glucophage, a diabetes medication, received
an exclusivity period worth about $640 million, yet it is barely used
for children. Less than one percent of its prescriptions are written
by pediatricians. And six out of the 10 drugs most widely used in
children without adequate labeling are not eligible for pediatric exclusivity because they are already off-patent. So should we be considering this differential and how much it is worth to the drug companies because ultimately the consumers pay the cost and how can
we incentivize studies in these very important drugs? I mean, if the
companies can simply decline to do the studies, then as Mr. Green
was exploring, that money then is entirely borne by the taxpayers.
Are these issues that we need to deal with? In my opinion I think
they are. So either or both of you actually
Dr. KWEDER. I will take a stab. These are really difficult issues.
One of the things that we do when we have a company that declines an initial written request, to go to your last point first, sometimes there is a long period of time that passes that they have been
thinking about that and events occur in the interim that make that
written request for example, we look very carefully to make sure
that this is something that we want the taxpayers to really fund.
Sometimes new information has come to light while they were
thinking about that written request that changes the public health
value equation. So we would make a decision to put that lower on
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the priority list for NIH funding. The struggle that the public has
in assessing value is looking at the cost of studies, the financial
gain that companies receive in terms of exclusivity, the cost to the
public of generic drugs, those are all factors I have to say the monetary costs have not really been part of the equation for FDA in
deciding what to ask for in the way of studies. We have really
based our decisions on seeking study data on what we perceive to
be a potentially important public health benefit.
To use the example of the Glucophage that you raised, that is
one of the oldest oral diabetic agents on the market; and while the
population of pediatric users today may be small, we have an epidemic of obesity in pediatric population that is growing in this
county. In particular in Type II diabetes, the type that is associated
with obesity, that is a mainstay of therapy among diabetics. So we
expect that physicians are going to increasingly be seeking to use
those kinds of treatments in children. So it was very important we
felt from a public health standpoint to really understand whether
that drug was safe in children and whether it was effective. We
learned that it is not effective in children. That is an enormously
important public health benefit and prevents children from being
exposed to a drug that is not effective and may only have risks. I
dont know how we could attach a monetary value to this, and that
has been our struggle in thinking about how to assign different values in terms of
Ms. SCHAKOWSKY. But clearly the companies are assigning a
monetary value when they decline to do a study.
Dr. KWEDER. Yes, they are.
Ms. SCHAKOWSKY. I am not trying to put a price tag on the life
of a child but there certainly is a cost benefit analysis and it is
pretty easy for the companies to say, well, it is off-patent, we decline.
Dr. KWEDER. Yes.
Ms. SCHAKOWSKY. I wondered if you had any comment doctor,
even though I am out of time, Mr. Chairman. Can I ask him if he
has any comments?
Mr. PALLONE. We will ask Dr. Mattison and then we will move
on.
Dr. MATTISON. Again, we focus our attention on the off-patent
drugs because we assume that those will get the least attention by
any other interested group, and we feel that by focusing our attention on that group of drugs and identifying those that provide the
greatest public health benefit in terms of what do we know versus
what would we like to know to improve those drugs, we at the NIH
can make the best impact possible under BPCA.
Ms. SCHAKOWSKY. Thank you. Thank you, Mr. Chairman.
Mr. PALLONE. Thank you and I thank all three of you for your
input in answering our questions, and I think as you know you
may get additional questions from us within the next 10 days or
so; and please follow through. Thank you.
Dr. KWEDER. We will, and thank you very much.
Mr. PALLONE. And if the next panel could come forward and I
ask that the panel be seated.
Let me start by introducing each of you. On my left is Ms. Lori
Reilly who is vice president for policy and research for PhRMA; and
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then we have Dr. Marcia Crosse who is director of health care
issues for the GAO; and then we have Dr. Gorman, Richard
Gorman, who is chair of the AAP section on Clinical Pharmacology
and Therapeutics for the American Academy of Pediatrics; we have
Dr. Peter Lurie who is deputy director of Public Citizens Health
Research Group; we have Ms. Susan Belfiore who is testifying on
behalf of Elizabeth Glaser Pediatric AIDS Foundation; we have Mr.
Ed Rozynski who is vice president for Global Government Affairs
at Stryker Corporation; and last is Mr. Donald Lombardi who is
president and CEO of the Institute for Pediatric Innovation.
We are going to give each of you 5 minutes. You can, of course,
submit additional written statements if you like with the committees permission afterwards; and we will start with Ms. Reilly.
Thank you.
STATEMENT OF LORI REILLY, VICE PRESIDENT, POLICY AND
RESEARCH, PHARMACEUTICAL RESEARCH AND MANUFACTURERS OF AMERICA
Ms. REILLY. Thank you Chairman Pallone and members of the

