[House Hearing, 110 Congress]
[From the U.S. Government Publishing Office]
ASSESSING THE IMPACT OF A SAFE AND
EQUITABLE BIOSIMILAR POLICY IN THE
UNITED STATES
=======================================================================
HEARING
BEFORE THE
SUBCOMMITTEE ON HEALTH
OF THE
COMMITTEE ON ENERGY AND COMMERCE
HOUSE OF REPRESENTATIVES
ONE HUNDRED TENTH CONGRESS
FIRST SESSION
__________
MAY 2, 2007
__________
Serial No. 110-40
Printed for the use of the Committee on Energy and Commerce
energycommerce.house.gov
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COMMITTEE ON ENERGY AND COMMERCE
JOHN D. DINGELL, Michigan,
Chairman
HENRY A. WAXMAN, California
EDWARD J. MARKEY, Massachusetts
RICK BOUCHER, Virginia
EDOLPHUS TOWNS, New York
FRANK PALLONE, Jr., New Jersey
BART GORDON, Tennessee
BOBBY L. RUSH, Illinois
ANNA G. ESHOO, California
BART STUPAK, Michigan
ELIOT L. ENGEL, New York
ALBERT R. WYNN, Maryland
GENE GREEN, Texas
DIANA DeGETTE, Colorado
Vice Chairman
LOIS CAPPS, California
MIKE DOYLE, Pennsylvania
JANE HARMAN, California
TOM ALLEN, Maine
JAN SCHAKOWSKY, Illinois
HILDA L. SOLIS, California
CHARLES A. GONZALEZ, Texas
JAY INSLEE, Washington
TAMMY BALDWIN, Wisconsin
MIKE ROSS, Arkansas
DARLENE HOOLEY, Oregon
ANTHONY D. WEINER, New York
JIM MATHESON, Utah
G.K. BUTTERFIELD, North Carolina
CHARLIE MELANCON, Louisiana
JOHN BARROW, Georgia
BARON P. HILL, Indiana JOE BARTON, Texas
Ranking Member
RALPH M. HALL, Texas
J. DENNIS HASTERT, Illinois
FRED UPTON, Michigan
CLIFF STEARNS, Florida
NATHAN DEAL, Georgia
ED WHITFIELD, Kentucky
BARBARA CUBIN, Wyoming
JOHN SHIMKUS, Illinois
HEATHER WILSON, New Mexico
JOHN B. SHADEGG, Arizona
CHARLES W. ``CHIP'' PICKERING,
Mississippi
VITO FOSSELLA, New York
STEVE BUYER, Indiana
GEORGE RADANOVICH, California
JOSEPH R. PITTS, Pennsylvania
MARY BONO, California
GREG WALDEN, Oregon
LEE TERRY, Nebraska
MIKE FERGUSON, New Jersey
MIKE ROGERS, Michigan
SUE WILKINS MYRICK, North Carolina
JOHN SULLIVAN, Oklahoma
TIM MURPHY, Pennsylvania
MICHAEL C. BURGESS, Texas
MARSHA BLACKBURN, Tennessee
Professional Staff
Dennis B. Fitzgibbons, Chief of
Staff
Gregg A. Rothschild, Chief Counsel
Sharon E. Davis, Chief Clerk
Bud Albright, Minority Staff
Director
(ii)
Subcommittee on Health
FRANK PALLONE, Jr., New Jersey, Chairman
HENRY A. WAXMAN, California NATHAN DEAL, Georgia,
EDOLPHUS TOWNS, New York Ranking Member
BART GORDON, Tennessee RALPH M. HALL, Texas
ANNA G. ESHOO, California BARBARA CUBIN, Wyoming
GENE GREEN, Texas HEATHER WILSON, New Mexico
Vice Chairman JOHN B. SHADEGG, Arizona
DIANA DeGETTE, Colorado STEVE BUYER, Indiana
LOIS CAPPS, California JOSEPH R. PITTS, Pennsylvania
TOM ALLEN, Maine MIKE FERGUSON, New Jersey
TAMMY BALDWIN, Wisconsin MIKE ROGERS, Michigan
ELIOT L. ENGEL, New York SUE WILKINS MYRICK, North Carolina
JAN SCHAKOWSKY, Illinois JOHN SULLIVAN, Oklahoma
HILDA L. SOLIS, California TIM MURPHY, Pennsylvania
MIKE ROSS, Arkansas MICHAEL C. BURGESS, Texas
DARLENE HOOLEY, Oregon MARSHA BLACKBURN, Tennessee
ANTHONY D. WEINER, New York JOE BARTON, Texas (ex officio)
JIM MATHESON, Utah
JOHN D. DINGELL, Michigan (ex
officio)
------
Professional Staff
John Ford, Senior Counsel
Jack Maniko, Counsel
Robert Clark, Policy Coordinator
Ryan Long, Minority Chief Counsel for Health
Melissa Sidman, Clerk
C O N T E N T S
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Page
Hon. Frank Pallone, Jr., a Representative in Congress from the
State of New Jersey, opening statement......................... 1
Hon. Mike Rogers, a Representative in Congress from the State of
Michigan, opening statement.................................... 3
Hon. Henry A. Waxman, a Representative in Congress from the State
of California, opening statement............................... 3
Hon. Nathan Deal, a Representative in Congress from the State of
Georgia, opening statement..................................... 5
Hon. Gene Green, a Representative in Congress from the State of
Texas, opening statement....................................... 6
Hon. Mike Ferguson, a Representative in Congress from the State
of New Jersey, opening statement............................... 7
Hon. John D. Dingell, a Representative in Congress from the State
of Michigan, opening statement................................. 8
Hon. Tim Murphy, a Representative in Congress from the
Commonwealth of Pennsylvania, opening statement................ 8
Hon. Marsha Blackburn, a Representative in Congress from the
State of Tennessee, opening statement.......................... 9
Hon. Lois Capps, a Representative in Congress from the State of
California, opening statement.................................. 10
Hon. Hilda L. Solis, a Representative in Congress from the State
of California, opening statement............................... 11
Hon. Heather Wilson, a Representative in Congress from the State
of New Mexico, opening statement............................... 11
Hon. Jim Matheson, a Representative in Congress from the State of
Utah, opening statement........................................ 12
Hon. Joe Barton, a Representative in Congress from the State of
Texas, prepared statement...................................... 12
Hon. Tammy Baldwin, a Representative in Congress from the State
of Wisconsin, opening statement................................ 14
Hon. Darlene Hooley, a Representative in Congress from the State
of Oregon, opening statement................................... 14
Hon. Anna G. Eshoo, a Representative in Congress from the State
of California, opening statement............................... 15
Prepared statement........................................... 16
Hon. Jan Schakowsky, a Representative in Congress from the State
of Illinois, opening statement................................. 17
Hon. Bart Gordon, a Representative in Congress from the State of
Tennessee, prepared statement.................................. 18
Hon. Edolphus Towns, a Representative in Congress from the State
of New York, prepared statement................................ 18
Witnesses
Janet Woodcock, M.D., Deputy Commissioner, Chief Medical Officer,
Food and Drug Administration................................... 20
Prepared statement........................................... 22
Answers to submitted questions............................... 176
William Schwieterman, M.D........................................ 63
Prepared statement........................................... 66
David Schenkein, M.D., vice president, clinical hematology/
oncology, Genentech, Incorporated.............................. 77
Prepared statement........................................... 78
Answers to submitted questions............................... 182
Geoffrey Allan, president, chief executive officer, chairman of
the board, Insmed, Incorporated................................ 87
Prepared statement........................................... 89
Answers to submitted questions............................... 157
Richard F. Kingham, partner, Covington & Burling................. 91
Prepared statement........................................... 94
Bruce Downey, chairman of the board, Generic Pharmaceutical
Association, chairman and chief executive officer, Barr
Pharmaceuticals, Incorporated.................................. 115
Prepared statement........................................... 116
Answers to submitted questions............................... 161
Ruth Hoffman, executive director, the Candlelighters Childhood
Cancer Foundation.............................................. 121
Prepared statement........................................... 123
Ed Weisbart, M.D., chief medical officer, medical affairs,
Express Scripts, Incorporated.................................. 125
Prepared statement........................................... 127
Answers to submitted questions............................... 168
Submitted Material
AARP, statement.................................................. 145
William Samuel, director, Department of Legislation, AFL-CIO,
statement...................................................... 152
Scott McKibbin, special advocate for prescription drugs, State of
Illinois....................................................... 153
Priya Mathur, vice-chair, health benefits-board of
administration, California Public Employees' Retirement System,
statement...................................................... 140
Coalition for a Competitive Pharmaceutical Market, statement..... 142
ASSESSING THE IMPACT OF A SAFE AND EQUITABLE BIOSIMILAR POLICY IN THE
UNITED STATES
----------
WEDNESDAY, MAY 2, 2007
House of Representatives,
Subcommittee on Health,
Committee on Energy and Commerce,
Washington, DC.
The subcommittee met, pursuant to call, at 10:05 a.m., in
room 2123 of the Rayburn House Office Building, Hon. Frank
Pallone, Jr. (chairman) presiding.
Members present: Representatives Pallone, Waxman, Gordon,
Eshoo, Green, DeGette, Capps, Allen, Baldwin, Schakowsky,
Solis, Hooley, Matheson, Dingell, Deal, Wilson, Pitts,
Ferguson, Rogers, Myrick, Sullivan, Murphy, Burgess, Blackburn,
and Barton.
Also present: Representative Inslee.
Staff present: Jack Maniko, John Ford, Bobby Clark, Virgil
Miller, Lauren Bloomberg, Melissa Sidman, Jesse Levine, Nandan
Kenkermath, Chad Grant, and Ryan Long.
OPENING STATEMENT OF HON. FRANK PALLONE, JR., A REPRESENTATIVE
IN CONGRESS FROM THE STATE OF NEW JERSEY
Mr. Pallone. This hearing is called to order. Today the
subcommittee is meeting to hear about assessing the impact of a
safe and equitable biosimilar policy in the United States.
Needless to say, the topic of today's hearing is of great
importance and has generated a lot of interest over the past
few months. Recent advancements in science have resulted in a
new class of innovative medicines commonly referred to as
biologics. These biotech drugs are complex molecules that are
typically derived from living organisms which are designed to
treat a number of chronic and often debilitating diseases.
While older versions of these products have existed for many
years, manufacturers have made great strides in developing a
broader range of biologic products that treat a greater number
of conditions and illnesses. Diabetes, cancer, heart disease,
multiple sclerosis are among a range of devastating illnesses
for which there are now new treatments because of improvements
in the research and development of biologics. As a result,
these lifesaving and life-enhancing therapies have given
patients and their families a renewed sense of hope for a
longer and better life.
Because of the great promise biologics hold, they are one
of the fastest-growing components of the pharmaceutical market.
Unfortunately, however, they are one of the most expensive. The
price of a biologic can be substantial as well as prohibitive.
Take insulin, for example. It was noted in a recent New York
Times article that the drug cost State Medicaid programs $500
million in 2005. Furthermore, people who suffer from diabetes
in this country, as well as Government and private insurers,
spend a combined $3.3 billion a year on insulin. Researchers
have suggested, however that the price of insulin might drop 25
percent if generic or follow-on versions were made available.
The savings would accrue to many, including patients,
employers, and insurers. Competition from generic versions of
chemical drugs have proven to be an effective way to help lower
healthcare costs. As we all know, a generic drug can cost 30
percent to 80 percent less than its equivalent brand-name drug.
In 2005, the average prescription filled with a brand-name
product cost $95.54. The average cost for a generic filled with
a generic drug was $28.71, and that is a savings of nearly $70
on the average prescription.
We need to apply what we learn from generic versions of
chemical drugs and biologic products so that we can produce
measurable savings. That is what I believe that Mr. Waxman has
attempted to, with introduction of his legislation. He has
introduced a bill called the ``Access to Lifesaving Medicine
Act'' of which I am a co-sponsor. In 1984, you all know that
Mr. Waxman paved the way for safe and affordable generic drugs
to enter the market easily, and we were still preserving
incentives for brand-name companies to develop new and
innovative therapies. As we search for a way to lower costs and
preserve innovation with biologics, Mr. Waxman is once again an
authoritative voice in this debate, and I thank him for
directing our attention to this important issue. Thank you,
Henry.
Congress, I believe, needs to approve a pathway for generic
biologics to be brought to the market, and this will be a
priority for our subcommittee. I know many of my other
committee members, and I will mention Mr. Inslee, Mr. Green,
Ms. Baldwin, Ms. Eshoo, and others have also indicated their
eagerness to address this important issue; and I am looking
forward to gathering their input as we move forward as well.
While I am a co-sponsor of the Access to Lifesaving
Medicine Act, I will be the first to admit that the legislation
is not without controversy. Over the course of the past few
months, I have heard from numerous stakeholders on this issue
and believe that each side has its own merits. Several
questions continue to arise. What level of science will be used
to determine comparability standards for these new products?
What amount of science should be used to determine
interchangeability? Who should make such determinations? Should
it be Congress or the expert agency that we have typically
charged with the regulation of drugs and biologics? How do we
preserve innovation while achieving price competition? And how
do we strike a balance between protecting intellectual property
but ensure that generic versions of biologics are approved and
enter the market in a timely manner. These are some of the
questions whose answers will shape the debate and help us
determine how the FDA approves safe and effective generic or
follow-on versions of biologic products.
I just want to thank all of our witnesses for being here
today. You represent the experts in the field and will tell you
that the members of the subcommittee are eager to hear what you
have to say and ask questions of you, so thank you for being
here and I am certain that today's hearing will be extremely
informative for all of us.
Mr. Deal will be here soon, so I will now introduce the
gentleman from Michigan, Mr. Rogers.
OPENING STATEMENT OF HON. MIKE ROGERS, A REPRESENTATIVE IN
CONGRESS FROM THE STATE OF MICHIGAN
Mr. Rogers. Thank you, Mr. Chairman. I will be brief. I am
looking forward to the testimony.
I do get concerned about the direction we take. The average
biologic takes about 15 years in development, $1.2 billion to
develop. And the harder we make it for people to go through
that process, or at least some degree of certainty to recoup
their losses and their investment, it concerns me greatly. I am
not sure that we are going to insert any great innovation to
cheaper and better and quality drugs.
My other great concern in the bill is that we haven't
really addressed the security issue. A lot of these biologics
now are using twin-strand therapeutic issues. Bryson, abrin,
viscumin, things that were highly regulated by the FDA; and if
we had to throw this open, I get very, very concerned about how
we keep and maintain the safety and security of those
particular agents when developing these biologics.
So I have a lot of questions today, and I look forward to
the debate and I know all our intentions are good; and
hopefully at the end of the day, we will do no harm before we
seek to do any good.
Thank you, Mr. Chairman. I yield back.
Mr. Pallone. Thank you, and I recognize Mr. Waxman.
OPENING STATEMENT OF HON. HENRY A. WAXMAN, A REPRESENTATIVE IN
CONGRESS FROM THE STATE OF CALIFORNIA
Mr. Waxman. Thank you, Mr. Chairman, for calling this
hearing today.
Biotech drugs, also known as biologics, have emerged as one
of the fastest-growing categories of drugs. Some of these
medicines are literally lifesavers for people with a host of
serious diseases, but these products are also among the most
expensive medications for U.S. consumers. Patients who need
these drugs often have to pay hundreds of thousands of dollars
a year for them. Although it is true many people have insurance
to cover the cost of these drugs, those who have 20 percent co-
pays still owe thousands of dollars a year, and it is obviously
a very serious problem for the 47 million uninsured. They have
to pay the whole price. More likely than not, they go without
the lifesaving drugs.
The rapidly escalating cost of biotech drugs will have
drastic consequences for the healthcare system. These medicines
are steadily driving up the cost of Medicare, Medicaid, and
health insurance overall. This is a burden that cannot be
sustained. The Federal Government will be hard pressed to
afford it. The private sector is already pleading for relief.
I have long believed that marketplace competition is the
best way to bring down drug prices, but unless the FDA is given
the clear, legal authority to approve copies of biologics,
there will be no generic competition for biotech drugs, leaving
employers, insurers, and the Federal Government to pay the
staggering monopoly prices we have today.
Earlier this year, Mr. Chairman, you and I and some of our
colleagues introduced the Access to Lifesaving Medicines Act.
This bill ensures only safe and effective biologics will be
approved. It gives FDA complete discretion to require a full
complement of testing, including clinical testing on the
product, if FDA believes that is necessary to require tests. If
FDA does not believe it is necessary is only another way to
delay generic competition.
There are a lot of issues to be discussed here, patient
safety, intellectual property rights, the incentives for
innovation to name a few; but I would like to note that since
we first introduced this bill the debate on these issues has
dramatically changed. At first the opposition claimed there
should not be an abbreviated pathway for generic biologics at
all. Now, the question that everyone is asking, even the
opposition, is not if but how to establish a pathway. It is
important to note there is a very broad base of support for
this legislation. There is currently a wide-ranging coalition
of over 40 consumer groups, health plans, and businesses who
have endorsed the bill. With so many supporters of the bill, we
had some hard decisions about our witnesses today and we
obviously could not have all of them present. So I would like
to ask unanimous consent to add to the printed record the
written statements of some of these groups that could not be
here today. I have statements from the AARP, the Coalition for
Competitive Pharmaceutical Marketplace, the California Public
Employees Retirement System, and the AFL-CIO.
These and many other groups all recognize that the time to
move forward with establishing an abbreviated pathway is now.
Opponents have attempted to attack the bill by arguing
competition will only lower prices by a small amount. Well,
even a small amount could bring in billions of dollars of
savings. We have to find a way to introduce competition into
this market. We need that balance that we tried to achieve in
1984, and we were successful at doing it, giving incentives for
development of new products but bringing about the benefits of
competition in the marketplace. Too often we hear now, as we
heard in the mid-1980's, we need all the incentives. Give us a
permanent monopoly. Don't provide competition, these
competitors are not as good, they can't be as safe. Well, let
us look a little bit more skeptically because those were the
arguments we heard then. They were wrong then and they are
wrong now. Thank you, Mr. Chairman.
Mr. Pallone. Thank you, Mr. Waxman. Without objection we
will introduce those statements into the record.
Mr. Deal. Mr. Chairman, could I ask unanimous consent that
others might introduce similar-type comments on this, any other
member of the committee?
Mr. Pallone. Absolutely.
I will recognize the ranking member.
OPENING STATEMENT OF HON. NATHAN DEAL, A REPRESENTATIVE IN
CONGRESS FROM THE STATE OF GEORGIA
Mr. Deal. Thank you, Mr. Chairman. This morning's hearing
addresses an exciting and changing realm of the pharmaceutical
industry. The biologic pharmaceutical market has grown
dramatically in recent years, and the FDA has steadily approved
new biologic medications. Growth in this market is only
forecast to increase in the future. I am sure most members at
this point understand that biologics have a greater complexity
than traditional drugs, and there is not an appropriate pathway
at the FDA for follow-on protein products. I would hope this
hearing would help guide the committee to inform us about what
framework would be suitable for the approval of follow-on
products in a manner that assures patient safety because for
me, that is the heart of this issue.
I realize there are varying opinions along this line. Some
contend legislation ought to mandate clinical trials while
others feel this determination should be left to the FDA.
Certainly we must ensure the FDA has the tools to approve safe
and effective medications and allow them to use their
discretion and expertise when evaluating follow-on product
applications.
We also ought to act in a way that will adapt to the
changes and signs in the field of biotechnology in the coming
years. While the Hatch-Waxman Act was passed over 20 years ago,
legislation has largely stood the test of time and provided a
workable solution to get low-cost generic products to
consumers. As the biologic drug market continues to grow and
the science advances, legislation should be able to accommodate
those changes, not hinder them, recognizing that while the
science may not be there today, it could be tomorrow.
