[Senate Hearing 110-543]
[From the U.S. Government Publishing Office]



                                                        S. Hrg. 110-543
 
        ENSURING SAFE MEDICINES AND MEDICAL DEVICES FOR CHILDREN

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

                                HEARING

                                 OF THE

                    COMMITTEE ON HEALTH, EDUCATION,
                          LABOR, AND PENSIONS

                          UNITED STATES SENATE

                       ONE HUNDRED TENTH CONGRESS

                             FIRST SESSION

                                   ON

   EXAMINING ENSURING SAFE MEDICINES AND MEDICAL DEVICES FOR CHILDREN

                               __________

                             MARCH 27, 2007

                               __________

 Printed for the use of the Committee on Health, Education, Labor, and 
                                Pensions


  Available via the World Wide Web: http://www.gpoaccess.gov/congress/
                                 senate

                     U.S. GOVERNMENT PRINTING OFFICE
34-475 PDF                 WASHINGTON DC:  2008
---------------------------------------------------------------------
For Sale by the Superintendent of Documents, U.S. Government Printing Office
Internet: bookstore.gpo.gov  Phone: toll free (866) 512-1800; (202) 512ï¿½091800  
Fax: (202) 512ï¿½092104 Mail: Stop IDCC, Washington, DC 20402ï¿½090001


          COMMITTEE ON HEALTH, EDUCATION, LABOR, AND PENSIONS

               EDWARD M. KENNEDY, Massachusetts, Chairman

CHRISTOPHER J. DODD, Connecticut     MICHAEL B. ENZI, Wyoming,
TOM HARKIN, Iowa                     JUDD GREGG, New Hampshire
BARBARA A. MIKULSKI, Maryland        LAMAR ALEXANDER, Tennessee
JEFF BINGAMAN, New Mexico            RICHARD BURR, North Carolina
PATTY MURRAY, Washington             JOHNNY ISAKSON, Georgia
JACK REED, Rhode Island              LISA MURKOWSKI, Alaska
HILLARY RODHAM CLINTON, New York     ORRIN G. HATCH, Utah
BARACK OBAMA, Illinois               PAT ROBERTS, Kansas
BERNARD SANDERS (I), Vermont         WAYNE ALLARD, Colorado
SHERROD BROWN, Ohio                  TOM COBURN, M.D., Oklahoma

           J. Michael Myers, Staff Director and Chief Counsel

           Katherine Brunett McGuire, Minority Staff Director

                                  (ii)

  




                            C O N T E N T S

                               __________

                               STATEMENTS

                        TUESDAY, MARCH 27, 2007

                                                                   Page
Dodd, Hon. Christopher J., a U.S. Senator from the State of 
  Connecticut, opening statement.................................     1
Alexander, Hon. Lamar, a U.S. Senator from the State of 
  Tennessee, opening statement...................................     4
Clinton, Hon Hillary Rodham, a U.S. Senator from the State of New 
  York...........................................................     4
Belfiore, Susan, Elizabeth Glaser Pediatrics AIDS Foundation, 
  Princeton, New Jersey..........................................     7
    Prepared statement...........................................    10
Gorman, Richard, M.D., FAAP, Pediatrician and Chair of the 
  American Academy of Pediatrics' Section on Clinical 
  Pharmacology and Therapeutics, Baltimore, Maryland.............    11
    Prepared statement...........................................    14
Maldonado, Samuel, M.D., MPH, FAAP, Vice President and Head of 
  Pediatric Drug Development Center of Excellence, Johnson and 
  Johnson Pharmaceutical Research and Development, Raritan, New 
  Jersey.........................................................    17
    Prepared statement...........................................    19
Campbell, Robert, M.D., Professor, Department of Orthopaedics, 
  University of Texas Health Science Center at San Antonio, San 
  Antonio, Texas.................................................    22
    Prepared statement...........................................    24
Rozynski, Ed, Vice President, Global Government Affairs, Stryker 
  Corporation, Washington, DC....................................    31
    Prepared statement...........................................    33
Brown, Hon. Sherrod, a U.S. Senator from the State of Ohio.......    40
Allard, Hon. Wayne, a U.S. Senator from the State of Colorado....    43

                          ADDITIONAL MATERIAL

Statements, articles, publications, letters, etc.:
    Advanced Medical Technology Association (AdvaMed)............    48
    Pharmaceutical Research and Manufacturers of America (PhRMA).    53
    Society for Cardiovascular Angiography and Interventions.....    58
    American Academy of Orthopaedic Surgeons (AAOS)..............    59

                                 (iii)

  


        ENSURING SAFE MEDICINES AND MEDICAL DEVICES FOR CHILDREN

                              ----------                              


                        TUESDAY, MARCH 27, 2007

                                       U.S. Senate,
       Committee on Health, Education, Labor, and Pensions,
                                                    Washington, DC.
    The committee met, pursuant to notice, at 1:09 p.m. in room 
SD-430, Dirksen Senate Office Building, Hon. Christopher J. 
Dodd, presiding.
    Present: Senators Dodd, Clinton, Brown, Alexander, and 
Allard.

                   Opening Statement of Senator Dodd

    Senator Dodd. The committee will come to order and I want 
to welcome my colleague and good friend, Lamar Alexander, who 
chaired this committee for some time. I've enjoyed his 
friendship and also working with him immensely during our time 
here together in the U.S. Senate. I thank you for being with us 
this morning. I want to thank our witnesses as well, for their 
participation, some of whom I've dealt with a lot over the 
years on a variety of issues affecting children and families 
and I want to thank Senator Kennedy for calling this important 
hearing on ensuring safe medicines and medical devices for 
children.
    At today's hearing, we'll look at two programs that are due 
to be reauthorized this year, the Best Pharmaceuticals Act, 
BPCA and the Pediatric Research Equity Act, the PRE Act as well 
as--there are three of those--as well as an initiative I've 
introduced, the Pediatric Medical Device Safety and Improvement 
Act of 2007.
    I want to take a minute here before we get into the 
substance of this and he's not here any longer. He doesn't sit 
at this dais any longer but of all the bills I did for so many 
years involving this issue and others, Mike DeWine of Ohio was 
a very valued partner on these issues and he was defeated last 
fall for re-election. But he did a wonderful, wonderful job, 
time and time again, on these questions and I just want the 
record to recognize that a lot of what we're talking about here 
doesn't happen miraculously, it happens because good people on 
the both sides of the political spectrum and isle care about 
these issues and Mike DeWine was one of those people and so I'd 
like the record to reflect my deep appreciation of Mike's work 
in this area over the years.
    The story of the Better Pharmaceuticals Act for Children is 
one of huge successes for children and their families, children 
with a wide range of diseases such as HIV/AIDS, cancer, 
allergies, asthma, neurological and psychiatric disorders and 
obesity, can now lead healthier, more productive lives as a 
result of new information about the safety and efficacy of 
drugs they use to treat and manage their diseases, where 
previously there was none.
    Pediatric drug studies conducted by the BPCA showed that 
children may have been exposed to ineffective drugs, 
ineffective dosing, overdosing or the side effects that were 
previously unknown. Since BPCA's passage in 1997 and its real 
authorization in 2000, the FDA has requested nearly 800 studies 
involving more than 45,000 children in clinical trials. Useful 
new pediatric information is now part of product labeling for 
119 drugs as a result of those efforts.
    By comparison, just to put it in perspective for you, in 
the 7 years prior to the adoption of BPCA, there were only 11 
studies of marketed drugs that were completed in that 
timeframe. In the past 10 years, there has been a nearly 20-
fold increase in the number of drugs studied in infants and 
children and adolescents since BPCA was enacted.
    The labeling changes resulting from clinical studies under 
BPCA have informed physicians of the proper dosing and the 
examples of Viracept, a protease inhibiter used in combination 
therapy for the treatment of HIV and Neurontin, a pain relief 
medication used to treat children with chronic pain. For 
children with epilepsy, BPCA studies informed physicians that 
the drugs Keppra and Trileptal could be used safely and 
effectively at an even earlier age than previously known. BPCA 
studies of Imitrex showed no better results than placebo for 
the treatment of migraine headaches in adolescents. These 
studies also showed serious adverse events due to Imitrex in 
pediatric populations and therefore the drug is not recommended 
to migraines in anyone less than 18 years of age.
    Recent studies of BPCA by the Government Accounting Office 
and by several authors at Duke University and in articles that 
appeared in the Journal of the American Medical Association 
have demonstrated that the program is a success and identified 
opportunities to strengthen the program. Authors of the recent 
JAMA article found that outside BPCA, FDA is limited in the 
number and scope of studies to which it can require pediatric 
data for existing products on the market.
    Contrary to statements that have been made about the 
program, data from this article showed that only a minority of 
drugs studied under BPCA, about 20 percent, had more than $1 
billion in annual sales. In fact, the median drug granted 
exclusivity was a small market drug with annual sales of $180 
million and 30 percent of the drugs showed had sales of less 
than $200 million. This article went to say that a universal 
reduction in the length of pediatric exclusivity from 6 to 3 
months would mean that products with small profit margins may 
not be submitted for pediatric testing.
    I recently circulated legislation to reauthorize BPCA, 
which I believe is a balanced and workable proposal that 
addresses several of the recommendations made by the General 
Accounting Office and the JAMA article. The author is including 
a provision to address the minority of cases where pediatric 
exclusivity has far exceeded the carrot it was intended to 
provide for drug sponsors.
    I want to thank the many individuals and organizations in 
the pediatrics community and the pharmaceutical industry that 
worked with this subcommittee and the committee in crafting 
this proposal and support the provisions contained within. 
Specifically, I'd like to recognize the work of Mark Del Monte 
of the American Academy of Pediatrics and Elaine Vining and 
Jeanne Ireland with the Elizabeth Glaser Pediatric Aids 
Foundation for the countless hours that they have devoted in 
order to provide my office with ideas and technical assistance 
for the reauthorization of BPCA.
    BPCA has had a long history of bipartisan support. I want 
that to be the future of this initiative as well. I've not 
formally introduced this proposal as a bill in the hopes that 
it will garner bipartisan support upon introduction. After all, 
the safety of our Nation's children is not a partisan issue--it 
should never be.
    We'll also hear from expert medical device witnesses at 
today's hearing. The legislation I've introduced, the Pediatric 
Medical Device, Safety and Improvement Act provides a 
comprehensive approach to ensuring that children are not left 
behind as cutting edge research and revolutionary technologies 
for medical devices advance. Like drugs, where far too long 
children were treated like small adults, could just take 
reduced doses of adult products. Many essential medical devices 
used extensively by pediatricians are not designed or sized for 
children.
    According to pediatricians, the development of new medical 
devices suitable for children's smaller and growing bodies can 
lag 5 or 10 years behind those for adults. The Pediatric 
Medical Device Safety and Improvement Act improves incentives 
for devices for small markets while still preserving the 
ability to ensure the safety of new products once on the 
market. It provides assistance to innovators, streamlines 
regulatory processes and elevates pediatric device issues at 
the FDA and NIH.
    This legislation has been many years in the making and 
support for the legislation represents a broad range of 
interests, including the Medical Device Trade Association. 
Development of the bill involved the import and guidance of 
pediatricians, device manufacturers, both small and large ones, 
innovators and patient advocates.
    We're going to hear testimony this afternoon shortly from 
Dr. Ed Rozynski from the Stryker Corporation, a medical device 
company that has been a long-standing and vigorous supporter of 
this initiative and I look forward to hearing your testimony.
    As a parent of two young children, it is essential that 
products used in children's growing bodies, whether they be 
drugs or devices, are appropriately tested and designed 
specifically for their use. We must continue the tremendous 
success of BPCA and PREA by strengthening both programs through 
the reauthorization process this year. I'm a strong supporter 
of both programs and pleased to be an original co-sponsor of 
the reauthorization of PREA and my colleague from New York who 
has been the leader on this issue since her days at the White 
House and then here. I commend her immensely for her work so 
I'm going to turn in a minute for some opening comments, if I 
can, Senator and I thank you for your work in this area.
    It is essential that we use these past experiences of both 
programs to ensure they continue to thrive in the future and 
that we have enough sense to look as to how they've developed 
over the last few years to make appropriate changes in the 
legislation so that we reflect what has occurred and what we've 
learned over the past number of years as well. So with that, 
let me turn to my colleague from Tennessee and again, my thanks 
to Lamar Alexander for his wonderful leadership on so many of 
these issues during our tenure here together and I thank you 
immensely for that.

                 Opening Statement of Senator Alexander

    Senator Alexander. Thank you, Senator Dodd, Mr. Chairman 
and Senator Clinton. I enjoyed working with Chris Dodd on these 
issues and we've done that for the last 4 years and we'll 
continue to do more. I want to salute him for his leadership on 
helping to make sure that drugs that are prescribed for 
children are--that more is known about how safe they are when 
they are used and I want to salute Senator Clinton for her work 
on the Pediatric Research Equity Act. These two laws work 
together.
    I don't have very much to say about either one of them. I'm 
looking forward to the testimony today and I look forward to 
working with Senator Dodd and Senator Clinton on making sure 
that we reauthorize the legislation. I don't think there is any 
disagreement, at least from my part, about whether we would 
reauthorize the legislation. The only questions that remain and 
that's why we have these hearings and discussions, is just how 
we should reauthorize them. What should we consider, what have 
we learned in the last few years and what should we do going 
forward?
    Sometimes a statistic helps put things in--and relief in my 
State of Tennessee. In 1999, seven babies who were prescribed 
an antibiotic to treat whooping cough became so seriously ill 
that they needed stomach surgery. The Center for Disease 
Control linked their illness to the antibiotic, which had never 
been tested in young children. My information is that 
currently, only about one-third of drugs prescribed to children 
have been studied and labeled for children. That leaves too 
many physicians making guesses and it leaves too many worried 
parents.
    So we believe we have some good legislation here. I should 
add that Senator DeWine did make a significant contribution to 
both pieces of legislation when he was here. I think he was the 
principle co-sponsor of both Senator Clinton's bill and Senator 
Dodd's bill and we salute him for that. So I look forward to 
working with my colleagues to reauthorize the legislation, to 
find the appropriate way to do it and I look forward to the 
hearing. Thank you, Senator.
    Senator Dodd. Thank you very much, Senator.
    Senator Clinton.

                      Statement of Senator Clinton

    Senator Clinton. Thank you so much and of course, Senator 
Dodd has such a long history of being on the forefront of all 
of the efforts we've made in the Congress over a number of 
years now, on behalf of children and families and it is a real 
pleasure to be here with both he and Senator Alexander. I'm 
pleased to be Senator Dodd's co-sponsor on the Pediatric 
Medical Devices Safety and Improvement Act when that is finally 
offered because it will improve the number and types of medical 
devices designed for pediatric populations and I particularly 
want to thank the witnesses today, who are going to give the 
guidance that Senator Alexander said that we need to have and I 
welcome back Susan Belfiore and her family because she has been 
an advocate on behalf of these issues, along with her family, 
for a number of years now.
    The type of drugs and the number of drugs that are 
available for children has been an issue for me for many years. 
Back during the Clinton Administration, I first worked with the 
Food and Drug Administration and the Elizabeth Glaser Pediatric 
AIDS Foundation and other patient groups to establish the 
Pediatric Rule, which requires that drug manufacturers ensure 
medications marketed for pediatric use are safe and effective 
for our children. Then when this regulation was challenged in 
court, I worked with my colleagues in the Senate, Senator Dodd 
and Senator DeWine, to get the Pediatric Rule enacted into law.
    This landmark law, the Pediatric Research Equity Act was a 
real step forward. We can look at the changes and realize how 
much has occurred and yet still know we have a long way to go. 
As of the early 1990s, only about 20 percent of drugs contained 
specific pediatric dosing information but we know that children 
are not just little adults and a drug that reacts one way in an 
adult's body can have serious consequences in a child and as 
Senator Alexander said, we sometimes tragically discover this.
    We've put pediatricians, in the past, into a guessing game, 
trying to determine if a drug appropriate for an adult would 
have the same pharmacological effect on a child. But thanks to 
the combined efforts, the Pediatric Research Equity Act and the 
Best Pharmaceuticals for Children Act, we're now able to use 
the best evidence to make better healthcare decisions for 
children.
    We are now requiring submission of pediatric clinical trial 
data for new drug applications so that we can be better assured 
that drugs marketed for children are safe and effective. 
Indeed, more than 1,000 new and supplemental drug applications 
have fallen under the scope of the Pediatric Rule and the 
Pediatric Research Equity Act. The Best Pharmaceuticals for 
Children Act and the Pediatric Research Equity Act have managed 
to increase our understanding of the way drugs work in a 
pediatric population.
    For example, we've learned that a drug commonly prescribed 
for migraines in adults is not effective in pediatric 
populations and may actually cause serious adverse 
consequences. We've learned that methylphenidate, a drug 
prescribed for Attention Deficient Hyperactivity Disorder is 
processed more by adolescents than other age groups, therefore 
it requires different dosages. We've been able to collect data 
on drugs commonly used in children, like Azithromycin, an 
antibiotic used to treat bronchitis, pneumonia and respiratory 
infections as well as drugs that are not so commonly used but 
that help keep children alive, like Emtriva, one of the newer 
drugs we have to treat AIDS.
    But both of these acts are scheduled to expire in September 
if they are not reauthorized. So that's why this hearing is so 
timely and important and I'll be introducing the Pediatric 
Research Improvement Act legislation that would reauthorize the 
Pediatric Research Equity Act and make permanent the FDA's 
authority to require submission of pediatric clinical trial 
data for drugs designed for children.
    I just want to emphasize this one point. When both of these 
bills were passed, they had what are called sunsets, which 
means that you have to go back and reauthorize them. I think 
that there is general agreement that the Best Pharmaceuticals 
Act probably is one that a sunset is important for, to make 
sure that the incentives that Senator Dodd designed are working 
the way they should but it seems a little strange that we would 
have to reauthorize the Pediatric Rule. We don't have sunsets 
on getting adult clinical data to determine what happens with 
drugs in adults. We shouldn't have any kind of sunset on 
getting the same data for children. I think we should make this 
Pediatric Rule permanent and I will be introducing legislation 
to do that.
    It will also improve the ability of the FDA to require 
testing on already marketed drugs when drug companies refuse to 
carry out that testing on their own and better coordinate the 
incentives in these important laws. So I'm very pleased to be 
here and to continue to work with my colleagues, led by Senator 
Dodd, to get this done.
    Senator Dodd. Thank you immensely for that and again, 
thanks for your terrific work on these issues over the years. 
It has been a pleasure to work with you and it is a good cause. 
It is making a difference every day.
    We are delighted to have our witnesses with us. Let me 
briefly introduce them. Susan Belfiore, we welcome you back and 
your wonderful family. You and your husband, for those who are 
not familiar here, Susan Belfiore has five children and she is 
going to testify on behalf of the Elizabeth Glaser Pediatric 
AIDS Foundation and all of us up here have worked with the 
Foundation over the years on a number of different issues. She 
and her husband adopted four children from Romania, all of whom 
are HIV positive and Mrs. Belfiore will talk about the impact 
that the Pharmaceuticals for Children Act and the Pediatric 
Research Equity Act have had on her children and her family. 
It's wonderful to have you with us. You are so knowledgeable 
and we admire you immensely for the gift of life and what 
you've done for these delightful children you have.
    Dr. Richard Gorman is a practicing pediatrician from 
Baltimore, Maryland and we thank you and I admire that gray 
hair you've got on your head, Doctor. It's forming a caucus 
here occasionally, of gray hairs.
    [Laughter.]
    Senator Dodd. He is Chairman of the American Academy of 
Pediatrics section on Clinical Pharmacology and Therapeutics. 
Previously, Dr. Gorman ran a pediatric emergency department, an 
ambulatory center and was Medical Director of the Maryland 
Poison Center and we thank you immensely. I say this over and 
over again, over 26 years of working with these issues, but for 
the American Academy of Pediatrics, family medical leave never 
would have become the law of the land. The childcare 
legislation never would have happened. Infant screening, 
premature birth legislation that Senator Alexander and I have 
worked on together--it's just a remarkable group of physicians 
and I thank you every time you come before this committee, for 
the difference you've made as a group of doctors who has just 
been really terrific over the years. We thank you for your 
work.
    Dr. Samuel Maldonado is Vice President and Head of the 
Pediatric Drug Department Center of Excellence at Johnson & 
Johnson, pharmaceutical research and development. He joined J&J 
in February 2000 as Director of Pediatric Drug Development, 
received his degree from the National University of Honduras 
and his MPH from George Washington University and you've had a 
variety of other experiences over your career and we thank you 
immensely for your work and the contributions that J&J has made 
to our efforts here today. I also point out that he ran the 
FDA--joined the FDA rather, as a Medical Officer in the 
Division of Anti-Infected Drug Products and was subsequently in 
the Division of Anti-Viral Drug Products as well, so you have 
wonderful experience here.
    Dr. Robert Campbell is a Professor of Orthopedics at the 
University of Texas, the Health Science Center at San Antonio 
and is a pediatric orthopedic surgeon, an inventor and a father 
of five children as well. He invented and developed and brought 
to market a life saving pediatric surgical device known as the 
vertical expandable prosthetic titanium rib. We call it VEPTR, 
which is what it is affectionately known as, which was approved 
as a humanitarian device exception in 2004 after 14 years of 
FDA trials. That is a new definition of tenacity, Doctor, for 
your work in that regard and we thank you today for being with 
us.
    I've mentioned Ed Rozynski already, who is the Vice 
President of Global Government Affairs at Stryker Corporation. 
They are a leading medical technology company and have been a 
leader in products of significance for children over the years. 
Stryker has been an early and vigorous supporter of the 
legislative effort to ensure the safety of medical devices used 
in children and I thank them for their leadership in this 
effort. I would point out that Mr. Rozynski is a student of 
International Health and Care Systems for the past 20 years. 
Among his many accomplishments, working with past 
Administrations and the FDA to ensure that U.S. companies could 
export medical devices to other major industrialized countries 
where they have been approved but which have not been granted 
U.S. approval. So we thank you for your efforts on behalf of 
people around the world as well.
    With that, let me begin with you Susan. I'm not going to be 
rigid about this but if you'd keep an eye on the clock, I want 
to just tell you any documentation--all of your statements, 
their full contents will be included in the record here today 
so if you can kind of get through this in 5 or 6 minutes so we 
can move along and then have a good question and answer period 
here on some of these issues, I'd appreciate it very much. 
Welcome to the committee.