subcommittee for having me here today. My name is Lori Reilly,
and I am vice president for policy and research at the Pharmaceutical Research and Manufacturers of America, otherwise known
as PhRMA.
I have seen firsthand the benefits of this program. While I am
here today in my capacity representing PhRMA, I am also a mother; and I have seen the benefits firsthand of this program. When
my youngest daughter was born, at about 6 weeks of age my husband noticed that she had a strange, wheezing sound when she
was breathing. Obviously this is alarming as a parent to hear that
and we were worried about whether she was getting enough air
and whether she had the ability to breathe correctly. After seeing
our pediatrician and a pulmonologist and an ear, nose, and throat
specialist, she was diagnosed with a rare condition called
laryngomalacia which is a fancy term for a floppy voice box which
thankfully self-corrects itself in about 18 months. One of the other
symptoms in addition to having trouble breathing is significant
reflux or vomiting and this was causing a problem because she was
having an inability to gain weight. Thankfully there was a drug
available that was approved under BPCA that allowed my pediatrician to prescribe the drug to her that controlled that symptom and
also allowed her to gain weight. So I thank Congress personally for
enacting these very important provisions because I am not unlike
many other parents in this country and families that have seen
firsthand the benefits of this program.
As the FDA has said, the current pediatric exclusivity program
has done more to further research and generate clinical information for pediatric populations, and it is a very important program.
By the end of 2006 alone, FDA had issued nearly 400 written requests for almost 800 studies to be done on pediatric patients. In
comparison, when you look back prior to the enactment of this program, from 1990 to 1997, only 11 drugs had been studied in children. So clearly we have made a lot of progress in a short period
of time.
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Companies are responding to written requests from FDA in very
high numbers. Back in 2001, FDA had estimated that about 80 percent of the time companies would respond proactively to a written
request; and in fact, they are doing that anywhere from 81 to 84
percent of the time depending on the data that you look at. And
not only are companies responding in high amounts, they are also
responding to broad categories of disease. According to the GAO,
about 17 broad categories of disease including cancer, which is obviously a very significant condition, was the most studied condition
under the pediatric exclusivity program.
In less than 10 years since the program began, over 120 drugs
and conditions have had new labeling changes as a result of this
program, and in fact nearly 90 percent of all drugs that have been
granted exclusivity under BPCA have received important labeling
changes. And this is important because when we look at, for example, a study that was done in JAMA and you look at the time period between 2002 and 2004, there were 59 drug products that received exclusivity under BPCA. And prior to 2002, about 34 percent
of those drugs had been used and physicians were prescribing these
drugs, either making a dosing error or placing a child at risk of serious adverse events. So having this critical information available
to patients and doctors is vitally important.
While the benefit of this program has continued to grow over
time since its inception, also growing are the cost, time, and complexity to do these studies. Companies have continued, however, in
engaging in this research despite the increase in time and costs.
From 2000 to 2006, the average number of patients per written request increased 178 percent while the average number of studies
requested by the FDA in a written request increased by 60 percent.
Sponsors have also been increasing the proportion of the safety and
efficacy tests, often the most expensive and time-consuming of all
tests done by companies from 25 percent in 2000 to 40 percent in
2006. The time required to complete pediatric studies has also increased significantly. It has doubled in fact in the last 6 years. And
the average cost to complete a written request has increased eightfold. Given these significant increases we have seen in the cost,
time, scope, and complexity of studies, it is PhRMAs position that
Congress should not adopt significant modifications to these programs that may inevitably reduce incentives for companies to engage in this kind of research. As we know, these provisions have
had a tremendously positive impact on the lives of children, but
there is much more to be accomplished. The program is working
well, and its basic features should not be altered. Changes in the
current program have the potential to reduce incentives that exist
for companies to engage in this very important research.
As mentioned above, the cost, time, and complexity of these studies is increasing. Given these factors, Congress should not increase
the hurdle that companies must go through to qualify for pediatric
exclusivity. As I mentioned earlier in my testimony, companies
have pursued pediatric studies for a broad range of conditions,
about 17 in total; but the majority of drugs studied under these
programs were not high-selling drugs, nor were they blockbuster
drugs. In fact, 60 percent of the drugs studied were not even in the
top 200 selling drugs. Some of these drugs included medicines for
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HIV/AIDS, leukemia, anti-infectives and others. Again, only about
10 percent of the drugs studied under this program are what you
would consider blockbuster drugs.
As with drug development in general, blockbuster drugs and
higher-revenue drugs, support the ability of pharmaceutical companies to invest in research for lower-selling, lower-volume drugs.
And in the case of pediatrics, not only have blockbusters allowed
companies to invest in research for lower volume or lower-selling
drugs and clearly companies are, it has also given the companies
the ability to build needed infrastructure for pediatric programs.
This infrastructure includes hiring researchers that have particular
expertise in pediatric populations and building the kind of in-house
infrastructure needed. Unique expertise is required to develop
drugs for use in children, and thanks to the pediatric incentive,
companies have made significant investments in building capabilities in this area.
We must preserve the pediatric exclusivity as it is currently
structured to ensure that pediatric drug development is not hindered. Diminishing or reducing the value of incentives, for instance, by reducing the exclusivity period or tiering it for certain
products could also create unintended consequences throughout the
program. In addition, BPCA and PREA are complimentary programs and should remain connected as they have to date. Together
these two programs have worked extremely well to generate new
information on pediatric use.
In conclusion, PhRMA strongly urges Congress to reauthorize
BPCA and PREA without modification. The increasing rate of industry study proposals and FDA written requests shows continuing
progress which could be significantly undermined of these two programs were allowed to expire. In addition, we urge Congress to proceed with caution when considering changes to the incentive that
could have unintended consequences to pediatric research. Thank
you.
[The prepared statement of Ms. Reilly follows:]
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Mr. PALLONE. Dr. Crosse.
STATEMENT OF MARCIA CROSSE, DIRECTOR, HEALTH CARE
ISSUES, U.S. GOVERNMENT ACCOUNTABILITY OFFICE
Ms. CROSSE. Mr. Chairman and members of the subcommittee,

I am pleased to be here today as you examine pediatric therapies.
My remarks are based on GAOs recent report on the Best Pharmaceuticals for Children Act, BPCA. I will focus on studies conducted
under BPCA for on-patent drugs, for off-patent drugs, and the impact of the statute on the labeling of drugs for pediatric use. As we
have heard here today, when FDA determines that a drug may provide health benefits to children, it may issue a written request of
the drug sponsor to conduct pediatric drug studies. A drug sponsor
can also propose to FDA that a written request be issued for a particular drug, but FDA makes the determination of whether this is
warranted. Only a minority of the studies that sponsors proposed
resulted in FDA issuing a written request.
BPCA has been relatively successful in promoting the study of
on-patent drugs. Drug sponsors agreed to study over 80 percent of
the on-patent drugs for which FDA issued written requests. Studies
have been completed for about one-third of these drugs. Of those
drug studies completed and submitted to FDA, over 90 percent
have resulted in FDA granting pediatric exclusivity. A total of 73
drugs to date under BPCA and 136 drugs under BPCA and its
predecessor, FDAMA. FDA grants exclusivity regardless of whether
the studies show the drug should be used to treat children. Indeed
a finding that a drug should not be used in children can be just
as valuable as a finding that shows positive results.
In contrast to the relative success of the process when drug sponsors agree to conduct the requested studies, the picture is much
less positive when the drug sponsor declines. To date, the study of
only one on-patent drug has been initiated when the drug sponsor
declined the written request. BPCA allows FDA to refer declined
written requests for on-patent drugs to the Foundation for the National Institutes of Health, FNIH, an independent, non-profit corporation that raises private sector funds for research including for
BPCA studies. Through 2005, drug sponsors declined 41 written requests for on-patent drugs and FDA chose to refer nine of these to
FNIH for funding. FNIH subsequently agreed to fund the study of
one of these drugs, even though all its available funding for BPCA
studies could only provide partial support for this research. As of
June 2006, FNIH had only raised about $4 million to fund BPCA
studies, and the study of this one drug was estimated to cost about
$8 million. Similarly, few off-patent drugs have been studied under
BPCA. Through 2005, NIH had identified 40 off-patent drugs it recommended for study and FDA issued written requests for 16 of
these drugs. However, drug sponsors declined 15 of these 16 written requests. NIH subsequently used its appropriations to fund
studies for half of these off-patent drugs. Under BPCA the most
frequently studied drugs were those used to treat cancer, neurological and psychiatric disorders, metabolic diseases, cardiovascular
disease, and viral infections. In addition, about half of the 10 drugs
most frequently prescribed for children have been studied under
BPCA. Moreover, almost 90 percent of the drugs that have been
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granted pediatric exclusivity have had important labeling changes,
but the process for reviewing the study results and making these
changes can be lengthy. The labeling of drugs was often changed
because pediatric drug studies revealed that children may have
been exposed to ineffective drugs, ineffective dosing, overdosing, or
previously unknown side-effects. For the drugs we examined, they
took between 238 and 1,055 days or almost 3 years for FDA to approve the labeling changes when the agency required additional information to support the proposed changes.
In conclusion, BPCA has made important contributions to increasing the knowledge of appropriate usage of drugs in children.
The drugs studied under the statute are used to treat children for
a broad range of diseases and many serious or life-threatening conditions. However, the provisions to promote the study of a drug
when the sponsor declines the written request or when a drug is
off-patent have worked less well. Funding has not been sufficient
to ensure that in these situations studies of the drugs are undertaken.
Mr. Chairman, this concludes my prepared remarks. I would be
happy to respond to question that you or other members of the subcommittee may have.
[The prepared statement of Ms. Crosse follows:]
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Mr. PALLONE. Thank you, Dr. Crosse. Dr. Gorman.
STATEMENT OF RICHARD L. GORMAN, M.D., F.A.A.P., CHAIR,
AAP SECTION OF CLINICAL PHARMACOLOGY AND THERAPEUTICS, AMERICAN ACADEMY OF PEDIATRICS
Dr. GORMAN. Mr. Chairman and members of the committee, I am