One of the most difficult aspects of this issue is to
provide a balance between incentives for innovation while
allowing similar lower-cost products to come to market. Hatch-
Waxman provides these incentives for innovation in the form of
market exclusivity and patent term restoration. As we strike
this balance, I believe we do need to provide some period of
market exclusivity as an incentive for innovation while
ensuring that the judicial process and patent litigation can be
resolved in a fair and timely manner. Other countries are
already acting on this issue, and the Congress needs to provide
a pathway for the approval of follow-on biologics in this
country. We have an opportunity to provide patients access to a
lower cost alternative for their needed medications. While the
fund is unclear, the degree of savings that could be achieved
with a follow-on protein product for status quo is no longer
acceptable and ignores the possibilities presented by generic
biologics. By no means does the committee face an easy task.
This is a complex subject, and we must wrestle with a number of
scientific, regulatory, intellectual property, and safety
issues. However, I do believe we can resolve and balance these
issues in order to provide patients' access to safe, lower-cost
medications.
Thank you, Mr. Chairman. I will yield back my time.
Mr. Pallone. Thank you. I recognize our vice chair, Mr.
Green.
OPENING STATEMENT OF HON. GENE GREEN, A REPRESENTATIVE IN
CONGRESS FROM THE STATE OF TEXAS
Mr. Green. Thank you, Mr. Chairman, for holding the hearing
on follow-up biologics and the issues we must consider for
developing a pathway for regulatory approval of biosimilars.
This extremely complex issue and whatever way we resolve it
will have significant implications for employers, innovators,
generic industry, and most importantly, the patients who depend
on these life-improving and lifesaving therapies. There is no
question we have to get this right, and this hearing represents
a good first step toward the goal by giving Members a chance to
dig deeper into this issue and weigh the risk and benefits of
any movement forward on biosimilars.
I think we can agree that there needs to be the regulatory
pathway in this country to follow-on biologics. Canada, the
European Union, and Australia each put in place pathways for
the approval of follow-on biologics.
We have also recognized the undeniable fact that biologics
are very different from small molecule drugs and present unique
concerns about safety and effectiveness. Unlike small molecule
drugs, biologics are created using living cells that are
intended to imitate proteins that will naturally occur in the
body if the patient were healthy. The time and expense that
goes into making biologics is much greater than the process of
manufacturing a small molecule drug. So it is no surprise that
these therapies are quite expensive for consumers and
purchasers. I share the goal of lowering patients' cost of a
follow-on pathway but not at the expense of those same
patients' safety and not if it results in stifling the
innovation that would produce new, more effective therapies and
potentially a cure for the incurable diseases we see too many
of our family members and neighbors fight day in and day out.
The issue of drug safety is at the heart of this debate and
the primary reason why I co-sponsored the legislation sponsored
by my colleague from Washington, Jay Inslee. We all seem to
come to the same conclusion that an exact replica of a biologic
product cannot be made. The questions remain what effect does a
small change in the amino acid sequence produce and is that
effect large enough and concerning enough to warrant additional
clinical trials before the follow-on biologic is available to
the public? Can we in good conscience consider these follow-on
drugs safe if they have never been tested on a human
population? Several of my colleagues will certainly reply that
the FDA is equipped to make that decision on a case-by-case
basis and that we shouldn't be legislating science. I have no
doubt the FDA has top-rate scientists on its payroll and are
more than capable of making these decisions. But it would be
disingenuous for us to point to the Vioxx and Ketek and why we
need drug safety reform at FDA and in the next breath give FDA
carte blanche authority to approve any follow-in biologic
without some sort of clinical trials for safety and
effectiveness.
We also need to make sure we don't cut off our nose to
spite our face in this debate. Biologics offer tremendous
promise in the treatment of disease, but there are too many
patients out there waiting for the improved treatment or cure
that can only be achieved through innovation. My concern is we
will rush to facilitate copies of old therapies at the expense
of new therapies. Any action by this committee is to balance
the desire to lower the cost of biologics with the need to
preserve the incentives for innovation so that more Americans
can benefit from the therapeutic promise of biologic products.
Mr. Chairman, I hope the committee will keep this delicate
policy balance at the forefront of the debate as we move
forward, and again, I would like to thank our witnesses for
appearing today; and I yield back my time.
Mr. Pallone. Thank you. I recognize my colleague from New
Jersey, Mr. Ferguson.
OPENING STATEMENT OF HON. MIKE FERGUSON, A REPRESENTATIVE IN
CONGRESS FROM THE STATE OF NEW JERSEY
Mr. Ferguson. Thank you, Mr. Chairman, and thank you for
holding this hearing.
The creation of a pathway for the approval of follow-on
biologics is really a tremendous opportunity, and it has to be
done with a great deal of thought and with thorough
consideration for all of the potential risks and benefits that
might come with such a pathway; and it has to be done with
obviously a great deal of scrutiny and a great deal of
thoughtfulness.
It is a great opportunity but is one that has to provide
the framework to ensure that the public is not placed in danger
by being exposed to replicas of these complex biologics that
haven't been thoroughly vetted for safety. We must ensure that
the approval of follow-on biologics is based on the same
rigorous standards of safety and purity and potency that is
applied by the FDA for the approval of the original biological
product. I think common sense would dictate that.
Clinical trial data and evidence are vital for establishing
the safety and efficacy of highly complex biologic products.
Testing has to be done to avoid putting patients at risk for
effects of an adverse immune system response. In addition to
safety, we also have to handle this opportunity correctly so as
not to risk the development of future lifesaving therapies. We
must include proper protections to foster innovation and
further secure our position as the world's medicine chest,
leading the world of lifesaving therapies to humanity's most
horrific diseases. The creation of a pathway for approval to
follow-on biologics is laudable, but we should not rush to
create a pathway while being blinded by potential savings from
follow-ons. We shouldn't rush to save a buck and put people's
lives in danger.
A recent analysis from the healthcare research firm,
Avalare, finds that follow-on biologics will save about $3.6
billion over 10 years. Now, $3.6 billion is a lot of money. It
is considerable, but we have to ask the question of what is the
cost of those savings?
Mr. Chairman, we have a great opportunity but also a
tremendous responsibility. Today is the first step toward
taking on that responsibility and taking advantage of this
opportunity. I look forward to working with you and the others
on this committee to make sure that we get this right. And I
yield back.
Mr. Pallone. Thank you. I now recognize the chairman of our
full committee, Mr. Dingell.
OPENING STATEMENT OF HON. JOHN D. DINGELL, A REPRESENTATIVE IN
CONGRESS FROM THE STATE OF MICHIGAN
Chairman Dingell. Thank you for holding this hearing. It is
important. We are here to discuss the anticipated impact of a
safe and equitable biosimilar policy in the United States. When
the Congress granted the Food and Drug Administration the
authority to approve generic versions of pharmaceuticals in
1984, we could not have foreseen the need for a similar pathway
for generic biologics. Since then, the biotechnology industry
has grown tremendously, and a number of biological products are
on the market, treating a variety of medical conditions
including life-threatening illnesses such as cancer, multiple
sclerosis, diabetes, and HIV/AIDS. In some instances, these
biological products are the only available therapy. In others,
biotechnology represents a clear clinical advantage over all
other available therapies. As this industry continues to
discover potentially lifesaving therapies, more patients will
depend on these products. Unfortunately, not all patients can
afford these needed therapies and must therefore forego needed
treatments. We must find a way to ensure greater access as this
science progresses. There is broad agreement that we should
create a pathway for biosimilars.
As we explore this idea, it is necessary that our solutions
are grounded in science and fair to consumers. Innovators as
well need financial stability to sustain their research into
groundbreaking therapies. One issue that confronts us now as
policymakers is the science behind biosimilars. What standards
will ensure that the generic biologics are as safe as the
original products? How will they function in the human body?
Should clinical trials be required for approval of biosimilars?
Can a generic product be created that is genuinely
interchangeable? Can and should a manufacturer of a biosimilar
product duplicate the innovator's manufacturing process to
avoid potentially adverse reactions? Patients' safety must be
our guiding principle in searching for an appropriate pathway.
I am pleased that this hearing is being held today. I look
forward to the testimony of our witnesses as well as the input
of our members. It is my intention to work with my colleagues
on the committee to craft a sensible and fair biosimilar policy
and to work with my colleagues to achieve this goal in the
110th Congress. Your efforts this morning, Mr. Chairman, and
this hearing is a very important part of our effort in that
regard. Thank you.
Mr. Pallone. Thank you, Chairman Dingell. Mr. Murphy.
OPENING STATEMENT OF HON. TIM MURPHY, A REPRESENTATIVE IN
CONGRESS FROM THE COMMONWEALTH OF PENNSYLVANIA
Mr. Murphy. Thank you, Mr. Chairman. This hearing again
points out the cycle of the issues Congress must deal with. We
want medications that will save our lives, enhance our lives,
and also treat disease. In order to do that, we need research
and development work which costs billions of dollars. Clinical
trials must be undertaken in a scientifically balanced and
reliable fashion, that we want Government agencies such as the
FDA to review them carefully to test the products while they
are trying to balance the pressure to get drugs to the public
and the market in order to save lives and treat disease but at
the same time having pressure on them to make sure they test
them for all the safety factors. All this comes in the context
of the public's call for affordable drugs because what good is
a drug to treat a disease if you can only window-shop that
medication and cannot really use it.
And so we are here dealing with the issue of generic or
biosimilars, to cut costs to provide some market competition,
to drive costs down, but make sure that the companies have
enough money left at the end for their research and development
which, of course, takes us back to the beginning of this whole
cycle. It is a matter that Congress constantly must deal with
that is an important part of our role here. The issues that we
must deal with in any of these bills that deal with biosimilar
drugs is to make sure that we do have portions in them that
drugs do not get to market unless thorough testing is part of
that and to make sure throughout this whole process that we are
dealing with safety, affordability, and continuing on ways that
maintain the research track which has given us so many
medications which have saved our lives.
In all of this, I hope we continue to focus on patients as
we move through healthcare issues such as these that emphasize
patient quality, patient safety, and patient choice. These
biosimilar drugs would provide all three of those if we do this
right. So I am looking forward to the comments from the
panelists today.
Thank you, Mr. Chairman. I yield back.
Mr. Pallone. Thank you. And now I recognize the gentlewoman
from Colorado.
Ms. DeGette. Mr. Chairman, I think we all have the same
goals of finding the balance, and I am looking forward to
hearing the testimony so I will waive my opening statement.
Mr. Pallone. Thank you. The gentlewoman from Tennessee.
OPENING STATEMENT OF HON. MARSHA BLACKBURN, A REPRESENTATIVE IN
CONGRESS FROM THE STATE OF TENNESSEE
Mrs. Blackburn. Thank you, Mr. Chairman. I do want to thank
you for holding the hearing and to our witnesses that will be
with us today.
We have all talked about the complex issue that follow-on
biologic medications present because they are similar, because
they are not identical like a generic drug; and so we do have
to carefully consider the standards for approval, the potential
of risk that are in that approval pathway.
When the healthcare costs are skyrocketing, and we hear
this every time we come in for a committee hearing, we know
that people are looking for new options for lowering drug
costs; and we do know that patient safety has to be a priority.
And Mr. Chairman, I hope that we will continue our discussion
on this issue at another time and look at the intellectual
property protections and infringements that may be there and
the need for recognition of that as we view what is going to be
a follow-on process.
We had the hearing a few weeks back with the FDA
Commissioner von Eschenbach, and Ketek, the drug that is there
to fight the bacterial infections, the side-effects that were
there with the clinical trials, the problems that existed. So I
think it is interesting that we are looking at a follow-on
biologic approval pathway that would not require further safety
testing.
So I am looking forward to the discussion today. I am
looking forward to what we set as a pathway and hearing from
our witnesses and having a discussion not only on the issue of
safety which is before us today but also the scientific
liability and legal consequences that may be a part of this
process, and I yield back.
Mr. Pallone. Thank you. The gentlewoman from California,
Mrs. Capps.
OPENING STATEMENT OF HON. LOIS CAPPS, A REPRESENTATIVE IN
CONGRESS FROM THE STATE OF CALIFORNIA
Mrs. Capps. Thank you, Mr. Chairman. In 1984, Congress
passed a bill that created a pathway for generic versions of
traditional chemical drugs. It was a difficult and contentious
time. But we have seen over the past 23 years how effective
this has been on accessibility to medications and lowering drug
prices, most importantly, providing continued incentives for
drug innovation without compromising public safety.
So here we are in 2007 looking at a way to create a pathway
for generic versions of biologic drugs, and we are now tasked
with preserving the same goals of innovation and safety.
Supporting innovative research into new lifesaving medications
is vitally important. I know this especially because my State
of California is such a world leader in biotechnology. I have
been impressed with how important it is that we make sure to
address patient protection and market exclusivity. However, it
is extremely important also that we improve patients' ability
to afford lifesaving medications. Quite frankly, with no
competition on the markets, biologics remain out of economic
reach for most of the people who need them.
I hope to hear today from witnesses on how we can balance
innovation with patients' needs for cheaper, more accessible
drugs. Just as for generic chemical drugs, generic biologics
have the potential to reduce costs for consumers. But we also
have to ensure that as we reduce drug prices, we maintain
safety and effectiveness. Recent drug recalls highlight the
importance of FDA's role in ensuring the safety of our drug
supply. We can't stress this point enough. So I look forward to
hearing about FDA's ability to assess follow-on biologic
safety. Also, I hope to hear more about the FDA's capability to
determine whether clinical trials may be necessary to determine
if the drug is safe for the public and in what way they can be
conducted. Scientific discovery has been moving at an
astronomical pace, and we in Congress need to encourage it as
much as possible. However, we also need to ensure that these
discoveries reach those who would benefit from them and that
the treatments are safe and effective.
I look forward to listening to today's witnesses as we
explore this very important topic. And I yield back the balance
of my time.
Mr. Pallone. Thank you. Dr. Burgess.
Mr. Burgess. Thank you, Mr. Chairman. I will waive my
opening statement and reserve time for questions.
Mr. Pallone. Next we have Ms. Solis.
OPENING STATEMENT OF HON. HILDA L. SOLIS, A REPRESENTATIVE IN
CONGRESS FROM THE STATE OF CALIFORNIA
Ms. Solis. Thank you, Mr. Chairman. Thank you for holding
this hearing today as we begin the discussion on whether FDA
has the authority to approve similar versions of biologic
medicines. I would like to thank my colleagues, Representatives
Waxman, Inslee, Baldwin, and Green for their leadership on
follow-on biologics or biosimilars. Recent scientific and
technological advances have led to the development of biologic
medicines which have great potential to address numerous
diseases, including diabetes, cancers, HIV and AIDS, all of
which affect many underserved communities, including the one
which I represent.
The strides we have made in science are exciting. The
manufacture of biologic medicines has the potential to save
millions of lives, and biologics account for approximately $30
billion in sales. However, the cost of developing and
manufacturing these biologics are extremely high; and the
average cost of a 1-day supply of biologic medicines is $45. As
a result, the cost for patients, insurers, private companies,
and Government payers are quickly growing. And I am very
concerned about the high cost of these medicines, especially
the cost of those treatments for many who lack healthcare
insurance or who are underinsured. We must strike a critical
balance between patient safety and patient access to lifesaving
medications.
I am committed to ensuring that all people have access to
affordable medicines that are safe and effective. Despite the
differences between chemical drugs and biologics, I believe
that there is a way to provide patients with generic biologic
medicines without compromising safety. The scientific experts
at FDA should be allowed to have flexibility to determine what
clinical tests are required, and we must find a balance to make
sure that new medicines continue to be developed.
I look forward to hearing from our witnesses. I yield back
the balance of my time.
Mr. Pallone. Thank you. I now recognize the gentlewoman
from New Mexico.
OPENING STATEMENT OF HON. HEATHER WILSON, A REPRESENTATIVE IN
CONGRESS FROM THE STATE OF NEW MEXICO
Mrs. Wilson. Thank you, Mr. Chairman, and thank you for
having this hearing. I think we all recognize that there are
some very difficult balances here. We all want a path or some
kind of pathway for generic biologics. We are all concerned
about safety, and of course we need to protect intellectual
property rights and give predictability to investors so that we
will allow and encourage continued innovation in the future.
And I think there is probably also general agreement that
the certification process for saying that something is
essentially identical is much more difficult in this case
because we are talking about living organisms. We are not
talking about a chemical compound. Products made from living
tissue use proteins to change the course of a condition and
have a therapeutic effect on a disease. This is very different
from dealing with chemical compounds, and I think all of us
recognize the very difficult balances we are going to have to
strike here and what was difficult with the generic drug law,
as my colleague from California mentioned, what was very
difficult at that time will be multiplied tenfold in getting
this right because the compounds are quite different and the
legislation that addresses this will be a very difficult
balance to strike.
Nonetheless, I commend the chairman and members of his
committee for their determination to tackle this issue to see
whether there is something we can do so that we create a
pathway for generics that might be at less cost for a new class
and a new kind of therapy in the area of medicine.
Thank you, Mr. Chairman.
Mr. Pallone. Thank you. I recognize the gentleman from
Utah.
OPENING STATEMENT OF HON. JIM MATHESON, A REPRESENTATIVE IN
CONGRESS FROM THE STATE OF UTAH
Mr. Matheson. Thank you, Mr. Chairman. I think it is very
important that we are talking on this issue, and I am pleased,
Mr. Chairman, that you are conducting this hearing. I think
this is a great opportunity for the legislative process to
produce a good result because this is a complicated issue.
There are some different pieces of legislation that have been
introduced now that kind of lay down some different points of
view on the issue. But my sense, having met with a number of
stakeholders over the last few weeks about this, is that there
is a reasonable solution; and if we work in a comprehensive and
bipartisan way, I think that that reasonable solution will be
attained and I think we can build consensus.
I look forward to participating in this hearing today and
in the future hearings and being part of driving towards a
reasonable solution.
With that, Mr. Chairman, I yield back the balance of my
time.
Mr. Pallone. Thank you and I now recognize our ranking
member of the full committee, Mr. Barton.
Mr. Barton. Thank you, Mr. Chairman. I will put my full
statement into the record. I think this is an important
hearing. It is a new subject and something that we need to get
right, we need to get right on a bipartisan basis, and I look
forward to the testimony and the work product that follows.
[The prepared statement of Mr. Barton follows:]
Prepared Statement of Hon. Joe Barton, a Representative in Congress
from the State of Texas
Mr. Chairman thank you for holding this hearing. The issue
of follow-on biologic products has been the source of great
debate.
This is an important, but very complex issue. Some have
suggested rushing the legislative process and include follow-on
biologic legislation on the reauthorization of the Prescription
Drug User Fee Act. I think that this is an imprudent course of
action and does a disservice to the deliberative nature of our
committee. To do so will result in policy that is not fully
vetted and the unintended consequences of our actions in this
case could risk lives.
I believe it is important that the terminology we use this
debate be accurate and precise. Generic biologics are not on
the immediate horizon; the science just isn't there. Some have
coined that term for use in this debate, but it not accurate
and muddies the waters of our discussions. Generic denotes that
the products are the same and can be freely substituted.
Follow-on products are not the same and can have different
characteristics that could result in different safety and
efficacy profiles.
No one should have a patent in perpetuity. As we have seen
with the Hatch-Waxman law of 1984, competition in
pharmaceuticals can lead to lower prices without jeopardizing
research and development into new products. follow-on biologic
competition could be a good thing if done right. I believe we
can and should create a pathway for follow-on biologic products
to be approved without having to undergo the full blown
biologics license application process. However, any abbreviated
pathway must have two important elements.
First, we should not short-change safety in the interest
of brevity. These are fundamentally different products. We will
have two witnesses today who will testify to the science of
these biologic products. The development of living organisms
into a therapeutic treatment safe for humans is not an easy
task and it is difficult top replicate. Most importantly,
however, is that any minor modification to the sequencing of
the properties of the product could have a profound effect on
the safety profile of the product. For generic drug
applications under section 505(j) of the Food, Drug, and
Cosmetic Act, applicants are not required to undergo clinical
tests to be granted approval. This can be done because the
generic applicant is producing essentially the same product
that is bioequivalent. Some have suggested that concept be
translated to the approval of follow-on biologic products.
Chemical and biologic products are truly apples and oranges,
and we should not minimize these differences or complexities of
the issues before us today.