 STATEMENT OF SUSAN BELFIORE, ELIZABETH GLASER PEDIATRIC AIDS 
               FOUNDATION, PRINCETON, NEW JERSEY

    Mrs. Belfiore. Mr. Chairman and distinguished committee 
members, thank you so much for having me and my family here 
today. I am Susan Belfiore, mother of five children, four whom 
are HIV positive.
    I want to thank Senator Dodd, Senator Clinton, Senator 
Alexander, Senator Kennedy, and Senator Enzi for your 
leadership on this issue. My family and I participated in a 
conference 5 years ago to speak about the new Pediatric Rule 
legislation. I am honored to be back again today to let you 
know the difference that it has made in our lives and how 
important it is that medications continue to be tested 
specifically for use in children.
    This issue is not settled by any means but the progress we 
have made is because of you. Thank you. You are all true 
champions for children. I would 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 would like to take a moment to acknowledge my family 
behind me--my husband Bill and the five reasons why we're here 
today: our children. Ramona, Ionel, Loredana, Mihaela, and 
Aiden.
    Senator Dodd. Why don't you stand up to be recognized?
    [Applause.]
    Mrs. Belfiore. We are here today because our family, like 
so many other families throughout the country are dependent on 
the latest medications to keep our children healthy. As you 
heard, four of our five children have the AIDS virus. Mihaela 
and Loredana are taking life-sustaining medications.
    Clearly, this is an issue that is close to my heart. As a 
parent, there is nothing more difficult than knowing your child 
is sick. You can often feel scared and frightened. But our 
family believes in miracles. But miracles won't happen without 
the correct medication and the correct dosing. Both of these 
can be achieved only through pediatric testing.
    I still remember the first time when our then 8-year-old 
Mihaela was put on a cocktail of drugs that many AIDS 
patients--adult AIDS patients--were using. We took the 
medications out of the pillboxes and put them into a container 
that was decorated with horses. Mihaela loves horses. We had a 
silly hat party at the dining room table. We wanted to focus on 
what was positive instead of the fact that for a very long time 
and maybe for the rest of her life, Mihaela might be dependent 
on the these medications to keep her healthy.
    But the truth is, Mihaela and Loredana and thousands of 
children like them are dependent on the latest medications to 
keep them healthy, strong 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, 
many kids won't have a chance. They cannot afford to rely on 
guesswork. We've tried that and I can tell you personally, it 
does not work.
    This binder here is the record of my children's medical 
life. For the past 14 years, I have cataloged all aspects of 
their health, charting their blood work every 3 months, what 
medications they are taking, what reactions they might be 
having to the medications.
    Ten years ago, we thought Mihaela was taking an effective 
drug regimen for HIV. She was not. It turns out she had been 
under-medicated because the drug she was taking had not been 
sufficiently tested for use in children. Mihaela's 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 
because it means your child has lost access to one more drug in 
a regime and a very limited supply of options. When the options 
run out, children suffer. I recently looked at a picture of the 
press conference from 5 years ago. I believe Senator Dodd's 
office has shared a copy of the picture with you--I was shocked 
when I saw Mihaela. She was underweight and she looked sick. 
When you're in the moment, you don't realize it, until you go 
back. I could see how poorly she was doing.
    In the last 5 years though, things have been really 
different. I have to say that again. For the last 5 years, 
things have been really 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, her energy is incredible and she is free 
of infections. And the best part of it is that for the last 4 
years, she has had undetectable virus in her system. She now 
loves and rides horses more than ever before.
    My family's personal struggle is with HIV. But I have to 
point out that the value of these laws goes beyond HIV and 
beyond my individual family. My family and I are here for 
parents and children--all parents and all children, not just 
those living with AIDS. We have heard the statistics--about 
three-quarters of prescription medications have not been tested 
for use in children. These drugs are for everything from 
cancer, asthma, HIV and AIDS.
    Now I understand that testing drugs for use in children is 
an additional expense for the drug companies. I also understand 
that it can be difficult to conduct studies because of a 
variety of enrollment issues. That is why BPCA includes an 
incentive for companies to do pediatric studies. That law is 
working well and it should be continued and I know others on 
this panel will speak to you more about that.
    But this issue is just not about profit and the bottom 
line. It must be about the value of a child's life. To be 
honest, I wonder why testing medication in children is even a 
question. As adults, we wouldn't take medications that have not 
been tested for us, so why then, would we give them to our 
children?
    That is why I strongly believe that the Pediatric Research 
Equity Act should be made permanent. My children come from a 
country that didn't have the resources to invest in its 
children, all its children, especially sick ones. Those were 
horrific times for Romania and they did the best they could. 
But I am here to say that we can do better. In the end, it's 
all about the children.
    When it comes to medication, we know children are not just 
small adults. We know these laws work. We know there are still 
so many drugs out there that have not been tested for children 
and we know that now that we have this awareness, there can be 
no going back.
    I appeal to you on behalf of my children and millions of 
children that are just as precious and important as they are, 
to reauthorize these laws as soon as possible. Surely we can 
agree that children deserve nothing less than the same 
information about safety and dosing of drugs that we demand for 
ourselves as adults.
    Thank you again for inviting me here today on behalf of all 
parents. Thank you so much for all you do for children.
    [The prepared statement of Mrs. Belfiore follows:]

                  Prepared Statement of Susan Belfiore

    Mr. Chairman and distinguished committee members. Thank you so much 
for having me and my family here today. I am Susan Belfiore, mother of 
5 children, 4 of whom are HIV-positive.
    I want to thank Senator Dodd, Senator Kennedy, Senator Enzi, 
Senator Alexander, and Senator Clinton for your leadership on this 
issue. My family and I participated in a press conference 5 years to 
announce the new Pediatric Rule legislation. I'm honored to be back 
again today to let you know the difference it has made in our lives and 
why it's 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. And I 
wanted to thank you.
    I'd 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'd like to take just a moment to acknowledge my family behind me--
my husband Bill, and the five reasons why I am here: my children, 
Ramona, Ionel, Loredana, Mihaela, and Aiden. We are here today because 
our family--like so may other families throughout the country--is 
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 feel scared. Frustrated. Terrified. Helpless. You put your 
trust in doctors, and researchers, and the latest medications--and then 
you force yourself to believe.
    Our family believes in miracles. But miracles won't 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 8-year-old daughter 
Mihaela on the 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 alive.
    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, these kids won't have a chance. 
They cannot afford to rely on guesswork. We've tried that, and I can 
tell you personally that it just doesn't work.
    This binder is the story of my children's medical life. In it I 
have cataloged all the details of their illnesses--everything, 
including drug regimens, drug reactions, blood work, and 
hospitalizations. It's a visible reminder, to me, of the control and 
responsibility I have against a disease where so much is unknown.
    Seven 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. Mihaela's 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 and even die.
    Recently I looked at a picture of that press conference from 5 
years ago. I was shocked when I saw Mihaela. She was underweight. She 
looked sick. When you're in the moment, you don't realize it, until you 
go back. In this photo, you can really see just how poorly she was 
doing.
    In the last 6 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. Her love of horses has grown too.
    Thank you.
    My family's personal struggle is with HIV. But I have to point out 
that the value of these laws goes beyond HIV, beyond my individual 
family. I, and my family, are here for all parents, and especially for 
all children, not just those living with HIV and AIDS. We've 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 and allergies, to high blood pressure and HIV/AIDS.
    As parents, we need to know that we are doing the very best that we 
can for our children. We never give up. We never say no to what our 
children need, especially when it comes to medicines that can save 
their lives. And I can't imagine our government leaders would either.
    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. That's why BPCA includes an incentive for companies 
to do pediatric studies. That law is working well and should be 
continued. And I know others on this panel will talk to you more about 
that.
    But this issue cannot just be about profits and the bottom line. It 
must be about the value of a child's life. To be honest, I wonder why 
the idea that all medications should be studied for children is even a 
question. As adults, we wouldn't 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.
    My children come from a country that didn't have the resources to 
invest in all its children--especially sick ones. Those were horrific 
times for Romania and they did the best they could. But I'm here to say 
that we can do better. I'm here today to tell you that my children, and 
millions of children like them, are worth investing in. It sounds like 
such a strange thing to say. How can there even be a question?
    And this investment doesn't just apply to drugs. Senator Dodd has 
introduced legislation that applies the lessons we have learned about 
safe drugs for children to the world of medical devices. Children often 
rely on medical devices, such as heart pumps and ear implants, to treat 
serious conditions and illnesses. Yet there are so few medical devices 
designed specifically for children. So doctors must improvise, and 
sometimes, children are hurt in the process. Let us not repeat past 
mistakes and leave children behind as science and technology move 
forward.
    In the end, this is all about children. These laws are basic 
investments in our children's future. We know they work and we know 
they are saving lives.
    I appeal to you on behalf of Ramona, Ionel, Loredana, Mihaela, 
Aiden, 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.

    Senator Dodd. Thank you very, very much, Mrs. Belfiore. We 
appreciate it very much and thank you for bringing your family 
along. It's wonderful to have you here with us today and seeing 
you all doing so very, very well. I remember very well the 
gathering about 5 years ago when we saw all of you. It's nice 
to have you back with us. Thank you for coming. Thank you for 
your testimony and your work as well.
    Dr. Gorman, thank you for joining us.

STATEMENT OF RICHARD GORMAN, M.D., FAAP, PEDIATRICIAN AND CHAIR 
  OF THE AMERICAN ACADEMY OF PEDIATRICS' SECTION ON CLINICAL 
       PHARMACOLOGY AND THERAPEUTICS, BALTIMORE, MARYLAND

    Dr. Gorman. Mr. Chairman and members of the committee, I am 
Richard Gorman, a practicing pediatrician who has taken care of 
infants, children and adolescents for over 25 years. I thank 
the committee for holding this hearing on the need for safe and 
effective drugs and medical devices for children and after 
reading Susan's testimony last night, I took out the same set 
of pictures and I remembered that press conference and Senator 
DeWine and Senator Frist and Senator Clinton and yourself 
standing there in the front of the room, realizing that 
something good had happened for children that day. I wanted to 
bring that back up because it was a wonderful time for us as 
well.
    Senator Dodd. Thank you.
    Dr. Gorman. If I learned anything at the last conference, 
it's that you should never have to speak after Susan.
    [Laughter.]
    Dr. Gorman. Which was exactly my placement the last time as 
well. This is another learning experience for me. In my 
practice at Pediatric Partners in Maryland, I see first-hand 
the pediatric therapeutic benefits of increased pediatric 
information. With over 80,000 pediatric visits annually to our 
practice sites, my partners and I can attest to the importance 
of pediatric drug studies.
    I am here today on behalf of the American Academy of 
Pediatrics to discuss the Best Pharmaceuticals for Children Act 
and the Pediatric Research Equity Act, which are critical 
public policy successes for children. I wish to extend the 
Academy's sincerest thanks to both Senators Dodd and Clinton 
for their long support for championing these important bills.
    I can say without reservation that in the last decade, we 
have gained more useful pediatric drug information through 
these two laws than we had in the previous 70 years. It is 
vitally important for children that these laws be reauthorized. 
The Academy is pleased to support the draft BPCA 
reauthorization proposed for release by Senator Dodd and the 
PREA reauthorization legislation soon to be introduced by 
Senator Clinton.
    In previous testimony before Congress, I have described 
children as the canaries in the mine shafts. They have always 
acted as the early warnings of unknown dangers in therapeutics. 
BPCA and PREA work together to help protect our children from 
these dangers. These two pieces of legislation create an 
effective two-pronged approach to generate knowledge about the 
drugs we use in children.
    However, despite the important advances resulting from BPCA 
and PREA, there is still much more to learn. Still today, 
nearly two-thirds of drugs used in children are not labeled for 
them. When children are in hospitals, 80 percent of them 
receive at least one drug that is for an off-labeled use, much 
like the Arthrithomycin used in the State of Tennessee, for 
these children with pertussis that were a little young to get 
that medicine. Therefore for children, off-label use remains 
the rule and not the exception.
    Mr. Chairman, in my written testimony, I have elaborated on 
the recommendations for improvements for these legislations in 
several areas. We believe that Senators Dodd and Clinton have 
addressed AAP's concerns well in their respective 
reauthorization bills. Both proposals work together to maximize 
the historic opportunity to pass a well-coordinated and 
effective packet of legislation that will benefit all children.
    The proposed legislation increases the dissemination, the 
transparency and the tracking of pediatric drug information. It 
streamlines and integrates the FDA Administration of BPCA and 
PREA to improve the uniformity, the consistency and the quality 
of pediatric studies and it expands the study of off-patented 
or generic drugs and addresses gaps in the understanding of 
pediatric therapeutics.
    In addition, Senator Dodd's proposal for adjusting the 
exclusivity extension is a balanced compromise that will 
preserve the quality and the number of pediatric studies gained 
through BPCA.
    It also addresses the concerns regarding excessive profits. 
We know that 6 months of additional marketing exclusivity has 
been very successful in the past in creating pediatric studies.
    The AAP pledged to review any proposal for limiting the 
exclusivity awarded under BPCA using two criteria. First, any 
change must not reduce the number of drugs studied in children. 
The GAP found that drug sponsors agreed to conduct studies and 
proposals to written requests from the FDA 81 percent of the 
time. Any proposal that will decrease the number of favorable 
responses to a written request would undermine the essential 
goal of BPCA.
    We have data published in the medical journals to show that 
simply cutting the incentive from 6 months to some lesser 
number will certainly reduce pediatric studies and we cannot 
support those proposals.
    The second criteria we were using was administrative 
simplicity. Proposals using complicated formulas are likely to 
bog down the FDA and give rise to endless disputes between 
sponsors and the agency, including litigation. We cannot risk 
deterring or delaying important information getting into the 
hands of families and their healthcare providers.
    The changes proposed by Senator Dodd are straightforward 
and as clear as possible. It targets only those blockbuster 
drugs for which an appropriate reduction in exclusivity will 
not reduce acceptance of, and successful completion of, written 
requests for blockbuster drugs.
    We also support Senator Clinton's legislation that makes 
PREA a permanent part of the Food and Drug Act. The FDA 
currently has permanent authority to ensure the safety of drugs 
in adults. Children deserve the same. When PREA is 
reauthorized, it should be made permanent. Congress should not 
need to debate every few years whether or not they should 
continue to require safety testing for drugs for children.
    It is useful, however, to re-evaluate the exclusivity 
program periodically to ensure that incentive offered achieved 
its desired goals, despite the dynamic pharmaceuticals market. 
Congress should have the opportunity every 5 years to analyze 
whether BPCA continues to strike the right balance between 
achieving critical pediatric information and providing an 
appropriate incentive to maintain the number and quality of 
pediatric studies.
    In closing, I would like to thank the committee again. I 
would like to reiterate the strong support of the American 
Academy of Pediatrics for reauthorization of the Best 
Pharmaceuticals for Children Act and the Pediatric Research 
Equity Act. We urge their renewal as part of the package of FDA 
bills under consideration by this committee for the sake of all 
the children in the United States. I'll be happy to answer any 
questions later.
    [The prepared statement of Dr. Gorman follows:]

          Prepared Statement of Richard L. Gorman, M.D., FAAP

    Mr. Chairman, members of the committee, I am Richard Gorman, M.D., 
FAAP, a practicing pediatrician who has taken care of infants, children 
and adolescents for over 29 years. I am here today representing the 
American Academy of Pediatrics (AAP) in my official capacity as chair 
of the AAP Section on Clinical Pharmacology and Therapeutics. It is 
through my practice, Pediatric Partners in Ellicott City, Maryland 
where I see firsthand the pediatric therapeutic benefits of increased 
information on drugs used in children. With over 80,000 pediatric 
visits annually in four clinical sites in three counties in Maryland, 
my partners and I can attest to the importance of pediatric drug 
studies legislation.
    The pediatric academic research community that includes the 
Ambulatory Pediatric Association, American Pediatric Society, 
Association of Medical School Pediatric Department Chairs, and the 
Society for Pediatric Research also supports and endorses the Academy's 
testimony. These societies comprise academic generalist pediatricians, 
pediatric researchers, and full-time academic and clinical faculty 
responsible for the delivery of health care services to children, the 
education and training of pediatricians, and the leadership of medical 
school pediatric departments.

                      THE SUCCESS OF BPCA AND PREA

    I am here today on behalf of the American Academy of Pediatrics to 
discuss the Best Pharmaceuticals for Children Act (BPCA) and the 
Pediatric Research Equity Act (PREA), which represent critical public 
policy successes for children. I begin my testimony today by saying 
enthusiastically and without reservation that in the last decade we 
have gained more useful information on drugs used in children through 
BPCA and PREA than we had in the previous 70 years.
    I wish to extend the Academy's sincerest thanks to Senators Dodd 
and Clinton for their long support and for championing these important 
bills. 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 pediatric pharmaceuticals 
where previously there was none. It is vitally important for infants, 
children and adolescents that these laws be reauthorized.
    In previous testimony before Congress, I have described children as 
``the canaries in the mineshafts,'' acting as early warning of unknown 
dangers. Legislative progress on drug safety for all Americans has most 
often been made after the tragic injuries or deaths of children. 
Despite this history, little progress was made in the effort to include 
the pediatric population in therapeutic advances until passage of the 
pediatric studies provision of the Food and Drug Administration 
Modernization Act of 1997 (FDAMA). This provision was later 
reauthorized as BPCA in 2002, and PREA was enacted in 2003. With the 
passage of this legislation, we have started to remedy the alarming 
lack of pediatric drug labeling and information available to 
pediatricians and other health professionals.
    BPCA and PREA work together as an effective two-pronged approach to 
generate pediatric studies. PREA provides FDA the authority to require 
pediatric studies of drugs when their use for children would be the 
same as in adults. BPCA provides a voluntary incentive to drug 
manufacturers of an additional 6 months of marketing exclusivity for 
conducting pediatric studies of drugs that the FDA determines may be 
useful to children.
    Since the passage of FDAMA over a decade ago, FDA has requested 
nearly 800 studies involving more than 45,000 children in clinical 
trials through a written request. The information gained from these 
studies resulted in label changes for 119 drugs.\1\ By comparison, in 
the 7 years prior to FDAMA, only 11 studies of marketed drugs were 
completed, though 70 studies were promised. Similar data tracking 
PREA's effectiveness is not publicly available. AAP hopes this year's 
reauthorization will create that tracking system.
---------------------------------------------------------------------------
    \1\ American Academy of Pediatrics. Pediatric studies lead to more 
information on drug labels. AAP News. 2007;2:20-25.
---------------------------------------------------------------------------
    As a clinician, I cannot overstate the importance of what we have 
learned through the pediatric studies generated by these laws. 
Children's differing metabolism, growth and development, and size have 
very large effects. The performance of medications in children's bodies 
is even more dynamic and variable than we anticipated. Indeed, we have 
really learned, once again, that children are not just small adults. 
And the more we learn, the more we realize we didn't know.
    For example, pediatric studies and resultant labeling have:

     given pediatricians the ability to give the correct dose 
of pain relief medicine to children with chronic pain that were 
previously under dosed (Neurontin);
     warned ICU physicians that a drug used for sedation in 
ICUs had twice the mortality rate as another drug combination 
(Propofol);
     given pediatricians and child psychiatrists important 
information on both the relative effectiveness and serious side effects 
of anti-depressant medication in adolescents (Prozac, Paxil, et al.);
     given children increased relief of pain from medicines 
taken by mouth, breathed into the lungs, given through the vein, and 
absorbed through the skin; and,
     alerted both pediatricians and parents about unexpected 
side effects of medications that have allowed for a more complete 
discussion of both the risks and benefits of a particular therapeutic 
course.

    What a tremendous improvement over the shrugging shoulders and the 
resigned look and the soft sigh when we had to say: ``I'm sorry, we 
just don't know enough about this drug in children.''
    If a drug is not labeled for children, pediatricians are faced with 
two difficult choices: (1) not using a medication that could provide 
relief and help to the child because it is not labeled for use in 
pediatrics or (2) using the medication off-label based on limited 
studies and/or the clinical experience of health professionals. BPCA 
and PREA have given pediatricians more information to avoid this 
necessary but inadequate practice.
    Better labeling has lead to better therapeutics for children, 
reducing medical errors and adverse effects. Lack of proper information 
for pediatric patients related to dosing, toxicity, adverse effects, 
drug interactions, etc. can lead to medical errors and potential 
injury. Medication errors produce a variety of problems, ranging from 
minor discomfort to substantial morbidity that may prolong 
hospitalization or lead to death. Another important factor underscoring 
the need for better labeling is the increasing effort of private and 
public payors to limit reimbursement for drugs prescribed off-label.
    Increased pediatric studies also encourage the creation of child-
friendly drug formulations. Even the most effective drug cannot improve 
a child's health if the drug is unavailable in a formulation that a 
child can take (e.g., pills vs. liquid) or if the taste is unpalatable. 
Compliance with a prescription often relies on the formulation. If a 
parent has to struggle with the child every time a dose is needed, the 
likelihood of completing the full prescription to obtain maximum 
benefit is greatly reduced. Again, here BPCA and PREA have been 
successful in informing what pediatric formulations are effective for 
children.

                BPCA AND PREA ARE STILL ESSENTIAL TOOLS

    Despite the advances resulting from BPCA and PREA, there remains 
much progress to be made. Children remain second-class citizens when it 
comes to drug safety and efficacy information. Currently, nearly two-
thirds of drugs used in children are still not labeled for children.\2\ 
Almost 80 percent of hospitalized children receive at least one drug 
prescribed to them for an off-label use.\3\ For children, off-label use 
is the rule, not the exception, because of the scarcity of prescribing 
information for this population. Therefore, both BPCA and PREA are 
still crucially important and must be reauthorized this year, including 
needed improvements.
---------------------------------------------------------------------------
    \2\ United States Government Accountability Office. Pediatric Drug 
Research. (GAO-07-557); 1.
    \3\ Shah SS, Sharma VS, Jenkins KJ, Levin JE. Off-label Drug Use in 
Hospitalized Children. Arch Pediatr Adolesc Med. 2007;161:282-290.
---------------------------------------------------------------------------
    This year is the first time BPCA and PREA will be reauthorized 
together, providing Congress with an historic opportunity to pass a 
well-coordinated and effective package of legislation for the benefit 
of all children. We recommend the following improvements.
    Increase the dissemination, transparency, and tracking of pediatric 
drug information. Dissemination of pediatric information to families 
and healthcare providers should be increased in both BPCA and PREA. If 
families choose to involve their children in a clinical trial for a 
drug, then the drug label should reflect that study. The Government 
Accountability Office (GAO) found that about 87 percent of drugs 
granted exclusivity under BPCA had important label changes.\4\ This is 
good news but it is our view that every drug label should reflect when 
a pediatric study was done (either through BPCA or PREA) and the 
results of the study, whether the results are positive, negative, or 
inconclusive. Moreover, FDA and drug sponsors must do more to 
communicate these label changes to pediatric clinicians. FDA should 
continue and expand its periodic monitoring of adverse events for both 
PREA and BPCA as this has been a useful tool to evaluate drug therapies 
after approval.
---------------------------------------------------------------------------
    \4\ GAO 2007; 16.
---------------------------------------------------------------------------
    The transparency of the written request process used by FDA can be 
improved. Increased transparency will be beneficial to pediatricians, 
sponsors and families. AAP recommends that written requests be made 
public at the time FDA awards exclusivity and that each written request 
be allowed to include both off-label and on-label uses. Moreover, 
because we recognize that FDA has improved the pediatric study written 
requests since 1997, we recommend that the Institute of Medicine be 
engaged to review a representative sample of all written requests and 
pediatric assessments under PREA. This scientific review will provide 
recommendations to FDA to continue to improve the consistency and 
uniformity of pediatric studies across all review divisions within the 
FDA's Center for Drug Evaluation and Research.
    Information regarding the number of written requests issued as well 
as information regarding pediatric studies and label changes made as a 
result of BPCA is tracked and posted at FDA's Web site. This 
information is key to understanding the operation of the law for 
children and we recommend that FDA also be required to track this 
information for PREA and make such information available.
    Integrate and strengthen BPCA and PREA administrative processes. In 
general, BPCA and PREA processes are working well at FDA but more often 
as parallel programs than one administratively integrated pediatric 
study program. AAP supports the expansion of the existing internal FDA 
pediatric committee to include additional kinds of expertise within the 
agency and an integrated approach to the review and tracking of all 
pediatric studies requested or required by FDA, including the ability 
to require labeling changes.
    Expand study of off-patent drugs. BPCA and PREA work well for new 
drugs and other on-patent drugs for which increased market exclusivity 
provides an appropriate incentive. However, for generic or off-patent 
drugs, BPCA and PREA have had a less effective reach. At the last BPCA 
reauthorization, Congress tasked the National Institute for Child 
Health and Human Development (NICHD) with creating a list of off-patent 
drugs needing further study in children and with conducting those 
needed studies. Although Congress never appropriated any funding to 
NICHD for this purpose, NICHD nevertheless has made significant 
progress identifying important off-patent drugs in need of study and 
starting clinical trials to study these drugs. AAP recommends that the 
role of NICHD be expanded in the current reauthorization to include 
study of the gaps in pediatric therapeutics in addition to generic or 
off-patent drugs. We also recommend PREA be strengthened so that needed 
pediatric studies can be conducted while drugs remain on patent.
    BPCA also contains a mechanism through which pediatric studies of 
on-patent drugs declined by the sponsor can be referred to the 
Foundation for the National Institutes of Health (FNIH). FNIH is given 
authority to collect donations from pharmaceutical companies to fund 
such studies. Unfortunately these donations were not forthcoming, and, 
as reported in the GAO report, no studies have been completed using 
this mechanism. The Academy recommends retaining the legal authority of 
FNIH to maintain an emphasis on children and raise money from drug 
companies for important pediatric needs, such as training pediatric 
clinical investigators, building pediatric research networks and 
studying pediatric disease mechanisms. However, the mandate to conduct 
pediatric studies of on-patent drugs should not be continued.
    Maintain quality and number of pediatric studies while addressing 
``windfalls.'' Providing drug companies 6 months of additional 
marketing exclusivity has been enormously successful in creating 
pediatric studies. The studies and label changes highlighted earlier in 
my testimony demonstrate this. Recent data shows that for the large 
majority of drugs, the return to companies for responding to a written 
request has not been excessive. The Journal of the American Medical 
Association published a study in February that showed the return to 
companies for performing pediatric studies varies widely.\5\ Most 
companies who utilize BPCA made only a modest return on their 
investment in children.\6\ However, for about 1 out of 5 companies with 
annual sales greater than $1 billion, the returns garnered through 
exclusivity have been very generous. Concerns regarding the returns to 
these ``blockbuster'' drugs have been voiced by several Members of 
Congress and a number of proposals have surfaced to limit or change the 
patent extension.
---------------------------------------------------------------------------
    \5\ Li JS, Eisenstein EL, Grabowski HG, et al. Economic Return of 
Clinical Trials Performed Under the Pediatric Exclusivity Program. 
JAMA. 2007;297:490-488.
    \6\ The median annual sales of a drug receiving pediatric 
exclusivity were $180 million with a return on investment of 1.5 times 
the cost of the study.
---------------------------------------------------------------------------
    Any proposal to amend the pediatric exclusivity provision must not 
reduce quality and number of pediatric studies. The Academy has pledged 
to review any proposal for limiting the exclusivity awarded under BPCA 
using two criteria: first, any change must not reduce the number of 
drugs studied in children. GAO found that drug sponsors agreed to 
conduct studies in response to a written request from FDA 81 percent of 
the time.\7\ Any proposal that will decrease the number of companies 
responding favorably to a written request from FDA would undermine the 
essential goal of BPCA. We now have data to show that simply cutting 
the incentive from 6 months to some lesser number across-the-board will 
certainly reduce pediatric studies and we cannot support such 
proposals.
---------------------------------------------------------------------------
    \7\ GAO 2007; 12.
---------------------------------------------------------------------------
    The second criterion is administrative simplicity. Proposals for 
using complicated formulas are likely to bog down the administration of 
the program by FDA and give rise to endless disputes between sponsors 
and the agency--including litigation. We cannot risk deterring or 
delaying important information getting into the hands of families and 
their health care providers. Every additional variable that Congress 
gives FDA to evaluate, when considering awarding the incentive, adds an 
additional level of complexity and moves FDA further from its core 
regulatory expertise.
    However, this does not mean that this issue should not be 
addressed. When this committee acts to reauthorize the exclusivity 
extension, we encourage you to make changes that are straightforward 
and as clear as possible, targeting only those ``blockbuster'' drugs 
for which an appropriate reduction in the exclusivity will not reduce 
acceptance and successful completion of written requests.
    Make PREA a permanent part of the Food and Drug Act and continue to 
reevaluate BPCA. The FDA currently has the permanent authority to 
ensure the safety of drugs used in adults. Children deserve the same. 
When PREA is reauthorized, it should be made permanent. Congress need 
not debate every few years whether we should continue to require safety 
and efficacy information on drugs used in children. It is useful, 
however, to reevaluate the exclusivity program periodically to ensure 
that the incentive offered achieves its desired goal despite changes in 
the dynamic pharmaceuticals market. Congress should have the 
opportunity every 5 years to analyze whether BPCA continues to strike 
the right balance between achieving critical pediatric information and 
providing an appropriate incentive to maintain the number and quality 
of pediatric studies for on-patent medication.