Richard Gorman, a pediatrician and member of the American Academy of Pediatrics, and I have practiced pediatrics for over 25 years
taking care of infants, children, and adolescents in my private practice. I thank the committee for having this hearing on the need for
safe and effective medicines.
It is through my practice, Pediatric Partners in Ellicott City that
I see firsthand the therapeutic benefits of increased information on
drugs used in children. With over 80,000 pediatric visits annually
in our four clinical sites in three counties in Maryland, my partners
and I can attest to the importance of pediatric drug studies and the
legislation that supports them.
I am here today on behalf of the American Academy of Pediatrics
to discuss the BPCA and the Pediatric Research Equity Act which
represent critical public policy successes for children.
I begin my testimony today by saying without reservation that
in the last decade we have gained more useful information on
drugs through BPCA and PREA than we have had in the previous
70 years. These two pieces of legislation have advanced medical
therapies for infants, children, and adolescents by generating substantial new information on the safety and efficacy of these drugs
where previously there was none. Since the passage of FDAMA
over a decade ago, FDA has requested nearly 800 studies involving
more than 45,000 children in pediatric trials. The information
gained from these studies have resulted in label changes for 128
drugs. Medical and clinical pharmacology review summaries of over
76 drugs are now publicly available on the FDAs Web site. It is
vitally important that these laws be reauthorized.
In previous testimony before Congress, I have described children
as the canaries in the mine shaft, acting as early warnings of unknown dangers in therapeutics. BPCA and PREA working together
have changed this by creating an effective, two-pronged approach
to generating new pediatric studies. PREA provides FDA the authority to require pediatric studies of drugs when their uses for
children would be the same as adults. BPCA provides voluntary incentives to drug manufacturers for an additional 6 months of marketing exclusivity for conducting pediatric studies of drugs that
FDA determines may be useful for children.
Despite these important advances, there is much more we still
need to do. Children remain second-class citizens when it comes to
drug safety and efficacy information. Currently two-thirds of the
drugs used in children are not labeled for them. Almost 80 percent
of hospitalized children receive at least one drug prescribed for
them for an off-label use. For children, off-label use remains the
rule and not the exception. Both BPCA and PREA are crucially important and must be reauthorized this year, including needed improvements.
The FDA bill recently passed in the Senate reauthorizes BCPA
and PREA, and we applaud the Senates work. The studies gen-
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erated under BPCA provide information beyond safety and produce
information on dosing, efficacy, and importantly the lack of efficacy
and off-label use.
PREA created a new presumption that all drugs would, in fact,
be studied in children at the time of the application, thus preventing the need for a safety program to trigger drug studies after the
drug is on the market. Mr. Chairman, in my written testimony I
have elaborated on recommendations for improvement to BPCA
and PREA in several areas. The American Academy of Pediatrics
urges this committee to pass a reauthorized bill which increases
the dissemination, the transparency, and the tracking of pediatric
drug information; streamlines and integrates the Food and Drug
Administrations administration of BPCA and PREA to improve the
uniformity, consistency, and quality of pediatric studies; expands
the study of off-patent drugs and generic drugs and addresses the
gaps in understandings of pediatric therapeutics; and crafts a balanced compromise that will preserve both the quality and the number of pediatric studies gained through BPCAs exclusivity extension and also addresses the concerns regarding excessive revenues
for blockbuster drugs. And lastly, the AAP wants PREA to become
a permanent part of the Food and Drug Act and allow for the periodic re-evaluation of BPCA to ensure that incentives remain fair
and continue to yield pediatric information.
In conclusion, I would like to thank the committee again for allowing me the opportunity to share with you the strong support of
the American Academy of Pediatrics for reauthorization of Best
Pharmaceuticals for Children and the Pediatric Research Equity
Act. We urge their improvement and renewal for the sake of all
children throughout the United States. I will be glad to answer any
questions you may have.
[The prepared statement of Dr. Gorman follows:]
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Mr. PALLONE. Thank you. Dr. Lurie.
STATEMENT OF PETER LURIE, M.D., M.P.H., DEPUTY
DIRECTOR, PUBLIC CITIZENS HEALTH RESEARCH GROUP
Mr. LURIE. Good morning, and thank you for the opportunity to
testify before the committee. You have already heard a lot about
the successes of the Act, and I think that they are clear and dont
merit challenge exactly, but those arent the right questions. The
right questions are firstly whether or not the system could be more
successful and second, whether or not these successes or perhaps
even greater ones could have been obtained through an alternative
method, and I will address those two questions in turn.
First, are there gaps, and I think there are three. We have heard
some of them from Dr. Crosse on off-patent, on-patent, and I will
talk especially about the diseases that have been studied.
The biggest deficiency is in off-patent drug studies, and I dont
think that is a surprise to anybody given the way the BPCA is
structured. As Dr. Crosse testified, very few of the off-patent drugs
for which studies have been requested have in fact been done. In
83 percent of the studies requested by the NIH, no study has been
done. So I think we are looking at a significant problem there. In
part this is because the NIH has received no appropriations specifically for these pediatric studies. And even with respect to on-patent
drugs, there are problems as well. According to the GAO, 19 percent of written requests from the FDA were turned down, presumably because there wasnt enough money to be made from conducting studies; and the BPCA does provide a mechanism for the study
of those written requests that have been declined, but as we have
heard in the end not one of those studies has in fact been funded.
So those are the first two points.
The third is that the kinds of diseases being studied are, not surprisingly, those diseases that are likely to have large sales in
adults because that is where the great majority of the pharmaceutical market is. So market-based solutions result in these kinds
of market-based distortions. Using two different data sources, GAO
determined that only four or five, depending on which data source
you looked at, of the 10 most commonly prescribed pediatric drugs
had in fact been studied under the BPCA. And a group of researchers in the Netherlands which has just implemented a BPCA-like
solution of its own has studied the United States experience, and
what they found was that the profile of drugs being studied much
more closely mirrored in the adult population prescribing habits
than it did in the pediatric. For example, the top three drug categories that were granted pediatric exclusivity matched precisely in
both category and sequence the top three prescribing categories for
adults and none of the three top-prescribing categories for children
appeared in the top three for which pediatric exclusivity was granted. So we have a clear distortion there.
So, first, it is not really working as well as some people have
said, and second, my point is that there are other ways of receiving
these exact benefits without the kinds of handouts to industry that
have so far characterized this initiative. And of course, the obvious
model here is the PREA which has already produced 55 labeling
changes, all of these of course without any need to resort to a pat-
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ent extension. Recent published research shows the exclusivity provisions under the BPCA can be absurdly generous. Nine drugs
were studied, and for the current 6-month patent extension, the net
economic returns on individual drugs were as high as $508 million
with a median of $134 million. For one drug product with $3.8 billion in sales, the economic benefit to the sponsor was 74 times as
high as its expenses, a 7,400 percent profit margin, and the median
was a 12.4 times net gain for the companies.
And the costs of this are substantial. As mentioned earlier by
Ms. Schakowsky, the FDA estimated in 2001 that the total value
of the 6-month patent extension would be on the order of $13.9 billion. Much of this will come out of the pockets of consumers but
now with Medicare Part D, the Government will be footing the bill
for its own generosity as well. Unless there is a strong reason to
believe that pediatric use will be minimal, conducting pediatric
studies should be seen as the responsibility of all companies seeking to market or to continue marketing a drug, not an undertaking
for which companies should be rewarded, let alone as generously
as they currently are. The FDA should have the authority to compel such studies by expanding the provisions of PREA no matter
what the stage in the drugs lifespan without having to resort to
patent extensions.
I mentioned in my written testimony that the pediatric testing
process is not transparent, and I shant go into that in detail, just
to mention briefly that the FDA does not make clear when the
studies are actually being conducted and when they might be completed. There are delays in label changes of the order of time that
we have heard, and in addition, if you think that doctors can instead rely upon published medical literature as a substitute while
they are waiting for the label change to actually take place, that
is not the case because in many cases, particularly if the result is
negative, the companies dont bother to publish.
Let me just make a couple of brief comments on medical devices
which are general comments but apply in the pediatric situation as
well. First, the medical device approval standard is too low. To receive permission for a device to be approved, the standard is that
there must be, quote, reasonable assurance that the device is safe
and effective, a much lower standard than for drugs where the
standard is substantial evidence of effectiveness for the claimed
conditions. So the result is we can see, with otherwise equal data,
a device being approved where a drug would not, and that is potentially diverting people from effective drugs to less effective or ineffective devices. The vagus nerve stimulator is a good example of
this, and in that particular case the people from the drug division
of the FDA told the Senate finance committee that had data of that
quality been submitted to them, they would not even have permitted the filing of a new drug application, instead, the device
wound up being approved.
A second problem involves the 510(k) process which in effect is
a less-than-full pre-market review for most devices including most
class 3 devices which are the most invasive of those class 3 devices.
Intended at the time of the enactment of the amendments to be the
exception rather than the rule, a 510(k) is now the route to approval for 99 percent of new class 3 devices. Moreover, a device can
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be considered substantially equivalent under the 510(k) through a
predicate device, the already approved device, even if it does not
have the same technological characteristics as the predicate device.
A recent example of this is something called Repetitive
Transcranial Magnetic Stimulation, rTMS system, in which even
though the predicate device, electroshock therapy, electricity, this
device was considered for approval under 510(k) as being substantially equivalent, even though it used magnets. This makes no
sense at all and makes it far too easy for devices to get on the market without proper approval.
In parallel to the situation under drugs, the medical device testing process is also not transparent; and the Institute of Medicines
report on that makes it quite clear. Quote, the most obvious deficits in FDAs performance are the lack of effective procedures for
monitoring the status of required post-market studies and the lack
of public information regarding such studies. In that respect as
well, we need to see an improvement in transparency.
That is the end of my comments.
[The prepared statement of Dr. Lurie follows:]
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Mr. PALLONE. Thank you. I have been letting some of you go beyond 2 minutes only because I am interested in what you are saying, but we cant be going too long. Let me go next to Ms. Belfiore.
Thank you.
STATEMENT OF SUSAN BELFIORE, PRINCETON, NJ
Ms. BELFIORE. Thank you. Mr. Chairman, Ranking Member