I am looking forward to the testimony today that can shine
some light on the true scientific and safety issues this
committee should consider when drafting legislation to approve
follow-on biologic products.
Ensuring safety is our utmost priority, but we must also
consider the consequences our actions will have on the
development of new drugs and cures that have yet to be
discovered. Two weeks ago, we heard the testimony of Jim Thew,
who suffers from Lou Gehrig's disease. Only one drug is
available to treat this devastating disease, and that drug is
over 10 years old. We cannot close the door to innovation
because by doing so we will be closing the door to hope for the
millions of Americans who want and need the next breakthrough
therapy that will treat Lou Gehrig's, cancer, and a host of
other diseases.
To protect innovation and medical progress we must protect
the incentives necessary to induce investment in these areas.
Allowing a follow-on to be approved a few short years after the
innovator product may reap some short-term savings, but it will
have a devastating impact on American companies' ability to
produce new therapies. We can not be short-sighted in this
debate. Like every other industry, intellectual property must
be respected and protected. If it is not, we will see a
dismantling of the biotechnology industry in this country,
capital will find its way into other industries, and sick
Americans will get sicker.
Again, it is important to note that we are not talking
about products that are the same as we have for chemical drugs
approved under the Food, Drug, and Cosmetic Act. These
therapies are different and thus the paradigm established under
Hatch-Waxman of a short exclusivity period followed by patent
restoration may not be appropriate. We must recognize this
fundamental difference and build a regulatory scheme that
accounts for it. If a follow-on manufacturers only has to
develop a product that is comparable and not the same it may be
easier to engineer around patents. I look forward to hearing
from our witnesses on what should be the appropriate incentives
for continued innovation.
Again, Mr. Chairman, thank you for holding this hearing.
We have a distinguished panel of witnesses. I urge all Members
wto take an active, engaged role today because these are
complicated issues. This committee has a history of being
deliberative busy, we should develop policy based off the facts
at hand. This is especially true when we are talking about
products that are so important to the well being of millions of
Americans.
----------
Mr. Pallone. Thank you. I recognize the gentlewoman from
Wisconsin.
OPENING STATEMENT OF HON. TAMMY BALDWIN, A REPRESENTATIVE IN
CONGRESS FROM THE STATE OF WISCONSIN
Ms. Baldwin. Thank you, Mr. Chairman, and thank you to the
witnesses for joining us today. I am really pleased that this
subcommittee is taking up the issue of creating a pathway at
the FDA for approval of biosimilars, and as many have noted
this is a complicated issue full of highly technical,
scientific terms and procedures. The fact that we have so many
ways to refer to this issue, biosimilars, biogenerics, generic
biologics, follow-on biologics, illustrates just how
complicated the issue is and how it clearly warrants thoughtful
and thorough discussion. So I appreciate the opportunity to
delve into some of the details.
Mr. Chairman, I believe that we should have an established
process by which the FDA can approve biosimilar products.
Biologics have shown great promise in fighting a variety of
diseases and conditions, and I believe that we must ensure that
patients have access to affordable treatment. That said, I
think we also need to remember those patients who are still
waiting for their miracle treatment to be discovered. I do not
think that we should compromise future innovation so that we
can save a finite amount of money today. There is a balance
that can and actually must be struck between mere term cost
savings and future innovation. I was proud to join my
colleagues, Mr. Inslee and Mr. Green, in introducing a bill
that seeks to strike this balance. The bill establishes a
pathway, ensures that patient safety protections are in place,
yet gives the FDA flexibility in this area and provides
incentives for scientists to continue innovating and developing
potentially lifesaving treatments.
Mr. Chairman, I think one final thing for us to remember is
that the majority of biotechnology companies are not mega-
corporations or even profitable businesses. The majority of
biotech companies are small, private startups who are years
away sometimes from even having a commercial product. They are
made up of a few highly talented scientists who have made a
discovery and who want to continue to explore and refine this
discovery in hopes of one day curing cancer or finding a
treatment for Alzheimer's or growing new skin for burn victims
or responding to a host of genetic disorders for which there is
no treatment or cure or creating a better treatment for a
disease that already has a treatment, like diabetes. We should
encourage this innovation so that future patients can have
access to needed treatments just as we should ensure that
current patients have access to affordable treatments today.
Thank you, Mr. Chairman.
Mr. Pallone. Thank you. I recognize the gentlewoman from
Oregon.
OPENING STATEMENT OF HON. DARLENE HOOLEY, A REPRESENTATIVE IN
CONGRESS FROM THE STATE OF OREGON
Ms. Hooley. Thank you, Mr. Chairman. The Drug Price
Competition and Patent Term Restoration Act of 1984, better
known as the Hatch-Waxman, was instrumental in expanding access
to pharmaceuticals by instituting competition and thus lowering
prices. I believe it is important for Congress to examine the
creation of a pathway to allow the Food and Drug Administration
to approve follow-on biologics. Creating a pathway for follow-
on biologics are generally much more complex than the small-
moleculed generic drugs that have been approved under the
process established by Hatch-Waxman.
First and foremost, as we discuss the creation of a follow-
on biologics pathway, safety must obviously be our No. 1
concern.
Second, Congress must ensure science and scientists guide
the approval process. Hatch-Waxman struck an appropriate
balance between expanding access to affordable generic
medications while still encouraging innovation. Biologics have
provided some extraordinary pharmaceutical breakthroughs that
have made a real difference in the lives of people. However, in
part because of that complexity and the very high cost of
bringing biologics to market, they are often extraordinarily
expensive. It is not uncommon to see treatment cost in the
thousands and sometimes tens of thousands of dollars a year per
patients in some biologics. The savings that a follow-on
biologic pathway may provide to consumers and the increased
access that would result would be an important step forward.
However, it is also imperative that innovators be allowed to
recoup their investment. If we do not include reasonable
protection for innovators, we may discourage the development of
new products in the future; and that would be even worse for
consumers in the current situation.
America is a leader in pharmaceutical innovation, and I am
committed to ensuring that we continue that legacy. I look
forward to a discussion of intellectual property and patent law
issues raised by biosimilars, and I look forward to our
witnesses.
Thank you.
Mr. Pallone. The gentleman from Oklahoma.
Mr. Sullivan. I waive my opening statement.
Mr. Pallone. Ms. Eshoo.
OPENING STATEMENT OF HON. ANNA G. ESHOO, A REPRESENTATIVE IN
CONGRESS FROM THE STATE OF CALIFORNIA
Ms. Eshoo. Mr. Chairman, thank you for having this hearing.
I am going to place my printed statement in the record. I just
want to say a couple of things and that is in this hearing that
you have called, which is a very important one, Assessing the
Impact of a Safe and Equitable Biosimilar Policy, I think the
two words that are really the operative words are safe and
equitable. And we are going to explore that today. I am
troubled by different parts of Mr. Waxman's bill. He has always
been thoughtful when it comes to issues relating to the FDA.
The quarrel here is not pathway. Everybody is for a pathway. I
think everyone that has spoken has used that word in their
opening statement. We agree on that. Do we all want lifesaving
drugs and processes to continue to help save people's lives and
improve their lives? Everybody wants that. So there isn't any
disagreement about that. How this is done is really the rub of
the whole debate, and that is what we have to explore. I have
really never seen in legislation that has come before this
Health Subcommittee, since I have been on it since 1994, when a
legislation actually defined structural characteristics. I
mean, I thought that was the job of the FDA.
So I am looking forward to this debate. I think we need to
have bipartisan legislation in this area. Why? Because that is
what the American people will ultimately have confidence in. We
have to build that consensus. So I look forward to it. I am
eager to hear from the witnesses and question them and thank
you for having this very important hearing.
[The prepared statement of Ms. Eshoo follows:]
Prepared Statement of Hon. Anna G. Eshoo, a Representative in Congress
from the State of California
Thank you Mr. Chairman for holding what I expect will be an
enlightening hearing about a very important issue.
The greatest advances in medicine in recent decades has
been the development of powerful treatments and therapies for
disease that not only treat their symptoms, but also attack
them at the molecular level. This is made possible by
biotechnology.
We've mapped our own genome and are developing an
understanding of how deadly diseases like cancer, diabetes,
HIV, and heart disease actually attack the body and its organs.
Biotech researchers are able to analyze the mechanisms of a
disease, understand how it functions, and create
countermeasures that can cause the disease to stop reproducing,
attack itself, or starve it for nutrients. Other biologics help
the human body develop an effective response or, in some cases,
repress an overactive immune response.
This research is cutting edge, it's risky, and it's
expensive. The biotech industry spends billions on research
into new biologic treatments, but only a few hundred new
biologics are currently in clinical trial, and only a handful
of ``blockbuster'' treatments have emerged.
An example is Genentech, which is considered a founder of
the biotech industry over 30 years ago, and remains one of the
largest companies in the industry. Today it has only 14
products on the market. The vast majority of biotech firms have
only a single product approved or a small handful in
development, and it costs upwards of a billion dollars to bring
a single biologic to market.
I think it's imperative to consider this framework as we
evaluate any proposal to allow ``copycat'' versions of these
life-saving products to take advantage of the research and
investment made in biotech.
A lot of the discussion in the debate over follow-on
biologics has focused on increasing ``access'' to life-saving
medicine. Certainly the high cost of biologics can stress
patients and families, insurance companies and health care
providers. We should look at ways to make biologic products
more cost-effective. However, simply making copies of products
already on the market will not increase the number of biologic
products options available to patients. There will be nothing
to copy if we don;t ensure sufficient incentives exist to
develop these already life-saving medicines in the first place.
Finally, we can't lose sight of what I believe is our most
fundamental responsibility, and that of the FDA--protecting the
American public.
Whatever else we do, patient safety has to remain our
foremost objective and we shouldn't limit the FDA's authority
to establish mechanisms to ensure the safety and efficacy of
any medicines introduced in the market.
I agree with those who have said that a pathway for new
versions of biologic products whose patents have expired is
necessary. We also should rely on sound science and develop a
system that preserves incentives for the development of new
therapies and cures, protects patients, and allows for
competition.
I look forward to the witnesses' testimony and their
responses to our questions.
----------
Mr. Pallone. Thank you. The gentlewoman from Illinois, Ms.
Schakowsky.
OPENING STATEMENT OF HON. JAN SCHAKOWSKY, A REPRESENTATIVE IN
CONGRESS FROM THE STATE OF ILLINOIS
Ms. Schakowsky. Thank you, Mr. Speaker. Let met take a
second to express my thanks for your leadership in bringing
this extremely important legislation before our subcommittee.
Biopharmaceuticals are growing at an astonishing rate in
the United States, almost twice that of traditional medicines.
So as our country, this Congress, and this committee take on
the challenge of finding cost savings in our healthcare system,
this certainly seems like a good place to start. While opinions
vary about the level of the savings patients and the Federal
Government could gain from a pathway for generic biologics, no
one seems to dispute that the potential for savings exists; and
I think it is important to recognize that this discussion is
taking place at the State level, too. In my own State of
Illinois, for example, a compilation of approximately 100
biopharmaceuticals cost $33.2 million last year and the number
of prescriptions for these drugs rose nearly 30 percent. In
1984, the need to bring affordable prescription drugs to those
who need them was recognized with the passage of the Hatch-
Waxman Act which now brings generic versions of drugs to
consumers at about one-third of the cost. Ensuring that this
kind of access to lifesaving medicines is expanded to biologics
is a critical goal. I think that above and beyond the potential
for cost savings lies an obligation, one that I think no one
would dispute, to provide Americans with effective and safe
medications in a timely way.
Scott McKibbin, a special advocate for prescription drugs
for the State of Illinois, is an expert on issues relating to
access to safe prescription drugs. He has prepared testimony
for the subcommittee's hearing today. I would ask unanimous
consent, Mr. Chairman, to submit his remarks into the record.
Mr. Pallone. Thank you.
Ms. Schakowsky. No, I wanted to submit remarks into the
record from Scott McKibbin.
Mr. Pallone. Absolutely. So ordered and I indicated earlier
that we would allow members on both sides to submit additional
statements.
[The information appears at the conclusion of the hearing.]
Ms. Schakowsky. Let me just finish. Mr. McKibben's
testimony is an account of how State budgets are being
stretched to the limit as they struggle to maintain access to
often lifesaving biologics.
I look forward to hearing from each of our witnesses today
as well as working on the issue in the near future. Thank you,
Mr. Chairman.
Mr. Pallone. Thank you. The gentleman from Tennessee, Mr.
Gordon.
Mr. Gordon. Thank you, Mr. Chairman. I have a splendid
opening statement that I am going to submit for the record. I
think it is time to hear from our witnesses, so let me just
quickly say that healthcare costs are rising at 7 percent a
year, much outpacing economic growth in this country. It is
certainly the fastest-growing part of the Federal budget.
Probably for most families and businesses, it is probably the
fastest-growing part of their budget. So we need to look for
savingswhere we can, and I think generic drugs is certainly one
area.
However, I am concerned that follow-on biologics at this
point cannot be safely put in that same category; but I
compliment Mr. Waxman for putting this issue in play, and I
agree with Mr. Matheson that after a thorough review of this
that we can come up with a good solution here. And so I am
anxious to hear from our witnesses. Thank you.
[The prepared statement of Mr. Gordon follows:]
Prepared Statement of Hon. Bart Gordon, a Representative in Congress
from the State of Tennessee
Each year, health care consumes a larger portion of the
Nation's gross domestic product. Health care spending is
growing at 7 percent a year--far outpacing our economic growth.
Clearly, we must find ways to bring down the cost of health
care. The broader use of generic drugs will surely help. But,
sound science must support the decisions we make to ensure
patient safety is protected.
I have serious concerns about the assertion that biologics
can be treated the same as chemical pharmaceuticals. Biologics
are very different from traditional chemical drugs both in
their structural complexity and the way they are manufactured.
Any process for review and approval of generic biologics or
bio-similars must recognize these differences.
Generic chemical drugs can be examined in a laboratory with
a simple test to show that the compound is identical to the
brand name drug. Biologics can not be tested in the same way.
Currently, there is no simple battery of tests to ensure that a
generic biologic is not only comparable to the original
biologic but can be safely substituted for the original
biologic. We need a process of characterization of the
biologics to ensure that the medication is what we believe it
should be.
The Food and Drug Administration has told Congress that it
could be a decade or more before the science is available to
safely approve generic versions of biologic drugs. I hope it
will take less than a decade to develop reliable tests for
biologic drugs. And, we should look closely at the European
model that relies heavily on clinical testing before
deployment.
Mr. Chairman, I thank you for holding this hearing and look
forward to learning more from the witnesses on these issues.
----------
Mr. Pallone. Thank you. I think that concludes our opening
statements. Any other statements for the record will be
accepted at this time.
[The prepared statement of Mr. Towns follows:]
Prepared Statement of Hon. Edolphus Towns, a Representative in Congress
from the State of New York
Thank you, Mr. Chairman, for holding this important
hearing today on what is truly a very complex issue.
Advances in science during the past 25 years have resulted
in tremendous breakthroughs in how diseases are treated today.
Biotechnology has been at the forefront of these advances and
holds the greatest hope for patients who suffer from
devastating diseases such as cancer, multiple sclerosis, and
diabetes. These biotech treatments, called biologics, are
highly complex proteins made from living cells--they are
fragile molecules which are thousands of times larger than the
simple, small molecule chemical pills that we find in our
medicine cabinets. This molecular complexity requires a costly
research and development process that results in a high price
for healthcare payers.
I thank the chairman of this committee for bringing forth
the debate on how to lower these costs and provide greater
access to these life-saving drugs for our constituents. I
believe that Congress should act this year to establish an
abbreviated process for follow-on-biologics, just as we did in
1984 for chemical pills through Hatch-Waxman. However, the
science is different and far more advanced than in 1984 and we
need to take that into account as we craft a new pathway for
follow-ons. While a generic company can take a chemical pill
and replicate its structure to make an exact copy, I understand
the same may not be true for biologics.
Since follow-on products will be made from different cell
lines and produced through different processes than the
original innovator products, it seems that there will
inevitably be variability in any attempted copies. Given these
differences, the traditional generic drug approval pathway
seems inappropriate. It is imperative that the FDA know how any
differences between biological products and processes will
affect a patient before we allow shortcuts to be taken in the
approval process, and I believe that clinical trials are
crucial to ensuring patient safety. Dr. Janet Woodcock
testified in front of the Oversight and Government Reform
Committee last month that it will likely be a matter of 10
years before the science is available to fully classify and
compare these drugs. In our rush to save dollars, we must not
ignore that there is a great deal that we do not know, and I
look forward to learning more from Dr. Woodcock this morning.
The issue of follow-on biologics is a very complex one and
it would be irresponsible of this Congress to act in this area
without knowing all of the scientific facts. We need to be sure
that we understand the science before we rush into legislating.
I urge the committee to do just that--take the time and not
rush the learning process and not stick a bill onto the first
moving vehicle.
To balance the concerns over cost, patient safety, and
protection of U.S. innovation, I became a co-sponsor of H.R.
1956, the Patient Protection and Innovative Biologics Medicines
Act. This bill was introduced by our colleagues,
Representatives Inslee, Baldwin, and Green and takes a balanced
approach to the issue. Any legislation we move out of this
committee must strike the appropriate balance in getting
follow-on biologic medicines approved and on the market, while
at the same time providing incentives for innovation so that
America retains its lead in the field of biotechnology and the
next-generation of life-saving medicines continue to be
developed.
We are all aware of the critical problem of rising health
costs, and the havoc it is wreaking on budgets. There is
probably nothing more welcome in these halls than a chance to
save taxpayers money on healthcare. Visions of dollars saved
are a powerful motivator. My concern is that we don't stampede
common sense in the rush to save money. Let's not, for example,
create a bill that eliminates rewards for creating the latest,
most ground-breaking medicines. Let's be sure to include clear
safety requirements that are appropriate for the level of
complexity of the different drugs. Let's allow doctors, not
insurers, to decide which of these drugs are appropriate for
patients. This is a new scientific arena that Congress is
entering. Dr. Jane Woodcock testified in front of the
Government Oversight Committee last month that it will likely
be a matter of 10 years before the science is available to
fully classify and compare these drugs. In our rush to save
dollars, we must not ignore that there is a great deal that we
do not know. In situations where we don't know, I feel we must
err on the side of protecting patients from undue harm, and
protecting their futures by not squelching the pipeline for new
treatments.
Any legislation we move out of this committee must strike
the appropriate balance in getting follow-on biologic medicines
approved and on the market, while at the same time providing
incentives for innovation so that America retains its lead in
the field of biotechnology and the next-generation of life-
saving medicines continue to be developed.
Thank you Mr. Chairman, for holding this hearing today so
that we all may learn more about this issue. I yield back.
----------
Mr. Pallone. I did want to mention without objection that
Mr. Inslee will be joining us. He is not on this subcommittee
but is on the full committee, so he will be joining us for
questions of the witnesses.
So let me move onto our first panel which just consists of
one witness. Dr. Woodcock, if you want to come forward?
Welcome. Dr. Janet Woodcock is Deputy Commissioner and Chief
Medical Officer for the Food and Drug Administration. You have
5 minutes for an opening statement which becomes part of the
hearing record, and you may in the discretion of the committee,
submit additional brief statements in writing for inclusion in
the record. Right now I recognize you for 5 minutes. Thank you
for joining us.
STATEMENT OF JANET WOODCOCK, M.D., DEPUTY COMMISSIONER AND
CHIEF MEDICAL OFFICER, FOOD AND DRUG ADMINISTRATION
Dr. Woodcock. Mr. Chairman and members of the subcommittee,
thank you for the opportunity to testify about the scientific
and regulatory framework surrounding follow-on biologics. In
considering the complex scientific issues at hand, I have not
only relied on my experience in leading the Center for Drug
Evaluation and Research for over a decade, but also in my 8
years of experience in working for the Center for Biologics
Evaluation and Research, or CBER. While in CBER, I served as
Acting Deputy Center Director and Director of the Office of
Therapeutics in which capacity I oversaw the approval of
biotechnology products to treat serious illnesses such as
cancer, multiple sclerosis, and cystic fibrosis.