                               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 BPCA and PREA. We urge 
their renewal as part of the package of FDA bills under consideration 
by this committee for the sake of all children throughout the United 
States.
    I would be happy to answer any questions you may have.

    Senator Dodd. Thank you very much, Dr. Gorman. We're very 
grateful for your testimony. Dr. Maldonado, we appreciate your 
presence.

STATEMENT OF SAMUEL MALDONADO, M.D., MPH, FAAP, VICE PRESIDENT 
 AND HEAD OF PEDIATRIC DRUG DEVELOPMENT CENTER OF EXCELLENCE, 
 JOHNSON AND JOHNSON PHARMACEUTICAL RESEARCH AND DEVELOPMENT, 
                      RARITAN, NEW JERSEY

    Dr. Maldonado. Good afternoon, Mr. Chairman and members of 
the committee. My name is Samuel Maldonado. I am Vice President 
and Head of the Pediatric Drug Development Center at J&J and I 
appreciate the opportunity to testify today on these two 
programs.
    I believe they have made a significant contribution to 
improving the availability and safety of medicines for 
children. Johnson & Johnson as a company and I personally 
applaud the leadership of this committee and especially Senator 
Dodd, in advancing issues related to children's health, the 
area to which I have dedicated my own life and career.
    A pediatrician by training, I have spent almost a decade at 
the FDA as a Medical Officer where I participated in many 
aspects of the regulatory process for development of pediatric 
medicines, including the Chair of the Working Group that helped 
develop the FDA's views on how medicines already approved for 
adults should be properly studied in children.
    In almost two decades of work in pediatrics and drug 
development, I have seen many policies put forward with the aim 
of helping to ensure safe and effective medicines for children. 
None have had as profound and positive an impact as the Best 
Pharmaceuticals for Children Act, known as BPCA, together with 
the Pediatric Research Equity Act or PREA.
    I urge you to renew these important pieces of legislation 
and grant them the permanence they merit by removing their 
sunset clauses. Together, BPCA and PREA working in synergy, 
provide both an incentive and a requirement crucial to the 
success of a robust program. PREA gives the FDA the authority 
to require pharmaceutical companies to conduct pediatric 
studies for certain uses in clinical development.
    BPCA goes beyond PREA, encouraging manufacturers to ask, 
where are the unmet needs for children? And then pursue 
meaningful answers to that question under the guidance and 
direction of the FDA.
    Since their enactment, BPCA and PREA have been catalysts 
for unprecedented advancements in pediatric drug research. The 
transformation that has been observed in pediatric drug 
development has been astounding, as the statistics outlined in 
my written testimony attest.
    Prior to the flood of new data that BPCA and PREA have 
helped generate, pediatric pharmaceutical care was in many ways 
a guessing game. I saw this firsthand on an almost constant 
basis.
    I just want to share with you one of the examples. Early in 
my career, when I was a Fellow at the FDA, I took an interest 
in metronidazole, a highly effective antibiotic used so widely 
that it was and still is administered even to premature babies. 
After reviewing the literature, I found no clinical data 
whatsoever, even in the dose that was recommended for children. 
There was only a paper written by Dr. John D. Nelson, an expert 
so well respected that he is considered the grandfather of 
pediatric infectious diseases. So I contacted him and asked him 
how he arrived at the dose? He said, ``Son, I thought it was a 
good dose.'' This is, of course, no criticism of Dr. Nelson. He 
made his best judgments, as did we all, in the face of limited 
information. But when the health and well-being of children are 
at stake, we know that best judgments absent clinical data just 
aren't good enough. Children and all patients deserve better.
    Under BPCA and PREA, pharmaceutical companies of all sizes, 
including J&J, are pursuing pediatric studies like never before 
and the benefits have been significant.
    In recent years, pediatric information has been developed 
for a large number of medicines and formulations have been also 
developed for dose medicines. Formulations that remain 
available for children long after BPCA has expired--or the 
exclusivity has expired.
    At Johnson and Johnson, we have conducted pediatric studies 
in areas ranging from autism to cancer to infectious diseases. 
We have found that several medicines approved in adults were 
also effective in children, often at different doses but we 
have also found that some medicines used in adults do not work 
in children. These findings and continued studies have expanded 
our understanding of pediatric therapeutics and improve our 
development process for pediatric medicines.
    To sustain the progress that BPCA and PREA have made 
possible and to strengthen the framework for future pediatric 
studies and infrastructure, the sunset clauses in both pieces 
of legislation should be permanently removed. By removing the 
sunset clauses, Congress will convey the powerful message that 
pediatric drug development is here to stay and drug safety and 
effectiveness for children is firmly among the Nation's highest 
priorities. The sunset clauses' removal will also help industry 
create and sustain the necessary infrastructure to continue 
improving pediatric therapeutics. All pediatricians know that 
more pediatric studies are needed. You can help them and the 
children they serve to get what they need.
    In conclusion, the permanent renewal of BPCA and PREA is 
vital to continued progress in ensuring safe and effective 
medicines for children. No regulatory effort or legislation 
before these has come close to stimulating the kinds of 
advancements in pediatric drug safety and effectiveness that 
we've seen over the past decade.
    Thank you again, Mr. Chairman and the committee, for your 
work on behalf of children's health and for giving me the 
opportunity to speak to you today. I look forward to answering 
any questions you may have.
    [The prepared statement of Dr. Maldonado follows:]

        Prepared Statement of Samuel Maldonado, M.D., MPH, FAAP

    Good afternoon, Mr. Chairman and Members of the committee. My name 
is Dr. Samuel Maldonado, and I am Vice President and Head of the 
Pediatric Drug Development Center of Excellence at Johnson & Johnson 
Pharmaceutical Research and Development, speaking today on behalf of 
Johnson & Johnson, one of the world's largest providers of pediatric 
medicines. I am honored to come before you today as part of this 
important hearing to examine and affirm the best path forward to ensure 
safe and effective medicines for children.
    Johnson & Johnson as a company and I personally applaud this 
committee for its leadership in advancing issues related to children's 
health. Indeed, it is the area to which I have dedicated my own life 
and career: After receiving my medical degree and completing my 
residency in pediatrics, I pursued a combined post-doctoral fellowship 
in pediatric infectious diseases and regulatory medicine at Children's 
National Medical Center, George Washington University, and the Food and 
Drug Administration (FDA) before serving at the FDA as a Medical 
Officer in the Center for Drug Evaluation and Research.
    While at the FDA, I participated in several important aspects of 
the scientific and regulatory process relating to improving the 
development of pediatric medicines, including as Chair of the FDA 
Pediatric Pharmacokinetic Working Group that wrote the FDA Pediatric 
Pharmacokinetic Guidance for Industry, which set forth FDA's views on 
how medicines already approved for adults could be properly studied for 
children.
    Today, my experience in pediatrics and in drug development spans 
almost two decades. In that time, I have seen many policies put forward 
with the aim of helping to ensure safe and effective medicines for 
children. None have had as profound and positive an impact as the 
pediatric provisions of the Food and Drug Administration Modernization 
Act of 1997 (FDAMA), appropriately renewed and expanded in 2002 as the 
Best Pharmaceuticals for Children Act (BPCA). This legislation provides 
for the possibility of 6 months of marketing exclusivity for a medicine 
in exchange for the voluntary completion of pediatric drug studies. As 
a result, it has spurred a tremendous increase in pediatric drug 
studies that is enhancing our knowledge of how medicines work in 
children, in turn leading to the development of safer and more 
effective prescription medicines for children.
    As we consider the topic today of ensuring safe medicines for 
children, I urge you to give priority attention to the need to renew 
the BPCA and its complementary legislation, the Pediatric Research 
Equity Act or PREA, this year. Moreover, I urge the committee to give 
these vital pieces of legislation the permanence they merit by removing 
the sunset clauses in both that are holding back, I believe, an even 
greater realization of their potential to stimulate further progress in 
pediatric drug research.

  BPCA AND PREA: CATALYSTS FOR UNPARALLELED ADVANCEMENTS IN PEDIATRIC 
                 DRUG RESEARCH, SAFETY & EFFECTIVENESS

    The reasons for reauthorization of BPCA and PREA are clear, 
numerous, and resounding. Together, they provide both an incentive and 
a requirement crucial to the success of a robust pediatric program. 
With that synergy in play, they have helped bring to light gaps in our 
understanding of pediatric pharmaceutical care and have created a 
highly successful incentives framework to foster the collection of 
targeted data to fill those gaps.
    PREA gives the FDA the authority to require a pharmaceutical 
manufacturer to conduct pediatric studies for certain uses under 
clinical development. BPCA goes beyond PREA, encouraging manufacturers 
to ask, ``Where are the unmet needs for children?''--including off-
label uses--and then to pursue meaningful answers to that question 
under the guidance and direction of the FDA.
    It is useful to remember that these laws were passed only after 
years of efforts by the FDA to encourage more pediatric studies and 
improved labeling for medicines that FDA knew were being used in the 
care of children. In 1994, FDA issued a regulation that it hoped would 
encourage sponsors to seek approval for pediatric uses. FDA also 
improved and streamlined the types of studies that could be used to 
bridge between adult and pediatric doses of medicines. That these 
efforts were not successful underscores the exceptional success of BPCA 
and PREA.
    I have personally observed a night-and-day difference between 
pediatric drug development prior to the passage of BPCA and since. The 
transformation in this field has been nothing short of astounding, as 
the numbers alone attest: Since the pediatric study incentive program's 
original passage in 1997, there have been 492 pediatric proposals 
submitted to FDA. As of September of last year, the FDA had requested 
782 pediatric studies. To date, the Agency has granted pediatric 
exclusivity for 132 approved products. More than 45,000 pediatric 
patients have participated in the studies over the last 10 years. 
Pharmaceutical companies of all sizes are pursuing pediatric studies 
like never before, for products at all levels of the sales volume 
spectrum.
    The Center for the Study of Drug Development at Tufts University 
reported this month that the cumulative number of completed pediatric 
studies, subsequently accepted by the FDA, rose from 58 in 2000, when 
BPCA was first renewed, to 568 in 2006. In that same time period, the 
number of full safety and effectiveness pediatric drug studies 
conducted rose by a full 60 percent. This includes research into 
therapies for rare childhood diseases, including a significant number 
of pediatric cancer indications and treatments for serious illnesses 
such as pediatric AIDS, Crohn's Disease, bronchopulmonary dysplasia, 
and many others.
    My personal experience as a pediatrician prior to BPCA and PREA--
and the experiences of countless others in my field--substantiate the 
night-to-day transformation that has occurred with these important 
pieces of legislation. Prior to the flood of new data that BPCA and 
PREA have helped to generate, pediatric pharmaceutical care was in many 
ways a guessing game.
    One experience from my early career aptly illustrates this 
predicament for pediatricians prior to the increase in pediatric 
clinical data: When I was carrying out my fellowship at the FDA, I took 
a keen interest in metronidazole, a widely used antibiotic in both 
adult and pediatric care administered even to premature babies but for 
which there appeared no clinical data to support the standard pediatric 
daily dosage of 30 milligrams for kilogram of body weight (mg/kg/day). 
After extensive review of the literature, I found only one reference to 
the 30 mg/kg/day dose for metronidazole, cited in a paper by Dr. John 
D. Nelson, the ``grandfather of pediatric infectious diseases.'' A 
venerated expert, I contacted him to ask him how he arrived at the dose 
he recommended. He responded by saying, ``Son, I just thought it was a 
good dose.''
    This is, of course, no criticism of Dr. Nelson. He made his best 
judgments--as did we all--in the face of very limited information. But 
when the health and well-being of children are at stake, we know that 
best judgments absent clinical data just aren't good enough. Children--
and all patients--deserve better.
    At Johnson & Johnson, we have conducted pediatric studies in areas 
ranging from autism to cancer to infectious diseases. We have found 
that several medicines approved in adults were also effective in 
children, but often at different dose levels. Perhaps more importantly, 
we have found that some medicines used in adults do not, in fact, work 
in treating pediatric diseases. These findings and continued studies 
have steadily expanded our understanding of pediatric therapeutics, 
making possible important improvements to our development process for 
pediatric medicines.
    How have all of these studies improved pediatric care in practice? 
To start, thanks to BPCA and PREA, we now have a wealth of new, more 
targeted, and complete information to help pediatricians and parents 
make the best possible treatment decisions for children in their care. 
This new information has helped us better understand the most 
appropriate drug dosing and access for pediatric patients, making 
treatment regimens safer and more effective.
    According to a new study in the Journal of the American Medical 
Association (JAMA), prior to BPCA, about 70 percent of medicines used 
in children had been dispensed without adequate pediatric dosing 
information. In the 10 years since this legislation, close to 120 drug 
labels--or approximately 90 percent of the labels for products studied 
under BPCA and PREA--have been modified to reflect new pediatric-
specific data. And as BPCA and PREA have made pediatric data collection 
and information dissemination common practice in the pharmaceutical 
industry, the time needed to make label changes to reflect this 
pediatric-specific data has fallen by 34 percent. This improved 
labeling includes, where necessary, information on products shown to be 
less effective or ineffective in pediatric patients. Switching 
pediatric patients off of less effective or ineffective medicines 
reduces unwarranted exposures, improving safety.
    In addition, pediatric studies conducted since BPCA and PREA have 
resulted in the development of pediatric-specific formulations for a 
large number of medicines--formulations that have remained available 
long after pediatric exclusivity has expired.
    Not surprisingly, the American Academy of Pediatrics (AAP) has 
hailed BPCA and PREA as ``extraordinarily successful in generating 
important new information about the safety and efficacy of drugs used 
by children.'' Of course, even with all of this success, there is still 
much to learn in this area, hence the AAP's pronouncement that ``we 
must not lose momentum in the quest for safer medications for 
children.''
    Johnson & Johnson echoes this sentiment. The area of pediatric drug 
development, as I've witnessed it, has burgeoned only in the last 10 
years. There remains great need and potential for further discovery. To 
sustain the level of momentum that BPCA and PREA have spurred, and to 
strengthen the framework for further pediatric drug studies and 
infrastructure, we strongly believe that the sunset clauses in both 
pieces of legislation should be removed swiftly and permanently.
removing the sunset clauses in bpca and prea: sound policy for ensuring 

            FURTHER ADVANCEMENTS IN PEDIATRIC DRUG RESEARCH

    Five-year sunset clauses were included as part of the original 
FDAMA pediatric provisions, BPCA, and PREA bills because it was unclear 
at the time whether these measures would actually be able to achieve 
their intended goals of encouraging pediatric drug development. But 
after 10 years and two re-evaluations, it is abundantly clear that BPCA 
and PREA have not only achieved their intended goals, they have 
exceeded them, and millions of sick children and their families have 
already benefited as a result.
    By removing the sunset clauses, Congress will remove the 
uncertainties created every 5 years and encourage the creation of a 
more sustainable infrastructure for pediatric drug development. Even 
despite all of the successes of BPCA and PREA in stimulating 
participation in pediatric drug development across companies of all 
sizes, the sunset clauses in them remain major hindrances, discouraging 
companies from formally organizing pediatric infrastructures.
    By ``infrastructure,'' I mean much more than merely brick, mortar, 
and layers of management. The building of sustainable pediatric drug 
development infrastructures from company to company and across the 
board means training people to be better researchers in pediatrics, 
developing new and better tools for measuring outcomes in pediatric 
clinical trials, and fine-tuning mechanisms of study to more fully and 
precisely account for the inherent heterogeneity of pediatric patients. 
Suffice it to say that this requires significant and sustained 
investment.
    In the absence of a consistent and predictable exclusivity 
provision, there will remain a considerable and understandable 
reluctance among companies with countless competing research priorities 
to devote dedicated resources to formal pediatric divisions. This is 
especially true as the cost, size, number, and complexity of pediatric 
studies has increased and the absolute value of the pediatric 
exclusivity has decreased.
    By removing the sunset clauses, Congress will convey a powerful 
message: Pediatric drug development is here to stay, and drug safety 
and effectivenesss for children is firmly among the Nation's highest 
priorities. The sunset clauses' removal will also help the advocates of 
pediatric drug development in industry to encourage their respective 
institutions to create and sustain the necessary infrastructure to 
continue improving pediatric therapeutics. Furthermore, it will provide 
a platform from which those companies that have made investments in 
pediatric drug development infrastructures can confidently increase 
those investments, including expansion into new research areas.
    Every pediatrician knows that more pediatric studies are needed. 
You can help them get what they need.

                               CONCLUSION

    In conclusion, there is no question that renewal of Best 
Pharmaceuticals for Children Act and the Pediatric Research Equity 
Act--absent their sunset clauses--is vital to continued progress in the 
area of ensuring safe and effective medicines for children. No 
regulatory effort or legislation before these has come close to 
stimulating the kinds of advancements in pediatric drug safety and 
effectiveness that we've seen over the past decade.
    I am confident that with the continuation of BPCA and PREA, we will 
see similarly sweeping advancements in this area for decades to come.
    Thank you again, Mr. Chairman and the committee, for your tireless 
work on behalf of children's health and for giving me the opportunity 
to speak to you today. I look forward to answering any questions you 
may have.

    Senator Dodd. Thank you, Doctor, very much.
    Dr. Campbell.

 STATEMENT OF ROBERT CAMPBELL, M.D., PROFESSOR, DEPARTMENT OF 
ORTHOPAEDICS, UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN 
                  ANTONIO, SAN ANTONIO, TEXAS

    Dr. Campbell. Mr. Chairman and members of the committee, 
thank you for this opportunity to testify today regarding safe 
medicine and medical devices for children. I am Dr. Robert 
Campbell, a pediatric orthopedic surgeon, an inventor and the 
father of five children. I am a Professor of Orthopaedics at 
the University of Texas Health Science Center at San Antonio.
    Throughout my career, I have cared for children in need of 
medical technology that was not readily available to them but 
the primary reason I was invited to appear before you today is 
that I both invented, developed and brought to market, a life 
saving pediatric surgical device known as the Vertical 
Expandable Prosthetic Titanium Rib, also known as VEPTR. This 
was approved as a Humanitarian Device Exemption device in 2004, 
after 14 years of FDA trials.
    I am here to help provide you with some insight from 
someone who has been in the trenches and about how this pending 
legislation can help the children who need devices.
    Children deserve access to devices that are safe, effective 
and made just for them but they are frequently denied access 
because there is a relatively small market for pediatric 
devices but little incentive for manufacturers to make them. We 
physicians must commonly jury-rig existing devices for 
children.
    The VEPTR was invented to replace such a jury-rigged device 
that had been used to save the life of a 6-month-old full-time 
ventilator-dependent infant born with scoliosis and missing 
ribs. I made many mistakes in developing VEPTR. I had no 
experience in device development or knowledge of FDA 
requirements. I had no mentor. But learning through trial and 
error over the years, supported by grants from the National 
Organization of Rare Disorders and Orphan Products Division of 
the FDA and luckily, identifying child advocate manufacturers, 
we succeeded after 16 long years. Many hundreds of pediatric 
devices, however, have never been developed and probably won't 
be under current conditions but children deserve better.
    I am here today to express my strong support of this bill 
and express my sincere gratitude to Senator Dodd and Senator 
Clinton for their commitment to achieving safe and effective 
medical devices for all children.
    The following provisions address many of the obstacles we 
faced when developing the VEPTR device for children. This bill 
creates a contact point at the NIH and requires the FDA, NIH 
and the Agency for Health Quality and Research to work together 
on identifying important gaps of knowledge and improve 
pediatric medical device development.
    An important component of this is the ability to survey the 
pediatric medical providers' rank and file in order to learn 
the actual unmet pediatric device needs. The bill also 
establishes 6-year demonstration grants to support nonprofit 
consortia to provide critically needed support in helping 
innovators with pediatric device ideas to navigate the system 
successfully and bring new pediatric devices to market. The 
consortium will mentor inventors and connect them to 
manufacturers and available Federal resources. It will also 
coordinate with the NIH contact point for pediatric device 
development and the FDA for facilitation of pediatric device 
approval.
    The profit restriction on Humanitarian Device Exemption of 
approved devices has limited the effectiveness of the provision 
by forcing device manufacturers to only recover their research 
and development costs. By eliminating the profit prohibition 
for children, the bill increases the incentive for companies to 
manufacture pediatric devices, especially the small 
manufacturers who are likely to embrace an affordable pediatric 
device development pathway with definable, affordable 
regulatory requirements.
    The bill will also result in improvements in the way the 
FDA tracks the number and type of devices approved for use in 
children and will strengthen postmarket safety.
    I would like to thank the committee for allowing me the 
opportunity to share my support of the Pediatric Medical Device 
Safety and Improvement Act that will help future innovators to 
avoid my mistakes and my frustrations so that they can get 
their devices off the napkin and into the device shelf in a 
safe and timely fashion for the pediatric patients who need 
them.
    I urge the members of the committee to support this 
legislation. I thank you for asking me to be here and I will be 
glad to address any questions you may have.
    [The prepared statement of Dr. Campbell follows:]

          Prepared Statement of Robert M. Campbell, Jr., M.D.