Deal, and distinguished committee members, thank you so much
for having me here today. I am Susan Belfiore. I am the mother
of five children. Four of those five children, my husband and I
adopted from Romania, and they are HIV-positive.
I am honored to be here today to let you know the difference that
the pediatric drug legislation has made in our lives and why it is
so important to continue to test drugs specifically for children. This
issue is not settled by any means, but the progress we are making
is because of you. You are all true champions for children. I would
like to give a special thanks to Ms. Eshoo and Mr. Waxman for
their longstanding leadership on this issue. My children would like
to be here today. They have lobbied hard to be here today to thank
you personally, but alas, they have finals.
I would last like to thank the Elizabeth Glaser Pediatric AIDS
Foundation for the work they do for children and families. Our
children are living healthier, better lives because of their work.
I am here today because our family, like so many families
throughout the country, are dependent on medications to keep their
children strong and healthy. As you just heard, four of our five children have the AIDS virus. Our daughters, Mihaela and Loredana,
are taking live-sustaining drugs. So clearly this is an issue that is
close to my heart. As a parent, there is nothing more difficult than
knowing that your child is sick. You can often feel scared and helpless, yet our family believes in miracles but miracles cannot happen
without the correct dosing. Both of these can be achieved only
through pediatric testing.
I still remember the first time we put our then 8-year-old
Mihaela on a cocktail of drugs that was used by many adult AIDS
patients. We took the medications out of the pill boxes, put it in
a special box that was decorated with horses. Mihaela loves horses,
and we had a silly hat party that night at the dining table. We
wanted to turn the whole event into something that was positive
instead of focusing on the fact that for the rest of her life, Mihaela
will be dependent on the latest medications to keep her healthy.
But the truth is that Loredana and thousands of children like them
are dependent on the latest medications to keep them strong,
healthy, and alive. That is why the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act are so important.
Unless these laws are continued, our children wont have a chance.
They cannot rely on guesswork. We tried that, and I can tell you,
it does not work.
This binder here contains my childrens medical life for the last
14 years. I have cataloged all aspects of their health, every 3
months, blood work being done, medications that they were taking,
any adverse effects to the medication, and illnesses.
Ten years ago we thought Mihaela was taking an effective drug
regime for HIV. She was not. It turns out she had been under
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medicated because the drug she was taking had not been studied
sufficiently for use in children. Mihaelas health suffered. Her virus
increased, and once again, she started to pick up opportunistic infections.
Mihaela had only used this medication for a few years before
forming a resistance. As a mother, I can tell you resistance is a
scary word. It means that your child has lost access to one drug
regime in a very limited supply of options, and when options run
out, children suffer.
I recently looked at a picture of Mihaela from 5 years ago when
we first came to Congress to advocate for the Pediatric Research
Equity Act. I was shocked when I saw the picture of her standing
there that day. She was underweight, she had a look about her
that you might know as being very familiar with the AIDS virus,
more advanced stages of the AIDS virus. She had failure to thrive.
When I was in that moment, I didnt realize it. I didnt realize it
until I went back and I looked at that photo.
In the last 5 years, though, things are very different. For the
first time, Mihaela is taking medication that was tested specifically
for use in children. The results have been dramatic. Mihaela has
grown, she has put on weight, and she is free of infections. And for
the last 4 years, Mihaela has had undetectable virus in her system.
She now rides horses more than ever before.
My familys personal struggle is with HIV, but I have to point
out that the value of these laws goes beyond HIV and my individual family. My family and I are here for all parents today. You
have heard the statistics, about three-quarters of all medication
has not been tested for use in children. The drugs are from everything from asthma, cancer, to HIV and AIDS.
Now, I understand that testing for drugs for use in children is
an additional expense for the drug companies. I also understand it
can be difficult to conduct studies for a variety of enrollment
issues. That is why BPCA includes an incentive for companies to
do pediatric studies. The law is working well and it should be continued.
But this issue is not just about profits and bottom line. It must
be about the value of a childs life. To be honest, I wonder why the
idea that all medications should be studied for use in children
should even be a question. As a adults we wouldnt take medication
that is not tested for us, so why would we give it to our children.
That is why I strongly believe the Pediatric Research Equity Act
should be made permanent.
I appeal to you on behalf of my children and millions of children
like them. Surely we can agree that our children deserve nothing
less than the same information about safety and dosing that we require of ourselves.
Thank you again for inviting me here today, and on behalf of all
parents, thank you so much for what you are doing for our children. I can tell you personally, it really is making a difference.
[The prepared statement of Ms. Belfiore follows:]
STATEMENT
OF
SUSAN BELFIORE
Mr. Chairman, Ranking Member Deal and distinguished committee members.