The success of FDA's current generic drug program has
spurred interest in considering abbreviated application
pathways for more complex molecules. Currently there are over
9,000 approved therapeutically equivalent generic drugs on the
market that constitute more than 60 percent of prescriptions
written in the United States. FDA's office of generic drugs
currently approves generics at the rate of more than one per
calendar day. These generics provide affordable medicines for
millions of Americans.
The topic for discussion today is variously referred to as
follow-on proteins, follow-on biologics, generic biologics,
biosimilars, and so forth. Many of these terms are very
imprecise and confusing. Largely what the interest is is in
copies of biotechnology-produced protein products that FDA
calls follow-on proteins. In the U.S., proteins are regulated
either as drugs under the Food, Drug, and Cosmetic Act or as
biological products under the Public Health Service Act.
Whether regulated as drugs or biological products, proteins fit
into the category of complex molecules that can be difficult to
fully characterize. Copies of protein products that are
regulated as drugs may be considered for abbreviated
application pathways that exist under section 505 of that Act.
For the very simplest peptide products, manufacturers may be
able to demonstrate that they contain the same active
ingredient as the innovator product and thus may be considered
under 505(j) which is what is commonly regarded as the generic
drug pathway.
In contrast, copies of approved protein products that are
regulated as drugs would currently be considered for
abbreviated applications under 505(b)(2), as scientific
techniques are not available to demonstrate sameness of these
types of molecules.
Now, as already hasbeen said, an abbreviated pathway,
though, does not exist for copies of protein products that are
approved under the Public Health Service Act. FDA has approved
several follow-on proteins under 505(b)(2) including a
recombinant, hyaluronidase and a recombinant version of human
growth hormone.
We are currently preparing a guidance document on the
general scientific framework for preparing abbreviated
applications for follow-on proteins under 505(b)(2), and we
expect to follow this with guidance on technical issues such as
immunogenicity and physical characterization methods.
FDA is frequently asked how difficult or feasible it is to
approve a copy of an existing protein using an abbreviated
pathway such as 505(b)(2). Simple proteins that can be
extensively characterized by analytical and functional tests
can often be shown to be very similar to an approved protein,
and thus the manufacturer might not have to perform extensive
clinical testing. However, the clinical tests needed, even for
simple proteins, would still be more than what is ordinarily
done for a small-molecule generic drug. In contrast, very
complex proteins, especially those that are difficult to
characterize functionally are more challenging. Using today's
science, it would not be possible by using analytical and
functional tests alone to be sure that a complex follow-on
product was very similar to an innovator product. Therefore,
more extensive clinical testing would probably be needed.
However, this clinical testing might still fall short of what
would be needed for stand-alone new drug application.
Protein products vary in their physical complexity and how
well their mechanism of action is understood and the relevance
of functional tests as adequate surrogates for their effects,
the complexity of their clinical indications, and many other
factors. These all must be taken into account in determining
how much additional data would be needed to be submitted in an
application for a follow-on protein under 505(b)(2). These
determinations require a significant amount of scientific and
medical expertise. However, FDA is well-prepared to undertake
these evaluations given our over 20-year history of regulating
recombinant products.
I will be very pleased to answer your questions.
[The prepared statement of Dr. Woodcock follows:]
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Mr. Pallone. Thank you, Dr. Woodcock. I am going to
recognize myself for 5 minutes for questions, and then we will
go around the committee; and each member will have some
questions.
Many people have focused on your previous testimony before
the Oversight and Government Reform Committee which you
reiterated in your written testimony today. Specifically you
state, and I quote, that
the amount and type of new data that will be needed to
demonstrate the safety and effectiveness of a follow-on protein
product will be influenced by the extent to which the follow-on
protein product can be demonstrated to be sufficiently similar
to an approved protein product to permit some degree of
reliance on the findings of safety and effectiveness for the
approved product.
Now, you went on to discuss the clinical trial should not
be conducted simply for checking a box as part of the
regulatory procedure for FDA approval, and I am hoping that you
can expand on these statements today. But specifically, can you
tell me whether or not you think clinical trials should be
required or mandatory for every follow-on protein as you used
the term and that applies for FDA approval or do you think that
it makes more sense to allow the FDA to have the authority to
determine what types of studies or level of science is required
to determine approval which is basically what Mr. Waxman has
proposed in his legislation.
Dr. Woodcock. With the science we have today, we are not
able to determine everything about a protein product based on
tests in the test tube so to speak, in the laboratory, and in
animals. And we would foresee right now, with the science we
have today for protein products, we would be looking at
additional clinical trials. Depending on the situation, those
might be very limited. They might really have to do with the
safety issue called immunogenicity, the ability or the
propensity of the protein to cause an immune response in
people. That is something we really have great difficulty
predicting just from laboratory tests, and it is influenced to
a great extent by the kind of contaminants that are in the
product which has to do with how the product is produced.
Mr. Pallone. So you want the flexibility as to whether to
have the clinical trials, depending on the circumstance?
Dr. Woodcock. I think it needs to be considered that the
science will advance over time. As many of the members have
alluded to, science is advancing very rapidly. What we can do
today is somewhat limited, but analytical and functional
technologies are advancing rapidly and we may be able to make
more exact comparisons in the future.
Mr. Pallone. OK. I wanted to ask about the issue of
interchangeability. You stated in your testimony today, and I
quote,
from many follow-on protein products, in particular the
more complex proteins, there is a significant potential for
repeated switches between products to have a negative impact on
the safety and/or effectiveness. Therefore, the ability to make
determinations of substitutability for follow-up protein
products may be limited.
That is your quote.
Now, has the FDA ever approved a follow-on protein product
as interchangeable with a reference product and if so, can you
characterize these products in your ability to determine
interchangeability? In other words, were these products simple
or more complex molecules and depending on the level of
complexity what levels of studies were used to determine
interchangeability?
Dr. Woodcock. We have not approved protein products as
interchangeable. We have not. We have ideas, as I said. We are
considering issuing a guidance on immunogenicity, and that
would include this issue of switching. Immunogenicity does not
really enter in so much with small molecules. Some small
molecules actually do cause an immune response, but under the
generic program that we have, they are identical. We know that
generic copies are identical to the original copies and would
be expected to have the same immune response. However, with
proteins, proteins themselves, even one product, an innovator
product, will vary slightly from batch to batch because they
are very complex. So we don't know if you were taking one and
if you were switching to another and you switch back and so
forth if this might set up an immune response that wouldn't
occur if you had just stayed on the same product all along. And
that could be very dangerous in some circumstances.
Mr. Pallone. OK. And then lastly I wondered if you could
comment on whether or not you think it would be appropriate to
have open and public procedures for all stakeholders to
participate in the development of criteria for the approval of
follow-on products, as well as what types of post-markings,
surveillance, or studies should be required of follow-on
protein products? Should the market for pre-market approval and
requirements for post-marketing differ from follow-on protein
products than reference or products or should they be the same?
Dr. Woodcock. That is a lot of questions.
Mr. Pallone. I know.
Dr. Woodcock. We attempt to always have an open and public
process for the scientific and technical standards that are
used to approve products, and actually we work internationally
with the other international regulatory bodies on standards so
that different trials don't have to be repeated in different
countries and so forth. So it is very important to have an open
and public process. We have had multiple scientific meetings,
some with various scientific bodies at the New York Academy of
Sciences on various aspects of characterization of proteins and
so forth and so on. So yes, it is very important that we have
continuing, high-level scientific input and dialogue on all of
this, including the clinical parts of it.
Mr. Pallone. OK. Thank you. Mr. Deal.
Mr. Deal. Thank you, Dr. Woodcock, for being here today. We
are dealing here with two statutes, and you referenced the
Food, Drug, and Cosmetic Act, specifically 505(b)(2) as a
certain pathway and then of course the section 351 of the
Public Health Service Act that I believe you say is where the
biologics have generally been registered, is that correct?
Dr. Woodcock. That is correct.
Mr. Deal. Would the pathway for follow-on biologics need to
be addressed in both of those statutes?
Dr. Woodcock. As I said, we have already approved several
follow-on proteins under 505(b)(2). There is a pathway already
there. We have approved human growth hormone which is a
recombinant product and hyaluronidase which is actually a very
complicated protein. So that pathway is currently available.
However, the protein products approved under 505 are typically
only the hormones and the enzyme products. Most of the others
are under the Public Health Service Act which does not have a
pathway.
Mr. Deal. So specifically as to the Public Health Service
Act, there would need to be a pathway of some sort. One of the
issues that we have all been concerned about is the safety and
effectiveness of a follow-on or any product, and I believe you
said FDA has the capacity to make those determinations. Am I
correct that the current law does not mandate the way that you
determine that in terms of mandating clinical trials, that that
is simply something you have done under the auspices of
legislation, that you have set out those kind of protocols?
Dr. Woodcock. Under the Public Health Service Act?
Mr. Deal. Yes.
Dr. Woodcock. The Public Health Service Act requires that
the products be pure, potent, and so forth and safe. It does
not require specifically clinical trials or any given----
Mr. Deal. But you have the ability to do those trials
because you are charged with the safety and efficacy issue?
Dr. Woodcock. Right, and obviously the products have to be
safe and effective.
Mr. Deal. Right. I want to get into a little bit of a
detailed discussion about an area that I still don't fully
understand. We have had private conversations and in trying to
make an analogy to the current generic drugs, the discussion
dealt with what FDA can do with the data from the licensed or
patented product. And there was a distinction that you made
between having access to the data and being able to rely on the
data for follow-ons or for generics.
As I understand it Hatch-Waxman allows you to rely on the
data for abbreviated new drug applications, is that correct?
Dr. Woodcock. That is correct.
Mr. Deal. OK. Would you elaborate on what you need in this
area of follow-on biologics as it relates to this already-
accumulated data? What are your restrictions and what do you
foresee as reasonable expansions of your current right to
either rely on or have access to the data?
Dr. Woodcock. To explain this to the members who may not
be--this is pretty arcane, I think. Our legal interpretation of
the current statute that we rely on says that we rely on the
fact of the approval of the innovator product. We are not going
in and comparing the data that is in the application of the
innovator product to the data that is submitted by the generic
manufacturer, all right? So we are relying on the fact that it
was approved, safe, and effective and we can bridge back to
that approval by the fact that the generic small molecule is
the same small molecule and it also is the same dosage for them
and so forth and it is bio-equivalent, all right? So then we
say if you meet those criteria, then the fact that we approved
that product pertains to the generic product.
With follow-ons, it is a little more complicated for the
505(b)(2) world. We are also still relying upon the fact of the
approval of an innovator product, but the follow-on protein may
not be an exact copy. But again, we are not going in and
looking at the data in the innovator application and applying
it to the follow-on.
For future products that we would look at, this of course,
is somewhat limiting to the FDA in the fact that we can't make
direct comparisons of perhaps the pharmacokinetics of one
product to the pharmacokinetics of the follow-on product unless
that is in the literature somehow or somehow otherwise
available. So the extent to which we can approve complicated
follow-on products is somewhat governed by the ability to which
we can refer to and look at data about an innovator product. We
cannot do that now.
Mr. Deal. Thank you. My time has expired.
Mr. Pallone. Thank you. Mr. Waxman?.
Mr. Waxman. Thank you, Mr. Chairman. Dr. Woodcock, as I
understand what you are saying is that it is a lot easier to
approve the generics under the Hatch-Waxman Act because you are
showing that it's the same drug in effect. Now we have
something a little bit more complicated, but we shouldn't throw
up our hands and say it is impossible because under a quirk in
the FDA law now, you are able to approve a follow-on drug for
some proteins that would be in that category of these
biogeneric drugs, is that correct?
Dr. Woodcock. That is correct. We have approved some.
Mr. Waxman. You have approved some? So you have some
experience. You have said to us that some of these others are
going to be more complicated and therefore more difficult
because the science hasn't caught up with it. The biotech
industry argues in their testimony today that any legislation
authorizing approval of follow-on biologics must require
substantial pre-clinical testing and clinical studies including
comparative clinical trials to determine whether there are
significant differences between follow-ons and reference
products in terms of safety and effectiveness. Do you believe
good science will always into the future require that
substantial pre-clinical and clinical studies include
comparative clinical studies and effective are going to be
required? Is that micromanaging FDA too much?
Dr. Woodcock. I believe that there will always be
substantial non-clinical, in other words, laboratory and to
some extent there will be animal studies in the foreseeable
future comparing two products or characterizing the follow-on
product. That is just a routine standard for any drug that we
get onto the market, as it would have very extensive testing
before it would be put on the market.
For 505(b)(2)'s, the extent to which clinical trials would
be required depends on all the factors I went over in my oral
testimony. There are a great many factors that have to be
brought into play, and there is a spectrum of----
Mr. Waxman. Well, science is going to evolve. Right now you
would probably agree that there ought to be clinical trials for
some of the biologic generics, in other cases you might not. I
guess the question is would it be mandated that under every
circumstance there would be a clinical trial and wouldn't that
end up requiring unnecessary and therefore unethical trials in
the future if we required it by statute rather than leaving it
to FDA's discretion?
Dr. Woodcock. Well, as we said in the testimony, requiring
trials simply to require trials is not usually considered a
fair use or ethical use of human subjects. We should do trials
in people if we need information in people. Right now as I said
for proteins, we believe we will need immunogenicity trials in
people because we cannot predict the immunogenicity answers
without doing human trials.
Mr. Waxman. Do you believe it is better to have a statute
that freezes the science as of the date of enactment or that
gives FDA the flexibility to tailor requirements as science
evolves?
Dr. Woodcock. Because the science is so dynamic and none of
us can predict where the science is going to go over the next
decade, it is evolving unbelievably fast, obviously we all need
to be humble before that and have a scheme that I think allows
the science to operate.
Mr. Waxman. You responded to Mr. Pallone that public
process is important for establishing standards for drug
approval. I understand you to mean general standards applicable
to all drugs or biologics, is that correct?
Dr. Woodcock. It depends on the question. I think it is
very important in this area, follow-ons, that we stay up to
date with the science; and therefore, we have a dynamic public
process that keeps giving us the scientific input that we need.
Mr. Waxman. Well, do you think it appropriate to always
have a public process to establish the correct approval
standards for each new product before FDA can take any action
or would that cause unnecessary delays?
Dr. Woodcock. We have not done that. For example, with the
hyaluronidase product that we approved and so forth. So it is
going to depend on the situation. In some cases, it might be
desirable to have a public process because of so many open
questions. In other cases, obviously the path will be very
clear.
Mr. Waxman. Well, I guess it comes down to in my mind these
are some tough decisions. Who ought to make them, politicians
here in Washington with Congress saying this is how you must
decide the science or should we give you the flexibility with
the standards and ask you to make sure the product meets those
standards? That is what we have done with all other drugs, both
the new drugs especially and other generics or simple or only
has to be a copy. In this case, it is not just a copy, but the
decision has to be made; and I would trust the FDA to make that
decision, not Members of Congress spelling it all out.
Thank you, Mr. Chairman.
Mr. Pallone. Thank you, Mr. Waxman. Our ranking member, Mr.
Barton.
Mr. Barton. Thank you, Mr. Chairman. Dr. Woodcock, if
currently I am a manufacturer of a biologic drug and I am
making it in batches, is each batch identical?
Dr. Woodcock. Not to the state that you would use for
identical for chemical drug because we can't tell. For most of
the complex proteins, they have a range of forms within the
product. It isn't just one protein. There are minor variations
in most products that are part of the product. Second, the
extent of those variations will change a little bit from batch
to batch.
Mr. Barton. When you say a little bit, what percentage
terms? Half a percent, a thousandth of a percent?
Dr. Woodcock. Maybe half a percent or so.
Mr. Barton. Now, will each batch have the same efficacy,
the same result?
Dr. Woodcock. What we do is we control variability to the
point that the product, whether it is a drug or a biologic,
should have the same clinical effect time after time. That does
not mean though that that product is identical time after time.
And that is true with any manufacturing process. You have to
control variability down to the point where it doesn't make an
impact on the customer.
Mr. Barton. Well, if the patent expires on a biologic and
the same manufacturer in the same location using the same
equipment and the same process and the same ingredients made
the same product after the patent expired, would that be the
same as a generic drug for a biologic drug?
Dr. Woodcock. The innovators continue often to make their
products after the patent expires. They continue to market
their products under their brand. That is still considered the
innovator drug.
Mr. Barton. It would not be considered generic-similar
drug?
Dr. Woodcock. No. Now, sometimes manufacturers take that
product and they give it a different name and they market it.
Mr. Barton. We understand what a generic is for a normal
drug. We understand that for biologics, you really can't call
it a generic but is it fair to say that it is similar to a
generic?
Dr. Woodcock. It would be similar to a generic because the
doctors and patients could use it and expect to have the same
effect as the innovator drug.
Mr. Barton. Your standard is going to be the same clinical
effect, then you are going to label it as a biologic-similar
generic, generic-similar?
Dr. Woodcock. That would be one scheme, all right? However,
we wouldn't label as interchangeable as we already discussed,
that one could be switched for the other unless that had been
proven that that was safe to do.
Mr. Barton. We are kind of going around each other here.
What I am trying to get at, when the pharmaceutical reps come
in to see me and I assume everybody else on this committee,
they don't come right out and say, oh, no, we don't want the
generic for biologics. They are not fighting that. They are
just saying make sure you do the clinical trials, make sure
that it has the effect, depending on the standard that the FDA
establishes. You could make it almost impossible, you, the FDA,
to have an equivalent to a generic drug for biologics. Do you
understand what I am saying?
Dr. Woodcock. I do. First of all, let me say we have
approved several follow-on recombinant proteins under the Food,
Drug, and Cosmetic Act already. They have very similar
indications to all the other products that they are similar
to----
Mr. Barton. What I am trying to get at, and I am not doing
it in a very efficacious fashion, but I want to hear somebody
like yourself, the FDA, says it makes good policy sense to set
up a scheme to do biologic follow-ons because we think it is
possible and we think it would save consumers money if we do
it, instead of these are too large and too complex protein
molecules and we just don't think it makes sense because they
are so dissimilar to regular drugs.
Dr. Woodcock. Yes. Well, as I have said, we feel it is
possible and we are doing it under the pathway, where we have a
legal pathway. We have done these approvals already, No. 1.
Number 2, however difficult it might be now for some proteins,
it can be expected in the future as science evolves, we will be
able to make these comparisons more readily and we will be able
to do this more easily.
Back in 1984 after the first of the generic drug amendments
were passed, there was a period where there was great
difficulty in establishing the standards and so forth. But as I
said, we now have 9,000 generic drugs.
Mr. Barton. What do we need to do as a Congress and this
subcommittee to make it easier to facilitate the review and
approval of biologic follow-ons?
Dr. Woodcock. There is no pathway under the Public Health
Service Act. So although there is a pathway under 505(b)(2) of
the Food, Drug, and Cosmetic Act, and we are using that
pathway, there is no similar pathway under the Public Health
Service Act.
Mr. Barton. Do you think it is possible legislatively to
create such a pathway?
Dr. Woodcock. We would look forward to working with the
Congress on these discussions.
Mr. Barton. Thank you, Mr. Chairman. That is the answer I
wanted.
Mr. Pallone. Thank you. Our vice chairman, Mr. Green?
Mr. Green. Thank you, Mr. Chairman. Dr. Woodcock, since
biologics are derived from living cells and there is always the
chance the patient would develop an undesirable immune system
response to a follow-on biologic, the safety issues concerned
to me and many patients on biologic therapies already have
vulnerable immune systems, is it correct to say that we do not
currently have laboratory animal models that can correctly and
reliably predict unwanted immune responses for humans?
Dr. Woodcock. That is correct.
Mr. Green. Within the large group of biologic products, I
understand we know a great deal about insulin and human growth
hormone but considerably less about other newer therapies.