    Chairman Kennedy, Senator Enzi, and members of the committee, thank 
you for this opportunity to testify today regarding safe medicine and 
medical devices for children.
    I am Dr. Robert Campbell, a pediatric orthopaedic surgeon, an 
inventor, and the father of five children. I am a Professor of 
Orthopaedics at the University of Texas Health Science Center at San 
Antonio and hold the President's Council/Dielmann Chair in Pediatric 
Orthopaedic Surgery. I work primarily at Christus Santa Rosa Children's 
Hospital in San Antonio. I am a specialty surgical fellow of the 
American Academy of Pediatrics and serve on the Medical Advisory 
Committee of the National Organization of Rare Disorders. Throughout my 
career, I have cared for children in need of medical technology that 
was not readily available to them and my work has made me keenly aware 
of the need for better medical devices for children.
    The primary reason I was invited to appear before you today is that 
I invented, developed, and brought to market a life saving pediatric 
surgical device known as the Vertical Expandable Prosthetic Titanium 
Rib (VEPTR), which was approved as a Humanitarian Device Exemption 
(HDE) device in 2004 after 14 years of FDA trials (see attached). I am 
here to help provide you with some insight about the problems of 
pediatric device development from someone who has ``been in the 
trenches'' and about how this pending legislation can help the children 
who need devices.

   THE NEED FOR SAFE AND EFFECTIVE MEDICAL AND SURGICAL DEVICES FOR 
                                CHILDREN

    Mr. Chairman, as a pediatric orthopaedic surgeon, I am very pleased 
to hear my colleague, Dr. Gorman, describe the gains made in the field 
of pediatric pharmacology as a direct result of actions taken by 
Congress. I support his view that the Best Pharmaceuticals for Children 
Act and Pediatric Research Equity Act are critical laws to children and 
must be reauthorized. But just as the need existed in 1997 when this 
committee and Congress acted to help children by increasing the study 
of drugs, Congress now has the opportunity to take the same kind of 
action with an equally important need: children's medical and surgical 
devices.
    As a surgeon who has treated the orthopaedic diseases of children 
for over 20 years, I have been frustrated many times that the ``shelves 
are bare'' when I need a modern device for their care. A surgeon from 
the 1950s would recognize many of the pediatric instruments and devices 
in my operating room because there has been little progress. We 
pediatric sub-specialists are an endangered species, with less 
physicians each year choosing to join our ranks for complex reasons, 
especially in orthopaedics,\1\ \2\ and one reason for this may be that 
we don't have the up-to-date technology to care for children that is 
available to our adult counterparts.
---------------------------------------------------------------------------
    \1\Huurman W. Report of the Pediatric Orthopaedic Work Force 
Committee of the Pediatric Orthopaedic Society of North America. 2003.
    \2\ Bell MJ, Catterall A, Clarke NMP, Hunt DM. ``Children's 
Orthopaedics and Fracture Care.'' Special Report. British Orthopaedic 
Association. July 2006.
---------------------------------------------------------------------------
    Children need medical devices that meet their unique needs. Devices 
for children should take into account their smaller size, accommodating 
their growing bodies and active lifestyles.
    Children deserve access to devices that are safe, effective, and 
made just for them. Yet today many devices are not made with these 
considerations in mind, and some necessary devices are not made at all. 
Because pediatric disease is generally rare, there is a relatively 
small market for pediatric devices and there appears to be little 
incentive for device manufacturers to make them. Device manufacturers 
have different marketplace challenges than pharmaceutical companies. 
New medical and surgical devices quickly become obsolete, so large 
markets are needed to justify their development and regulatory costs. 
As a result, children are frequently denied access to the latest 
technology in life-changing or life-saving devices. Other times, 
physicians must ``jury-rig'' existing devices to accommodate their 
young patients.
    But when children need a medical device that is unavailable, the 
consequences can be tragic. Twenty years ago, I became involved with a 
child that needed a pediatric device to survive that did not exist. 
Instead of accepting the inevitable, we decided to do whatever was 
necessary to provide him with a chance for life. None of us at the time 
had the slightest idea about how to develop a medical device, but since 
it was critically needed, we had to try it. None of us realized the 
ultimate cost of that decision, and how it would take 16 years from 
drawing the first blueprint to having an approved pediatric implant 
available on the ``device shelf '' for other surgeons to use. I wish to 
share what we learned through that experience.

                         THE TITANIUM RIB SAGA

    The Vertical Expandable Prosthetic Titanium Rib (VEPTR) device, 
also known as the titanium rib, was invented to save the life of a 6-
month-old full-time ventilator-dependent infant born with scoliosis and 
missing ribs.
    In 1987, Dr. Melvin Smith, a pediatric general surgeon, was 
consulted by the family about tracheostomy care of this child. Although 
he was expected to die soon, Dr. Smith felt it might be possible to 
salvage the situation somehow and he asked me to get involved in a last 
ditch effort to save his life. There was no known commercially 
available chest wall prosthesis for this age group, and there was no 
way to stabilize his scoliosis without stopping growth of the spine. We 
managed to come up with a possible solution and, with nothing to lose, 
the family gave us permission to operate on the child as soon as 
possible. At surgery we ``jury-rigged'' an artificial chest wall of 
orthopaedic fracture pins, wired vertically to support the lungs and 
control the scoliosis. It was a difficult surgery, but to our 
amazement, it worked, and days later the infant was weaned off his 
ventilator for the first time and went on to be weaned off oxygen. We 
were very happy about the initial outcome.
    But since our patient survived and was growing, we were now faced 
with new problems. The crude ``jury-rigged'' chest wall device would 
not grow with the patient, and the lung underneath would try to grow, 
but would eventually be compressed with adverse effect on its growth. 
The non-growing fracture pins would also tend to tether the growing 
spine and worsen the scoliosis. We could change out the crude device 
frequently in major surgery, but sooner or later we would have a 
catastrophic complication.
    A new device had to be invented for this child and it needed to be 
safe to implant, just as effective as the ``jury-rigged'' device, but 
expandable in a simple fashion with minor surgery to avoid major 
complications. And it was needed quickly. I promised Dr. Smith that I 
could develop such a device with my engineering background, and assumed 
it would be an easy matter to get an orthopaedic manufacturer to make 
it. The confidence of the naive is boundless.
    The engineering blueprints of the first VEPTR device were drawn up 
10 months later. It was a simple metal device with only two moving 
parts that could perform the same function as the fracture pin device, 
but was safer to implant and easy to expand as the child grew. I 
thought the job was mostly done at that point, but little did I realize 
that I had just made the first small step in a very long journey. I 
contacted multiple orthopaedic companies to make the device. They were 
sympathetic, but did not have the resources to make a pediatric device 
for one patient with a rare birth defect. I was getting discouraged as 
the months went by and the patient grew worse.
    Finally, an orthopaedic custom device company, Techmedica 
Corporation of Camarillo, California, was recommended to me and they 
seemed receptive to making the device. Although they knew that making a 
completely new pediatric device would cause a substantial financial 
loss for them, with little hope of enough subsequent patients to 
recover development costs, they proved to be advocates for children and 
did accept the challenge. All they asked for in return was that, if the 
surgery proved to be successful, we would publicize their role in the 
surgery. We began an emergency effort to quickly produce a working 
device.
    Six months later the first VEPTR device was manufactured and we 
successfully replaced our ``jury-rigged'' device with it in April 1989. 
When news of the new surgical device for rare birth defects of the 
spine and chest wall came out, we were inundated with desperate 
families trying to find treatment for their children. We were able to 
develop five new surgeries to help these children using the VEPTR 
device as its basis, but there was too much patient volume to continue 
treatment under the custom device provisions, so the FDA was approached 
for guidance. I was asked to provide a personal briefing for the FDA 
chief of devices. He was quite supportive of our efforts to develop a 
new implant for these lethal birth defects, and authorized a sole site 
FDA feasibility study which was began in 1991 with Techmedica 
Corporation as the sponsor.
    Things went well for the next few years with encouraging clinical 
results. To their credit, members of the FDA permitted several minor 
modifications of the device by Techmedica Corporation during this time 
to enhance pediatric patient safety. This was cited by the 2005 
Institute of Medicine Report ``Safe Medical Devices for Children'' as a 
favorable example of pediatric device development.
    During this period we received critical seed grant funding from the 
National Organization of Rare Disorders to support our research. Based 
on the preliminary clinical trial results made possible by the NORD 
support, we were able to secure further substantial grant support from 
the FDA Office of Orphan Product Development that enabled us to 
complete our sole site FDA study and initiate a multi-center FDA VEPTR 
trial.
    A few years into the feasibility trial we were devastated to learn 
that Techmedica Corporation was to be closed by their large corporate 
parent. New patients needed VEPTR devices, and treated patients needed 
new larger devices because of growth, but we now had no way to provide 
them. We needed a new guardian angel to make the VEPTR, but had no idea 
where to find one. Incredibly, the angel found us.
    Soon after the Techmedica Corporation closure, I was approached 
during an orthopaedic trauma course by a device product manager with 
the Synthes Spine Company, Mr. Paul Gordon, who was interested in 
knowing more about the VEPTR device. We soon learned he was a champion 
for pediatric patients. He convinced us that his company had the 
resources and the commitment to children to successfully take over the 
development of the VEPTR device. Through his efforts, I next met with 
upper management of the company and, eventually, the private owner of 
this major spine company, Mr. Hansjorg Wyss.
    Mr. Wyss proved to also be an advocate for children and, although 
the device had little chance of producing a profit, he gave his full 
support in 1994 for the engineering refinement of the VEPTR device and 
for involvement of the Synthes in-house regulatory division in the 
design of a FDA VEPTR multi-center trial. A large investment was made 
to upgrade the VEPTR device to a more standardized design that was 
easier to implant, and the multi-center Synthes VEPTR trial began in 
1996.
    The first new hospitals to join the VEPTR FDA multi-center trial 
were Children's Hospital of Pittsburgh and then Boston Children's 
Hospital. Another five children's hospitals eventually joined the 
study. These hospitals provided additional experience with VEPTR 
treatment to confirm the San Antonio results of safety and 
effectiveness, and by 2001 there appeared to be adequate experience to 
consider an FDA application for approval, but in 2002 FDA brought up a 
concern that there were no controls for the VEPTR study. Subsequently a 
Humanitarian Device Exemption (HDE) application was filed by Synthes in 
2003 with approval by the FDA on August 24, 2004, concluding the 14-
year FDA study of the VEPTR device.

             THE LESSONS LEARNED FROM THE VEPTR EXPERIENCE

    I made many mistakes in developing this device over those 14 years. 
I had no mentor. I had no experience in developing a device from an 
engineering viewpoint. I had no knowledge of the FDA requirements for 
device development. It was basically a trial and error experience for 
many years.
    I did not know which manufacturer was the best choice for VEPTR. 
Small companies can be responsive to small pediatric projects, but do 
not have large budgets for device development or the regulatory 
resources to secure FDA approval. Large publicly owned companies have 
those resources, but can't justify non-profit pediatric device projects 
to their stockholders. We were extremely lucky that we found companies 
who could be responsive to the needs of children in spite of the many 
obstacles. Many individuals at the FDA clearly were advocates for 
development of children's devices, but a clear and transparent 
regulatory pathway for VEPTR approval did not exist. I had limited 
knowledge about what financial resources were available for support of 
the VEPTR study. The grants of the National Organization of Rare 
Disorders and the Orphan Products Division of the FDA were crucial 
support for the success of the VEPTR trial, but additional resources 
would have been helpful for a study that eventually took 14 years to 
complete. There were numerous additional problems during the VEPTR 
trial that could have been better addressed if we had access to 
resources and mentorship, but they did not exist at the time.
    The VEPTR pediatric device is now available for children only 
through hard work by many individuals across the United States, 
commitment of device manufacturers without regard for their economic 
well-being, and luck. Many hundreds of other pediatric devices have 
never been developed and probably won't be under current conditions. 
With what I have learned from the VEPTR experience, I have gone on to 
personally help mentor a handful of physicians trying to develop 
devices for children, but really a broad, expert, well-organized 
national system is needed for this. Children deserve better. 
Legislative and regulatory changes are absolutely necessary so that 
others do not have to have the same struggle as we did.
    My chance to contribute to a new approach to pediatric device 
development began in June 2004, when I came to Washington, DC. from San 
Antonio to participate in a series of meetings hosted by the American 
Academy of Pediatrics, Elizabeth Glaser Pediatric AIDS Foundation, 
National Organization for Rare Disorders (NORD), the National 
Association of Children's Hospitals, and the Advanced Medical 
Technology Association (AdvaMed). The ``stakeholder'' meetings resulted 
in a series of recommendations for improving the availability of 
pediatric devices. Those meetings were a key turning point in that they 
were the first broad-based dialogue that engaged stakeholders in all 
aspects of pediatric devices from health care providers, manufacturers, 
and Federal Government regulators.
    Subsequently, the Institute of Medicine produced a strong report in 
2005 entitled, ``Safe Medical Devices for Children.'' The IOM found 
flaws in safety monitoring and recommended expanding the FDA's ability 
to require post-market studies of certain products and improving public 
access to information about post-market pediatric studies. IOM 
reported:

        [T]he committee must conclude that FDA has lacked effective 
        procedures to monitor the fulfillment of postmarket study 
        commitments. The agency has lacked a basic, searchable listing 
        of devices for which further studies were specified as a 
        condition of their approval for marketing. Furthermore, it has 
        not maintained any system for systematically monitoring the 
        status of these study commitments based on periodic reports or 
        updates from either its own staff or sponsors.\3\
---------------------------------------------------------------------------
    \3\ Field MJ and Tilson H., eds. Safe Medical Devices for Children, 
Committee on Postmarket Surveillance of Pediatric Medical Devices, 
Board on Health Sciences Policy; Institute of Medicine of the National 
Academies, 2005, p. 195.
---------------------------------------------------------------------------
          FDA can ask for clinical studies prior to clearing devices, 
        although clinical data are submitted for only a small 
        percentage of devices that go through clearance. FDA cannot, 
        however, order postmarket studies as a condition for clearance. 
        It can (but rarely does) order studies subsequent to clearance 
        through its Section 522 authority. Studies that are ordered 
        subsequent to the approval or clearance of a device are limited 
        to 3 years (which often means a shorter period of evaluation 
        for most individual study subjects). This may be too short a 
        period for certain safety problems or developmental effects to 
        be revealed.\4\
---------------------------------------------------------------------------
    \4\ IOM, p. 226.

    In July of 2005, the American Academy of Pediatrics established the 
Task Force on Pediatric Medical Devices to work with Congress to 
advance legislation to meet medical and surgical device needs of 
children. I am pleased to be a member of the Task Force.
    The recommendations produced by the stakeholder meetings in 2004 
and the IOM report on device safety in 2005 point to the need for 
Congress to pass legislation that both stimulates device development 
and manufacture as well as increases the safety monitoring of pediatric 
medical devices, particularly after they are on the market. The 
Pediatric Medical Device Safety and Improvement Act 2007, S. 830, 
strikes the right balance and puts forward a comprehensive package that 
serves a critical step forward for children.

   SUPPORT FOR THE S. 830, THE PEDIATRIC MEDICAL DEVICES SAFETY AND 
                            IMPROVEMENT ACT

    I am here today to express my strong support of S. 830 and to 
express my sincere gratitude to Senator Dodd for his commitment to 
achieving safe and effective medical devices for all children. This 
legislation is the result of huge effort put forward by present and 
former members of this committee, patient and provider groups, and 
device manufacturers. This bill will help children get the safe medical 
and surgical devices they need by strengthening safety requirements and 
encouraging research, development, and manufacture of pediatric 
devices. The following provisions address many of the obstacles we 
faced when developing the VEPTR device for children.
Defining the Need for Pediatric Devices
    The bill streamlines Federal agency processes by creating a 
``contact point'' at the National Institutes of Health (NIH) and 
requires FDA, NIH, and the Agency for Health Quality and Research to 
work together on identifying important gaps in knowledge and improve 
pediatric medical device development. An important component of this is 
the ability to survey the pediatric medical providers' ``rank and 
file'' in order to learn the actual unmet pediatric device needs.
Facilitating Pediatric Device Development and Manufacture Through 
        Mentorship
    The bill also establishes 6-year demonstration grant(s) to support 
nonprofit consortia to provide critically needed support in helping the 
innovators with pediatric device ideas to navigate ``the system'' 
successfully and bring new pediatric devices to market. The consortium 
will match inventors with appropriate manufacturing partners, provide 
mentoring for pediatric device projects with assistance ranging from 
prototype design to marketing, and connect innovators with available 
Federal resources. The consortia will also coordinate with the NIH 
``contact point'' for pediatric device development and the FDA for 
facilitation of pediatric device approval.
Improving the Humanitarian Device Exemption (HDE)
    The Humanitarian Device Exemption (HDE) was meant to be a tool for 
approving devices intended for small populations (less than 4,000 
patients), which often included children and those with rare 
conditions, but the profit restriction on HDE-approved devices limits 
the effectiveness of the provision by forcing device manufacturers to 
only recover their research and development costs. By eliminating the 
profit prohibition for children, the bill increases the incentive for 
companies to manufacture pediatric devices, especially the small 
manufacturers who are likely to embrace an affordable pediatric device 
development pathway with definable, affordable regulatory requirements.
Tracking Pediatric Device Approvals and Streamlining Device Development
    S. 830 makes needed improvements in the way FDA tracks the number 
and type of devices approved for use in children or for conditions that 
occur in children. At present, FDA cannot satisfactorily produce data 
on the number and type of devices marketed for pediatric uses. The bill 
requires FDA to track new devices granted pre-market approval or 
approved under the humanitarian devices exemption and report on the 
number of pediatric devices approved in each category.

                    STRENGTHENING POSTMARKET SAFETY

    As recommended by the IOM, this bill grants the FDA increased 
authority to ensure that approved medical devices are safe for 
children. Under this law, the FDA would be able to require postmarket 
studies as a condition of approval or clearance for certain devices 
under section 522, if used significantly in children. This legislation 
also allows the FDA to require a study of longer than 3 years if 
necessary to ensure that the study is long enough to capture the effect 
of a child's growth on the safety and efficacy of a medical device. A 
database of such studies would be made available to the public. New 
postmarket authority can address the current limited amount of 
available data on devices for children and to create a mechanism for 
ensuring that needed pediatric studies are conducted for a sufficient 
length of time. The legislation is crafted so that there is no delay in 
approval or clearance for a device.

                               CONCLUSION

    I would like to thank the committee for allowing me the opportunity 
to share my support of the Pediatric Medical Device Safety and 
Improvement Act, S. 830. This bill represents a historic step forward 
for children's medical and surgical devices similar to those steps 
taken on drugs. It will help future medical inventors of pediatric 
devices to avoid my mistakes and my frustrations so that they can get 
their devices ``off the napkin'' and into the pediatric patients who 
need them, in a safe and timely fashion.
    I urge the members of the committee to support this legislation. I 
would be happy to take any questions you may have.





                          Summary of Testimony

    Chairman Kennedy, Senator Enzi, and members of the committee, thank 
you for this opportunity to testify today regarding safe medicine and 
medical devices for children.
    I am Dr. Robert Campbell, a pediatric orthopaedic surgeon, an 
inventor, and the father of five children. I am a Professor of 
Orthopaedics at the University of Texas Health Science Center at San 
Antonio. Throughout my career, I have cared for children in need of 
medical technology that was not readily available to them, but the 
primary reason I was invited to appear before you today is that I both 
invented, developed, and brought to market a life-saving pediatric 
surgical device known as the Vertical Expandable Prosthetic Titanium 
Rib (VEPTR), which was approved as a Humanitarian Device Exemption 
(HDE) device in 2004 after 14 years of FDA trials. I am here to help 
provide you with some insight from someone who has ``been in the 
trenches'' about how this pending legislation can help the children who 
need devices.
    Children deserve access to devices that are safe, effective, and 
made just for them, but they are frequently denied access to them 
because there is a relatively small market for pediatric devices with 
little incentive for manufacturers to make them. Physicians must 
commonly ``jury-rig'' existing devices for children. The VEPTR was 
invented to replace a ``jury-rigged'' device used to save the life of a 
6-month-old full-time ventilator-dependent infant born with scoliosis 
and missing ribs.
    I made many mistakes in developing VEPTR. I had no experience in 
device development or knowledge of FDA requirements. I had no mentor. 
But, learning through trial and error, supported by grants from the 
National Organization of Rare Disorders and the Orphan Products 
Division of the FDA, and luckily identifying child advocate 
manufacturers, we succeeded after 16 long years. Hundreds of other 
pediatric devices, however, have never been developed and probably 
won't be under current conditions. Children deserve better.
    I am here today to express my strong support of S. 830 and to 
express my sincere gratitude to Senator Dodd for his commitment to 
achieving safe and effective medical devices for all children. The 
following provisions address many of the obstacles we faced when 
developing the VEPTR device for children.
    The bill creates a ``contact point'' at the National Institutes of 
Health (NIH) and requires FDA, NIH and the Agency for Health Quality 
and Research to work together on identifying important gaps in 
knowledge and improve pediatric medical device development. An 
important component of this is the ability to survey the pediatric 
medical providers' ``rank and file'' in order to learn the actual unmet 
pediatric device needs.
    The bill also establishes 6-year demonstration grant(s) to support 
nonprofit consortia to provide critically needed support in helping the 
innovators with pediatric device ideas to navigate ``the system'' 
successfully and bring new pediatric devices to market. The consortium 
will mentor inventors and connect them to manufacturers and available 
Federal resources. It will also coordinate with the NIH ``contact 
point'' for pediatric device development and the FDA for facilitation 
of pediatric device approval.
    The profit restriction on Humanitarian Device Exemption (HDE)-
approved devices has limited the effectiveness of the provision by 
forcing device manufacturers to only recover their research and 
development costs. By eliminating the profit prohibition for children, 
the bill increases the incentive for companies to manufacture pediatric 
devices, especially the small manufacturers who are likely to embrace 
an affordable pediatric device development pathway with definable, 
affordable regulatory requirements.
    The bill also will result in improvements in the way FDA tracks the 
number and type of devices approved for use in children and will 
strengthen post-market safety.
    I would like to thank the committee for allowing me the opportunity 
to share my support of the Pediatric Medical Device Safety and 
Improvement Act, S. 830. It will help future innovators avoid my 
mistakes and my frustrations so that they can get their devices ``off 
the napkin'' and onto the shelf in a safe and timely fashion for the 
pediatric patients who need them. I urge the members of the committee 
to support this legislation.

    Senator Dodd. Thank you, Doctor, very, very much and Mr. 
Rozynski, we thank you for being here as well.

  STATEMENT OF ED ROZYNSKI, VICE PRESIDENT, GLOBAL GOVERNMENT 
         AFFAIRS, STRYKER CORPORATION, WASHINGTON, DC.