Thank you so much for having me here today. I am Susan Belfiore, mother of 5 chil-
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dren, 4 of whom are HIV positive. Im honored to be here today to let you know
the difference pediatric drug legislation has made in our lives and why its so important that medications continue to be specifically tested for use in children.
This issue is not settled, by any means, but the progress we have made is because
of you. You are all true champions for children.
Id also like to thank the Elizabeth Glaser Pediatric AIDS Foundation for everything they do for children and families. Our children are living healthier lives because of their work.
I am here today because our familylike so may other families throughout the
countryis dependent on medications to keep our children healthy. As you just
heard, four of our five children are living with the AIDS virus. Mihaela and
Loredana are taking life-sustaining medications.
So clearly, this is an issue that I hold close to my heart. As a parent, there is
nothing more difficult than knowing your child is sick. You can often feel scared and
helpless. Our family believes in miracles. But miracles wont happen without the
correct medication and their correct dosing. Both of these can be achieved only
through pediatric testing.
I still remember the first time we put our then eight-year-old daughter Mihaela
on a cocktail of drugs used by many AIDS patients. We took the medications out
of the pill boxes and put them into a container decorated with horses. Mihaela loves
horses. We had a silly hat party at the dining room table. We wanted to turn the
whole event into something that was positive, instead of focusing on the fact that
for the rest of her life, Mihaela would be dependent on the latest medications to
keep her healthy.
But the truth is that Mihaela and Loredana and thousands of children like them
ARE dependent on the latest medication to keep them healthy and strong and alive.
And that is why the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act are so important. Unless these laws are continued, many kids
wont have a chance. They cannot afford to rely on guesswork. Weve tried that, and
I can tell you personally that it just doesnt work.
This binder is the story of my childrens medical life. For the last 14 years, I have
cataloged all aspects of their health. Charting their blood work every three months,
their medications, and their reactions to these medications.
Ten years ago, we thought Mihaela was taking an effective drug regime for HIV.
She was not. It turns out she had been undermedicated because the drug she was
taking had not been studied sufficiently for use in children. Mihaelas health suffered. Her virus increased. Once again, she started to pick up opportunistic infections.
Mihaela had only used this medication for a few years before forming a resistance.
As a mother, resistance is a very scary word because it means your child has lost
access to one more drug regime, one in a very limited supply of options. And when
the options run out, children suffer.
Recently I looked at a picture of Mihaela from 5 years ago when we first came
to Congress to advocate for the Pediatric Research Equity Act to become law. I was
shocked when I saw Mihaela. She was underweight. She looked sick. When youre
in the moment, you dont realize it, until you go back.
In the last five years, though, things have been different. For the first time,
Mihaela has taken medication that WAS tested specifically for use in children. The
results have been dramatic. Mihaela has grown, put on weight, and has been free
of infections. And for the last 4 years she has had undetectable virus. She now rides
horses more than ever.
My familys personal struggle is with HIV. But I have to point out that the value
of these laws goes beyond HIV, beyond my individual family. My family and I are
here for all parents and children, not just those living with HIV and AIDS. Weve
all heard the statistic: About three-quarters of prescription medications have not
been tested for use in children. These are drugs for everything from asthma to cancer to HIV and AIDS.
Now, I understand that testing drugs for use in children is an additional expense
for drug companies. And I also understand that it can be difficult to conduct the
studies because of a variety of enrollment issues. Thats why BPCA includes an incentive for companies to do pediatric studies. That law is working well and should
be continued.
But this issue cannot just be about profits and the bottom line. It must be about
the value of a childs life. To be honest, I wonder why the idea that all medications
should be studied for children is even a question. As adults, we wouldnt take medications that were not tested for us. So why would we give them to our children?
And that is why I strongly believe that the Pediatric Research Equity Act should
be made permanent.
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I appeal to you on behalf of my children, and millions of other children just as
precious and important as they are, to reauthorize these laws as soon as possible.
Surely we can agree that our children deserve nothing less than the same information about the safety and dosing of drugs that we demand for ourselves as adults.
Thank you again for inviting me here today. And on behalf of all parents, thank
you so much for all you do for our children. I can tell you personally, you are making a real difference.
Mr. PALLONE. Thank you so much, and thank you for being here
today to tell the story. I appreciate it. Mr. Rozynski.
STATEMENT OF ED ROZYNSKI, VICE PRESIDENT, GLOBAL
GOVERNMENT AFFAIRS, STRYKER CORPORATION
Mr. ROZYNSKI. Good afternoon, Chairman Pallone, Ranking