However, human insulin and human growth hormones, so-called
simple proteins, the following example in Europe has suggested
that testing for a negative immunity response is critical. For
example, and this is a very long question that I will run out
of time just going through it, but Novo Nordisk worked to
develop the second generation of insulin, one that would be
fast acting to help control mealtime rise in blood glucose for
individuals with diabetes. Two of their next generation drug
candidates were fully characterized and both included only one
different amino acid. During pre-clinical studies in Europe,
Novo Nordisk pulled one candidate because of increased tumor
potential found in rats. The other candidate, which hadonly one
amino acid, NovoLog, which during trials was determined to have
a safety level on par with human insulin.
We have a second example of the European system, Omnitrope,
a second-generation human growth. Because Europe requires
clinical trial data for biosimilar applications, the
manufacturer conducted a clinical trial and again, I could go
on.
Is there any instance in which you think a clinical trial
to determine immune system response is unnecessary?
Dr. Woodcock. For very short peptides which are not really
proteins. They are very, very short, small protein-like
molecules. That would probably be the case. However, at this
time, as I said, for proteins we feel we would need a human
trial for immunogenicity at the minimum because we cannot
predict immunogenicity from the lab and animal tests. However,
I also would like to say that a change in even a single amino
acid is not a trivial change whatsoever. That is a very big
change and it is easily detectible and we would know all about
it. That wouldn't be identical to an innovator product because
it would be an obvious change. We refer to that as a second-
generation product because it has been changed for some reason.
Mr. Green. OK. So to answer the question, you think
clinical trial, even those for second generation are needed?
Dr. Woodcock. Currently for immunogenicity. Clinical trials
might also be needed to answer other questions if there are
remaining uncertainties. I think it is important to understand
that there is a wide range of clinical trials. An
immunogenicity trial can be fairly straightforward. You expose
people to the product and you see what happens to the immune
response.
Mr. Green. In response to Chairman Pallone's questions
about interchangeability, you touched on dangers that result in
patients from switching biologic products. Given your answer to
the question, would you have concerns with Congress allowing,
for example, a pharmacist to dispense a follow-on product
outside a physician's orders?
Dr. Woodcock. The system we have right now, the States
regulate of course the practice of pharmacy, but FDA provides a
rating, an interchangeability rating, for products that we
approve. And if they get that rating, that means that FDA
thinks they are interchangeable, and often then the States will
follow that and allow the switching at the pharmacy level.
Mr. Green. OK.
Dr. Woodcock. So at this point in time for proteins, none
of those have been granted interchangeability.
Mr. Green. And I guess our concern, we want to make sure
the tests are done particularly on the second generation.
Thank you, Mr. Chairman. I yield back my time.
Mr. Pallone. Thank you. The gentleman from Michigan, Mr.
Rogers.
Mr. Rogers. Thank you, Mr. Chairman. I am just going to go
down just a little bit of a different path if I may here. The
CDC and the Department of Agriculture have deemed 44
particularly dangerous pathogens and toxin, they call them
select agents, like ricin or anthrax, smallpox, others I
mentioned in my opening statement. You are aware that some of
these biopharmaceutical companies are using some of these
select agents in the development of their product, is that
correct?
Dr. Woodcock. Yes. Obviously the Government would be aware
any time a select agent is being used in manufacturing.
Mr. Rogers. But that is not something you regulate through
the FDA? It is regulated through Agriculture, CDC, if they are
going to get access and use these particularly dangerous select
agents. Do I understand that correctly?
Dr. Woodcock. If for research or experiments that don't
involve humans, the FDA may not be involved, similar to what
research goes on at universities or companies. Once
manufacturing is leading to human trials, then the FDA is
involved, including the manufacturing.
Mr. Rogers. So the manufacturing side but if I am going
through the process of developing a product, would you have
anything to do with them gaining access?
Dr. Woodcock. No, as I said, similar to universities or
other sites, this is regulated by the entities you referred to.
Mr. Rogers. And I only bring this up, I was in Libya
recently and was at a factory where they were making, and have
subsequently cooperated with the United States and have turned
it over, but they were making mustard gas and they were using
one of these 44 particularly dangerous agents to try to
weaponize this particular agent. So it is pretty dangerous
stuff which is why we regulate it, and you would agree that we
need to continue to regulate that pretty closely, do you not?
Dr. Woodcock. Certainly.
Mr. Rogers. If we are going to expand this, I am concerned,
how do we make sure--we go through a pretty select process now
for these companies which following the regulation costs money,
right, and adds to this $1.2 billion in their development. How
is the FDA going to ensure that we do not allow these select
agents from these products widespread use and increase the
number of entities acquiring and using select agents?
Dr. Woodcock. Well, first of all, let me say that the vast
majority of biological products are not made from select agents
or have nothing to do with select agents. What you are talking
about is some of the vaccines and perhaps certain cancer
therapies that may have various toxins linked to them.
Mr. Rogers. And pain care, as well, is it not? It is my
understanding that there are those that who working to--when
they are talking about some pain treatments?
Dr. Woodcock. That is possible, however----
Mr. Rogers. Anatoxins, tetrotoxins.
Dr. Woodcock. Right. The types of biotech products that are
being talked about here today, the vast majority of them do not
involve any of that, OK? That is a very small universe that I
would think everyone would agree requires very good oversight.
Mr. Rogers. But it is important that we keep an eye on
those, don't you think?
Dr. Woodcock. Absolutely.
Mr. Rogers. And so if we are going to get into this, don't
you think that we ought to be very careful about how we look at
who has access to these types of select agents? It is very
important that these biopharmaceutical companies have access
for research on these kind of things. They can have some
certainly medicinal effects. I guess the venom from an
Australian marine cone snail is even used in some of these
developments. We should encourage that but my fear is that we
throw open the door. Is this something that the FDA has thought
about if we go to this next generational research entities
using these dangerous toxins?
Dr. Woodcock. Well, let me reiterate, generally the firms
doing follow-ons will not be engaged in R&D of that type. They
are not going to be engaged in basic research and so forth.
They are going to be focused on making copies of these existing
products.
Mr. Rogers. But in order to do that you would have to have
these select toxins if that in fact is a component----
Dr. Woodcock. If it is a component, yes, and that can
exist. It is a very small universe and requires and has very
special controls on it.
Mr. Rogers. It is a small universe now but if we go to
generics just by definition, won't it be a larger universe?
Dr. Woodcock. Yes, I can't predict where the market--it
depends on how attractive the particular agents are for
copying.
Mr. Rogers. In the average time of that 15 years and $1.2
billion, how much of that was FDA or Government money, on the
average in the development of a biotech drug? Does the FDA give
them money?
Dr. Woodcock. No.
Mr. Rogers. So pretty much all of that money is private-
industry generated, and wouldn't you think it is important that
when we go through this we should try to find some answer here
but shouldn't we protect that private investment of $1.2
billion? There's not enough money in the world for us to come
up with that $1.2 billion?
Dr. Woodcock. Right. I think that is one of the tasks
before Congress.
Mr. Rogers. Thank you, Mr. Chairman.
Mr. Pallone. Thank you. The gentlewoman from Wisconsin.
Ms. Baldwin. Thank you, Mr. Chairman. Dr. Woodcock, we have
certainly heard from some innovators that because they make
manufacturing changes to their products, sometimes without
clinical trials, sometimes with, that perhaps the logical next
step is that we could allow generic companies to make
biosimilars without requiring clinical trials. But I wonder if
there is an equivalency here because sometimes the simple
manufacturing changes by brand manufacturers, like changing a
filter, for example, are these the same as the type of changes
that can be anticipated and I think expected of a follow-on
biologic company that does not have access to the original cell
line or the original manufacturing process? I wish you would
speak to that.
Dr. Woodcock. There is obviously a great spectrum of
changes that could be made to a product, and manufacturers
frequently make small changes to their production process. They
often have to do extensive testing, but it is usually not to
human testing but it might be very extensive laboratory and
sometimes, say, animal pharmacokinetic tests. And even
sometimes change of filter has resulted in a dramatic change.
It is very interesting.
So change of a whole manufacturing site, a new cell line,
and so forth is of much greater magnitude and would require
even much more extensive testing, whether it was the innovator
manufacturer or there was a follow-on. Change to a whole new
manufacturer with a whole new process in cell line and so forth
is the largest kind of change you can imagine and would require
obviously more testing and so forth than any of these other
kinds of changes.
So there is a spectrum. FDA has a lot of experience
regulating these manufacturing changes within the innovator
industry, and we also bring that experience to bear in looking
at a much bigger change which is a whole new manufacturer of
the product.
Ms. Baldwin. Just one other question. As you approach this
topic and of course, we are delving into it more deeply and
learning a lot about a very complex issue, but it seems to me
that when you start out regulating something that there is very
little experience with, one wants to start erring on the side
of caution by going slow and engaging in strong safety studies.
And I just would ask very generally, would the safety
assessments that you spoke of during your testimony be as
strict as those for the original biologic? Is that what you
would contemplate at this point?
Dr. Woodcock. As I said, there is a spectrum. In some
cases, very extensive safety testing in humans may really not
be necessary because we know enough about the product from long
time clinical experience as you said, for example, insulin.
There are many, many varieties of insulin on the market right
now. In other cases, we might need extensive clinical safety
testing. In some cases we may need human pharmacokinetic
studies and pharmacodynamic studies and pardon me if I am
getting into too much jargon here, but there is an ever-
widening spectrum of clinical testing that could be done
depending on how much certainty remains. After you look at all
the pre-clinical testing that has been done and you compare the
two products and you say how uncertain are we? Well, if we are
very, very uncertain still, it is going to require a lot more
human testing. If we are pretty certain and we have a lot of
confidence, then it will maybe require immunogenicity testing,
perhaps not much more.
Ms. Baldwin. Thank you.
Mr. Pallone. Mr. Ferguson.
Mr. Ferguson. Thank you, Mr. Chairman. Dr. Woodcock, thank
you for being with us today. I want to read a quotation,
something you said last week. I quote, ``Unlike small molecule
drugs whose chemical composition can easily be determined to be
the same as an approved product, the very nature of protein
products makes comparison of one protein to another, including
to establishing safety and efficacy, more scientifically
challenging.'' I thought that was important and particularly in
light of several questions that I have. I have several and I
want to get through them as quickly as I can, so I would
appreciate your brevity as well.
Do the safety concerns with biologic products dictate the
need for pre-market and post-market clinical studies and post-
market surveillance for follow-on biologic products as well?
Dr. Woodcock. As I have said, there is a spectrum.
Ordinarily we would expect some pre-market clinical studies. I
think we may well expect some post-market clinical observations
at least to confirm what we have found pre-market.
Mr. Ferguson. Other countries obviously do this already.
The U.S. in your opinion would not want to be the first country
that leaves the door open to follow-on biologics without
clinical trials, is that correct?
Dr. Woodcock. We have approved several follow-on biologics
already. They have had clinical trials. We regard that most
proteins now would require some degree of clinical testing.
Mr. Ferguson. Should we do it without clinical trials?
Dr. Woodcock. We shouldn't do anything that leaves us with
too much uncertainty about the results. We need to know that
the products would be safe and effective.
Mr. Ferguson. Do you think a lack of clinical trials leaves
uncertainty?
Dr. Woodcock. Currently it would because we can't predict
immunogenicity.
Mr. Ferguson. OK. Under what circumstances could the FDA
anticipate that no clinical data would be needed to approve a
follow-on? Is there any circumstance that you can think of
currently?
Dr. Woodcock. As I said, right now for peptides, which are
related to proteins, very simple peptides are of the same
magnitude, of size, and complexity of certain small molecules;
and we can approve very short peptides as generic drugs without
anything but a bioequivalence trial. Don't forget, even generic
drugs ordinarily have a human trial of bioequivalence.
Mr. Ferguson. But of course that sounds pretty dissimilar
from most follow-on biologics which of course as you have said
and others have said are incredibly complex?
Dr. Woodcock. That is correct.
Mr. Ferguson. Are there situations where the FDA would not
find clinical investigation of immunogenicity warranted?
Dr. Woodcock. We feel that for proteins right now we would
need clinical testing for immunogenicity.
Mr. Ferguson. In the absence of any accurate or reliable
laboratory or animal model to predict unwanted immunogenicity
in humans, how can we be sure that a follow-on protein product
which has never been administered to a human being before won't
induce some unwanted immune response?
Dr. Woodcock. We can't be sure and that is why we need to
do testing.
Mr. Ferguson. OK. In looking at Mr. Waxman's bill, I see a
listing of differences between follow-on biologic and innovator
that would be required to be deemed to be, quote, highly
similar by the FDA. Do you believe that Congress should be
telling the FDA in statute how to make these comparability
determinations right now given the technology or the
information that we have right now?
Dr. Woodcock. I think this is a very complicated area that
requires some extensive discussion because of the complexity of
proteins.
Mr. Ferguson. Would you be satisfied or comfortable if
Congress decided at this moment, given what we know right now,
for the Congress to tell the FDA how and when to make these
decisions?
Dr. Woodcock. I think that----
Mr. Ferguson. That is a yes or no if you can do it. I am
almost out of time.
Dr. Woodcock. I can't do it. Thank you.
Mr. Ferguson. It sounds like you would not be comfortable
right now, is that accurate? Would you have other questions,
concerns?
Dr. Woodcock. We look forward to working with the Congress.
Mr. Ferguson. She is good, you got to give it to her. She
is good. It seems to me there is a major disconnect between the
standards that FDA imposes on innovator products and the one
that some are espousing that we use on follow-on biologics.
There is a big disconnect there. And if we give the FDA
authority to approve follow-ons, what agency initiative will be
necessary to reconcile these very two different sets of
standards if we were to approve something say in Mr. Waxman's
bill?
Dr. Woodcock. Now, I can't comment directly on the pending
legislation. I do believe as I said earlier that the science is
going to continue to evolve, and as the Congress contemplates
this, they should make room for evolving science because it
will change over the decade in a dramatic way; and what we are
capable of doing now, which is a lot but somewhat limited in
making comparisons, is going to change over time.
Mr. Ferguson. Thank you very much. I appreciate it.
Mr. Pallone. I think, Dr. Woodcock, we are going to have to
let you catch your breath or something here as we move on. Next
is the gentlewoman from California, Ms. Eshoo.
Ms. Eshoo. Thank you, Mr. Chairman. Thank you, Dr.
Woodcock, for your testimony. It is instructive and
enlightening, and if I am hearing correctly what you have
presented both in your opening statement and in your response
to the questions that members have posed is, well, several
things, but that when it comes to safety and efficacy, it is
either in the clinical trial or in the trials that the FDA
conducts. Is that correct?
Dr. Woodcock. We don't conduct any trials, OK?
Ms. Eshoo. But you require them?
Dr. Woodcock. Yes.
Ms. Eshoo. But you require them. Now, my understanding is
from what you have said is that there can be an immune response
to biologics, and it seems to me that this is a key hurdle
because when it comes to biologics that the cure can be worse
than the disease, I mean, in the complexity of it.
Dr. Woodcock. The proteins are much more prone than the
small molecules to cause various types of immune responses.
Ms. Eshoo. Now, if a biotech company notified the FDA that
it was making changes to its cell line or its manufacturing
process, altering the manufacturing process, what would be the
response of the FDA today?
Dr. Woodcock. Manufacturers are very well aware before they
make any changes to a marketed product, or even a product
within the investigational process, they have to get approval
from the FDA to make those changes before those products would
be used in people.
Ms. Eshoo. All right. Now, if we move to the follow-on
biologics that are obviously being proposed with all of the
laudable outcomes of broader and more affordable access to
them, what do you prescribe as being the process for that? I
think that is where the disagreement comes. I really do. I
think it is not whether it should happen or not but how to do
it, and I think that is the rub of the debate.
Dr. Woodcock. Well, I think I can describe what we are
doing under 505(b)(2) right, under the Food, Drug, and Cosmetic
Act. And what we do there is the follow-on product is required
to submit very, very extensive physical and functional
characterization, in other words, laboratory testing
comparisons to the innovator product, animal testing of
different kinds, and then you have to decide how much clinical
testing is needed, depending on how certain you are from all
that other work that----
Ms. Eshoo. But you don't believe that there should be a
shortcut where the FDA is prohibited from requiring what you
just described, if in fact the FDA believes that it should take
place?
Dr. Woodcock. Many of these products will require
additional clinical testing to give you the level of certainty.
Ms. Eshoo. Yes. Let me ask you this. There is a provision
that requires the FDA to find a biologic follow-on and the
referenced biologic to contain, ``highly similar, principle
molecular structural features if they are'', and I am going to
read this because I am not a scientist but I have to rely on
the exact language in the proposed legislation, two protein
biological products with, ``minor differences in amino acid
sequence.'' You have talked about amino acids and what they
represent which to me is kind of scary if you fool around with
them. Two polysaccharide biological products with differences
in post-polymerization modifications, two glycosated protein
products with differences in structure between them solely due
to post-translational events, infidelity of translation or
minor differences in amino acid sequence. This is statutory
language. Have you ever seen this before in legislation?
Statutory language that is that specific?
Dr. Woodcock. It is very specific.
Ms. Eshoo. Well, it is highly specific. Well, you are not
going to answer this. I am just going to put this out to my
colleagues that are still here. I don't know if you understand
this and I don't know if you could all stand by this, but I
don't think this is the role of the Congress. I really don't. I
think it is up to the FDA to make the call on defining this
particular--we shouldn't get into statutory language and be
prescribing this.
Mr. Pallone. Will the gentlelady yield?
Ms. Eshoo. No, because I don't have that much time. I would
like to but I can't. I would like to ask you, Doctor----
Mr. Pallone. Actually, your time has run out.
Ms. Eshoo. Did you include the minute and 2 seconds I
didn't use in my opening statement?
Mr. Pallone. No.
Ms. Eshoo. No? Can I have that?
Mr. Pallone. It would be better if you did it as a written
question. We are going to allow written questions because she
is----
Ms. Eshoo. It is just in the European model and maybe
someone else will ask that and what----
Mr. Waxman. Mr. Chairman, I would like to ask unanimous
consent the gentlelady be given 2 additional minutes if she
would yield me one of them.
Mr. Pallone. Is there objection?
Ms. Eshoo. If there isn't, then I will just yield that time
to Mr. Waxman because I think Mr. Gordon is going to raise the
question about how the FDA views the European model in the
follow-on biologic areas. So I will yield the time to you.
Mr. Waxman. Thank you very much. Just on that one point
where we spell out in my bill this language about deeming
certain molecules, that is from an FDA reg and it is not
spelling out a broad universe, it is narrowing the universe of
possible follow-through drugs, and then once you narrow it,
then they have to meet the second standard in the legislation
which is that it is just clinically significant--no clinically
significant differences in terms of safety. So it is not
deeming something to be a generic, it is narrowing all the
different fields to make sure it is a good candidate to be a
follow-on biologic but we still require FDA to use that very
strict test in your scientific judgment whether it
Ms. Eshoo. Yes, can I just jump in here since I yielded
you?
Mr. Waxman. She is shaking her head yes.
Ms. Eshoo. You are still saying it is a regulation, though?
Mr. Waxman. Are you saying yes for the record? Am I
correct?
Dr. Woodcock. That is correct. See, in the original Hatch-
Waxman, you used the term same active ingredient. That doesn't
apply here because as we have discussed extensively, they are
not exactly the same. So the question arises, what actually
would be a candidate for being considered under some scheme?
How close does it have to be? That is the question.
Mr. Pallone. OK. Time is expired, and we move to the
gentlewoman from Tennessee.
Mrs. Blackburn. Thank you, Mr. Chairman. Dr. Woodcock, you
have been so patient and as you can tell, we are not scientists
and researchers but we all want to be certain that new
protocols and new therapies have the ability to make it to our
patients, and we want to be certain that there is a fairness
applied to this entire process as we look at the follow-on
process.
Let me come at this from a different angle. In my opening
statement I mentioned to you intellectual property concerns,
and I have thought, reading your testimony and we appreciate
that coming forward to us and then I also have a May 5 report
from CRS on the follow-on biologics that I have done a little
bit of reading on. So let us take it this way. You have got the
applications for approval of biologics, and these contain trade
secrets, correct?
Dr. Woodcock. Yes.
Mrs. Blackburn. OK. And when you render a finding that a
biologic is safe, pure, potent, you are relying in part on that
trade secret data, correct?