    Mr. Rozynski. Thank you, Chairman Dodd, Senator Alexander 
and members of the committee. Again, my name is Ed Rozynski 
from Stryker Corporation. I am the father of three growing 
boys, one who reluctantly cut class today to be here to listen 
to the testimony.
    [Laughter.]
    Senator Dodd. There will be a quiz at the end of this 
hearing.
    Mr. Rozynski. Senator Dodd, we sincerely appreciate your 
leadership role on children's 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 world's leading medical technology 
companies. We are the leader in orthopedics and in the other 
medical specialties. We have facilities around the country, in 
Massachusetts, New Hampshire, Tennessee, New Jersey, 
California, Michigan and Texas.
    Stryker's products are used in over 80 percent of the hip 
and knee replacements performed in the United States each year. 
We are also involved in bone regeneration technology and it is 
now being used on soldiers at Walter Reed.
    Stryker's commitment to children is not new. We are the 
leading manufacturer of orthopedic oncology prostheses in the 
United States and also craniofacial deformities, such as cleft 
lip and palate. We take very seriously our responsibility to 
ensure that our devices are safe and effective for use in 
pediatric patients. Soft tissue 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 any primary 
malignant bone or soft tissue sarcomas was amputation of the 
affected arm or leg. Since that time, Stryker has partnered 
with leading orthopedic oncology surgeons to develop limb-
sparing, surgical solutions, including growing prosthesis that 
can be elongated to account for a child's growth.
    As with cancer, the treatment of craniofacial deformities 
is an area in which Stryker also has medical products and 
solutions. We sponsor and partner with organizations, including 
Operation Smile, a nonprofit organization dedicated to 
repairing childhood facial deformities around the world. Last 
year, Operation Smile was able to provide free cleft lip 
surgeries to more than 8,000 children in 23 countries. These 
surgeries only took about 45 minutes and costing $240 per child 
and they have a positive, lasting impact on the lives of the 
children and their families.
    It is our sincere hope that this pediatric device 
legislation will spur the evolution of novel health care 
solutions for children.
    Given Dr. Campbell's fine testimony, I won't go through the 
provisions of the bill except to say, we support the money that 
is going to be put aside for grant programs, including the 
match making between inventors and manufacturers. We support 
the incentives that could help to develop more pediatric 
products. We support the pooling of information for the 
pediatric database so solutions can easily be shared among us 
and analyzed so we can come up with better products.
    In conclusion, Senator Dodd, we applaud you for introducing 
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 and coolest 
electronic gadgets. Each one of us would walk though a wall for 
our children. Therefore, we should not allow children's health 
care products to become the residual of products that we 
develop for the big people that they look up to. Children 
deserve our very best efforts. Children deserve special 
attention.
    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 sick child for regulator diagnosis and 
treatment in a far-away hospital. Stryker has decided that we 
will find a way to help provide charitable assistance to 
families and patients who are undergoing treatment for 
pediatric bone cancers at selected NIH Centers. We'd like to 
cover their expenses associated with such travel to these 
hospitals, expenses not covered by health insurance. These 
uncovered expenses often pose a serious impediment to a 
family's ability to provide for a child's care and recovery.
    We believe that our planned, voluntary charitable 
initiative will complement the advanced medical technologies 
for children that Stryker already develops and that all 
companies will be further encouraged to develop as a result of 
your legislation.
    Again, Mr. Chairman, I would be pleased to answer your 
questions or any that the committee may have. Thank you.
    [The prepared statement of Mr. Rozynski follows:]

                   Prepared Statement of Ed Rozynski

                              INTRODUCTION

    Good afternoon. Chairman Dodd, Ranking Member Alexander, and 
members of the committee, my name is Ed Rozynski. I am Vice President 
of Global Government Affairs for Stryker Corporation (``Stryker''). On 
behalf of Stryker, an early supporter of this bill, I am pleased to 
present testimony today to support the ``Pediatric Medical Device 
Safety and Improvement Act of 2007'' (S. 830) and highlight the 
importance of ensuring the development of medical technologies for 
children.
    Senator Dodd, we sincerely appreciate your leadership role on 
children's issues and specifically on this landmark legislation. Like 
you and your colleagues, we want children to have access to the fullest 
and best range of possible medical treatments, even if that means doing 
or inventing something new just for them.

          STRYKER AND ITS COMMITMENT TO PEDIATRIC POPULATIONS

    Stryker is one of the world's leading medical technology companies 
with the most broadly-based range of products in orthopaedics and a 
significant presence in the other medical specialties. Stryker 
Corporation is a Fortune 500 company with more than $5 billion in 
revenue and more than 17,000 employees. Stryker is committed to 
bringing the best possible solutions to patients, surgeons, and health 
care systems throughout the world. This philosophy has placed Stryker 
at the forefront of medicine's most promising breakthroughs in joint 
replacements, trauma, spine and micro implant systems, orthobiologics, 
powered surgical instruments, surgical navigation systems, endoscopic 
products, and patient handling and emergency medical equipment. 
Notably, Stryker's products are used in over 80 percent of the hip and 
knee replacement procedures performed each year in the United States.
    Stryker's commitment to children is not new. Our company is a 
market leader in products of significance for children. We are the 
leading manufacturer of orthopaedic oncology prostheses in the United 
States and have a significant presence in other medical specialties 
with a high percentage of pediatric cases, including craniofacial 
deformities such as cleft lip and palate. We also take very seriously 
our responsibility to ensure that our devices are safe and effective 
for use in pediatric patients.
    I'd like to take a few moments to tell you about some of our 
products that are commonly used in children.

        ONCOLOGY PROSTHESES AND CRANIOMAXILLOFACIAL TECHNOLOGIES

    There has been significant progress over the past two decades in 
the management of patients with musculoskeletal cancers that has 
improved both the survival rates and quality of life of afflicted 
individuals. Soft tissue and bone cancers represent less than 1 percent 
of all adult malignancies; however, they represent 15 percent of all 
malignancies in children. Twenty years ago, the standard treatment for 
any primary malignant bone and soft tissue sarcomas of the extremity 
was amputation of the affected arm or leg. Since that time, Stryker is 
proud to have partnered with leading orthopaedic oncology surgeons to 
develop limb-sparing, surgical solutions, including the implantation of 
a growing prosthesis that can be elongated to account for a child's 
growth.
    Often, a child's only chance to beat these aggressive forms of 
cancer is the removal of most, if not all, of an entire bone. Stryker's 
implant and instrument technologies are designed to allow not only for 
bone replacement with a prosthetic device but also soft tissue 
reattachment, which is critical to enable limb function following 
surgery. In children, there is often the need to have several surgeries 
to elongate the prosthesis to keep up with their growth, and Stryker 
provides solutions to meet this need.




    As with cancer, the treatment of craniofacial deformities is an 
area in which Stryker also has significantly improved and broadened its 
range of available medical products and solutions. With continued 
innovation of craniomaxillofacial technologies, Stryker hopes to 
continue to transform the lives of children facing challenges such as 
cleft lip and palate.
    We take pride in partnering with and sponsoring a range of medical 
organizations, including Operation Smile, a non-profit organization 
dedicated to repairing childhood facial deformities around the world. 
Last year, Operation Smile was able to provide free cleft lip surgeries 
to 8,531 children in 23 countries. These surgeries--on average taking 
45 minutes and costing $240 per child--have a positive, lasting impact 
on the lives of pediatric patients and their families.
    Finally, Mr. Chairman, I want to point out that children also 
suffer from other birth defects that, if left untreated, can cause 
permanent brain damage and/or severe disabilities. Craniosynostosis is 
a condition that results from premature fusion of the sutures or 
connections of the skull bones and has been estimated as a problem in 3 
of every 10,000 live births. When this occurs, the pressure on a 
child's brain becomes an immediate threat to the organ's regular 
development. The surgical solution for this condition is deconstructing 
the skull and then reconstructing it to be normal in shape and size to 
permit normal growth. Stryker's Inion BabyTM system allows 
surgeons to effectively accomplish this procedure through polymer-based 
re-absorbable plates and screws specifically designed to re-absorb 
faster than the adult version of this product to accommodate the faster 
growth rates of children's bones. The Inion BabyTM system is 
also often used in cleft lip and palate surgeries.

                      PEDIATRIC DEVICE LEGISLATION

    It is our sincere hope that the ``Pediatric Medical Device Safety 
and Improvement Act of 2007'' will further spur the evolution of novel 
health care solutions for children. This legislation provides a 
comprehensive approach for ensuring that children have access to 
medical devices that are manufactured with children's needs in mind.
    First, the bill fosters the innovation of new pediatric devices. It 
authorizes new money to create a grant program to support the 
establishment of non-profit consortia to promote pediatric device 
development, including ``matchmaking'' between inventors and 
manufacturers. The bill also establishes a point of contact at the 
National Institutes of Health (NIH) to help innovators and physicians 
access funding for pediatric device development.
    Second, the bill improves incentives for the development of devices 
for the pediatric market, which is very small. The cost of developing a 
new medical device and performing the required pre-market clinical 
studies can be enormous, often steering some manufacturers to serve 
larger, more established, and well known adult medical device markets.
    Current law for Humanitarian Device Exemptions (HDEs) permits the 
Secretary of Health and Human Services to approve for use in up to 
4,000 adults and/or children a year, a promising device that otherwise 
might not be approved. However, unlike for other FDA-approved medical 
devices, manufacturers are prohibited from making a profit on HDE 
products. The bill would lift the HDE profit restriction for new 
pediatric products only, in an effort to encourage more manufacturers 
to pursue the development of these products serving such small numbers 
of children.
    Equalizing the incentives between pediatric HDE products and full 
market approval products in this way--even if the costs per patient are 
higher--likely will spur companies to develop pediatric products that 
they otherwise might not have. Moreover, these products might be 
targeted for pediatric populations with no other treatment options 
except through the HDE approval process. Therefore, it is important to 
provide incentives for surgeons, hospitals, and manufacturers so that 
they stick with innovative concepts for pediatric products to ensure 
that they make it from concept to reality.
    Third, the bill facilitates the pooling and collection of more 
information about pediatric devices. Companies and other researchers 
are required to place certain pediatric postmarket studies and other 
research in a centralized, publicly available database so that 
information and solutions can be easily shared and analyzed. It also 
creates a mechanism to allow the Food and Drug Administration to track 
the number and type of certain higher-risk devices approved for use in 
children. In addition, the bill incorporates several recommendations 
made by the Institute of Medicine in its report on pediatric devices, 
including increasing the postmarket surveillance of medical devices 
used in children.
    Senator Dodd, we applaud you for introducing this legislation and 
look forward to continuing to work with you on refining the bill and 
advocating for its passage into law this year.

                               CONCLUSION

    In closing, I would like to say that Stryker is committed to 
working with others to find more and better solutions to the often 
costly and unique health care challenges of children.
    We see the hope and the benefit that our latest bone implants 
provide to children with cancerous tumors. In order to reach more 
children, Stryker has decided that we will find a way to provide much-
needed charitable assistance to families and patients who are 
undergoing treatment for pediatric bone cancers at selected NIH 
Comprehensive Cancer Care Centers in the United States. Specifically, 
we are looking for the best way to provide financial support for 
lodging, travel, and other non-healthcare expenses associated with 
travel to a Center of Excellence hospital for treatment--expenses not 
covered by health insurance and that often pose a serious impediment to 
a family's ability to provide for a child's care and recovery.
    We intend to finalize our plans and to announce them within the 
next several months, perhaps, in coordination with the passage of a 
much-needed pediatric device bill. We believe that Stryker's charitable 
initiative will complement the advanced medical technologies for 
children that Stryker already develops, and that all companies will be 
further encouraged to develop as a result of Chairman Dodd's 
legislation.
    I thank the committee for the opportunity to testify this 
afternoon, and I would be pleased to answer any questions the committee 
may have.

    Senator Dodd. Thank you very much, Mr. Rozynski. We 
appreciate your work and we admire the work of the Stryker 
Corporation. We've passed here, back in 1993, the Family 
Medical Leave Act, which is unpaid leave but in the next coming 
few weeks, we're going to be introducing a paid leave program 
as well that would provide the resources, hopefully for a lot 
of people who need to be with their children.
    I'll never forgot C. Everett Koop, the former Surgeon 
General of the United States testifying before this committee 
back many years ago when I first introduced the Family Medical 
Leave Act and telling this committee how the recovery rate of a 
child that has a parent or a loved one with them during a 
period of illness has just been well documented over the years 
and the ability to provide that opportunity for people to be 
together during those crises is absolutely immeasurable. So I 
appreciate the generosity and the idea of Stryker to be 
supportive of those families.
    I'm going to put the clock on here ourselves and take about 
5 or 6 minutes and turn to my colleague from Tennessee and my 
colleague from Ohio, who has joined us and I thank you very, 
very much for your being here and your interest in the subject 
matter as well.
    Let me turn, if I can, to Dr. Gorman. Some are suggesting 
that reducing the length of the pediatric exclusivity from 6 
months to 3 months across the board and you addressed this 
already but I wondered if you might comment further on it and I 
may ask Dr. Maldonado as well, for any comments on this and 
you, Dr. Campbell, if you have thoughts on that particular 
subject matter.
    Dr. Gorman. The Academy wishes there to continue to be the 
flood of studies for children and the 6-month provision that 
was previously in the legislation provided such a flood. We 
also, however, are very aware that the 6-months of exclusivity 
causes an increased economic burden because it delays, in some 
people's minds, the institution of the generic form of that 
medication.
    Reducing, as you presented in your introductory remarks, a 
lot of the drugs that went for exclusivity are, in fact, small 
market drugs, drugs that do not have large sales volumes when 
measured by the large pharmaceutical industry's measures of 
large, blockbuster drugs. To reduce those drugs to 3 months 
would, in fact, cut off the flow of studies. It would make it 
economically nonviable for manufacturers to do those studies 
without assuming too much risk.
    Senator Dodd. That's roughly about 80 percent of the 
companies we're talking about?
    Dr. Gorman. It looks like about 80 percent of the studies 
that--I'm sorry, of the drugs that were studied in the JAMA 
article. However, there are large drugs and blockbuster drugs 
that should be studied in children. Drugs become blockbusters 
because there are therapeutic advances or safety advances that 
should be shared by the entire population.
    But the economic benefit to the pharmaceutical company that 
does those is much larger and could be restricted and still 
give pharmaceutical companies enough of a profit margin to take 
the risk of doing those studies as well as provide some 
financial relief for the rest of the population.
    Senator Dodd. Dr. Maldonado, any thoughts?
    Dr. Maldonado. Yes, Senator Dodd, we recognize that a 
different incentive has been proposed. Your 6-month exclusivity 
has worked very well and I am happy to report to you that 
companies have not cherry-picked only blockbusters. We've done 
studies across the board.
    In my experience at J&J, what I've done to propose to my 
management to do pediatric studies and they know it well. I'm a 
physician, I'm a pediatrician. I'm going to come here in front 
of you, proposing development of drugs that are safe and 
effective for children or that I want to prove that are safe 
and effective for children, regardless of the economic 
incentive. In some of those drugs, you're going to have 
economic incentive. In others, you won't. But overall, this is 
our goal--to do what is right for children. Six months has 
worked very, very well. Going to 3 months will be quite a 
different experiment and this experiment for 10 years that you 
introduced 10 years ago and approved 5 years ago, has worked 
very, very well. A new experiment, we will have to see. But I 
am really very cautious about entering a new experiment and see 
faders. This is a success and we should continue it.
    Senator Dodd. Doctor, do you have comments on this at all?
    Dr. Campbell. Maybe a few, Senator. It seems like the 6 
months works. If it ain't broke, don't fix it. I'm a surgeon 
and I think a direct, simple approach is the best and I think, 
as Dr. Gorman and Dr. Maldonado has mentioned, there are some 
problems on the fringe that can be addressed separately.
    Senator Dodd. Well, 800 clinical trials is pretty 
significant. Those numbers blew me away. When we first 
introduced the legislation, going from 11 trials in 7 years, I 
thought we might get 20, might get 30 or 40 and I was going to 
consider that a pretty profound and significant number. When 
the numbers blew up and we saw that staggering number of tests 
being performed, it seemed to me that this was proving its 
value beyond anything we imagined when we introduced the 
legislation.
    So again, I don't disagree with you. I'd be concerned as 
well as to what the implications would be. If this is doing its 
job and we're obviously trying to address the blockbuster issue 
here, which is a legitimate issue, in a way that strikes enough 
of a balance that we don't end up doing damage to what has been 
a rather miraculous development in terms of the products that 
are produced as a result of these trials. So I'll keep that in 
mind.
    There have been some, Dr. Gorman--does the American Academy 
of Pediatrics support a clean authorization of BPCA? Someone 
suggested that and I, in my opening comments, made the point 
that this is an organic process here. With technology and other 
things that are occurring, I'd be tempted as the author of this 
legislation to see it become a permanent law and I've heard 
testimony of others who want that.
    I've also watched enough changes occurring here that it's 
worthwhile for us to go back periodically and take a look at 
how we're doing in this area. So that's sort of my reaction to 
it. Tell me what the American Academy's reaction is.
    Dr. Gorman. Well, speaking for the American Academy of 
Pediatrics, we think the last bill was really good and we think 
the new bill, with the changes that have been introduced, will 
be even better--better for children and better for the health 
care that they have.
    Voting for a clean reauthorization will overlook some of 
the problems logistically, of bringing the two programs closer 
together in a unified management inside the Food and Drug 
Administration. PREA and BPCA came from different roots and 
they have found different homes in the Food and Drug 
Administration that should, in fact, be unified so that all 
children's data that is presented to the Food and Drug 
Administration can be reported in a similar way, making it more 
transparent for both the regulatory agencies, the 
pharmaceutical industry and our caregivers, to understand the 
information that is coming out for kids.
    So no, we would not support a clean reauthorization. We 
think that there should be changes to improve the statute.
    Senator Dodd. Thank you very much.
    Senator Alexander. Thank you. This is a good hearing to get 
to come to because it's not this often that Congress actually 
passes a bill that works this well, it seems to me. I mean, 
this is very refreshing. He didn't hear the compliment but 
I'll--somebody will tell him later.
    [Laughter.]
    Senator Alexander. But let me--I can----
    Senator Dodd. I heard the compliment.
    Senator Alexander. Well, I'm deaf ears here. I wasn't 
here----
    Senator Dodd. If you'd like to repeat it, go right ahead.
    Senator Alexander. I just said it's not often Congress 
passes a law that works this well. That's all I was saying. I 
wasn't here when it was passed.
    So let me ask a couple of questions. If I'm understanding 
right, what we're saying is that this has been a really good 
thing, to have a fourth or a third of the drugs now available, 
tested for children, something like that and that it has worked 
pretty well. And that it has created a flood, is the word that 
has been used, of tests. If the flood is such a good thing and 
if the incentive encouraged a situation where--which is the 
number? Is it a fourth of the drugs or a third of the drugs 
that are now tested for children? Does anyone know the answer 
to that?
    Dr. Campbell. The number is in between those two numbers.
    Senator Alexander. About a third of all drugs that are 
available are tested for children? Am I saying that right? OK. 
Why shouldn't our goal be that two thirds or all drugs should 
be tested for children? And if giving a 6-month incentive 
created a flood of tests, would a 7-month incentive create a 
larger flood or an 8-month incentive create even more of a 
flood? Did you consider that when you considered your testimony 
today?
    Dr. Gorman.
    Dr. Gorman. Where there is so much pressure to cut down the 
profits of pharmaceutical companies that nobody thought that 
was realistic.
    Dr. Campbell. The 6-month incentive was the result, in 
previous legislation, of a fair amount of compromise between 
different people with different length determinations and like 
many good Congressional policies, it was one that was picked as 
a compromise number and as you've already stated, worked quite 
well.
    Senator Alexander. Yeah.
    Dr. Campbell. As Dr. Maldonado has said in his testimony, 
one of the things that he wishes for the most is that he wishes 
the pediatric infrastructure for doing these studies to become 
permanent and secure and I share that dream. So I want an 
authorization of BPCA that continues to provide a steady 
stream, a steady flood of studies and I don't magically know 
the number that will give us the most. But the numbers we have 
so far do work and there is some evidence out there that by 
looking at economic studies and I'm not an economist--but when 
you look at the economic return for companies, the economic 
return for the blockbuster drugs could be limited and still 
give enough of a financial incentive for corporations to 
continue to pursue those studies for children.
    Senator Alexander. Yes. Well, you've testified that 6 
months is fine in general but the blockbuster drugs--that 
profit might be reduced, was your conclusion. Did I get that 
right?
    Dr. Campbell. It could be reduced and still be enough of an 
incentive to continue to have companies do those studies.
    Senator Alexander. But I want to press this a little bit. I 
mean, it was a very bold move for the Congress and everybody 
that compromised and agreed that we're going to add 6 months to 
the wait for a generic drug, just to see if whether it might 
produce these tests and in fact, you got a flood of them. So if 
6 months got a flood and if you think they all ought to be 
done, then why wouldn't you go to 7, 8, or 9 months and have a 
big flood? Dr. Maldonado, what would your response to that be? 
I'm not recommending that. I'm just asking why wouldn't we, 
after this experience?
    Dr. Maldonado. It's fair and we think that 6 months has 
worked and it continues to work and this is a process that 
we're going--I don't want to recommend any other higher number 
because I don't know if it is going to increase or double the 
flood. I just don't know and I don't want to be perceived to be 
greedy but people have focused on the blockbusters and a 
journal article of a month ago actually shows that there are 
some studies that are done in which private companies lose 
money and I can tell you from our company, some examples in 
which we----
    Senator Alexander. So your argument is that the profits of 
blockbusters help pay for the less profitable trials?
    Dr. Maldonado. Absolutely, absolutely.
    Senator Alexander. But--Senator Dodd, this will be my last 
question, in this round anyway. If we're really happy with the 
results and we see the need for more--well, would you agree 
that--what percent of drugs should be tested for children? Is 
it 100 or is it 75?
    Dr. Maldonado. It's not a 100 because there are some drugs 
that are for diseases that only occur in adults and so it is 
not 100 percent.
    Senator Alexander. Well, is it 50 or 60 or 70?
    Dr. Maldonado. That's a very good question and I have not 
counted that but I will, now that you ask the question, I'll 
get back to you. But it's a fair amount of drugs that will have 
an application. The only thing is that sometimes in the life 
cycle, we put drugs out there in the market and we don't 
understand all the potential--we understand that it is safe and 
effective for the indication they have--is it later in the life 
cycle that we discover that they may have an application for 
children. Even we, having the expertise in-house, learn with 
time that there may be some applications for children later. 
But yeah, it's not 100 percent but maybe--I don't know--
probably 50 or 70 percent, something like that.
    Senator Alexander. Thank you. Senator Dodd, I think as we 
go through the legislative process--you've had such success 
with this legislation. I mean, in 5 years, we may want to talk 
about, is there a way we can get above 30 percent--just to some 
number. Maybe it's not within percentage, maybe it's some other 
way but is there a way to do that?
    Senator Dodd. Well again, certainly as I said earlier, we 
were stunned by the number of clinical trials that occurred 
immediately after the enactment of the legislation. We 
literally were talking about numbers that might have doubled or 
tripled the 11 tests that had been tried in 7 years. The idea 
that we'd get 800 in a decade was breathtaking. And very 
candidly, the reason we went through the process is--this is a 
legislation body and you don't sit and write legislation really 
but what you're trying to do is strike balances. There are 
those here who are very much opposed to the 6 months of 
exclusivity and would be against the bill. So I was trying, at 
the time, along with my colleagues here, to strike a balance 
here that we felt would draw enough of the companies in to work 
on this, that would not allow gouging to occur here at the 
expense of consumers and we didn't have any answer to the 
question of whether or not 6 months would do it or not. This is 
not going to be easy to get this through both Houses of 
Congress in the coming weeks before these laws expire.
    So I'd love to tell you there was some genius that showed 
up and said, I promise you that this number will get you what 
you want. Basically, it was a compromise to make sure we could 
enact the legislation. It's not more complicated than that and 
it's proved to be far more successful than we imagined and in 
fact, the good news has been as well, as far as I'm concerned, 
that a relatively small number of the companies have produced 
blockbusters in the sense here. The majority are coming out of 
smaller companies, if the JAMA reports and studies are 
accurate.
    So again, I'd love to see--and I think we may get closer to 
more--a higher percentage of these products being tested for 
children. We seem to be on that path here and the risk we run 
of monkeying around with this, in my view, on one side of the 
equation is, if you try to add to that 6 months, you're going 
to lose a lot of people who won't support a piece of 
legislation. You eliminate it all together and you're going to 
lose a bunch of other people on that. So I'm trying to strike a 
balance here that not only reflects the technology and the 
evidence that we've produced over the last 7 years but also 
reflects the political realities I have to deal with here as a 
Chairman of a committee trying to produce a piece of 
legislation that can pass. Old practicalities come into play 
here on this.
    Senator Brown.