Member Deal, and other members of the subcommittee. Mr. Burgess, thank you for your comments.
Again, my name is Ed Rozynski from the Stryker Corporation.
As an early supporter of the bill, we sincerely appreciate Congressmen Markey and Rogers leadership role on childrens issues and
this landmark legislation. Like you and your colleagues, we want
children to have access to the fullest and best medical treatments,
even if that means doing or inventing something new just for them.
Stryker is one of the worlds leading medical technology companies,
and is headquartered in Kalamazoo, MI. Stryker also has facilities
in New Jersey, Massachusetts, California, Texas, New Hampshire,
and Tennessee. Strykers products are used in over 80 percent of
the hip and knee replacement procedures performed in the United
States. Currently our bone healing and bone regeneration technology is being used for humanitarian purposes to save the limbs
and to repair the backs of soldiers at Walter Reed Hospital.
Strykers commitment to children is not new. We are the leading
manufacturer of orthopedic oncology prostheses and pediatric-related devices used to treat cranial facial deformities such as cleft lip
and palate. Soft tissue sarcomas and bone cancers represent less
than one percent of all adult malignancies. However, they represent 15 percent of all malignancies in children. Twenty years ago
the standard treatment for primary malignant bone and soft tissue
sarcoma was amputation. Since that time, Stryker has developed
limb-sparing solutions including a growing prosthesis that can be
elongated to account for a childs growth. With respect to cranial
facial deformities, Stryker partners with medical organizations
such as Operation Smile, a non-profit organization which last year
was able to provide free cleft lip surgeries to more than 8,000 children in 23 countries, on average taking 45 minutes and costing just
$242 per child. These surgeries have a positive, lasting impact on
the lives of children and their families.
It is our sincere hope that this pediatric device legislation will
encourage the evolution of novel healthcare solutions for children.
First, the bill authorizes new money to create a grant program to
promote pediatric device development including matchmaking between inventors and manufacturers. Second, the bill improves incentives to develop devices for the pediatric device market which
is very small, and I would want to underscore very small with respect to pediatric devices. These incentives at least directionally
should entice companies to think about developing pediatric prod-
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ucts that they might otherwise have neglected in favor of profitable
products developed for use in the much larger adult population.
Third, the bill facilitates the pooling and collection of more information about pediatric devices so that information and solutions
can be easily shared and analyzed within the community.
We are aware of ongoing discussions related to the post-market
surveillance provisions of the bill and hope successful resolution
will be reached on this issue. This bill has twin goals which together must be achieved, number one, bringing more pediatric devices to market and number two, improving information about pediatric devices. All stakeholders should work together to ensure
that both goals are achieved.
In conclusion, Chairman Pallone and members of the committee,
we applaud you for considering this legislation. We look forward to
continuing to work with you on refining the bill and advocating for
its passage into law this year. As parents, we say that we give our
children the very best. We protect them, we try to send them to the
best schools, we buy them nice clothes and give them the latest
gadgets. Therefore, we should not allow childrens healthcare products to become the residual of products that we develop for the big
people that they look up to. Children deserve our special attention,
children deserve our very best efforts. At Stryker, we see the hope
and the benefit that our latest bone implants provide to children
with cancerous tumors. Unfortunately, many families, even those
with health insurance, cannot afford to frequently take off work or
pay the cost to travel with their children, their sick child to a faraway hospital. Stryker will soon announce a plan to provide charitable assistance to families and patients to cover their expenses associated with travel to NIH Cancer Care Centers, expenses not covered by health insurance. These uncovered expenses often pose a
serious impediment to a familys ability to provide for their childs
care and recovery. We believe that Strykers charitable initiative
will compliment the advanced technologies for children that
Stryker already develops. It is our hope that we and other medical
technologies will be further encouraged to develop more pediatric
devices as a result of this legislation.
Again, thank you, Mr. Chairman. I would be pleased to answer
any questions the committee may have.
[The prepared statement of Mr. Rozynski follows:]
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Mr. PALLONE. Thank you, Mr. Rozynski. Mr. Lombardi.
STATEMENT OF DONALD P. LOMBARDI, PRESIDENT AND CEO,
INSTITUTE FOR PEDIATRIC INNOVATION
Mr. LOMBARDI. Thank you, Mr. Chairman and committee members. While a lot of the testimony has focused on how to research,
test, and regulate pediatric products, I would like also to ask that
Congress think about what it can do to stimulate the invention and
development of products that have the special requirements needed
for treating children.
My name is Don Lombardi. I am president and CEO of the Institute for Pediatric Innovation, a non-profit organization located in
Cambridge Massachusetts.
The challenges that industry faces in getting products developed
for children are also faced by pediatric hospitals in their attempts
to commercialize discoveries they make. I was the chief intellectual
property officer for Childrens Hospital Boston for 15 years, responsible for managing that organizations compliance with the BayhDole Act which focuses on the translation of research discoveries to
commercial products for the benefit of the public. The program was
very successful. Six products got onto the market, 10 more into
clinical development through our licensee companies. Twenty-five
new companies were started around our technologies. The program
brought in tens of millions of dollars of license revenues to Childrens Hospital.
The paradox? Very little of these products benefited children.
Most were based on very early stage biology research, and the investors and companies who took on these ideas to develop them
naturally focused on the largest and easiest to access adult markets. My experience at Childrens Hospital Boston is reflected as
well in the experience of the major pediatric hospitals everywhere.
You have heard a lot about the issues of the small market size
and the challenging regulatory pathways and the fact that children
arent small adults. I wont reiterate those issues. I would like to
add another perspective based on the experience in the tech transfer program at an academic institution such as these pediatric hospitals. The innovation process focuses on researchers, not on clinicians. Clinicians are the ones who know what is needed, not the
researchers. On the other hand, the clinicians generally lack the
time and the ability to create inventions and develop products. This
problem is a national-scale problem that needs novel approaches to
collaborations between the hospitals and industry and between
these parties and others who can provide pieces of the puzzle to develop products.
I left my job at Childrens Hospital Boston a year ago to create
the Institute for Pediatric Innovation to focus exclusively on the
practical translation of ideas into products for pediatric care.
Our plan is to form a small consortium of leading pediatric centers, and using this consortium as a microcosm of the market, carry
out a very careful needs analysis to determine what products are
needed to save lives, improve outcomes, reduce costs, increase satisfaction of patients, parents, and caregivers. We will then evaluate
and set priorities on the products based on three criteria, first,
which ones will have the highest impact; second, of these, which
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are commercially feasible; and third, of these, which can our specific consortium members add value both in the product design and
the clinical testing phase. From these we will select six or seven
products and develop detailed opportunity analyses of these products. We are going to focus initially on three categories of products.
The first is reformulated drugs. You have heard from other testimony about the off-label use of drugs. I have learned in an informal survey of five or six pediatric hospitals that some 60 percent
of the prescriptions written in institutions such as these are actually formulated off label by the pharmacies in the hospital, which
is an enormous of risk for patients and institutions themselves.
And I know from my conversations with these parties that there
are somewhere between 30 and 50 pharmaceuticals that pediatricians either do use or wish to use that are not available in the
proper dosage and delivery forms.
The second area is in the re-engineering of medical devices.
Again, as you have been told, this is not just downsizing devices.
There are a variety of specific pediatric bioengineering issues that
need to be addressed in the redesign and the re-engineering of
these products. These products need to adapt to the very different
physiology, material interactions with the body, impact on the patients skin and of course the very challenging issue of the dynamic
nature of both the anatomy and the physiology of the child.
Following this we will undertake what we call product imagination, brainstorming sessions that will bring together nurses, doctors, engineers and marketing people to imagine and develop product concepts for new products. For the new products as opposed to
the re-engineered and reformulated projects we are focusing initially on the needs of neonatal care. This is because we have a company which has agreed to fund this program. We expect that the
practices that we develop for developing new products we can also
apply in other areas with other companies in general pediatric surgery, cardiology, GI, and neurosurgery. Finally, I congratulate the
committee for its work in this area, and my recommendations
about legislation are included in my handout. Thank you very
much.
[The prepared statement of Mr. Lombardi follows:]
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Mr. PALLONE. Thank you. I know it is an unusually large panel
today. You can barely sit through it. But thank you for your testimony. I appreciate it. We are going to take some questions, and I
will start with my own questions for 5 minutes.
I wanted to ask Dr. Crosse, you noted that drug manufacturers
accepted 81 percent of FDAs written request to complete pediatric
studies, and this is with regard to the on-patent drugs.
Ms. CROSSE. Yes.
Mr. PALLONE. And I am concerned about what happened to the
other 19 percent of those. As I understand the process, they are referred to the Foundation for the National Institutes of Health for
funding. Would you say that the process of sending them to FNIH
is working or do you have any recommendations on how Congress