Dr. Woodcock. Yes.
Mrs. Blackburn. OK. So explain to me how you think you can
rely on the finding of one biologic to approve a second or
similar biologic without using that trade secret data and
without compromising that intellectual property which I see as
a private property right.
Dr. Woodcock. We don't have that ability now under the PHS
Act and so we do not approve follow-on proteins under the PHS
Act. Under the Food, Drug, and Cosmetic Act, the scheme that
was set up under Hatch-Waxman allows FDA to rely on the fact of
approval of prior products, and that is how we do it. We do not
rely, we don't go in and look at the data when we approve all
these generic drugs.
Mrs. Blackburn. So then you feel as if you are doing that
without exposure to the person that is the creator or the
intellectual property holder of a specific trade secret?
Dr. Woodcock. Well, obviously I probably don't understand
your question fully. To my understanding, Hatch-Waxman set up
kind of the balance between the protection of the innovator for
a certain amount of time, patent extensions and so forth, and
then the ability at the end of that for copies to come in and
the FDA to have the ability to approve copies.
Mrs. Blackburn. OK. I thank you for that. I think that for
some of us that represent so many individuals that work in the
innovative and creative community if you will, and in our State
of Tennessee as we see a biotech industry that is beginning to
grow, we look at lessons learned and places that we can go for
lessons learned. Much of that is through our creative
community, through our songwriters, through our auto engineers,
people who have seen copyright infringement, who have seen
intellectual property violations. And it raises a specific
concern and a guard, and they highlight that with us that there
is concern there that it is a very fine line, it is a very
complex issue, and that we have to step very, very carefully.
Following on with that, would you say yes or no, are we
jumping the gun to try to create a follow-on pathway? Are we
trying to get ahead of ourselves as Congress, as legislators?
Dr. Woodcock. Well, I have said, FDA has approved some
follow-on products where we have a pathway available. So
obviously FDA believes that this is possible. It is possible to
approve certain follow-on products. A pathway is not available
under Public Health Service Act, so that balancing that you
refer to, the innovation and need for innovation and the need
for affordable treatments is something only I think the
Congress can deal with.
Mrs. Blackburn. OK. Thank you. I yield back.
Mr. Pallone. Thank you. The gentlewoman from Illinois, Ms.
Schakowsky.
Ms. Schakowsky. Thank you, Dr. Woodcock. This is not an
area where I have any sort of expertise, so let me ask some
very basic questions.
Recently you testified at a House Oversight and Government
Reform hearing that the negative immunogenicity's response from
Eprex may have only been discovered in a 50,000-person clinical
trial. Has a pharmaceutical manufacturer ever submitted a
safety study of this size?
Dr. Woodcock. That is a good question. Possibly of that
magnitude. That is a very, very large study and so would be
very unprecedented.
Ms. Schakowsky. So it is not common?
Dr. Woodcock. No.
Ms. Schakowsky. So if not, then what types of tests could
have been conducted to provide FDA with relevant safety
information for this drug or others like it?
Dr. Woodcock. There is a wide-variety of laboratory tests
that can be done and animal tests to look at things like
immunogenicity, and limited human studies can be done. However,
with most rare drug side-effects, which would require 50,000,
100,000, 1 million people to be exposed, to find them we use
post-marketing to evaluate that because all drugs have rare
side-effects sometimes that are serious and to require them
before the drug would be put on the market would mean we
basically wouldn't have any drugs available to people. So we
need a robust post-marketing safety system to find these things
so that we can learn about them.
Ms. Schakowsky. So you again have to figure out the balance
of what you do pre-marketing and then if it is a cost benefit
sort of thing?
Dr. Woodcock. Yes, however, let me say that that is not the
only kind of immune response that can be negative. You can have
a very common immune response to a protein that can have an
adverse affect, and that could be picked up in a small trial.
So it really depends on what you are looking for.
Ms. Schakowsky. OK. I know that the ranking member asked
about different batches and whether they could be the same but
I wanted--but most comparability decisions are confidential,
there is one involving the biotech drug Avonex, that is public,
and I am wondering if you could tell us a little bit more about
what kind of changes the FDA permitted in that case without
repeating--and this is a follow-on used to treat relapses of MS
and it is made by Biogen which is a generic company as you
know--what kind of changes the FDA permitted in that case
without repeating the original safety and effectiveness trials?
Dr. Woodcock. Right. Those changes included manufacturing
site, the cell line, and they were very, very extensive changes
that were done; but very extensive characterization was done to
assure comparability of those two molecules.
Ms. Schakowsky. But it did not require the repeating of the
original safety and effectiveness trials?
Dr. Woodcock. That is correct. Now, the second manufacturer
had access to quite a bit of the data about the manufacturing
process and so forth that was originally done.
Ms. Schakowsky. There are several biologics that are
regulated under the Food, Drug, and Cosmetic Act that have been
approved based on abbreviated data; and I believe the FDA
provided a letter to Chairman Stupak and Chairman Dingell in
February citing these examples. And in some cases low
complexity products, that is what you have been talking about,
the short, have been rated interchangeable. So the FDA has
already demonstrated that it is possible to approve at least
some biologics based on abbreviated data and even make
interchangeable decisions. Am I just basically repeating what
you have already said?
Dr. Woodcock. Yes, the interchangeable decisions were for
peptides, and they were very, very small versions of protein
that are more like a small molecule drug. We have not approved
any proteins really under the (j) process, any recombinant
proteins.
Ms. Schakowsky. And I also have a question that I am
curious what the FDA views as the appropriate level of
discretion in this decision-making process. I guess you get
back to you want to work with us?
Dr. Woodcock. Yes.
Ms. Schakowsky. I thank you. Thank you, Mr. Chairman.
Mr. Pallone. Thank you. Dr. Burgess.
Mr. Burgess. I guess that statement is the key point, and
we do clearly need to work together on this. Let me just ask
you on some of the stuff we have heard this morning and your
written testimony, the parts you make about the hyaluronidase
that required the additional testing because of allergic
reactions because of its recovery from the tissue, if you end
up having to do all of that, are we still going to see price
savings in the product when it is delivered?
Dr. Woodcock. Well, obviously there is a debate about that.
However, it is the large-scale clinical safety and efficacy
studies that are the very expensive part of development, as
well as the R&D that goes into producing the innovation in the
first place. So there would be reduced costs to producing a
follow-on because you wouldn't have to do the original research
and you may not have to do the clinical efficacy studies.
However, it wouldn't be of the same magnitude of reduction of
cost of development that you would have for a small molecule.
Mr. Burgess. But in doing so, and I think Mrs. Blackburn
already addressed this, said in doing so, do you not out of
necessity have to use some of the proprietary information from
the original manufacturer?
Dr. Woodcock. Under the 505(b)(2) process we do not go into
the originator application and look at anything, but we know we
approved it so we are relying upon the fact of the approval.
Mr. Burgess. So the fact of approval, is it the public
domain and not proprietary information?
Dr. Woodcock. Right. Yes.
Mr. Burgess. Do you have any thoughts with all of the
questions you have been asked this morning in your extensive
testimony which we all appreciate, have you any thoughts about
how we go about minimizing uncertainty for the FDA in this
rather complicated new world that we find ourselves in?
Dr. Woodcock. Well, I agree that there need to be extensive
discussions and we look forward to working with the members.
Mr. Burgess. Do you have any thoughts as to how we on this
side of the table, not this side of the aisle, but how we can
give you the flexibility that you are going to require in order
to make room for this evolving science?
Dr. Woodcock. Well, for example, we feel probably that
under 505(b)(2) we do have a great deal of flexibility the way
that program has been implemented over the years, and we will
have approved follow-ons that have had extensive clinical
trials and we approved, for example, the hyaluronidase that
simply had a immunogenicity trial. Although hyaluronidase is a
very complicated protein. It shows the spectrum of things that
can be done under that scheme, under that pathway.
Mr. Burgess. Now, have there been products that you thought
initially this shows a lot of promise for follow-up biologic
that you have had to pull back and require additional testing?
Some of the things that you mentioned earlier, the change of
the filter, the change of the atmospheric pressure outside when
you filter the compound, the change of a stopper composition
that would perhaps be different from one lab to another?
Dr. Woodcock. Right. Well, for the more complicated
proteins, those issues pertain to manufacturing. Say if the
manufacturer wants to change sites which happens sometimes, or
open up a new site. Then all those factors from environmental
factors all the way to how the production process is done have
to be looked at very carefully to make sure they are making the
same product, and that is the same manufacturer.
Mr. Burgess. Even under the original manufacturer?
Dr. Woodcock. Yes.
Mr. Burgess. That is even before you get into a follow-on
situation?
Dr. Woodcock. Yes, we have a lot of experience in
regulating all these manufacturing changes because some of
these products, for example, become very successful and
additional production capacity, scale up, new plants and so
forth have to be opened. And in those cases, the manufacturer
has the burden of showing that the molecule they are making in
there will perform the same as the original one.
Mr. Burgess. Let me ask you, if we do this legislation, are
the people who work at the FDA, the people who are tasked with
ensuring that our Nation's drug supply is safe and effective,
do you detect any concern on the part of the staff of the FDA
that they are going to be under any pressure to deliver these
products before the testing is actually complete? Mr. Green
referenced Ketek and the Vioxx situations. Are we setting
ourselves up because this is inherently more complicated than a
Ketek or a Vioxx? Are we setting ourselves up for that? Let me
just ask you it this way. Do you detect concern among the
staff, the career people at the FDA, that we are tasking them
with something that is virtually impossible?
Dr. Woodcock. I think as I said we have the technical,
scientific, and medical expertise necessary to make these
decisions. We require adequate resources to do that, and
obviously if a new statute were passed, it would have to be
sensible. It would have to take all the parameters that have
been discussed today into consideration so that it could be
implemented properly.
Mr. Burgess. But again, are you detecting any undercurrent
from the staff that there is going to be--we are the ones that
are going to have oversight over that. You see the level of
expertise that we present today. You guys are the experts. Are
you detecting concern from the experts within the FDA itself
about how this is going to be regulated?
Dr. Woodcock. I think the experts' concern only is that we
need to have access to resources in the ongoing scientific
expertise that would enable them to make these decisions.
Mr. Burgess. Mr. Chairman, you have been very kind, and I
realize that means we have a vote. I mean, I think it is so
important that we give you the flexibility and you look back to
the days when Sir Alexander Fleming discovered penicillin, it
was more of a parlor trick that he was able to inhibit
bacterial growth in a Petri dish, and it wasn't until somebody
figured out the manufacturing process that made it clinically
useful. The same could be said for cortisol, that after it was
derived it was very, very difficult to come up with amounts
that would be clinically useful until that manufacturing
process came about. So we are kind of on the cusp of that type
of change in medicine right now. It is so important that we get
it right. I think we were read a passage from the bill, and the
part about the two similar saccharide repeating units, even if
the number of units differences, and there are differences of
the post-polymerization modification, saccharide being sure and
basically we are talking about the difference between cane
syrup or cellulose or a celery stock and you can see you could
end up with a completely different product that will have a
completely different intent. We have to be so careful as we go
through this, Mr. Chairman.
Mr. Waxman. OK. Let me yield.
Mr. Burgess. I would be happy to yield to my friend.
Mr. Waxman. I think your line of questioning is very
thoughtful and got right to the nub of it. Dr. Woodcock, you do
have this 505(b)(2) authority now which gives you all the
flexibility. If we had the same kind of provision giving the
FDA the same level of flexibility to require whatever you need
without any deadline to approve a drug, not approve it at all
until you reach that conclusion that it is just as safe and
effective, would that be sufficient authority for you?
Dr. Woodcock. I----
Mr. Waxman. You already worked with that.
Dr. Woodcock. I really can't comment. I can say that we are
approving drugs under that pathway right now, and that has
flexibility. It doesn't have some of the issues that pertain to
all the biological products that are now approved and have not
been under this scheme.
Mr. Pallone. There is no time left, and I have got to
figure out what we are doing here. We have 11 minutes before
the first vote. This is a 15-minute vote followed by two 5-
minute votes. I wouldn't be that long, so I am hoping you can
wait for us to come back because we have another three or four
members that would like to ask questions, OK?
Dr. Woodcock. I would happy to do so.
Mr. Pallone. Thank you. But maybe we will get in--let me--
there is a 15-minute vote of which there is 11 minutes left and
then two fives. If you would like to ask your questions, Mr.
Gordon, we can do that now? I just want the Members to know
after Mr. Gordon we will vote and come back.
Mr. Gordon. Dr. Woodcock, you are doing a good job. If you
were my chemistry teacher, I think I might have amounted to
something.
Let me ask you one question. It is my understanding that
the Europeans have already started a process for follow-on
biologics. Could you tell us what they are doing, what you
think are the pros and cons, and how it is similar, dissimilar
to what is happening here?
Dr. Woodcock. I think we have to realize that Europe has a
somewhat different setup and scheme than the United States, so
it is not really strictly extrapolatable to here. However, in
Europe the plan is that the EMEA, the medicines regulatory
agency will make these decisions. They did not have the
distinction between a Public Health Service Act and a Food,
Drug, and Cosmetic Act. These products were all under their
ordinary scheme already.
They have a program called Biosimilars, and for Biosimilars
the Medicines Agency will construct a guidance for each product
area and will put that guidance out and then submissions can
come in that conform with the guidance. We work very closely
with the Europeans, the EMEA, and we are quite aware of what
they are doing. And their approach to Omnitrope for example is
very similar to the approach that we took subsequently.
Mr. Gordon. Do you have an opinion as to the pros and cons
of what they are doing?
Dr. Woodcock. I don't know that their approach is, as I
said, directly applicable to here in the United States.
However, I think they are using good science and a public
process to move forward.
Mr. Gordon. Thank you. You represent your agency very well.
Dr. Woodcock. Thank you.
Mr. Pallone. Thank you. So we will now be in recess until
after these three votes, and then we will come back and you
will wait. Thank you, Doctor.
[Recess.]
Mr. Pallone. We are back in business. The gentleman is
recognized.
Mr. Inslee. Thank you. Dr. Woodcock, I wanted to focus on
the issue of clinical trials, the advisability of that. It is
important. My mother was an insulin-dependent diabetic, my
brother is an insulin-dependent diabetic, I am going to be in a
race with 5,000 insulin-dependent diabetics here in a couple of
weeks and I would like to tell them if we come up with a
biologic that it is going to be safe and we can have confidence
about that. I want to make sure I understand. You are of the
belief at this time given the present state of scientific
knowledge that it is important to have some level of clinical
trials for follow-on biologics to prevent unwanted
immunogenicity.
Dr. Woodcock. That is correct, and in some cases we may
need additional clinical trials, if there are additional things
that we aren't certain about.
Mr. Inslee. Now, you have also alluded to the potential
that there might be scientific advances to obviate the
necessity of clinical trials. You made some reference to that.
So I just wanted to ask you about that. Can you give us with a
reasonable degree of certainty that in fact that will happen
for all of these drugs?
Dr. Woodcock. No. I believe that the science of
characterization will advance over time, and therefore we will
be able to do better and better comparisons in the laboratory
and functional comparisons and so forth so that we will have
less uncertainty about how similar they are. We will be much
more sure about how similar they are. That doesn't mean though
that we will be able to completely rule out clinical trials.
Mr. Inslee. Could you say that in the next 5 years most
follow-on biologics scientific knowledge would advance so that
you would not require clinical trials for most incidents?
Dr. Woodcock. No, I think the opposite is true. Over the
next 5 years, we would need clinical trials of some sort for
most proteins, follow-on proteins.
Mr. Inslee. I and others have introduced a bill that would
have a statutory requirement for some level of clinical trials,
and frankly for the reason it is sort of like seatbelts. We
have requirements for seatbelts. There may be science developed
some day that we get arround airbags or some other, but the
best science we have right now we require seatbelts and that is
an appropriate legislative decision. So I am asking, I guess is
there any reason why we should be the first country to not
require clinical trials in these contexts?
Dr. Woodcock. I think from the FDA standpoint, we would
require clinical trials, say, under the 505(b)(2) whenever they
are necessary, and right now they are going to be necessary for
almost every protein. In the future, they may not be necessary
for some category of proteins. Right now, for example, for very
short peptides which are very tiny versions of proteins, we
don't think we need clinical trials other than perhaps the
bioequivalence type of studies, it would be done for a generic
drug.
Mr. Inslee. If Congress does require clinical trials on a
bill similar to mine or others, would there be any damage to
the pace of scientific inquiry by doing that? Is there any
downside in that regard?
Dr. Woodcock. I think it would depend on how specific you
were or how proscriptive you were. There are many kinds of
clinical trials, everything from bioequivalence trials that
mainly look at the pharmacokinetics of a drug to a codynamic
trial, safety trials, efficacy trials. Each of those have
different ramifications. So we think right now that we would
probably need in most cases immunogenicity trials as well as
probably human pharmacokinetic trials.
Mr. Inslee. And I think if you ran by your opening
statement, you would find that you pretty much described the
bill that I had introduced as far as giving you that level of
flexibility to determine which ones that would require some
clinical trials. And I for one believe it is appropriate for
Congress to set some level of protection. We have done this in
various contexts in the Food Quality Protection Act. We
established actually numerical requirements for pesticide
residues. In the 1996 Safe Water Drinking Act they had
numerical standards for lead, mercury residues and we thought
that that was appropriate. Could you tell us with any more
degree of certainty at all to characterize when you think
science probably will obviate the necessity of clinical trials?
Can you give us any greater certainty as to time, this decade,
the following decade?
Dr. Woodcock. As I said in the last hearing, I think within
this decade we will be able to characterize some of the very,
very simple proteins well enough that we probably will be able
to decide that they are similar enough to an innovative
product. That is within this decade. But there are many other
complicated products that are very important products that I
think we would still not be able to do them in the next 10
years.
Mr. Inslee. So I guess what you are saying we are dealing
in probabilities here. You think there is some probability that
within this decade some of the simpler proteins may be
categorized without this, but the bulk of them and the more
complex ones would not in this decade, is that a fair
assessment?
Dr. Woodcock. That is my prediction but I don't have a
crystal ball.
Mr. Inslee. Well, I thank you very much. Take care.
Mr. Pallone. Thank you. I think we are out of questions.
Thank you, Doctor. I really appreciate your testimony and
bearing with us through the votes and all that.
Dr. Woodcock. I am happy to do so.
Mr. Pallone. And we may send written questions to you
within the next 10 days or so for you to respond to.
Dr. Woodcock. We would be pleased to do that.
Dr. Woodcock. Thank you.
Mr. Pallone. And now we will have the second panel come
forward.
Welcome. Thank you for being with us today. I am just going
to introduce everybody with their titles here. First is Dr.
William Schwieterman who is from Tekgenics in Mobile, Alabama.
Next is Dr. David Schenkein, vice president, clinical
hematology/oncology at Genentech from south San Francisco; Dr.
Geoffrey Allen, president, CEO, chairman of Insmed Incorporated
from Richmond; Mr. Richard Kingham who is a partner in
Covington & Burling here in DC; Mr. Bruce Downey who is
chairman of the board of the Generic Pharmaceutical
Association, actually from Woodcliff Lake, New Jersey; and then
we have Ruth Hoffman, executive director of the Candlelighters
Childhood Cancer Foundation from Kensington, Maryland; and Dr.
Ed Weisbart who is the chief medical officer for Express
Scripts from Maryland Heights, Missouri.
Thank you for being here today. We have 5 minutes' opening
statements, and if you would like to submit some additional
information for the record that is pertinent, we will also
allow that and we will start with Dr. Schwieterman.
STATEMENT OF WILLIAM SCHWIETERMAN, M.D., TEKGENICS, INC.,
MOBILE, AL
Dr. Schwieterman. Thank you very much, Chairman Pallone,
and good morning members of the Subcommittee on Health, Energy
and Commerce.
My name is Dr. William Schwieterman, and I thank you for
the opportunity to appear before the committee today and
present a scientific and clinical perspective on the issue of
biogenerics.
One of the most disturbing experiences for a physician is
to know that a treatment is available to help your patient but
the cost may simply be beyond what your patient can afford.