                       Statement of Senator Brown

    Senator Brown. Thank you, Mr. Chairman and thank you all 
for your testimony. I think it's not a question but Senator 
Alexander's comments, I thought, were interesting. I have a 
couple of ideas about that. I think it's not a question of drug 
company profits as much as it is, do we want to delay generics 
where insurance companies and individuals and government 
taxpayers have to pay more for these drugs as they get the 
extension.
    Ten years ago, I was on the House--I was the Ranking 
Democrat on the House Energy and Commerce Committee, HELP 
Subcommittee and 10 years ago and 5 years ago, we faced this 
issue and passed the bill.
    But there was something else going on 10 years ago at the 
same time and that was--the same committee in the House. It was 
considering doubling the NIH budget over a 5-year period. So we 
were enacting the pediatric exclusivity bill to encourage 
clinical trials and encourage more research and what that would 
mean for children. At the same time, we were doubling the NIH 
budget and what that meant for medical research for children 
and everyone else.
    We are still and we should reauthorize pediatric 
exclusivity. The NIH budget, as you know, has been flat and 
what that has meant for research, especially children's 
research, is a downgrading of our abilities in this country to 
do the kind of research we need to do.
    I was just at Cincinnati's Children's Hospital, the second 
largest recipient of NIH dollars of any children's hospital in 
the country. There was some $90 million a year. They are 
finding, as are children's hospitals everywhere, that when they 
submitted a proposal to NIH, about one out of three proposals, 
one out of four proposals of 5 years ago was being accepted. 
Today, it's closer to one out of ten and when they get NIH 
dollars, they usually get a 20 percent discount from the 
dollars that they ask for and they get no adjustment for 
inflation during the course of the research they're doing.
    So it seems to me that if--I mean, this whole issue is--Dr. 
Gorman, you've illustrated and Dr. Maldonado--all of you, is a 
trade-off in part, on access versus the importance of clinical 
trial and the JAMA article, I believe, said--the study 13 out 
of 59 of these were blockbusters. I don't know how many of the 
46 remaining were hundreds of millions of dollars and how many 
were for small--literally small sales.
    But we don't want to prevent access, obviously, to generics 
for sure--I mean, we want to do what we can that way but I have 
an idea that I'd just like to bounce off of all of you that 
might be able to kind of address two public health problems. 
One is pediatric--the whole issue of clinical trials for 
children, which is what we're here for today. The other is 
pediatric health care research and since we're not going to 
increase NIH funding the way that we should in this Congress 
because of--whatever the reasons--the cost of the war, the cost 
of the tax cuts--whatever the reasons.
    Let me just bounce an idea that--an idea I'm working on and 
see what all five of you think about its workability. Drug 
makers, under this plan, conducting pediatric tests would have 
a choice. They could either choose to receive 3 months of 
additional market exclusivity or they could choose to receive 
the 6 months that they get under present law if they agree--if 
they opt for the 6 months, they have to agree to contribute, 
say 15 percent of the profits they earn during those 6 months, 
just from the profits from that drug alone, particularly if it 
is a blockbuster, it will be meaningful, 15 percent of those 
profits to a trust fund that would finance pediatric research 
centers, any one of a number of children's hospitals. I would 
argue Cincinnati but I would be accepting of any research 
hospital around the country that does pediatric research.
    So it would deal with giving the incentives for those small 
companies that aren't making a lot on their extension. It would 
not mean many--well, 10 percent of their profits so it would 
mean very few dollars or no dollars. For the blockbusters, it 
would mean--they are putting a significant number of dollars 
aside. They are still getting an extension, 6 months and a 
blockbuster means a lot of money.
    So my question--my offer to Senator Alexander on an 
additional month or two or how do you get the number from 30 
percent or so up to the optimal of 60 or 70 or 90 is something 
we thought about in the House 5 years ago in our committee and 
that is, you figure out what the cost of the research is and 
you reimburse two times, three times, four times--you basically 
give those companies that amount of money so you're paying for 
their research and then some. That might get us on some smaller 
companies somewhere, too. And I would be open to consider that, 
too.
    But if you would all comment, any of you comment on the 
idea. The choice is 3 months or 6 months, 10 percent of the 
profits go into pediatric testing and pediatric research. Any 
of you? You're all overwhelmed, apparently.
    [Laughter.]
    Senator Brown. And I know you haven't thought about it yet, 
so--I mean, you haven't had a lot of time to think about it.
    Dr. Gorman. Stop me from speaking so I will say that--only 
that one of the issues the Academy would have with that 
proposal is the complexity in its administration. 
Pharmaceutical companies are rightfully--they play their cards 
close to the vest about profits from any individual item. So if 
you're going to move forward with that, at least a suggestion 
would be to start looking at sales rather than profits, which 
can be more easily documented.
    Senator Brown. And a smaller percent, then. Thank you for 
that and I would add that if you talked and quoting another on 
the panel, the pediatric infrastructure to make it secure, to 
make it permanent, I think that these dollars would help us 
build an even better base in terms of being able to do that. 
Anybody else? Thank you.
    Dr. Maldonado. Yes, Senator, I think that the pediatric 
infrastructure is something that we have helped indirectly, for 
example, the PTLU--the pharmaceutical research units that are 
funded by NIH in part and we're developing that infrastructure 
in the hospitals. Remember that we don't do the research 
ourselves in our buildings. The research is done in 
universities and in places where the patients are.
    My concern is similar to Dr. Gorman, and that is how to 
administer that kind of program and not damper the incentives. 
But we are all for increasing the infrastructure there. But the 
administration can be a problem and I agree with you.
    Senator Brown. Others?
    Dr. Campbell. I would echo that. Something that is 
different--we don't know the agendas of the different players 
and there may be a corporate strategy, a pharmaceutical 
strategy where they are looking at profits in different areas. 
Right now, it seems to be very simple and then people can sort 
of put that on their long term thinking and come out with an 
outcome. But if we start getting--it's like our tax code. It 
gets real complicated and you just don't know where you're 
going to end at the end of the day. Once again, I'm a simple 
surgeon and if it's simple, I can usually get through the day.
    Senator Brown. Thank you. Did you want to add anything? 
Thank you, Senator Dodd.
    Senator Dodd. Senator Allard.

                  Opening Statement of Senator Allard

    Senator Allard. Mr. Chairman, thank you. I want to thank 
the panel for being here. I know you have to take time from 
your jobs and what not but this is important. And I would agree 
with my colleagues here that the Pediatric Research Equity Act 
and the Best Pharmaceuticals for Children Act seem to be 
working.
    So my first question--I'm going to do this direct, both to 
you, Dr. Campbell and Dr. Gorman. My background is that of a 
veterinarian so I've treated an animal from the size of a 
parakeet to an elephant. But I can understand the differences--
when it comes to pharmaceuticals, I can understand the 
differences in size and dosage and metabolic systems. But when 
we get to the devices and what not, if they are nonreactive in 
one species, from my experience, they are nonreactive in all 
the rest and it's just a matter of size, applying to that.
    So the question I have is on the Pediatric Medical Device 
Safety and Improvement Act, if that were passed, what kind of 
impact would it have on practice today and perhaps 
manufacturing today, if you could each respond to that in your 
respective fields.
    Dr. Campbell. I think that's a very important question and 
your analogy of using dosages and cross reactivity in species 
is important. But let me talk as an orthopedic surgeon. A 
disease of infancy changes things--bone infection can cause 
severe damage to the hip because of blood supply. It's very 
fragile in that time frame and may cause permanent catastrophic 
disability. The same infection in teenagers is less 
catastrophic because the blood supply has changed within the 
hip. So there are so many areas of complexity right now that 
aren't really dealt with with devices.
    Senator Allard. That could change the procedure but it 
doesn't necessarily change the device manufacturing, does it?
    Dr. Campbell. It would change how the device is used, the 
shape of it. In fractures of the hip, there are devices that 
could be made that could bypass the circulation and do a better 
job of immobilization. We're working on that.
    Senator Allard. I see.
    Dr. Campbell. So these nuances that are very critical for 
these children aren't dealt with very well by the manufacturers 
yet. But if we give them some encouragement then I think 
they'll be able to work with us better and understand these 
problems.
    Senator Allard. Dr. Gorman.
    Dr. Gorman. I think one of the incentives will be to 
address issues that become apparent when you use devices for 
children. An example from the more medical field but still a 
device was the incubators used for babies. When someone finally 
put a microphone inside them to find out how loud they were, 
you could hear what kind of resonance in the sound inside these 
incubators there was from the ambient noise surrounding them 
and when they realized the noise inside the incubator was 
louder than the noise outside the incubator, they redesigned 
them so to allow them to have more sonic separation from the 
ambient areas.
    Those kind of issues, which wouldn't come up for--or an 
adult would complain that it was too loud, children have to 
have it measured and then there has be a will and the finance--
--
    Senator Allard. That wasn't a factor so much of--I mean, 
that happened without this law. You realized what the best care 
was as soon as that came to light. I think the practice kind of 
changed, didn't it? You didn't actually need a law for that 
change to occur?
    Dr. Gorman. For that particular change where there are 
hundreds of thousands of incubators around the United States, I 
think that would be an easy change for a company to understand. 
It would make medical sense and financial sense. For devices 
that would be used less frequently, like tubes or masks to help 
babies breath--again, there would be, when you go to 
miniaturize something, sometimes it works very well in the 
sense you can just take something big and make it small but 
sometimes if you make it small, you exceed the limits of 
engineering as they presently are and having incentives or 
testing or grants to get prototypes built would be very 
important for the continued improvement of care for those 
children.
    Senator Allard. Thank you for your responses. Mr. 
Maldonado, we've been hearing lately that the pediatric, 
pharmaceutical and device industry and the best practices of 
pharmaceuticals has been working because it's more of the 
carrot and stick approach. Do you think--could you speak to the 
need for sort of a carrot and stick approach?
    Dr. Maldonado. That's why I said in my testimony, Senator, 
that these two laws actually work synergistically because what 
happens is that if a drug has been studied in adults for any 
indication, the FDA can evoke PREA until they sponsor--even if 
they didn't have it in their mind, you must do studies in 
pediatric patients for that indication.
    Now, BPCA, since this is an incentive, goes beyond that. So 
you come around a table and say, we're going to do this because 
we have to do it because FDA is requesting it but there are 
other opportunities for this drug in children. And we consult 
with many physicians around the United States, many experts and 
we came to a consensus that they are all opportunities and we 
pursue them, completely beyond the label, something that even 
has not occurred probably to the FDA and sometimes even to us 
as companies. But clinicians out there know and that knowledge 
is brought in-house and investments are going to go way beyond 
the label. And that's the beauty of both legislations and 
that's why I think they work so well.
    Senator Allard. Is it Susan Belfiore?
    Mrs. Belfiore. Yes.
    Senator Allard. What are your thoughts about the Pediatric 
Medical Device and Safety Act, from your experience with----
    Mrs. Belfiore. With the children?
    Senator Allard. With the Elizabeth Glaser Pediatric AIDS 
Foundation and you've been a mother of some HIV positive 
children.
    Mrs. Belfiore. Yes. I would say that thank God, we haven't 
had a lot of opportunities to use medical devices but I would 
say that the little bit that we have had--let me give you an 
example. When the children--as I said, go for blood work every 
3 months and starting at a very young age. They were 2-years-
old, 3-years-old, doing this. It made a huge difference whether 
or not there was a butterfly to take their blood work--that 
small needle for those small veins.
    They would kind of freak out when they would see someone 
come with these larger needles toward them and then the whole 
thing was traumatic and I would say, that's just one small 
instance where it made a difference in our lives. I can only 
imagine many of the other instances where medical devices could 
be used, where children--where physicians might have to use 
something for an adult and in that process, it might harm the 
child, just because there is not anything that is offered to 
them.
    Senator Allard. Mr. Chairman, I want to be sensitive to 
your time but can I ask one more question?
    Senator Dodd. Go right ahead.
    Senator Allard. OK. I would just like to hear from anybody 
on the panel on this question. Do you see any conflicts between 
how all three pieces of legislation we've talked about in this 
hearing are currently written or how they interact with one 
another? Do you see any problems with them? I assume that no 
response means you don't see any problems?
    Dr. Maldonado. Do you mean for the ones that are right now 
before----
    Senator Allard. Yes, the reauthorization bills that we have 
here, which are two of them and then the other legislation 
sponsored by Senator Dodd on the medical devices. Do you see 
any problems with those, any one of those three pieces of 
legislation, as they're written or how they might inter-react 
with one another? Do you see a problem with that?
    Dr. Maldonado. We are examining those legislations as a 
team in my company and we're going to be working with Senator 
Dodd and others to address some of the issues that we see.
    Senator Allard. OK. So you could be--you'll be giving us a 
written response on that?
    Dr. Maldonado. That's correct.
    Senator Allard. OK and Mr. Chairman, how soon do you ask 
for a written response to be provided?
    Senator Dodd. Well, we're going to ask--in fact, we're 
going to keep the record open for 10 days, because obviously 
not all members showed up here today to be a part of the 
hearing. Many of whom are not here have a strong interest in 
the legislation. We'll be reviewing the testimony and we'll 
undoubtedly submit some written questions to our witnesses and 
I'd ask them to respond, if you could, within the next 10 days 
to those questions, assuming you get the questions promptly 
here, which I would urge them to do so we can include them in 
the record. I don't want to speak for the Chairman here or the 
Ranking Member of the full committee but I think the goal is to 
be looking at a markup of these bills some time toward the 
middle of next month. So we're talking about something maybe a 
little less than a month from now to actually be beginning the 
process of legislating in this committee. We have expiration 
dates coming up in September, so the idea is to get these up, 
out of the committee if we can and then of course, helping the 
leaders schedule them appropriately on the floor debate and 
discussion. The other body is also engaging in a similar 
process. So there is a sense of some urgency, time-wise, to 
move along. So it will be important that if you get these 
questions from our colleagues, you are to respond to them as 
quickly as you can.
    Senator Allard. Can you get that response to us in 10 days, 
do you think?
    Dr. Maldonado. Yes, we will.
    Senator Allard. Very good. And we'll have some questions, 
too, Mr. Chairman. We'll submit those and ask that you respond 
within 10 days, if you would, please. Thank you very much.
    Senator Dodd. Thank you, Senator and let me just add--
Senator Brown left the room but I want to point out his 
suggestion, his idea is not a new one but there are two 
problems I see with it and I say this as someone who has great 
respect for Senator Brown and his interest and concerns about 
the legislation. One is, something like that could be construed 
as a tax, if you start asking for a levy on companies in 
exchange for the 6 months of exclusivity. And second, my 
greater worry is not so much that one but the worry I would 
have that considering that so many of these products are coming 
out of smaller companies and it's going to be so important that 
we keep that small manufacturer in the game here and if they 
continue to be attracted to what we're talking about here as a 
way to have these tests and to produce these products. I'd be 
very worried that an additional burden, while not intended for 
them, would have the effect of discouraging them, the 
calculation being that it's too risky for us to do this if, in 
fact, we come out of it with marginal profits anyway and this 
reduces it further. That might be enough to persuade them not 
to engage and again, given the data we have up to now, at least 
based on independent studies that have been done, a significant 
number of these tests are coming out of the smaller companies. 
So I would be very uneasy about what the implications could be 
on those companies and their decision to go forward with this.
    I have no difficulty at all in trying to get generic 
products out as quickly as we possibly can and what we've tried 
to do here is strike the balance on this. So there is nothing 
written in marble or concrete or stone about 6 months here but 
to parrot the remarks that have been made by the witnesses and 
others, it seems to be working and at this point here, I'd be 
reluctant over a period of 5 years, to change something that 
has produced pretty good results--in fact, I'd say fantastic 
results and the fears that others had at the outset about this 
providing a huge amount of profits in the blockbuster area have 
not proven to the be case up to now.
    Now obviously, we want to watch this and I'm supportive of 
coming back 5 years from now to review where we are, to make a 
determination as to whether or not that is still going to be 
the case.
    Mrs. Belfiore, I wanted to raise something with you because 
I was so fascinated by that book, your blue book over here, of 
all the records. What did you do before? Where did you go to 
get information to decide what medications to provide for your 
children? Or dosages of things? Who did you rely on for that?
    Mrs. Belfiore. Well, in the beginning, with this virus, as 
you know, there is not very--no one really knew. So when I 
first brought the children into the country, of course, their 
infectious disease specialist I relied on. But I also read 
everything I could get my hands on. And since there was not 
much information on children, I really went to the adult 
population and how is that being--how are they being treated?
    I'll give you an example and sometimes it worked and 
sometimes, like I told you with Mihaela, it didn't work. But 
early on, the protocol for children with HIV was to give them 
AZT as a mono-drug and I read that what was happening is that 
even in adults at that time, those who were just taking AZT 
alone were not doing as well as maybe even some who were taking 
no medications at all. They were not living as healthy lives 
and they were dying faster. So I went to my specialist, my 
infectious disease specialist and my children have been put on 
it, when it first came into country and I said to him, I'd like 
your support in taking my children off this drug. And he said, 
of course. We don't know what is going on right now. We don't 
know. We're just doing the best we can.
    So knowing is so important and for me to have these acts 
and all the work that everyone has put into these and these are 
not easy. To me, they sound complicated, these laws. But the 
fact that they are working and the fact that we would be able 
to get the information that we needed about the medications 
right there would be wonderful. I don't think parents have any 
idea, most parents out there. I have asked, do you know that 
three quarters of all drugs that are out there have never--
medications--have never been tested for children? And they have 
no idea.
    Senator Dodd. I know.
    Mrs. Belfiore. I didn't even know to ask when Mihaela was 
put on that cocktail of drugs, has it been tested for children? 
The thought never even crossed my mind.
    Senator Dodd. We had examples of this, by the way, because 
the assumption is, it's always the smaller dosage. We've 
actually had examples where actually a larger dose----
    Mrs. Belfiore. That's the situation here.
    Senator Dodd. So the assumption that smaller people take 
smaller dosages, in fact, proved to be incorrect.
    Mrs. Belfiore. Because they metabolize it quicker.
    Senator Dodd. Yeah, much more quicker. Well, we're going to 
keep at this and your testimony has been very, very helpful 
once again.
    Mrs. Belfiore. Thank you.
    Senator Dodd. I'm delighted to see your children and your 
family here and I thank you, Dr. Gorman, Dr. Maldonado, Dr. 
Campbell, for your excellent work. Congratulations. Mr. 
Rozynski, we thank you as well, for your work and we'll keep 
the record open for a few days here and respond to these 
questions that may come up.
    The committee will stand adjourned.
    [Additional material follows.]

                          ADDITIONAL MATERIAL

   Prepared Statement of the Advanced Medical Technology Association 
                               (AdvaMed)

    AdvaMed is pleased to submit this testimony in support of S. 830, 
the Pediatric Medical Device Safety and Improvement Act of 2007. We 
commend Senator Dodd for his advocacy on behalf of children and for his 
willingness to work with stakeholders in the development of the 
legislation. We believe the legislation will provide help in ensuring 
expanded access to medical devices for children. AdvaMed would like to 
continue to work with Senator Dodd and members of the committee to 
further improve and strengthen the legislation to enhance pediatric 
device access.

                           EXECUTIVE SUMMARY

    AdvaMed member companies produce the medical devices, diagnostic 
products and health information systems that are transforming health 
care through earlier disease detection, less invasive procedures and 
more effective treatments. Our members produce nearly 90 percent of the 
health care technology purchased annually in the United States and more 
than 50 percent of the health care purchased annually around the world. 
AdvaMed members range from the largest to the smallest medical 
technology innovators and companies. AdvaMed member companies have and 
continue to develop devices for pediatric use that:

     are used extensively in pediatric populations,
     were developed specifically for pediatric populations, or
     were specifically redesigned for pediatric populations.

    Recommendations to Improve Efforts to Develop Pediatric Devices. 
AdvaMed has a number of recommendations to amend S. 830 to improve and 
strengthen pediatric access which are summarized below and discussed 
more thoroughly in the full written statement.

    Eliminate Duplicative Provisions:

     The proposed Section 522 language would give FDA the 
ability to require postmarket surveillance even if there is no public 
health concern.
     The proposed postmarket surveillance database will be 
expensive and costly for FDA to manage and maintain. Such studies 
should more appropriately reside in a device clinical trial registry.

    New Pediatric Humanitarian Use Device Program:

     Provide the Secretary with authority to selectively raise 
the annual population cap for specific pediatric conditions when FDA 
determines the health of pediatric patients requires an increase.
     Allow existing pediatric HDEs to automatically qualify for 
the new pediatric HDE program to ensure that existing pediatric HDEs 
will remain on the market.

    Make Better Use of Existing FDA Regulatory Tools: While maintaining 
the existing standard of safety and effectiveness, where appropriate 
FDA should:

     Use objective performance criteria (OPCs), historical 
controls or well-documented case histories as endpoints to show 
effectiveness.
     Allow the extrapolation of clinical data between different 
sizes of the same device based on engineering testing and other non-
clinical data.
     Rely on non-clinical data for modifications of devices 
specifically approved for pediatric patient populations when such 
modifications are unrelated to changes in intended use.
     Allow the acceptance of 510(k) devices intended for adult 
populations with the same use as a pediatric device as predicates for 
the 510(k) pediatric device.
     Allow the acceptance--as an appropriate control for 
investigational pediatric devices--of devices intended for use in adult 
populations when such devices provide the only device-related means for 
treating, diagnosing or preventing diseases or conditions in pediatric 
patients and have become the standard of care for such patients.

    Compassionate Use of Pediatric Devices:

     Require FDA to develop regulations that would allow 
manufacturers to distribute no more than 100 unapproved devices 
annually to pediatric patients when such patients are afflicted with 
diseases or conditions that affect too few patients annually to justify 
the expense necessary to achieve an approved device under the HDE 
program. Appropriate controls would be specified in statute.

                    INNOVATING FOR CHILDREN'S HEALTH

    There are many challenges to pediatric device development which are 
described below. However, there are numerous devices already on the 
market that are used extensively in the pediatric population, or were 
specifically developed or redesigned for pediatric populations.
    These include, among others: pediatric spinal fixation systems, 
downsized fracture fixation hardware, and total joint prostheses that 
can be lengthened; diagnostic cardiac catheters, therapeutic cardiac 
catheters, vascular grafts, pacemakers and heart valves; syringes with 
the greater dose accuracy required for some pediatric medications and 
medication delivery systems that are less invasive (such as nasal or 
intradermal delivery devices); incubators, respirators and warming 
blankets; glucose meters; enteral pumps; septal defect closure devices 
and hydrocephalic shunts (including those with anti-microbial 
coatings); tracheal stents; cochlear implants; and diagnostic tests 
that are specific for diseases that more frequently afflict children 
(e.g., rotavirus tests) and diagnostic assays with pediatric 
indications (e.g., Albumin BCG & BCP, Alkaline Phosphatase, Amylase, 
Calcium, Carbon Dioxide, Cholesterol, etc.). Many of these have entered 
the market via the 510(k) review process--without the need of large 
clinical trials.