might improve that part of the process?
Ms. CROSSE. It hasnt been working well because FNIH has not
been able to raise sufficient private funds to cover the expenses of
conducting these studies. In the first 4 years that this arrangement
was underway, they were raising approximately $1 million a year.
During the 1-year course of our conducting our work they raised
no additional funds. They had raised a total of about $4 million
which was insufficient to fund even one study. It only covered the
cost of about half of the study expenses, and NIH stepped in with
its own appropriations to pick up the remaining expenses for this
drug because they felt it was so important to be studied.
We dont have specific recommendations for how this could be
covered. The arrangement seemed a logical one at the time. It still
called for private sector funding of the research, just as when the
companies, the drug sponsors, paid for the studies but contributions have not been sufficient to FNIH to come anywhere close to
filling the gap for these on-patent drugs when the drug sponsor declines.
Mr. PALLONE. OK. I am going to ask another money question,
but I dont want everybody to answer this. But if someone wants
to volunteer, we have been told by CBO that a continuation of the
pediatric exclusivity program would score under the budget rules
and as such a bill of this kind needs to have an offsetting tax increase or spending cut. Any of you want to recommend how to pay
for the extension of the pediatric exclusivity program? You dont
have to, but if anyone has an idea, I would like to hear it. Any volunteers here? Somebody is pondering. Dr. Lurie?
Mr. LURIE. Sure, dont reauthorize it in that sense. I mean, dont
do it through patent extensions, do it instead through mandatory
requirements as under PREA. That will save them money.
Mr. PALLONE. Well, that was easy, I guess. All right. Anyone
else? Otherwise I will move on.
Ms. Belfiore, I really appreciate your being here today because
your story about your family is truly compelling, and I wanted to
thank you for sharing that for not only what you said and your
family but for all the work that you do with the Elizabeth Glaser
Pediatric AIDS Foundation. I am a parent. I have three children,
and even as someone who is involved in developing these policies
I dont think that it occurs to me to ask a physician when our children are sick as to whether or not the medicines they prescribe
have been tested in children. In fact, almost three-quarters of the
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drugs prescribed to kids have not been tested as you have said, and
I think that is a startling statistic; and it is even more startling
for children who suffer from life-threatening illnesses. Do you know
how many drugs used for treating HIV/AIDS have currently been
studied for pediatric use and just comment if you will on that because I am concerned in particular with the life-threatening illnesses and whether or not BPCA or PREA could have an impact.
Ms. BELFIORE. I do not know the number as to how many have
been tested, but I do know that through BPCA that six new AIDS
drugs have been approved for children. I was saddened and also
happy to see that one of the drugs was the one that my daughter
Mihaela formed a resistance to because she had not been given
enough, saddened because she didnt get the use out of that drug.
It is a very good drug in the adult population. People get a long
time out of it, and my daughter did not get that time out of it.
But only because of this legislation is it now available for use in
children. So I compliment what is being done here. It really makes
a difference.
Mr. PALLONE. Thank you. I wanted to ask Mr. Rozynski. You
speak of the lifting of the HDE which I guess is Humanitarian Device Exemption profit restriction in the Markey-Rogers legislation.
Is this the most effective or is there any other incentives that you
would suggest?
Mr. ROZYNSKI. Well, first, we appreciate the lifting of the restrictions so that way you in effect balance the incentives that you have
in the adult population with those in the childrens population. We
dont have and we are not even seeking the concept of extended exclusivity for devices like you have for drugs. I am not sure that
there is really an easy additional incentive that you could provide.
So therefore, I would say instead to just make sure the regulatory hurdles do not change in such a way that there is a disincentive to go into the market. Right now I think that there is balance
in terms of how the FDA regulates this area. If the regulatory hurdles go too high, and as I say, we are not seeking any significant
incentives, what you may end up doing is not reaching those twin
goals of encouraging more devices, while at the same time having
adequate information on these devices. Now, with regard to information, I would like to say that Stryker and other companies are
prepared to give away in effect the knowledge that we have, the
studies that we have, and to put them in a public database so that
way if we cant figure out something in terms of ways to make this
better or to address areas where perhaps we had some shortcomings, we are opening up this information to the public so that
others can then perhaps use it to develop a better device. So we
are prepared to open up as part of this legislation the studies that
we do have and to share them in a public database as a way to
stimulate more activity in the area of pediatric devices.
Mr. PALLONE. All right. Thank you. Thank you very much, all of
you. Mr. Deal?
Mr. DEAL. Thank you. We have a variety of opinions here, some
that say the present system is working OK, others who say it needs
to be changed. But I think there is one thing that most everybody
seems to agree with and that is the off-patent drugs is an area that
we dont have any way to incentivize under the current system.
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Dr. Crosse, do you have any suggestions as to how to deal with
that particular issue? Obviously NIH is having difficulty coming up
with the funding to do that.
Ms. CROSSE. No, sir, other than providing funds that are specifically available for undertaking these studies. I cannot see any way
to incentivize the generic drug manufacturers to undertake the
costs of conducting these studies.
Mr. DEAL. OK. We have a smaller market obviously for pediatric
type applications of medicines. But I assume there are some drugs
that are exclusively developed and marketed just for pediatric patients. Ms. Reilly, do you have any idea of how large that is compared with the overall approval of drugs?
Ms. REILLY. Well, what I can tell you is that there are about 200
medicines in development today specifically for pediatric populations. So while this pales in comparison to the overall number of
drugs in development which is somewhere around 2,000 drugs in
development, there is significant progress underway in our companies in terms of looking at research for pediatric populations.
Mr. DEAL. And I assume that there are some drugs that from the
outset there is general acknowledgment that probably would never
be appropriate for pediatric patients.
Ms. REILLY. That is true. I mean, obviously there are a number
of drugs for which young children just dont happen to get those
diseases. Osteoporosis is one example. But I think one thing that
we have learned through the BPCA process is that for drugs, one
drug for example, Tamoxifen, which is a drug to treat breast cancer
was studied under the pediatric exclusivity program and was found
to be effective for treatment of a rare disease affecting young girls.
So I think even in the instances where we have drugs that one
would assume are only for an adult population, oftentimes our companies have done research and found that that use is effective for
different populations, in this case, a rare condition. And that was
made available under BPCA.
Mr. DEAL. Mr. Lombardi, in your testimony I gathered that you
were trying to figure out ways to develop this partnership between
the industry and the pediatric hospitals which obviously are a very
good incubator in which to either test devices or provide further research. You mentioned reformulation of drugs.
Mr. LOMBARDI. Yes.
Mr. DEAL. Now, I assume you were talking about off-patent
drugs that are reformulated for more specific purposes. Would you
elaborate on that and what obstacles do you encounter in that environment?
Mr. LOMBARDI. Thanks. Yes, we are focusing specifically, since
we wish to get near-term products available to the clinicians, we
are focusing specifically on off-patent drugs for which a better formulation or delivery method is needed. I will give an example.
While still at Childrens Hospital, we had a clinician who treated
lead poisoning for 30 years with a product that had never been approved for children or for lead poisoning, but was long ago approved by the FDA in adults for a different use. It comes in a pill
this size. It smelled of rotten eggs. It is a sulfur compound, and so
we needed to find a company that would take this compound and
reformulate it into something palatable, unsmelly, and digestible
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for children. We made an arrangement, what I call a risk sharing
arrangement in which they would risk and we would share to put
the research into developing this formulation. They used formulation technology that has been used in many other drugs. So we had
a compound that has a long experience in the clinic with adults
and 30 years with children, and a formulation technology that has
been previously used. So the question was how would we finance
the clinical development of this, and we found an angel investor
who studied this and realized that he could get the product
through the clinical stage if things went well for between $1 million and $1.5 million. So he formed a small virtual company to take
the product rights, and he has got his first investment now and the
project will be developed in the clinic; and at the end of this process, he will sell this product off to a company that has got a sales
force in pediatrics.
Mr. DEAL. Would that reformulated product be a patentable item
in and of itself?
Mr. LOMBARDI. Well, the composition is not patentable, but the
formulation is patentable. It is not a strong patent because people
can come up with an alternative formulation that may accomplish
similar results. But it will give this party a degree of exclusivity.
Mr. DEAL. Is there anything we can do in that arena that would
incentivize these reformulations? Is there anything there you see
either through the patent process or through some degree of exclusivity or something because it appears to me that more than likely
that is where the off-patent is going to produce results is in reformulation of some type.
Mr. LOMBARDI. I dont have a specific proposal, but I think if
there is a way of broadening the concept of the orphan exclusivity
to cover pediatrics for pediatric-specific formulations, that would be
helpful. Second, another area that we worked on was with a different formulation company on a different product, and that company applied for, and I understand recently was awarded, an SBIR
grant from the NIH for the development and clinical testing of that
product. So funding always helps because if the product development phase can be accomplished on monies that do not require a
return on investment, then the calculus for having the product be