Sadly, this is what many patients who need treatment with brand
biopharmaceuticals are facing in today's world. For this
reason, I strongly believe that Congress must give FDA the
authority it needs to create a workable, scientifically based
abbreviated approval pathway for biogenerics and given that I
also had the privilege of working at FDA in the area of
biotechnology for 10 years, I know that this can and should be
achieved.
I was heartened to hear during the House Oversight and
Government Reform Committee in hearing that the FDA Deputy
Commissioner Janet Woodcock also believed that this goal could
be achieved, stating that the FDA can be trusted to carry out
its mandate from Congress, whatever that might be and the long-
anticipated FDA white paper recently released by FDA also
validates their ability to prove biogenerics for efficacy and
safety.
I come before you today wearing three hats, as a physician,
as a scientist, and as a former FDA reviewer. From this vantage
point, I would like to make the following critical points.
First, with today's scientific advancements in technologies,
FDA can assure the safety and efficacy of biogenerics. Second,
the supporting science for this is not new. It has existed for
over a decade. The FDA white paper confirms that FDA has
already been using a science-based approach case by case to
approve biopharmaceuticals and more importantly changes in
biopharmaceuticals. Third, the issues raised in post-approval
brand product changes are reflective of the issues that are
raised with biogenerics. In other words, the same science that
determines comparability for the brand to biotech industry can
also be adopted to ensure the safety and efficacy of comparable
and interchangeable biogenerics. This point is particularly
important when it comes to the issue of conducting clinical
trials.
As Dr. Woodcock noted at another House hearing, it is a
common misperception that clinical trials are always the most
sensitive studies for detecting changes in safety or
effectiveness due to process changes. I agreed with her when
she went on to state, ``Where trials aren't needed, it is of
questionable ethics to repeat them, so use of human subjects
for trials that are not needed that are simply to check a box
on a regulatory requirement are not desirable.'' The necessity
and type of clinical trials required for biogenerics should be
determined based only upon a scientific standard established by
FDA on a case-by-case approach. Having worked extensively at
FDA with many physicians and scientists and listening to the
words of Dr. Woodcock and other FDA officials these past few
months, I also want to emphasize there is just one safety
standard at FDA and that standard has been and will continue to
be applying the review and approval of each and every biologic,
whether it be brand or generic. It is relevant to note that the
standards and science used for current biopharmaceuticals are
informative for us with respect to generics. A critical but not
often publicized fact about the biopharmaceutical industry is
that FDA does not require brand companies to perform large
clinical outcome studies to retest the product generated by new
manufacturing processes. This is because such an approach would
not only be infeasible but more importantly would ignore the
utility of existing sophisticated scientific analytic tools and
techniques for this purpose.
Let me briefly summarize what happens in these instances.
FDA starts with an assessment of extensive analytic
comparability data. With these data, and keeping in mind the
nature of the drug, the test used, and the disease being
studied, FDA decides how to proceed. The agency can give a
thumbs up and a thumbs down regarding each post-approval brand
manufacturer change and if thumbs up, have that change be
supported by analytic data coupled with pharmacokinetic or
pharmacodynamic studies or the studies just mentioned, plus
data from a large clinical outcome study.
It should also be noted the vast majority of brand
manufacturer changes need no further studies when data from
analytic tests show the product to be comparable. For a small
number of brand products that show small differences in
analytic tests for following manufacturer change, FDA may
require additional analytic and pharmacokinetic or
pharmacodynamic tests to be conducted in animals or humans.
The latter studies are clinical studies in the sense that
they are conducted in patients in the clinic but they are not
the large outcome studies commonly used to determine the
product's ultimate clinical effects. These pharmacokinetic and
pharmacodynamic studies almost always involve fewer than 100
patients and last weeks, not months. Rarely after a brand
manufacturing changes the FDA required that a brand company
take the last step, repeating a full-scale clinical outcome
study. In fact, of all the hundreds of brands of biologic
products changes, the vast majority were approved without large
clinical outcome studies.
In sum, FDA scientists and physicians routinely make
comparability determinations between similar biologic products
since manufacturing changes occur throughout the brand biologic
product development life cycle. The scientific essence and
basis of comparability determinations used by FDA is therefore
not new but rather has existed for over a decade to allow brand
biologic manufacturers to change and improve their
manufacturing processes.
The Access to Lifesaving Medicines Act will give the FDA
the authority and flexibility it needs to ensure the safety and
efficacy of biogenerics. It adopts the same scientific
principles, processes, and procedures that exist for the brand
biologic industry when making post-approval manufacturing
product changes in the biogeneric sector.
I would like to emphasize the need for science----
Mr. Pallone. Doctor, if you could summarize because you are
over the 5 minutes.
Dr. Schwieterman. Thank you. A truly workable pathway for
biogenerics is one that that is fully scientifically based,
consistent with regulatory experience, and brings safe and
effective biogenerics to patients in a timely manner. Thank you
so much.
[The prepared statement of Dr. Schwieterman follows:]
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Mr. Pallone. Thank you. Dr. Schenkein.
STATEMENT OF DAVID SCHENKEIN, M.D., VICE PRESIDENT, CLINICAL
HEMATOLOGY/ONCOLOGY, GENENTECH, INC.
Dr. Schenkein. Good afternoon, Mr. Chairman, and members of
the committee. My name is Dr. David Schenkein, and I am vice
president of Clinical Hematology and Oncology of Genentech. I
have been a practicing oncologist for the past 20 years, and I
am pleased to come before you today on behalf of the
Biotechnology Industry Organization.
Genentech is considered the founder of the biotechnology
industry. We began 31 years ago with the goal of developing a
new generation of therapeutics created from genetically
engineered copies of naturally occurring molecules important in
health and disease. Our mission is to end the death sentence
that cancer currently represents by creating medicines that
will transform cancer into either a curable illness or a
chronic condition.
In order to ensure that innovative biotechnology products
continue to reach patients and physicians, it is essential that
Congress adopt six key principles in creating any regulatory
pathway for follow-on biologics. First and foremost,
legislation must ensure patient safety. Patients should not
have to accept greater risks or uncertainties in using a
follow-on product and an innovator's product. In addition,
legislation must recognize that biologics are far more complex
than small-molecule chemical drugs. It must maintain the
physician-patient relationship and allow only treating
physicians to determine whether a follow-on product is
interchangeable for the innovator product. It must preserve
incentives for innovation, must ensure a transparent regulatory
process, and must continue to prioritize the FDA's review of
new therapies and cures.
In oncology we treat life-threatening illnesses. For many
patients the first therapy is the chance for a cure that
evaporates if the disease recurs, making it incurable. It is a
critical window of opportunity. Take for example the situation
that women with Her2 positive breast cancer face every day. At
diagnosis, women are treated with a balance of chemotherapy and
biologic Herceptin, along with surgery and radiation. For the
majority of these women, in part because of the effectiveness
of Herceptin, their cancer will not return. Imagine a situation
where a woman is treated with a follow-on biologic in this
setting that has even a slightly different profile which allows
her cancer to return years later. The disease has now spread
and her chances of survival are reduced significantly. What do
we tell that woman and her family, that we never tested that
follow-on biologic in humans but we thought it was similar
enough to Herceptin and relied on those data to support its
approval and to advocate for its use?
I firmly believe there will always be a need for clinical
testing of a follow-on biologic. The amount and type of testing
will depend on the specifics of the product and assessment of
potential risks, and those determinations should be left to the
FDA. Clinical trials will always be important to address
questions such as immunogenicity. I would never take a biologic
that had not been tested in humans. The risks are too high. New
legislation should not court the others who may be less
informed to do so.
In addition to scientific considerations, I would also like
to address the importance of incentives. As an oncologist, I am
extremely concerned about the potential that limited or no data
exclusivity would have on agavent or early stage cancer drug
development. It is in this setting that we hope to translate
breakthrough discoveries into cures. Insufficient data
exclusivity could strangle the incentives to continue investing
in trials beyond the advanced or metastatic setting. Agavent
studies are typically started only after positive phase three
trials in metastatic cancer and are after-return data late in
the patent life of the product. Trials of agavent therapy are
intended to catch the cancer at the time before it spreads
where our therapies could have the greatest impact for
patients.
The approval for Herceptin in the agavent setting occurred
8 years after the original approval in the metastatic setting
and involved more than 3,500 women in multiple randomized
clinical trials. These trials can take easily more than 5 years
from inception to completion at huge cost without any assurance
of clinical success. Herceptin in the agavent setting reduced
the risk of cancer occurrence by 50 percent, and if the cancer
doesn't recur, these women cannot die from it.
This is our mission, to beat cancer through science, but
without a substantial period of data exclusivity, it would be
difficult for Genentech and others to invest in this critical
but costly research. I am excited every day when I look at the
pipeline we have at Genentech. We are developing biologics that
starve tumors, cause cancer cells to self-destruct, and program
them to behave differently in the body. It is my hope and that
of BIO and Genentech that a transparent public process that
leverages known scientific considerations will provide a
framework and pathway for the approval of follow-on biologics.
The stakes are simply too high to risk patient safety and
potential cures by moving too quickly and not following the
science.
Again, I thank you for the opportunity to testify before
you today and look forward to answering any questions you may
have.
[The prepared statement of Dr. Schenkein follows:]
Statement of David Schenkein, M.D.
Good morning, Mr. Chairman and Members of the Committee. My
name is Dr. David Schenkein and I am vice president of Clinical
Hematology and Oncology at Genentech, a leading biotech company
headquartered in South San Francisco, California. I am pleased
to come before you today on behalf of the Biotechnology
Industry Organization (BIO) to offer my perspective on the
issues relevant to any proposed framework for the abbreviated
approval of follow-on biologics.
BIO represents more than 1,100 biotechnology companies,
academic institutions, state biotechnology centers and related
organizations across the United States and 31 other nations.
BIO members are involved in the research and development of
health care, agricultural, industrial and environmental
biotechnology products.
I hope you will find my contribution to this discussion
constructive and useful as you seek out a sound, science-based
path forward for follow-on biologics while preserving patient
safety and incentives for biomedical innovation.
By way of introduction, I have been a medical oncologist
and hematologist for over 20 years. I have spent most of my
career caring for patients with life threatening illnesses.
It's been my job to sit with patients and their families and
make decisions on the most appropriate therapy to choose---
many times a choice of risk benefit that has life and death
implications. Prior to joining Genentech, I spent 17 years in
academic and clinical medicine as an attending physician in
Hematology Oncology at the Tufts-New England Medical Center in
Boston, where I was an associate professor and held the
position of director of the Cancer Center. I will soon be on
the oncology faculty at the Stanford Cancer Center.
I previously served as the senior vice president of
Clinical Research at Millennium Pharmaceuticals in Cambridge,
where I oversaw the clinical development of Velcade, a first-in
class cancer therapy now approved to treat multiple myeloma and
non-Hodgkins lymphoma. In my current role at Genentech, I am
responsible for leading the medical and scientific strategies
for our BioOncology portfolio, including overseeing the
development of a robust pipeline of novel cancer therapies and
marketed products, including Avastin, Herceptin, Rituxan and
Tarceva.
My company, Genentech, is considered the founder of the
biotechnology industry. Genentech was founded 31 years ago with
the goal of developing a new generation of therapeutics created
from genetically engineered copies of naturally occurring
molecules important in human health and disease. Within a few
short years, Genentech scientists proved it was possible to
make medicines by splicing genes into fast-growing bacteria
that produced therapeutic proteins.
Today, Genentech continues to use genetic engineering
techniques and advanced technologies to develop medicines that
address significant unmet needs. Genentech is among the world's
leading biotechnology companies, with 14 products on the market
for serious or life-threatening medical conditions, over 50
projects in the pipeline and more than 10,000 employees.
The researchers and clinicians at Genentech are working to
fundamentally change the way cancer is treated by developing a
broad portfolio of innovative targeted therapies designed to
improve and extend the lives of cancer patients. Put simply, we
are trying to end the death sentence that cancer currently
represents by creating medicines that will transform cancer
into either a curable illness or a chronic condition. We strive
for the time when a diagnosis of cancer leads to a discussion
similar to the one that occurs today around high blood pressure
or diabetes.
I would like to begin by noting that I appreciate the
concern Congress has shown for patient access to biologic
therapies. It is a concern that I share--as does Genentech, and
as does BIO. While legislation on follow-on biologics has the
potential to increase access to some medicines, that
legislation must be well-founded in science and ensure that the
medicines to which access is provided are no less effective or
safe than medicines already on the market. I believe that
through the proper process, those critical goals can be met.
In order to ensure that new pioneer biotechnology products
continue to reach patients and physicians, it is essential that
Congress adopt six key principles as it explores the creation
of any regulatory pathway for follow-on biologics. I will touch
on these principles in my testimony, but will focus principally
on the first three since my expertise is as a physician and a
scientist.
Ensure Patient Safety. Patients should not have
to accept greater risks or uncertainties in using a follow-on
product than an innovator's product.
Recognize Scientific Differences Between Drugs
and Biologics. Biologics are much more complex than small
molecule chemical drugs.
Maintain the Physician-Patient Relationship. The
current state of science is not sufficient to establish
interchangeability for complex follow-on biologics.
Accordingly, Congress should ensure that patients are not given
follow-on biologics unless expressly prescribed by a physician.
Preserve Incentives for Innovation. Any statutory
pathway for follow-on biologics must include a substantial data
exclusivity period; must respect our intellectual property
rights; and must provide adequate notice and process rights.
Ensure Transparent Regulatory Processes. Any
legislation must require FDA to follow a transparent and public
process in determining data requirements for the approval of
specific follow-on biologics.
Continue to Prioritize FDA Review and Approval of
New Therapies and Cures. Congress must ensure that workload
associated with follow-on applications does not harm the FDA's
ability to efficiently review new drugs and biologics.
First and foremost, patient safety must be assured. I trust
that patient safety is a concern that we all share and that it
will be a guiding concern for Congress as you consider a
statutory pathway for follow-on biologics.
If follow-on biologics are to achieve the same standards of
safety and efficacy as pioneer biotechnology products, then
clinical trial evidence and data must be a fundamental
requirement, and must be conducted on a product-by-product
basis. The safety and effectiveness of a follow-on biologic
simply cannot be assured without clinical testing, and in
particular, immunogenicity testing, which is necessary to avoid
putting patients at risk of adverse effects from immune
reactions.
The stakes are too high to take the risk of moving too
quickly and not following the science. In oncology, like in
other therapeutic areas, we make our decisions on therapy
selection based on clinical data and a deep understanding of
both safety and efficacy: the risk to benefit ratio. Somewhat
unique to oncology is the life-threatening nature of the
illnesses we treat and the consequences of a wrong choice. For
many patients, the first therapy is a chance for a cure that
evaporates if the disease recurs, making it incurable.
Take for example the situation that women with Her2
positive breast cancer face every day. At diagnosis, women are
treated with a balance of chemotherapy, including the biologic
Herceptin, directed at the cancer protein along with surgery
and radiation. For the majority of these women, their cancer
will not return. Imagine a situation where a woman is treated
with a follow-on biologic in this setting that has even a
slightly different risk-to-benefit ratio, which allows her
cancer to return years later. The disease has now spread and
her chances of survival are reduced significantly. What do we
tell that woman and her family? That we never tested that
follow-on biologic in humans, but we thought it was similar
enough to Herceptin and relied on Herceptin's data to support
its approval and to advocate for its use?
To understand why we should always expect some need for
pre-market clinical testing and immunogenicity testing of
follow-on biologics, it is important to understand the nature
of biologics in general and how they differ from small molecule
therapies.
Differences Between Biologics and Drugs
With small molecule drugs--for example, the conventional
pills you see on pharmacy shelves and in medicine cabinets--you
are working with substances that are relatively small,
relatively simple in structure, and relatively easy to
replicate using carefully controlled processes. Most
importantly, their relatively small size and simple structure
allow precise characterization and detection of even minor
changes in the product.
Biologics are vastly different from small molecules in all
these aspects. In contrast to small molecules, biologics are
very large--typically several hundred- or thousand-fold larger.
They are produced not by well-controlled chemical processes but
by complex living cells and organisms through extremely
complicated and sensitive manufacturing processes.
As innovator companies' experience with respect to pioneer
biotechnology products has shown, and as FDA has long
emphasized through its regulation and guidance, small product
or manufacturing differences in biologics can result in
significant safety and/or effectiveness differences. To a far
greater extent than small molecules, biologics frequently can
bind to themselves to form pairs or aggregates, can change
their shape over time or with minor changes in conditions, and
can interact with materials in their containers and packaging.
They are relatively unstable and are sensitive to how they are
handled, processed and stored as they have the ability to
assume many forms and variants. They are typically not
homogeneous in chemical structure; rather, they are a large
family of molecules with related, but not identical,
structures. They cannot be fully characterized, so not only are
differences common, they can be extremely difficult to detect,
and their effects on the product's safety and efficacy are
extremely difficult to predict.
As a result, the regulation of biologics is largely based
upon strict control of the manufacturing process to minimize
the likelihood of changes to safety and efficacy. Additional
clinical testing is often required when substantial changes to
the manufacturing process occur, and certainly the type of
changes and differences in manufacturing necessary to producing
a follow-on product would meet such a threshold.
While the ability to characterize biological products using
physical, chemical, and biological testing has improved as
science has advanced, current laboratory testing--without
testing in patients--is still very far from sufficient to
ensure that a follow-on biologic is without differences from a
reference product. These differences could adversely affect its
safety or efficacy.
Furthermore, the methods used by innovators to demonstrate
continued safety and effectiveness after a manufacturing
process change are insufficient to demonstrate safety and
effectiveness of a follow-on biologic made by a different
manufacturer using a different process. When a biologics
manufacturer makes a substantial change to its process (e.g.,
new cell line), given the incomplete ability of laboratory
testing to identify or predict differences, FDA requires
substantial testing in humans (clinical testing) to validate
the comparability of the product. And clinical testing often
reveals differences. This is important because by definition,
the manufacture of a follow-on will necessarily involve very
substantial manufacturing changes--a new cell line, a new
facility, and a new process. These changes will result in a
different product, and vastly increase the likelihood of
clinically important differences, which can only be understood
through clinical testing in humans.
The manufacturer of a new follow-on biologic also faces
several limitations in its ability to identify clinically
important differences short of clinical testing. When a
manufacturer makes substantial changes in its manufacturing
process, that manufacturer is able to compare not only the
final product but also various components and intermediates
that are produced during various stages of the new and old
manufacturing process. For example, depending on the changes
made, comparisons might be made of the unpurified biologic
(made by the old and new processes), and/or of purified product
prior to formulation. Such comparisons may detect important
differences that remain in the final product, but at levels
that make them undetectable in the final product. Manufacturers
of follow-on biologics will not have these materials for
testing and will only have access to the final, marketed
reference product.
Additionally, optimal comparisons of ``before change'' and
``after change'' materials require an understanding of which
parameters are key to ensuring the safety and efficacy of the
molecule and what the best approaches are to assessing them.
This understanding comes from years of working with the
reference product, which is not available to manufacturers of
follow-on biologics. Further, when differences are detected,
the key question becomes whether the difference is clinically
important. While manufacturers of innovator products have
extensive experience that sometimes helps address this
question, the manufacturer of a new follow-on biologic will
have limited experience with the molecule.
Thus, the ability of an innovator to make changes to its
own manufacturing process, subject to the FDA's comparability
guidelines, is simply not analogous to a follow-on company
proving ``comparability'' when entirely different manufacturing
processes are used. A manufacturer of a follow-on biologic will
face significantly more limitations in demonstrating
``comparability'' than a manufacturer modifying its own
process. When we make changes that might affect the clinical
effects of a product, we also face an appropriate requirement
for clinical studies to ensure safety and efficacy. How can we
accept a lesser standard of evidence from the manufacturers of
follow-on biologics who face even greater limitations in
laboratory testing, without significant concerns for safety?