             WORKING TOGETHER TO DEVELOP PEDIATRIC DEVICES

    AdvaMed has been actively engaged with other stakeholders on the 
issues surrounding pediatric device development for several years. In 
June, October and November 2004, AdvaMed participated in a series of 4-
day-long stakeholder meetings to discuss and better understand 
pediatric device access issues and concerns. Stakeholders included FDA, 
the American Academy of Pediatrics, the Elizabeth Glaser Pediatric AIDS 
Foundation, the American Academy of Orthopedic Surgeons, the National 
Association of Children's Hospitals, the National Institutes of Health 
and the National Organization for Rare Diseases.
    In August 2004, AdvaMed also submitted comments\1\ in response to 
FDA's request for comments regarding barriers to the availability of 
pediatric devices and in response to the congressionally mandated 
Institute of Medicine's report on postmarket surveillance of pediatric 
medical devices. In 2005, AdvaMed participated in meetings with 
interested stakeholders (e.g., FDA, AAP and AAOS) to develop a template 
survey targeting three pediatric subspecialties (Cardiology, Pulmonary 
Medicine, and Neurosurgery). The goal of the survey was to identify 
important pediatric needs that could aid in formulating potential 
regulatory and legislative solutions.
---------------------------------------------------------------------------
    \1\ See Docket No. 2004N-0254: http://www.fda.gov/ohrms/dockets/
dailys/04/aug04/082504/04n-0254-c00011-vol1.pdf.
---------------------------------------------------------------------------
    One example of the need for continued dialogue among stakeholders 
was highlighted during the stakeholder discussions. Pediatric 
clinicians expressed concern that pediatric adverse events are not 
appropriately captured in FDA's adverse event database. When the FDA 
adverse event form (MedWatch Form 3500A) was distributed, the 
clinicians reported that hospital risk managers discourage reporting on 
the form. For manufacturers, the data provided in these MedWatch 
reports are critical to understanding the ongoing performance and 
safety of their devices in a variety of uses and patient populations. 
Information from these reports (along with other post-market 
surveillance activities) helps guide manufacturers on potential changes 
needed to mitigate the severity or frequency of adverse events. The 
information may also point to potential device changes to enhance 
clinical effectiveness and utility. Dialogue among key stakeholders 
about access to pediatric devices has resulted in progress but 
continued dialogue is required.

               CHALLENGES TO PEDIATRIC DEVICE DEVELOPMENT

    AdvaMed's engagement on the pediatric device issue over the past 
several years has helped us better understand the challenges the 
industry faces bringing new devices to children. Some of these are 
enumerated below.

     Identification of Pediatric Market: Importantly, a key 
barrier continues to be difficult in identifying and defining pediatric 
device requirements including the quantities of pediatric patients with 
unmet needs (which naturally varies by condition). The good news is 
that the recent focus on pediatric device access has resulted in a 
growing interest in serving the pediatric population. Recently, AdvaMed 
was contacted by an independent group that wants to re-engineer and 
optimize existing medical device technology for pediatric use. The 
group asked AdvaMed for pediatric market data--the type of data that 
would have been developed for three subspecialties by the template 
survey developed by stakeholders in 2005. More work, especially 
specific pediatric requirements, will be needed to transform this 
growing interest into real pediatric devices.
     Technical Barriers: There are numerous technical 
challenges associated with developing devices for pediatric 
populations. For example, not all devices function in the same manner 
when manufactured in the sizes needed for pediatric patients. Secondly, 
the fact that the pediatric anatomy is subject to change and shape, 
especially in younger patients, may limit the appropriateness of some 
devices intended for long-term use (e.g., permanent, weight-bearing 
implants). In addition, the selection of materials used in pediatric 
devices must take into account the different susceptibility of children 
to physical and chemical agents. The metabolic and hormonal changes 
children experience during growth may also need to be taken into 
account. These factors can limit the range of materials from which 
pediatric devices can be fabricated, complicating design challenges. 
Other technical issues manufacturers must consider include the array of 
sizes needed to meet pediatric needs, the likelihood of patient 
compliance with limitations associated with devices and the ability to 
anticipate the activity level and forces imposed by patients who may 
not be able to or willing to exercise significant self-control.
    The nature of establishing safety and effectiveness in pediatric 
populations is also different in devices than it is in drugs. This is 
not to say that many drugs don't require testing or reformulation for 
use in pediatric populations. However, for some devices, additional 
complexity can be introduced when defining test methodologies to 
demonstrate safety and effectiveness in pediatric populations. For 
example, separate animal testing in younger or smaller animals, along 
with the documentation and verification of the data for each separate 
model may be required. There are also technical challenges associated 
with retooling existing manufacturing lines or introducing new 
manufacturing lines (distinct from those used for adult devices) which 
may be required for many pediatric devices and models. All of these 
factors can add research and development complexity and cost.
     Small Pediatric Market Size: It is likely that for some 
pediatric device needs, the annual market will not be commercially 
viable for device companies. The complexity and cost associated with 
pediatric device development can be higher as noted above and yet 
manufacturers will in some cases be developing the device for a far 
smaller market.
     FDA Regulatory and Data Requirements Can Discourage 
Pediatric Device Development: FDA data and regulatory requirements can 
necessitate large pediatric clinical studies or require multi-year, 
multi-hospital studies with long-term results monitoring. Challenges 
include accruing sufficient clinical trial participants over a 
reasonable timeframe and within a manageable number of investigational 
sites to meet FDA requirements. For small populations of pediatric 
patients, the costs associated with conducting such trials may not be 
recouped. Further, for some pediatric conditions, the co-morbidities 
associated with the condition can make it extremely difficult to 
establish the effectiveness of the device. The clinical trial of a 
device that diagnoses or treats such a condition would likely 
experience many adverse events related to the co-morbidities making it 
difficult to assess the therapy under evaluation and generate enough 
data to establish the safety and effectiveness of the device using 
traditional clinical trial methodologies.
     Perception of Potential Liability Risks Associated with 
Pediatric Device Use: Finally, it is an unfortunate reality that the 
same conditions that have led to decreased availability of affordable 
malpractice insurance for pediatric surgeons has effects for device 
manufacturers. The perception exists that the financial liability 
arising from litigation involving a pediatric population is substantial 
and far greater than actions involving adult populations. The 
perception also exists that there may be an increased risk of liability 
associated with clinical trials involving pediatric conditions with 
many co-morbidities and congenital anatomic anomalies.
 advamed recommendations to further improve access to pediatric devices
    AdvaMed recommends the following additions and changes to S. 830 to 
help improve pediatric access to existing devices and increase the 
number of cleared and approved pediatric devices.

     Eliminate Duplicative Provisions: We believe the proposed 
522 language in S. 830 is unnecessary. FDA already has authority to 
require postmarket surveillance for any device raising a public health 
concern. The proposed language would give FDA the ability to require 
postmarket surveillance even if there is no public health concern. This 
is unnecessary given FDA's current broad, statutory authority and it 
may also discourage manufacturers from pursuing pediatric uses so as to 
avoid costly and unnecessary postmarket surveillance studies.
    Congress amended section 522 of the Federal Food, Drug, and 
Cosmetic Act in the Food and Drug Modernization Act of 1997 to give FDA 
expanded authority to require postmarket surveillance or longer studies 
when issues arise after a product has been cleared or approved. The 
existing 522 statutory criteria are quite broad and can already be 
applied to products that are expected to have significant use in 
pediatric patients. In fact, FDA itself has claimed broad authority 
under the FDAMA 522 language. In its recently released ``Guidance for 
Industry and FDA Staff--Postmarket Surveillance Under Section 522 of 
the Federal Food, Drug, and Cosmetic Act,'' FDA says the criteria it 
will use to determine whether to impose postmarket surveillance is 
``the delineation of an important unanswered postmarket question about 
a marketed device.''
    Finally, S. 830 requires FDA to develop a detailed post-market 
surveillance database. FDA is already developing a Web site for 522 
studies. In addition, it is our understanding that the provision in S. 
484 on clinical trial registries will be expanded to establish a 
registry for device trials, including postmarket surveillance studies. 
The proposed post-market surveillance database will be an expensive and 
costly proposition for FDA to manage and maintain. FDA has limited 
resources which are currently being supplemented by industry user fees. 
FDA's limited resources are more appropriately focused on other 
priorities.
     Improvements to the Proposed Pediatric HDE Program: 
AdvaMed supports the provision in S. 830 to add a pediatric-specific 
Humanitarian Device Exemption (HDE) program to the existing HDE 
program. The goal of this new program is to ensure pediatric access to 
needed devices. However, because there continues to be little 
information on the size of pediatric populations associated with 
specific conditions, it is unknown what affect applying the general HDE 
annual population cap of 4,000 (for designation as a Humanitarian Use 
Device (HUD)) to children's devices may have on the availability of 
devices to treat pediatric conditions.\2\ AdvaMed recommends the 
Secretary be given authority to selectively raise the cap for specific 
pediatric conditions when FDA determines the health of pediatric 
patients requires an increase in excess of the annual distribution 
number--based on medical, demographic and scientific information 
provided by a petitioner.
---------------------------------------------------------------------------
    \2\ An Humanitarian Use Device (HUD) is a device that is intended 
to benefit patients by treating or diagnosing a disease or condition 
that affects or is manifested in fewer than 4,000 individuals in the 
United States per year. To obtain approval for an HUD, an humanitarian 
device exemption (HDE) application is submitted to FDA. An approved HDE 
authorizes marketing of the HUD. However, an HUD may only be used in 
facilities that have established a local institutional review board 
(IRB) to supervise clinical testing of devices and after an IRB has 
approved the use of the device to treat or diagnose the specific 
disease.
---------------------------------------------------------------------------
    AdvaMed believes that selective and careful raising of the cap for 
HUD designation is unlikely to be abused as a ``shortcut'' path to 
market by medical device manufacturers. The HDE program currently 
requires a manufacturer to provide evidence of safety to FDA as well as 
likelihood of effectiveness--before FDA will grant an exemption. 
Further, under current HDE regulations, a manufacturer seeking an HDE 
must demonstrate that no comparable devices are available to treat or 
diagnose the disease or condition and that they could not otherwise 
bring the device to market. Furthermore, FDA currently actively wields 
its authority to withdraw HDEs as witnessed by FDA's recent HDE 
withdrawals.
    AdvaMed also believes that existing pediatric HDEs should 
automatically qualify for the new pediatric HDE program to ensure the 
continued availability of these HDEs and so as not to disadvantage 
those companies who have previously made significant investments in the 
development of pediatric HDEs. Not doing so may lead to voluntary 
withdrawals from the HDE program.
     Make Better Use of Existing FDA Regulatory Tools: S. 830 
includes an important reminder to FDA that it should use certain valid 
scientific evidence mechanisms at its disposal in order to improve 
pediatric device access. Specifically, the bill reminds FDA that it may 
use adult data to support a determination of reasonable assurance of 
safety and effectiveness and that it may extrapolate between pediatric 
subpopulations where appropriate. AdvaMed recommends that the 
legislation be expanded to include other, similar types of valid 
scientific evidence mechanisms.
    FDA frequently utilizes valid scientific evidence other than well-
controlled trials, but is reluctant to take advantage of some types of 
valid scientific evidence in the case of pediatrics. We believe that 
highlighting FDA's existing statutory and regulatory authority to 
utilize other forms of valid scientific evidence i.e., other than 
evidence from well-controlled trials, by explicitly reiterating this 
authority in pediatric device legislation--as Senator Dodd did with the 
extrapolation of adult data--will encourage FDA to accept such data 
when appropriate and result in more cleared and approved pediatric 
devices. Encouraging CDRH to make use of all forms of valid scientific 
evidence is also responsive to the extremely small numbers of pediatric 
patients with any one condition or disease state (which makes it 
difficult to accrue adequate clinical trial populations in a timely 
fashion). It will also help minimize the use of pediatric surgical 
interventions as the control, especially where numerous articles 
document the effectiveness of a particular off-label use of a device 
and it has become the standard of care. In some instances, particularly 
surgical interventions, doctors are reluctant to randomize pediatric 
patients to a control arm if the off-label use of the device is the 
pediatric standard of care. This barrier prevents the off-label use of 
the device from ever becoming on-label.
    AdvaMed's recommended statutory language would retain and emphasize 
the existing standard of reasonable assurance of safety and 
effectiveness. Importantly, under AdvaMed's language, FDA would retain 
full control. Where FDA has specific concerns, nothing would require 
FDA to clear or approve a device utilizing any of these forms of valid 
scientific evidence. See the attachment for a full description of 
AdvaMed's proposals in this area.
     Establish New Compassionate Use Pediatric Device 
Provision: During the 2004 pediatric stakeholder meetings, pediatric 
clinicians repeatedly reported that they felt compelled to ``jerry-
rig'' or modify existing devices to treat pediatric patients. While FDA 
has a custom device program intended to address this problem, 
manufacturers have been reluctant to participate because the rules are 
unclear and custom devices are limited to just a few patients. AdvaMed 
has heard from manufacturers that they, on occasion, are compelled to 
choose between complying with FDA requirements and pediatric patients 
with the knowledge and heavy burden that their decision to adhere to 
FDA requirements may result in a dire outcome for the child. Based on 
available information, it appears these situations are not infrequent. 
Unfortunately, the Dodd legislation does not address this critical 
situation.
    Rather than having pediatric clinicians across the country 
individually jerry-rig devices during surgery AdvaMed proposes a well-
regulated mechanism to provide device access for super-small, 
pediatric, orphan populations that are not likely to be served by the 
proposed pediatric HDE program. AdvaMed recommends that FDA be required 
to develop regulations that would allow manufacturers to distribute no 
more than 100 unapproved devices annually for pediatric patients when 
such patients are afflicted with diseases or conditions that affect too 
few patients annually to justify the expense necessary to achieve an 
approved device under the HDE program. Appropriate controls would be 
statutorily mandated including: (1) compliance with quality system, 
labeling, adverse event reporting, device tracking and post-market 
surveillance regulations; (2) device promotion would be limited to 
medical professionals and no claims of safety or effectiveness could be 
made; (3) the manufacturer would be required to notify the Secretary 
upon the first shipment of such a device; (4) maintenance of records of 
each shipment of such a device; (5) limitation of distribution to 
prescription use only; (6) institutional review board approval would be 
required for each use of such a device; and (7) informed consent 
prominently informing the patient and the patient's parent or legal 
guardian that the device not approved by the United States Food and 
Drug Administration would be required.

    In conclusion, AdvaMed looks forward to continuing to work with 
Senator Dodd and committee members toward consideration and approval of 
strong pediatric legislation to enhance pediatric device access.
                                 ______
                                 
Attachment.--AdvaMed Proposals Intended to Make Better Use of Existing 
  FDA Regulatory Tools to Enhance Pediatric Access to Medical Devices

    For each of the proposals below, AdvaMed's recommended statutory 
language would retain and emphasize the existing standard of reasonable 
assurance of safety and effectiveness. Further, under AdvaMed's 
recommended language, FDA would retain full control--nothing would 
require FDA to clear or approve a device utilizing any of these forms 
of valid scientific evidence.

    1. Proposal: Where appropriate FDA should use objective performance 
criteria (OPCs), historical controls or well-documented case histories 
as endpoints to show effectiveness.
    Background: Reliance on well-documented case histories and 
historical controls would take advantage of the existing literature, 
respond to the extremely small numbers of pediatric patients with any 
one condition (which makes it difficult to run statistically valid 
clinical trials in a timely fashion--as one person put it ``20 years of 
literature vs. years to put together a control group'') and help 
minimize the use of surgical interventions as the control where devices 
have been established as the standard of care..
    2. Proposal: Extrapolation of clinical data between different sizes 
of the same device based on engineering testing and other non-clinical 
data.
    Background: Currently, FDA requires clinical evidence on the full 
range of device sizes for a particular device and it can be difficult 
to assemble enough patients at either end of the size ranges to be 
valid. It is extremely challenging to get data on the smaller and 
larger sizes. This proposal would allow the use of non-clinical and 
bench data to approve the full range of sizes.
    3. Proposal: Reliance on non-clinical data for modifications of 
devices specifically approved for pediatric patient populations, when 
such modifications are unrelated to changes in intended use.
    Background: Modifications are frequently made to devices (e.g., 
material changes, etc.). Every time a modification is made to a device 
(e.g., material changes or minor design changes), FDA has often 
required that the device be cleared or approved again. The requirements 
for clinical data in this process limit improvements for pediatric 
devices. Due to the challenges associated with gathering clinical data 
for pediatrics (small populations, parental unwillingness to have 
children participate, timeliness, etc.), the intent of this provision--
for devices specifically approved for pediatric use--is to enable use 
of engineering and bench testing, rather than clinical testing for 
minor device changes when the changes are not related to the intended 
use of the device. FDA has the flexibility to do this, but should be 
specifically encouraged to do so in the case of pediatric products.
    4. Proposal: The acceptance of 510(k) devices intended for adult 
populations with the same use as a pediatric device as predicates for 
the 510(k) pediatric device.
    Background: Similar to the language proposed in the Dodd 
legislation which allows FDA to use adult data to support a reasonable 
assurance of safety and effectiveness in pediatric populations and to 
extrapolate data between pediatric populations, this provision would 
give FDA the authority, where the course of the disease or effect of 
the device is the same in adults and in pediatrics, to use the adult 
510(K) device as a predicate for the pediatric device. It is intended 
to be responsive to the extremely small numbers of pediatric patients 
with any one condition (which makes it difficult to run valid clinical 
trials in a timely fashion) and to help limit the number of children 
exposed to surgical controls. FDA can still require a clinical trial 
for a 510(k) device but the trial would be smaller and the time to 
market would be faster.
    5. Proposal: The acceptance--as an appropriate control for 
investigational pediatric devices--of devices intended for use in adult 
populations when such devices provide the only device-related means for 
treating, diagnosing or preventing diseases or conditions in pediatric 
patients and have become the standard of care for such patients.
    Background: Similar to the language proposed in the Dodd 
legislation which allows FDA to use adult data to support a reasonable 
assurance of safety and effectiveness in pediatric populations and to 
extrapolate data between pediatric populations, this provision is 
intended to provide FDA with authority to utilize as the control for an 
Investigational Device Exemption, devices that are not approved for 
pediatric use but that are already being used in pediatric populations. 
This would enable the adult data on already approved devices or these 
devices themselves to serve as the ``control'' for the pediatric trial, 
responding to the limited number of pediatric patients available for 
pediatric trials and reducing the number of children exposed to a 
surgical control.

  Prepared Statement of the Pharmaceutical Research and Manufacturers 
                           of America (PhRMA)

    The Pharmaceutical Research and Manufacturers of America (PhRMA) 
appreciates the opportunity to provide a written statement for the 
record regarding the reauthorization of the Best Pharmaceuticals for 
Children Act (BPCA). PhRMA is the Nation's leading trade association 
representing research-based pharmaceutical and biotechnology companies 
that are devoted to inventing new, life-saving medicines.

                HISTORY OF PEDIATRIC EXCLUSIVITY PROGRAM

    Historically in the United States, significant disincentives 
existed to conduct clinical trials for pediatric use (generally 
speaking under the age of 16) of a medicine developed primarily for 
adult use. Among other factors, exposure to product liability and 
medical malpractice were prominent disincentives. Prior to enactment of 
the pediatric exclusivity provisions in the Food and Drug Modernization 
Act of 1997 (FDAMA), there were concerns that many FDA-approved drugs 
had not yet been clinically tested in children. For example, about 70 
percent of medicines used in children had been dispensed without 
adequate pediatric dosing information.\1\ Growing recognition of the 
need for pediatric-specific information prompted action by Congress and 
the U.S. Food and Drug Administration (FDA).
---------------------------------------------------------------------------
    \1\ U.S. Pediatric Studies Incentive Led to New Labeling for Nearly 
100 Drugs, Impact Report, Tufts Center for the Study of Drug 
Development, Vol. 7, No. 4, July/August 2005.
---------------------------------------------------------------------------
    Congress responded by providing incentives to encourage 
manufacturers to conduct pediatric studies of medicines with potential 
uses as medicines for children. FDAMA included a provision that granted 
pharmaceutical firms a 6-month pediatric exclusivity upon the 
completion of studies on the effects of a drug upon children that meet 
the terms of a written request from FDA. The 6-month period begins on 
the date that the existing patent or data exclusivity protection on the 
innovator drug would otherwise expire. Pediatric exclusivity 
encompasses any drug product with the same active ingredient. Although 
FDAMA included a sunset provision effective January 1, 2002, Congress 
subsequently reauthorized these provisions in the BPCA in 2002. The 
BPCA sunsets on October 1, 2007, unless reauthorized.
    The BPCA, like the statute as it operated prior to passage of BPCA, 
provides a voluntary incentive to pharmaceutical companies of 6 months 
of marketing exclusivity for conducting pediatric studies of drugs that 
the FDA determines may be useful to children. The FDA can issue 
requests for pediatric studies of both on- and off-label uses of a 
drug. In order to qualify for pediatric exclusivity, FDA must first 
issue a written request for pediatric studies. An FDA written request 
contains such information as the indications and number of patients to 
be studied, the labeling that may result from such studies, the format 
of the report to be submitted to the FDA, and the timeframe for 
completing the studies. Response to the written request is voluntary. 
The pediatric studies must be completed by the deadline specified in 
the FDA's written request and submitted in the form of a new drug 
application (NDA) or a supplement. Six months of pediatric exclusivity 
is granted if the studies conducted ``fairly respond'' to FDA's written 
request and are conducted in accordance with ``commonly accepted 
scientific principles and protocols.'' Also as part of the 2002 
reauthorization, a new fund was established at the National Institutes 
of Health to support the study of off-patent drugs, which are not 
eligible for the incentive.
    In addition to the BPCA, the Pediatric Research Equity Act (PREA) 
gives FDA the authority to require studies of drugs for the on-label 
indication only, i.e., when the use being studied in children is the 
same as the approved adult indication. PREA gave FDA the authority to 
require manufacturers to conduct pediatric testing for certain new 
drugs and biologics and produce formulations appropriate for children, 
e.g., liquids or chewable form tablets. PREA applies to products that 
are already on the market only if FDA determines that the absence of 
pediatric labeling poses a significant threat and after it exhausts the 
possibility of funding the pediatric studies through other public and 
private sources. In addition, PREA also applies only if the product is 
likely to be used in a substantial number of children and represents a 
meaningful benefit over medicines already on the market.