able to sustain itself in the market changes significantly. Thank
you.
Mr. DEAL. Thank you.
Mr. PALLONE. Dr. Burgess.
Mr. BURGESS. Thank you, Mr. Lombardi. Mr. Rozynski, it seems
I guess fortuitous that you are sitting there together at the end of
the table because Mr. Rozynski, you talked about having the ability
for having someone to be a matchmaker between inventors and
manufacturers, and Mr. Lombardi, you are talking about stimulating research and development; and I hope you two will at least exchange business cards before the hearing is over because that does
seem like an enormously worthwhile activity. But Mr. Rozynski, I
wonder if you could tell us, from your perspective, are there concerns about the legislation we are working on or are there things
that we can do that will be injurious to going forward with new devices and new procedures, and what concerns would those be?
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Mr. ROZYNSKI. Thank you for the question. It is a very interesting question which we have thought about quite a bit. I would first
like to say that we support the legislation. We are here to support
it, and we want to see its passage. We believe that this is an important step forward. So we are not really looking to nitpick. But
I think about how devices are developed in the small populations,
I mean, we even have situations where we work with one doctor
on one child to develop one custom device. And so when you look
at some of the additional regulatory issues that are raised within
the bill which would require multi-year long studies, we agree with
a lot of that, but at the same time, we are trying to scratch our
heads and say what will this do to people who today serve that
market and want to continue to serve that market, that individual
patient, that doctor, that small population. Is there is a potential
regulatory hammer hanging over their head that they may end up
having all sorts of additional costs and additional studies that they
are going to have to do? So we are not against it, we are just saying this is really a difficult question. But in the end, we want to
make sure that the net effect of the legislation is to get more devices to market and to get more information developed. And as I
said, we are prepared with other companies to open up all of our
studies to share the information to do the match-making. But we
want to make sure when we change FDAs current authority, we
do not create such an imbalance that people are further encouraged
to go serve those adult populations as opposed to serving those
much smaller childrens populations where the incentives in the
end really in the area of medical devices are not highly financial.
You are not going to make a lot of money doing these custom devices, doing these small developments. So that is really the challenge, tomake sure we address those questions and we get the balance right.
Mr. BURGESS. And yet, I mean again, your compelling testimony
about the treatment of childhood sarcomas, I mean I can remember
a University of Texas football player at age 18 played a football
game, had a pathologic fracture, and 2 weeks later his leg was amputated to save his life. I mean, you have now changed that equation forever for the better. And I for one am grateful that those
things are available as there may indeed have been one doctor and
one manufacturer working together to try to come up with, hey,
can we do something better for this patient and now we can extrapolate it to still a small but a much wider population. So I guess
if we can build in the flexibility for the most unique situations into
the legislation, that is certainly something that I am interested in
trying to do.
Dr. Gorman, I think you and Dr. Crosse both discussed how because of the lack of the data and the research on pediatric indications, a lot of the things that you did during your practice life are
essentially off-label uses of medication; and I was an OB/GYN by
trade before I came to Congress, so I can promise you, I can think
of one or two compounds that actually stayed approved for use during pregnancy. No one wants that liability. We saw what happened
to Bendictin 30 years ago, and no one is going to take that chance
unless it is something exclusive to pregnancy like treating premature labor. And yet, we hear testimony from Dr. Zerhouni and
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others at NIH that we are embarking on an age of personalized
medicine. How do you see these studies on the pediatric side working in that environment? Will we just develop systems where because we are working on personalized medicine, just by its nature
we take into account the pediatric population and the obstetric population, the prenatal population as well as the adult population?
Mr. GORMAN. Pediatricians, maybe more than any other group,
are awaiting the world of personalized medicine where we can treat
the person with the disease, rather than the disease and the person. We have laid the ethical and legislative structure for the eventual advancement into all the populations that you talked about.
Today, NIH is studying vaccines in mothers to protect children. So
hopefully in your future or your childrens future as a practicing
OB/GYN, there will be more and more medications
Mr. BURGESS. No, they are not going to do that. My liability will
fix that for us.
Mr. GORMAN. Well, whatever career path they take, they will
have the ability to have drugs that are studied in their population
and personalized medicines that are studied in their populations.
But the framework that these particular pieces of legislation have
formulated, with all of their small warts but major successes at the
same time allows other groups of specialized populations to see the
path to their own successful futures.
Mr. PALLONE. I am sorry. We started voting, and there is only
about 8 minutes left.
Mr. BURGESS. I beg your pardon.
Mr. PALLONE. So I am going to just ask Markey to ask a few
questions, and then we are going to go over and finish up. Thanks.
Mr. MARKEY. I thank you, Mr. Chairman, and by the way, I
thank you for your leadership on this issue and the focused way
in which you are bringing all of these issues to the attention of the
Congress and I thank Chairman Dingell as well for his comments
yesterday on Avandia and the need for FDA reform. I agree with
him 100 percent that this is one more example why we need legislation to reform the drug safety system at the FDA, and I was extremely pleased that Chairman Dingell said that he plans to address FDAs shortcomings and safety while writing legislation to
reauthorize PDUFA. I think that is the right context for us to do
it.
I have just two quick questions. Dr. Gorman, what has happened
since 2004 to convince the American Academy of Pediatrics that it
is important to act now to get the legislative changes that is in the
Markey-Rogers bill?
Mr. GORMAN. One of the wonderful things about being a pediatrician in practice is that you get to see what works and doesnt work
and then get to modify what doesnt work, hopefully with things
that are more effective. For 10 years we have watched FDAMA and
BPCA, but now for 5 years we have watched PREA work; and we
have seen some things that it does very well, and we have seen
some things that it doesnt do as well as we would like. Some of
the BPCA and PREA use slightly different standards and slightly
different formulations of thought on how they approach pediatric
labeling. And we think they should be unified. We think that the
results that are generated from studies, both the positive and the
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negative, should be reflected on the labels that the American consumer uses when deciding and their practitioners on the safety of
the drugs.
Mr. MARKEY. And why is expanded post-market monitoring authority important?
Mr. GORMAN. We think that expanded post-marketing authority
is important for at least three separate reasons. One is that we
think that you get more safety data when a drug is being used by
2 million people than when it is being used by 300 people in a clinical trial. So the majority of data is presented after a drug is approved. So the safety data is there for being mined.
Mr. MARKEY. OK.
Mr. GORMAN. Second, there is the possibility that pharmaceutical
companies promise post-marketing studies that then dont get
done. And the track record for those being done is outlined in the
GAO report about how many were promised and how many were
performed. And third, we think that pediatric patients, because
they are a clean system, in other words, generally they have very
few other diseases, that they are a system in which you can see
safety signals more clearly.
Mr. MARKEY. OK. So, Mr. Rozynski, could you tell me why you
now believe that this Markey-Rogers Pediatric Devices bill should
pass as well?
Mr. ROZYNSKI. We are a very early and a very big supporter of
this bill. We think this bill is a step forward to focus attention on
the need for more pediatric devices. We do believe that there are
really twin goals here, of course, which are encouraging more pediatric devices and also encouraging the development and sharing of
pediatric device information. We want to make sure that both of
those goals work together. I know there have been a few questions
raised about when and where do you collect this additional information. We want to provide more information. We also want to
make sure that we do not request information in a way that we
continue to have companies migrate towards developing devices for
the adult population at the expense of the pediatric population. We
think this bill is a big step in that direction and at the same time,
we want to make sure that in the end, those twin goals are
achieved, which is more devices.
Mr. MARKEY. I thank you and I also want to clarify that the postmarketing provisions in our legislation will give the FDA more authority to require monitoring of pediatric devices at the Secretarys
discretion. It does not require clinical trials in the post-market setting. This was a recommendation of the Institute of Medicine, and
we dont have much time left on the roll call.
Mr. Chairman, again, I thank you for your leadership. I thank
Mr. Dingell for his comment, and I thank you for your indulgence.
Mr. PALLONE. Thank you, Mr. Markey, and thank you all. We
only have 3 minutes left, but I really do want to thank you all for
spending the time. As I always say, within the next 10 days, you
may get additional questions from some of us that we would ask
you to respond to in writing; and obviously, we are going to use
your testimony as we move forward with reauthorizing some of
these initiatives. So thank you again, and this hearing is now adjourned.
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[Whereupon, at 1:15 p.m., the subcommittee was adjourned.]
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Programs Affecting Safety and Innovation in Pediatric Therapies

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PROGRAMS AFFECTING SAFETY AND INNOVATION

COMMITTEE ON ENERGY AND

MAY 22, 2007

Serial No. 11049

U.S. GOVERNMENT PRINTING OFFICE

For sale by the Superintendent of Documents, U.S. Government Printing Office

15:17 Oct 06, 2008

COMMITTEE ON ENERGY AND COMMERCE

15:17 Oct 06, 2008

New Jersey, Chairman

15:17 Oct 06, 2008

15:17 Oct 06, 2008

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

15:17 Oct 06, 2008