    PEDIATRIC EXCLUSIVITY PROGRAM HAS GREATLY ADVANCED MEDICAL CARE 
                              OF CHILDREN

    The pediatric exclusivity program has been a tremendous success. 
According to FDA, the current pediatric exclusivity program has done 
more to spur research and generate critical information about the use 
of medicines in pediatric patients than any other government 
initiative.\2\ For example, by the end of 2006, FDA had issued 336 
written requests for 782 pediatric studies involving 46,000 
children.\3\ In comparison, between 1990 and 1997, only 11 products 
were studied in children.\4\ Moreover, the drugs studied under BPCA are 
used to treat more than 17 broad categories of diseases in children.\5\ 
And one of the most devastating diseases in children--cancer--was the 
most prevalent disease category for which drugs were studied under 
BPCA.\6\
---------------------------------------------------------------------------
    \2\ The Pediatric Exclusivity Provision, January 2001 Status Report 
to Congress,'' FDA, 2001.
    \3\ Pediatric Study Costs Increased 8-Fold Since 2000 as Complexity 
Level Grew, Impact Report, Tufts Center for the Study of Drug 
Development, Vol. 9, No. 2, March/April 2007.
    \4\ Jennifer Li, et al., ``Return of Clinical Trials Performed 
Under the Pediatric Exclusivity Program,'' JAMA, Vol. 297, No. 6, 
February 7, 2007.
    \5\ Pediatric Drug Research: Studies Conducted under Best 
Pharmaceuticals for Children Act,'' GAO-07-557 (March 2007), at 5.
    \6\ Id. at 21.
---------------------------------------------------------------------------
    The public health benefits of these developments are undeniable. 
According to the American Academy of Pediatrics, ``Pediatricians are 
now armed with more information about which drugs work and what 
doses.'' \7\ Likewise, a February 2007 study published in the Journal 
of the American Medical Association (JAMA) found that, ``The 
exclusivity program . . . represents a unique opportunity to expand our 
knowledge of the safety and efficacy of products used in children.'' 
The study concluded, ``. . . the greatest return of the exclusivity 
program is the benefits derived in obtaining new information relevant 
and applicable toward the care of children, and this benefit should not 
be compromised.'' \8\
---------------------------------------------------------------------------
    \7\ ``FDA Joins Children's Health Groups to Mark Historic Milestone 
for Pediatric Drugs,'' FDA Press Release, December 19, 2005.
    \8\ Jennifer Li, op cit.
---------------------------------------------------------------------------
    So far, the completed and ongoing studies have resulted in the 
development of new formulations to cover additional and younger 
patients and the development of novel clinical trial designs and tools 
to evaluate safety and effectiveness. Requests for studies have been 
made in a wide range of therapeutic areas, including treatment of 
fever, skin conditions, heart disease, HIV, seizure, cancer, endocrine 
problems, gastrointestinal disorders, and more. According to a recent 
U.S. Government Accountability Office (GAO) report, the most frequently 
studied drugs were those to treat cancer, neurological and psychiatric 
disorders, metabolic diseases, cardiovascular disease, and viral 
infections. GAO also found that nearly half of the 10 drugs most 
frequently prescribed for children have been studied under the BPCA.\9\ 
The range of conditions addressed, the variety of drugs being studied 
and the nature of the scientific data all confirm that the pediatric 
exclusivity incentive is working and successfully meeting the unmet 
medical needs in children.
---------------------------------------------------------------------------
    \9\ ``Pediatric Drug Research: Studies Conducted under Best 
Pharmaceuticals for Children Act,'' GAO-07-557 (March 2007).
---------------------------------------------------------------------------
    In less than 10 years, the program has resulted in studies on about 
120 diseases and conditions and has led to new labeling on about 120 
new or already approved drugs for use in children.\10\ The recent GAO 
study found that almost all of the drugs (87 percent) that had been 
granted pediatric exclusivity under the BPCA have had important 
labeling changes as a result of pediatric drug studies conducted under 
BPCA.\11\ According to GAO, the labeling of drugs was often changed 
because the pediatric drug studies revealed that children may have been 
exposed to ineffective drugs, ineffective dosing, overdosing, or 
previously unknown side effects.\12\ The Elizabeth Glaser Pediatric 
AIDS Foundation has stated, ``the [pediatric exclusivity] incentives 
are proven to deliver life-saving information for children--the same 
information that we expect and demand for ourselves as adults.'' \13\
---------------------------------------------------------------------------
    \10\ Pediatric Study Costs Increased 8-Fold Since 2000 as 
Complexity Level Grew, Impact Report, Tufts Center for the Study of 
Drug Development, Vol. 9, No. 2, March/April 2007.
    \11\ Pediatric Drug Research: Studies Conducted under Best 
Pharmaceuticals for Children Act, GAO-07-557 (March 2007).
    \12\ Id.
    \13\ ``FDA Joins Children's Health Groups to Mark Historic 
Milestone for Pediatric Drugs,'' FDA Press Release, December 19, 2005.
---------------------------------------------------------------------------
Legislation Acknowledges Inherent Difficulties in Conducting Pediatric 
        Studies
    The legislation also has been a success because it addressed one of 
the fundamental impediments that in the past hampered the conduct of 
pediatric studies--the small number of pediatric patients. Fortunately, 
most children are healthy. In the adult population, there are larger 
numbers of patients who suffer from diseases like heart disease and 
diabetes and are available for clinical trials. In contrast, with 
pediatric patients, serious and chronic illness is caused by a wide 
range of diseases, but for the most part there are few children 
affected by any particular disease. For example, fewer than 0.5 percent 
of patients with arthritis are children, and juvenile rheumatoid 
arthritis is a different disease than adult rheumatoid arthritis and 
osteoarthritis.
    This limited pediatric patient population has several 
consequences--first, clinical trials are more difficult to conduct with 
children. The trials are smaller because there are fewer children with 
a given condition. The children are also of different ages. As a 
result, they may need different, age-appropriate formulations of 
medicines for accurate and safe administration. In addition, the 
pharmacokinetics of drugs (i.e., the rate at which they are absorbed) 
varies by age.
    Coupled with these technical, scientific, ethical and medical 
issues, there are also unique regulatory requirements relating to the 
study of drugs in children. Sometimes, a development program for 
pediatric drugs must include the duplication of an entire clinical 
program for each of the pediatric age categories for which an 
indication is sought. So, for example, if the clinical development 
program included adults 16 years of age and older and the sponsor 
wishes to investigate safety and efficacy in children 12 to 16, 
tolerance studies may be required. These tests can be followed by 
bioavailability and finally safety and efficacy in children with the 
disease. If the sponsor then chooses to seek the indication in children 
ages 6 to 12, the initial studies would again be tolerance studies 
followed by bioavailability studies before the safety and efficacy 
studies could begin. This process could continue for the age groups 
below 6 years of age, i.e., 3 to 6, 1 to 3, 6 months to 1 year and less 
than 6 months.
    It is clear that a clinical development program necessary to 
address all age groups for children can be more extensive than a 
development program needed to address the age group 16 to 65. And, once 
formulations are produced and validated, studies are performed, 
regulatory hurdles are met, and labeling is ultimately changed, the 
market for most medications for children is very limited. The enactment 
of the pediatric exclusivity incentive in FDAMA and later reauthorized 
in BPCA have made these hurdles less daunting and more feasible for 
companies to overcome.

   DESPITE RISING COSTS AND ADDED COMPLEXITIES, COMPANIES ARE STILL 
                      RESPONDING TO THE INCENTIVE

    According to the Tufts Center for the Study of Drug Development 
(hereafter referred to as the Tufts Center), the cost, length, and 
complexity of pediatric studies have expanded significantly since 2000. 
Despite that trend, companies are still investing and engaging in this 
important research and responding to FDA written requests at very high 
numbers. The GAO found that most of the on-patent drugs for which FDA 
requested pediatric studies under BPCA were being studied.\14\ This 
conclusion is supported by the Tufts Center, which found an 84 percent 
industry response rate to FDA written requests for pediatric 
studies.\15\ This exceeds the 80 percent response rate expected in 
FDA's 2001 Status Report to Congress.
---------------------------------------------------------------------------
    \14\ Pediatric Drug Research: Studies Conducted under Best 
Pharmaceuticals for Children Act, GAO-07-557 (March 2007).
    \15\ Pediatric Study Costs Increased 8-Fold Since 2000 as 
Complexity Level Grew, Impact Report, Tufts Center for the Study of 
Drug Development, Vol. 9, No. 2, March/April 2007.
---------------------------------------------------------------------------
Scope, Time and Costs of Pediatric Studies Expanded Significantly in 
        Recent Years
    From 2000 to 2006, the scope of pediatric studies has expanded 
significantly. For example, the average number of patients per written 
request increased 178 percent between 2000 and 2006, while the average 
number of studies per written request rose 60 percent.\16\ There was 
also a doubling of the share of programs required to perform long-term 
follow-up studies (from 17 percent in 2000 to 33 percent in 2006) 
during this same time period.\17\
---------------------------------------------------------------------------
    \16\ Id.
    \17\ Id.
---------------------------------------------------------------------------
    Additionally, the time required to complete pediatric studies 
nearly doubled between 2000 and 2006. Several factors contributed to 
the lengthening of study times, including increased complexity and 
scope of studies, as well as the availability of patients, 
investigators, and facilities, access to FDA staff, to name a few.\18\ 
In addition to time, the average cost to respond to a written request 
increased 8-fold from 2000 to 2006. Total average out-of-pocket costs 
to complete a written request went from $3.93 million in 2000 to $30.82 
million in 2006 (nominal dollars).\19\ While these increases may have 
led some to speculate that the number of pediatric studies would 
decrease overall, the evidence clearly shows that this has not been the 
case.
---------------------------------------------------------------------------
    \18\ Id.
    \19\ Id.
---------------------------------------------------------------------------
Number of Efficacy and Safety Studies Grew by 60 Percent From 2000 to 
        2006; Most Studied New Drugs in Development and New Indications
    The cumulative number of pediatric studies completed since 1998 
rose from 58 at the end of 2000 to 568 at the end of 2006. Sponsors 
increased the proportion of efficacy and safety studies--the most 
expensive and time-consuming studies--from 25 percent in 2000 to 40 
percent in 2006. Sponsors are continuing to break new ground--for 
example, 20 percent of written requests were for new drugs in 
development, 40 percent were for unapproved indications, while just 40 
percent were for already approved indications.\20\ Thus, even in the 
face of rising costs and increasing scope and complexity of pediatric 
studies, sponsors continue to respond.
---------------------------------------------------------------------------
    \20\ Id.
---------------------------------------------------------------------------
        THE PEDIATRIC EXCLUSIVITY INCENTIVE SHOULD REMAIN INTACT

    The pediatric exclusivity incentive has had a tremendous positive 
impact on the lives of children. The current program is working well 
and its basic features should not be altered. Changes in the current 
program could reduce the incentive to conduct pediatric studies.
Exclusivity is Not a Guarantee
    It is important to remember that despite the incentive the 
pediatric exclusivity program has provided, pediatric studies are done 
at risk. As a preliminary matter, the FDA may determine that a 
company's studies do not fairly respond to the written request and 
therefore the company would be denied exclusivity. Further, programs 
may fail due to technical reasons, lack of sufficient patients, 
problems with study design, inadequate time to complete studies prior 
to loss of exclusivity, etc. In fact, according to the Tufts Center, 
about half of submitted pediatric studies led to an award of pediatric 
exclusivity; the rest were rejected or were still awaiting an FDA 
decision by the end of 2006.\21\
---------------------------------------------------------------------------
    \21\ Id.
---------------------------------------------------------------------------
    In addition, even when a company is granted exclusivity, the value 
of such exclusivity may be diminished (or nullified) due to other 
factors. For example, a successful Paragraph IV patent challenge by a 
generic competitor may nullify any pediatric exclusivity award. In this 
instance, a company does not benefit from the grant of pediatric 
exclusivity for the product at issue. Approval of new products in the 
same class may reduce market share for a product as well, thereby 
diminishing the value of any pediatric exclusivity. These scenarios are 
not easily predictable, particularly at the early stage of drug 
development in which pediatric studies must be contemplated. So, even 
in the instance where a company is granted pediatric exclusivity, there 
is not a guarantee of what the value of that incentive may be down the 
road due to potential early generic entry or diminished market share as 
a result of increased class competition.

Majority of Medicines Studied by Sponsors Were Not in the Top 200 
        Sellers; Blockbuster Drugs Receiving Pediatric Exclusivity Have 
        Helped to Build the Necessary Infrastructure for Sustainability 
        and Continued Growth of Pediatric Programs
    Pharmaceutical companies have pursued pediatric studies for many 
products that are not top-selling medicines. In fact, less than half of 
the products that received pediatric exclusivity were in the top 200 
selling drugs, according to the Tufts Center.\22\ Some of these include 
medicines for HIV/AIDS, leukemia, anti-infectives, antihistamines and 
anesthetic drugs. In addition, only about one-tenth of drugs awarded 
pediatric exclusivity were in the ``blockbuster'' category.\23\
---------------------------------------------------------------------------
    \22\ U.S. Pediatric Studies Incentive Led to New Labeling for 
Nearly 100 Drugs, Impact Report, Tufts Center for the Study of Drug 
Development, Vol. 7, No. 4, July/August 2005.
    \23\ Id.
---------------------------------------------------------------------------
    While blockbuster drugs represent only one-tenth of the drugs 
awarded pediatric exclusivity, the exclusivity benefits of one 
blockbuster drug can support pediatric studies for other drugs and can 
support and expand infrastructure for pediatric drug programs. As with 
drug development in general, higher revenue drugs support the ability 
of pharmaceutical companies to invest in research for medicines with 
lower expected revenue. In the case of pediatrics, not only have 
blockbuster drugs allowed companies to invest in research for lower 
revenue products, they have also given companies the ability to build 
pediatric programs and infrastructure over the past decade. Prior to 
enactment of the pediatric exclusivity incentive, such infrastructure 
did not exist.
    According to Dr. Floyd Sallee, M.D., Ph.D., a child psychiatrist 
and director of the pediatric pharmacology research unit at Cincinnati 
Children's Hospital Medical Center, ``There was no infrastructure for 
the research before . . . Drug companies have hired pediatric experts 
and there is a larger network of expertise to draw from.'' \24\ Dr. 
Sallee's comments were echoed by an industry expert, Dr. Stephen 
Spielberg, M.D., Ph.D., ``The legislation has encouraged the 
development of needed infrastructure, highly specialized staffing 
needed to develop pediatric formulations and to perform pediatric 
clinical studies.'' \25\ Similarly, the GAO has testified that, 
``Experts agree that, since FDAMA, there also has been significant 
growth in the infrastructure necessary to conduct pediatric studies . . 
. The pharmaceutical industry has also increased its capacity to 
conduct pediatric studies since enactment of FDAMA.'' \26\
---------------------------------------------------------------------------
    \24\ ``Drug Research and Children,'' FDA Consumer (January--
February 2003), http://www.fda.gov/fdac/features/2003/103 drugs_html.
    \25\ Testimony of Stephen P. Spielberg, M.D., Ph.D., before the 
Senate Committee on Health, Education, Labor, and Pensions, Hearing on 
Pediatric Drug Development, May 8, 2001.
    \26\ S. Rep. No. 107-79 (October 4, 2001).
---------------------------------------------------------------------------
    Revenues from top-selling products can support pediatric and adult 
drug research and development in other ``non-blockbuster'' areas. 
``Since research resources are allocated across drug portfolios . . . 
these medicines indeed provide the fuel to drive research and 
development of less remunerative compounds . . .'' \27\ Dr. Spielberg 
continued, ``For currently marketed drugs, establishing and maintaining 
excellent pediatric drug development programs can be driven to some 
extent by higher income medicines.'' \28\
---------------------------------------------------------------------------
    \27\ Id.
    \28\ Id.
---------------------------------------------------------------------------
    Congress has also recognized the relationship between the incentive 
and development of pediatric research infrastructure. ``The [Senate 
HELP] Committee is aware that the incentives created by the pediatric 
exclusivity provision have encouraged the drug industry to develop and 
expand its infrastructure and expertise in the study of drugs in 
pediatrics.'' \29\
---------------------------------------------------------------------------
    \29\ S. Rep. No. 107-79, October 4, 2001.
---------------------------------------------------------------------------
    The pediatric exclusivity incentive must be preserved to ensure 
that pediatric drug development is not hindered in the face of 
uncertainty over likelihood of reauthorization and rising research 
costs. Diminishing or otherwise reducing the value of the incentive 
could also create unintended ripple effects across the entire program. 
While some have argued the return some products (namely blockbuster 
drugs) have received as a result of pediatric exclusivity are not in 
line with the cost of the studies undertaken, the fact is that 
blockbuster drugs have created the ability for companies to invest in 
pediatric programs and infrastructure necessary to conduct research 
across a company's portfolio. Taking away or reducing the incentive for 
blockbusters could have unintended consequences across the program.
    Regardless of other aspects of health economics and health-care 
financing, the small number of pediatric patients with a specific 
disease available for study, the rising costs and added complexity of 
the studies, and the ultimate limited market for pediatric drugs will 
remain. That is why it is important to maintain the robust public 
policy that to date has so successfully promoted research on children's 
needs.

                               CONCLUSION

    PhRMA strongly urges Congress to reauthorize the BPCA. The 
increasing rate of industry study proposals and written requests for 
studies by FDA shows continuing progress, which would be significantly 
undermined if this important legislation 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.

   Prepared Statement of the Society for Cardiovascular Angiography 
                           and Interventions

    The Society for Cardiovascular Angiography and Interventions 
supports the Pediatric Medical Device Safety Act of 2007. We greatly 
appreciate this effort to expand pediatric patients' access to safe 
medical devices. This proposal will be an important step forward.
    The Society for Cardiovascular Angiography and Interventions (SCAI) 
is a professional association representing over 3,700 invasive and 
interventional cardiologists. SCAI promotes excellence in cardiac 
catheterization, angiography, and interventional cardiology through 
physician education and representation, and quality initiatives to 
enhance patient care.
    Fortunately, cardiovascular disease is far less common in the 
pediatric population than it is in the adult population. This good 
fortune does however frequently lead to unique challenges for the 
pediatric interventional cardiologist who treats these patients. Some 
of the challenges are clinical and we are more frequently solving those 
problems, saving children's lives and avoiding the trauma of surgery. 
Other challenges, and perhaps the most frustrating ones are related to 
obtaining the safe medical devices necessary to treat these patients. 
Devices that are available to our colleagues in Europe are not 
available in America. We support the FDA's efforts to ensure that only 
safe and effective medical devices are used on patients in our country, 
but when the entry barriers into the American markets are so high that 
manufacturers refuse to enter--some patients suffer and die needlessly. 
Required is an appropriate balance between the sometimes mutually 
exclusive goals of safety and availability.
    We are especially pleased that your legislation will require the 
FDA to issue guidance to institutional review committees (IRCs) on how 
to appropriately consider the use of the humanitarian device exemption 
(HDE) at their institution. When HDE devices are not part of an ongoing 
trial, IRC's (which focus on reviewing the care of patients in trials) 
are sometimes confused.
    We believe that giving the FDA explicit statutory authority to 
extrapolate from adult to pediatric patients in appropriate situations 
could help FDA officials expedite their review of some pediatric 
medical devices.
    We applaud the provision that allows companies to make a profit on 
HDE devices designed for children. This change will encourage the 
development of more devices by providing an opportunity for profit and 
also by reducing concerns about audits, specifically those using 
different assumptions which could determine a profit was made when a 
manufacturer calculated their financial situation differently. We note 
that the 4,000 cap is arbitrary and far below the limit that is placed 
on orphan drugs. We believe that more devices could be made available 
to pediatric patients and those with congenital heart disease if that 
cap is raised. We encourage you to consider such an increase either as 
a part of this legislation or broader FDA reform legislation.
    We also understand that there are some concerns on the part of 
industry about the section 522 provisions of this proposal. As 
clinicians, we are not in a position to evaluate the precise impact of 
those provisions but we certainly hope those concerns can be resolved.
    We look forward to working with you and your staff to support 
passage of this legislation and thank you once again for your efforts. 
SCAI's contact person regarding this legislation is Wayne Powell and he 
may be reached at (202) 375-6341 or [email protected].
                                 ______
                                 
   American Academy of Orthopaedic Surgeons (AAOS),
                                Washington, DC. 20002-5701,
                                                    March 22, 2007.
Hon. Edward M. Kennedy,
Chairman,
Committee on Health, Education, Labor, & Pensions,
Senate Dirksen Office Building,
Washington, DC 20510.

    Dear Chairman Kennedy: The American Association of Orthopaedic 
Surgeons (AAOS) representing 17,000 board-certified orthopaedists 
thanks you for your continued commitment to pediatric issues. As one of 
the founding members of the Orthopaedic Device Forum comprised of 
liaisons from the Centers for Medicare and Medicaid Services, the Food 
and Drug Administration (FDA), the National Institute of Arthritis and 
Musculoskeletal and Skin Diseases, the National Institute of Biomedical 
Imaging and Bioengineering, the Orthopaedic Research Society, the 
Orthopaedic Surgical Manufacturers Association, the American Society 
for Testing and Materials, and the American Orthopaedic Association, 
the AAOS has a long history of working directly with the FDA on 
concerns of advancing orthopaedic patient care.
    As stakeholders with significant use of medical devices, AAOS 
fellows treat many pediatric patients. Our association is committed to 
advocating for regulatory policies that provide for optimal patient-
centered care while adhering to the least burdensome provisions of the 
Food and Drug Administration Modernization Act (FDAMA).
    The AAOS appreciates your committee's willingness to work with all 
stakeholders on the Pediatric Medical Device Safety and Improvement Act 
of 2007 (S. 830). Bringing small volume products to the U.S. market is 
a complex problem with important nuances. Therefore, we are concerned 
that some of the provisions, if enacted into law, will have unintended 
consequences of discouraging the development of pediatric devices. Our 
letter will highlight some concerns with provisions in the legislation 
including postmarket surveillance, post-market surveillance 
investigations, humanitarian device exemptions, clinical trials 
database, and the proposed consortium.

                        POSTMARKET SURVEILLANCE

    The AAOS believes that a lengthy post-market surveillance mandate 
will hinder pediatric device development as there is no ceiling 
attached to the language. The FDA has sufficient authority in Sec. 522 
of the Federal Food, Drug, and Cosmetic Act to extend postmarket 
surveillance beyond 36 months and has negotiated 10-year postmarketing 
studies with the manufacturers of two of the last successful 
orthopaedic pre-market approvals. Several large manufacturers 
communicated their aversion to developing and producing devices with a 
long post-market surveillance review, particularly with small volume 
products, as they cannot recoup their development costs.

                POST-MARKET SURVEILLANCE INVESTIGATIONS

    Moreover, expertise on post-market surveillance event 
investigations resides within the Centers for Devices and Radiological 
Health. While the Office of Pediatric Therapeutics may serve as a 
coordinating center, they do not possess the experience to evaluate 
device adverse events. The AAOS suggests that this language be amended 
to reflect the appropriate Federal authorities assigned to investigate 
adverse events.

                  HUMANITARIAN DEVICE EXEMPTIONS (HDE)

    While the AAOS does not take a position on manufacturers' ability 
to capture a profit on HDE devices, the AAOS contends that a lengthy 
Institutional Review Board (IRB) process is a deterrent to at least two 
of the current manufacturers of pediatric HDEs in the U.S. market. 
Delays of up to 5 years were reported to the AAOS due to 
misunderstandings of the IRBs reviewing a marketed product rather than 
original research. Since the FDA issued a guidance document in January 
2006 on this topic, communication between the IRBs and the FDA about 
the contents of this guidance may facilitate more expeditious IRB 
reviews.
    In any case, humanitarian devices are generally sold in the tens or 
hundreds; as such, profit potential is limited. If profit potential is 
to be allowed on HDE devices, AAOS recommends the application of the 
same policy for all currently marketed humanitarian devices regardless 
of whether the indications are for use in pediatrics, adults, or those 
devices with general labeling. This policy will help ensure that the 
currently marketed HDEs remain on the U.S. market.
    Determining the number of humanitarian devices for an appropriate 
indication and then subsequently capping the number at 4,000, seems to 
be a sub-optimal use of resources. The AAOS suggests maintaining the 
cap of 4,000 and deleting any provisions to determine an annual 
distribution when submitting a humanitarian use device designation.

                        CLINICAL TRIALS DATABASE

    As you are aware, the FDA has very limited funding and as such, the 
AAOS finds the new clinical trials database to include information on 
Sec. 522 devices very resource intensive. This database is also 
duplicative of some post-market surveillance efforts currently underway 
at the FDA. To have useful public utility, databases should answer 
important research questions. This database does not appear to be 
linked to the adverse event databases at the FDA; therefore it appears 
to serve more of a public educational function, rather than a clinical 
outcomes function.

                               CONSORTIUM

    The AAOS appreciates that $6 million per annum will be devoted to 
pediatric device development through the consortium for fiscal years 
2008-2012. Substantial outcomes must be delivered and parties must be 
held accountable for considerable progress in the development of 
pediatric devices.

                  REGULATORY VS. LEGISLATIVE SOLUTIONS

    Our experience has affirmed that many problems can be solved with a 
change in regulatory interpretation or alterations to FDA regulatory 
policy. After 11 years, the Orthopaedic Device Forum accomplishments 
include device reclassifications, guidance document development, and 
defining a regulatory pathway for a previously un-marketed product all 
without legislative interventions.
    The AAOS supports significantly increased appropriations for the 
FDA to carry out the important mission of protecting and promoting the 
public's health. Furthermore, with our years of experience in working 
with the FDA, we hope that your office will consider the AAOS as a 
resource for FDA issues. We look forward to working with you.
            Sincerely,
                                      James H. Beaty, M.D.,
                                                    AAOS President.

    [Whereupon, at 2:40 p.m., the hearing was adjourned.]

                                    

      