Clinical trial evidence and data are fundamental for
evaluating and demonstrating the safety and effectiveness of a
follow-on biologic
In light of the limitations described above, and based on
my experience, I firmly believe that there will always be a
need for clinical testing of a follow-on biologic to provide
adequate assessment of potential changes. The amount and type
of testing will depend on the specifics of the products and
assessment of potential risks, and those determinations should
be left to the FDA. Clinical trials will always be important to
address questions such as immunogenicity, pharmacokinetics, and
common adverse events under controlled conditions before a
product is marketed. I would never take a biologic that had not
been tested in humans; the risks are too high. New legislation
should not cause others, who may be less informed, to do so.
Congress should not create two standards for these products--
those appropriately tested for safety and efficacy and those
that are not.
There are many examples of how seemingly minor changes in a
biologic's manufacturing process have resulted in significant
changes in the product--changes that could only be detected
through clinical testing. I would like to use some specific
examples to ensure that this Committee's members understand
that my concerns are not theoretical or alarmist in nature, but
are in fact very real issues that need to be considered.
In our case, Genentech was working with a business partner,
Xoma, to develop a product for psoriasis. When it came time to
transfer the technology from Xoma's facility to our own state-
of-the-art manufacturing plant, we were unable to produce
material that met the pre-defined statistical definition for
comparability. During Phase III testing, minor manufacturing
modifications were made to allow for large-scale material
production. The pharmacokinetic (PK) studies we conducted
suggested that the Genentech material achieved a slightly
higher serum concentration than the Xoma material. Because we
could not be sure that the product we produced at Genentech,
which was different than that produced at Xoma, was safe, we
agreed to do additional clinical testing. Fortunately,
Genentech was able to prove to the FDA that the new material
was safe, but FDA approval of the product was delayed by more
than a year.
While this is a good example of a manufacturing change
resulting in differences that, once re-tested, proved to be
acceptable, there are plenty of examples where seemingly minor
differences have had catastrophic consequences. Irrespective,
we agreed with the FDA's decision that we must re-test our
product to ensure its safety and effectiveness.
Immunogenicity Testing is Necessary to Avoid Putting Patients at Risk
of Adverse Effects From Immune Reactions
Special attention should be given to the problem of
immunogenicity: the ability of most or all biologic products to
stimulate an immune system response in the body, prompting the
formation of antibodies. Immunogenicity is particularly
important in the context of manufacturing changes for biologics
because (I) product differences that are difficult or
impossible to detect can lead to changes in immunogenicity; (2)
changes in immunogenicity can impact on safety and efficacy in
many ways and (3) immunogenicity can be assessed only through
clinical testing. The immune system evolved to distinguish
foreign proteins (e.g., bacteria, viruses, proteins from other
people) from its own proteins as a means of survival. This
means that our immune systems can be exquisitely sensitive to
differences in proteins.
Thus, there is great potential for seemingly minor changes
in therapeutic protein products, even those not detected by
physical, chemical, and biological testing, to result in
clinically significant changes in immunogenicity.
Most biologic products have some degree of immunogenicity;
that is, they will cause formation of antibodies in some
patients. For vaccines, this is desirable. For therapeutic
proteins, these antibodies can inactivate the protein or cause
it to be cleared from the body, resulting in a loss of efficacy
and the progression of the disease. Patients with hairy cell
leukemia treated with interferon alfa, for example, have been
reported to experience a relapse of disease when antibodies
develop. Similarly, some patients receiving insulin and blood
clotting Factors VIII and IX have been reported to lose
responsiveness after developing antibodies.
In addition to inactivating or clearing a drug, antibodies
bound to a drug can also play a direct role in causing various
adverse effects. Patients who have developed antibodies to
experimental biologics have experienced consequences including
joint swelling, fever, and encephalitis. Even for approved
biologics, it is not uncommon that the development of
antibodies during treatment increases the likelihood of having
adverse reactions, sometimes even severe, at the site of
subsequent injections or following subsequent infusion into the
blood stream.
In addition to these effects, and more serious still,
antibodies can also inactivate the body's naturally occurring
protein, resulting in adverse and even life- threatening side
effects. Patients who received an experimental biologic version
of thrombopoietin, a protein that stimulates production of
platelets critical for blood clotting, developed antibodies
which neutralized not only the biologic, but also their own
naturally produced thrombopoietin, resulting in problems with
bleeding.
The case of EPREX, a biologic product sold in Europe by
Johnson & Johnson companies, illustrates how even a seemingly
minor change can increase a product's immunogenicity and cause
harm to patients. In 1998, J&J changed the stabilizer in its
EPREX formulation at the request of European authorities
because of concern in Europe that the human serum albumin
stabilizer could theoretically transmit Mad Cow Disease. The
switch from the old stabilizer to another well-established one
seemed simple enough and relatively benign. Indeed, it was
intended to improve the safety profile. It was applied to a
variety of product presentations, including single-use vials
and pre-filled syringes with both Teflon-coated and uncoated
rubber stoppers.
However, shortly after this seemingly minor change, there
was an increase in the incidence of antibody-mediated pure red
cell aplasia (PRCA) among patients taking EPREX. Pure red cell
aplasia is a serious condition in which the bone marrow ceases
to produce red blood cells. Patients suffering this adverse
event must undergo blood transfusions weekly for the remainder
of their life. It took four years of extensive investigations
involving more than 100 experts from clinical, pre-clinical,
manufacturing, process sciences, logistics, quality,
analytical, and regulatory fields and in excess of one hundred
million dollars to identify the cause. The conclusion was that
uncoated rubber stoppers, when exposed to the new stabilizer,
released substances called leachates into the EPREX formulation
and that these substances were most likely responsible for the
increase in the product's immunogenicity and the resulting
increase in patients developing pure red cell aplasia.
It's important to note that the examples I have given are
just some of the cases in which immunogenicity concerns have
arisen. Most biologics have some degree of immunogenicity.
Immunogenicity levels can change with even slight changes in
their manufacturing process and can have clinically important
consequences. Scientifically, the only way to detect
immunogenicity is through clinical testing.
In summary, extensive experience confirms that
manufacturing differences, such as those between the processes
of an innovator and follow-on, are likely to lead to
differences in product safety or efficacy, which will be
detected best or only through clinical testing. That is not to
say that a full clinical testing program must be required for
follow- on biologic products. Abbreviated clinical testing will
sufficiently address key areas of uncertainty regarding safety
and efficacy on a product-by-product basis, particularly where
there exist good measures of desired effects (so called
pharmacodynamic measures) and where a high degree of similarity
is demonstrable. But experience has made clear that clinical
studies must be considered a necessary and mandatory part of
properly evaluating any and all biologic products, and must be
a fundamental foundation upon which any proposed regulatory
pathway for the approval of follow-on biologics is created.
In addition, we believe that a follow-on product should be
approved only for conditions for which the reference product is
approved. For all the reasons discussed earlier, the safety,
purity, and potency of the follow-on product for each
indication must be supported independently, and attention must
be paid to special safety risks (including possible
immunogenicity) in different patient populations.
Interchangeability and substitutability: Congress should
ensure that patients are not given follow-on biologics unless
expressly prescribed by a physician
Given the complexity of biologics, the high potential for
process differences to result in clinically meaningful product
differences, and the limited ability to detect differences
between a follow-on and reference biologic, a determination of
comparability for a follow-on product is particularly
challenging. Ensuring comparability of a follow-on biologic to
a reference biologic with an acceptable degree of assurance
will be made much more challenging by the follow-on
manufacturer's limited access to information about, and lack of
experience with, the innovator's process as well as their lack
of access to intermediate, in-process materials. As a result,
we believe that establishing the interchangeability of
different products is not feasible, and therefore, is a
decision that is only appropriately made by a treating
physician.
No amount of non-clinical testing of a biologic product can
ensure or predict it will have identical effects to another
product. Although clinical testing can place limitations on the
possible extent of differences, for most products, only
extensive comparison studies could rule out clinically
significant differences. For example, if a reference biologic
caused a serious or fatal effect in one patient in 1000, and a
new drug had twice the risk, it would take a study of about
50,000 patients to have a good chance of detecting this
important difference.
Given the risk of clinically important differences always
at play and the possibility that substituting products would
increase the risk of clinically important antigenicity, it is
imprudent and potentially dangerous to allow the follow-on
biologic to be considered ``interchangeable'' with its
reference product.
The European Union (EU) rightly acknowledged in its own
process of developing a pathway for follow-on biologics that
follow-ons can be similar, but never identical to an innovator
biologic. After very careful review of the data, the EU
recognized the danger of applying ``interchangeability'' status
to follow-ons, a misnomer that could lead physicians and
patients to inappropriately assume sameness and substitute one
for the other, with potentially serious adverse health
consequences. Just a few months ago, the French Parliament
adopted legislation to prevent follow-on biologics from being
treated in the same way as traditional generics, and banned the
automatic substitution of one biologic medicine for another.
Given the current paradigm allowing for the
substitutability of generic drugs with the innovator products
they copy, a determination of interchangeability in this
context would likely encourage the substitution of one product
for another. The FDA itself expressed concerns about
substitution of one biologic medicine for another in a
statement last September: ``Different large protein products,
with similar molecular composition may behave differently in
people and substitution of one for another may result in
serious health outcomes, e.g., generation of a pathologic
immune response'' (http://www.fda.gov/cder/news/
biosimilars.html, September 2006). Even if products have a
determination of comparability but not interchangeability,
substitution could occur, potentially unbeknownst to the
prescribing physician or patient and potentially with adverse
health outcomes.
In addition, it will be important for Congress to ensure
that follow-on biologics are assigned a unique name--one that
has not be adopted for any protein manufactured by a different
person--so that it is readily distinguishable from that of the
innovator's version of the product. Assigning the same name to
a product that is not the same would be confusing and
misleading to patients, physicians, and pharmacists, could
result in inadvertent substitution of the products, and would
make it difficult to quickly trace and address adverse events
that may be attributable to either the innovator or follow-on
product.
Furthermore, if aspects of a follow-on biologic's approach,
such as the designation of interchangeability, led to
substantial numbers of patients switching between therapies, it
could severely impair the ability of pharmacovigilance systems
to deal with emerging safety problems. When a new adverse event
emerges or a known one increases in frequency, it may be
impossible to attribute the adverse event to a specific product
if patients experiencing the event have received multiple
products. This is especially the case for some types of adverse
events, such as those due to immunogenicity, that tend to arise
in patients well after receiving the causative product. Should
a particular follow-on biologic be associated with such a
safety problem, the impact of being unable to determine which
``interchangeable'' biologic was responsible could be
devastating. The ability to detect that a new follow-on
biologic has a significantly higher risk would be highly
impaired and the difference in risk could go unnoticed. When
new risks are noticed, it could well be impossible to determine
to which ``interchangeable'' biologic it was attributable, and
appropriate use of the entire group of therapies might be
severely impaired because of a concern with one. Such a class
effect is not in the best interest of patients or the industry
generally, as overall confidence in biologics would be damaged.
Follow-on biologics should be properly evaluated through
post-marketing surveillance and post-marketing clinical studies
All approved follow-on biologics will inevitably be
associated with some risk that potential safety problems will
become apparent only in the post-marketing period because (1)
not all differences between a follow-on and reference product
will be detectable in pre-market testing, (2) one cannot
predict with certainty which differences may have adverse
impacts on safety and efficacy, and (3) some risks may become
apparent only after extensive use. To optimize patient safety
and to control such risks, it is critical that the FDA not be
limited in its ability to require post-marketing clinical
studies when appropriate. Follow-on manufacturers should also
be required to monitor a product for safety problems through a
robust post-marketing safety surveillance program.
After all of the attention Congress has given to the issue
of drug safety evaluation, it would be intellectually
inconsistent for this Committee to pass legislation that does
not put forth specific provisions enabling adequate regulatory
requirements for post-marketing safety surveillance programs
and clinical studies of follow-on biologics. It would be
equally problematic for any follow-on legislation to limit the
ability of expert reviewers to negotiate for post-marketing
clinical studies that could protect public safety.
Since it is not possible to make two biologic products
identical, follow-on biologics policy will, by definition,
allow abbreviated applications for molecules that are highly
similar to a reference, despite known or potential differences.
However, a follow-on product must be as similar to the
reference product on which it relies as can be achieved, in
view of current scientific knowledge and technological
capabilities. It must have the same route of administration,
dosage form, and strength as the reference product.
In addition, one must draw a line as to how much of a
difference should be allowed as there is no scientific basis
for allowing abbreviated testing of a new biologic on the basis
of it being only distantly related to an existing one. Some
differences are so substantial that the biologics should be
considered different products entirely.
Differences in Amino Acid Sequence
The amino acid sequence defines a protein. Even a minor
difference creates a different (mutant) protein, and a product
containing a mutant protein is a different product from the
non-mutant form. Given the potential for such a product to have
different effects, any such product should be subject to all
the standard safety and efficacy testing to which you would
subject any innovator drug.
Differences in even just one amino acid can have
devastating effects on the function of a protein. Single amino
acid mutations in a person can be lethal or result in serious
diseases such as sickle cell anemia and cystic fibrosis. Single
amino acid mutations in a virus can change it from benign to
deadly or from treatable to resistant to treatment. And single
amino acid changes in therapeutic biologics, sometimes made in
an attempt to improve potency, durability or other desirable
traits, often have adverse effects on the molecule, with the
potential to pose great danger to patients.
The AspB 10 insulin analogue is a prime example. This was a
biological product that had only one amino acid difference from
the insulin amino acid sequence. At the time it was being
studied, it seemed reasonable to think that this insulin
analogue would be safe. However, to the great surprise and
concern of all involved, when AspB 10 was given to laboratory
rats, it triggered the development of breast cancers.
When a change in an amino acid has occurred during
premarket development, FDA has required extensive testing of
the new molecule rather than assuming the properties of the
former molecule were retained. To allow marketing of new mutant
protein therapeutics with anything short of the testing
required of any new protein therapeutic potentially exposes
patients to very real risks.
As noted above, the need to tolerate some differences in a
follow-on biologic from its reference product arises from
technical limitations on the inability to exclude, or in some
cases to identify some differences. But there is no technical
limitation preventing a manufacturer of a follow-on biologic
from producing one with an amino acid sequence identical to
that of a reference.
Differences in Post-Translational Events
``Post-translational modification'' refers to the important
processes that occur after the backbone of a protein has been
synthesized. It can result in major chemical modifications of
the protein, such as attaching additional chemicals, modifying
the chemical structure, cross-linking, and removing large parts
of the protein. Post-translational modifications can, and often
do, have a major impact on the activity, half-life in
circulation, and immunogenicity of a protein. Many types of
post-translational modifications leave no scientific basis for
a determination of comparability and submission of abbreviated
applications.
Any difference in post-translational modification will
require significant clinical testing to determine what
difference it makes clinically. But many are so profound, they
should simply be considered to make the biologic a different
biologic, requiring a full application.
Preserve incentives for innovation
In order to preserve incentives to research, develop and
manufacture new innovative therapies and cures, as well as new
indications for such products, any statutory pathway for
follow-on biologics must also provide a substantial period of
data exclusivity; must respect intellectual property and other
legal rights; must provide adequate notice and process rights;
must ensure a transparent statutory and regulatory process; and
must continue to prioritize the review and approval of new
therapies and cures. The importance of these measures is
explained below.
Include substantial non-patent data exclusivity, during
which time follow-on manufacturers could not rely on the FDA's
prior approval of pioneer biologics to support approval of
their own products. Such data exclusivity is necessary because
a follow-on biologic may be similar enough to a pioneer
biologic for regulatory approval purposes, but different enough
to avoid infringing the innovator's patents. Thus, non-patent
exclusivity is necessary to maintain effective market
protection. Further, the fledgling nature of the biologics
industry, its heavy dependence on access to significant amounts
of high-cost public and private investment capital, and the
high risks and costs involved in the development of new
biologic medicines all warrant a substantial period of
exclusivity.
Respect intellectual property and other legal rights.
Follow-on biologic products should not be approved until after
all statutory protections, including data exclusivity and
patent protections, are no longer available for the approved
pioneer product. Any follow-on biologics pathway should fully
respect existing protections for trade secret and confidential
commercial information, and not permit the use of such
protected data for the purpose of approving follow on products.
It also must not abrogate or limit constitutional or statutory
rights of patent holders to protect against infringement.
Provide adequate notice and process rights. Any follow-on
biologics regulatory pathway should ensure that patent
challenges are litigated or otherwise resolved prior to
marketing approval of the follow-on product, in order to
protect the innovator's intellectual property rights and avoid
confusion in the medical, patient, and payer communities.
Further, any follow-on biologics regulatory pathway should not
create special patent litigation rules that favor follow-on
biologics manufacturers.
Ensure transparent statutory and regulatory processes.
Manufacturers of innovator products should be provided full and
fair opportunities to engage Congress and other stakeholders in
a meaningful public process. Establishing a balanced and
rigorous statutory pathway for follow-on biologics requires
deliberative evaluation of numerous complex scientific, legal,
intellectual property and economic issues. Further, any such
pathway must require that FDA follow a transparent and public
process in determining data requirements for the approval of
specific follow-on biologics.
Continue to prioritize FDA review and approval of new
therapies and cures. Any applications for approval of follow-on
biologics will raise novel and complex questions of science and
law, requiring substantial time and additional resources to
ensure a thorough regulatory review for safety, purity, and
potency. In order to avoid slowing down the FDA's review and
approval of new therapies and cures, many for currently
untreatable and serious diseases, Congress must ensure that
workload associated with these new applications does not harm
the FDA's ability to efficiently review new drugs and
biologics, and that new treatments continue to have the highest
review priority.
As an oncologist and leader of a comprehensive oncology
clinical development program, I am extremely concerned about
the potential that limited or no data exclusivity would have on
adjuvant--or early-stage--cancer drug development. It is in the
adjuvant setting that we hope to translate the breakthrough
discoveries into cures for many of the incurable cancers that
face us all. Limited data exclusivity in a follow-on biologics
bill will lessen or eliminate the incentive successful cancer
innovators have to continue investing in trials beyond the
metastatic--or advanced stage - disease setting, since
successful adjuvant trials are apt to return data suitable for
an FDA submission late in the patent life of the product.
This is a significant issue because it could hinder
research and development in the adjuvant setting. These studies
are typically started only after positive Phase III trials in
metastatic cancer and could take too long to be valuable and
allow us to re-invest further in developing innovative
therapies. Trials of adjuvant therapy are intended to catch the
cancer at the time before it spreads, where our therapies could
have the greatest impact for patients. Therefore, the need for
randomized controlled trials is at its strongest in the
adjuvant setting and requires a significant investment of time,
money and human resources, as these trials are much larger in
size. I will provide a couple of examples to help explain just
how important this is to patients and our ability to
potentially end the death sentence that cancer now represents.
In the case of our drug for HER2 positive breast cancer,
Herceptin, we were only able to show that the drug could cut
the recurrence of breast cancer in half in women with adjuvant
HER2 positive disease years after completing a rigorous
clinical trial and submission program in metastatic HER2
positive breast cancer. Prior to completing additional clinical
studies of Herceptin, a diagnosis of HER2 positive breast
cancer was among the most deadly a woman could receive. The
approval for Herceptin in the adjuvant setting occurred 8 years
after the original approval in the metastatic setting, and
involved more than 3,500 women in multiple randomized clinical
trials. These trials can take easily take more than 5 years
from inception to completion at the cost of hundreds of million
dollars each, without any assurance of clinical success.
The Herceptin adjuvant program marked a first step in a
major initiative to conduct studies of Genentech's targeted
therapies in earlier stages of disease. This is again a
critical issue when I think about the potential Avastin may
have to treat patients with early-stage cancer. There are
currently more than 300 clinical trials of Avastin underway
today in more than 20 tumor types--including ovarian, brain and
adjuvant colon cancer. Our investment in the robust Avastin
development program is based on what we learned about the
safety and efficacy of Avastin in metastatic colon, lung and
breast cancer trials over the past decade.
Avastin is designed to interfere with the blood supply to a
tumor by inhibiting VEGF, a protein that plays a critical role
in angiogenesis, the formation of new blood vessels to the
tumor. Genentech scientists identified the gene for VEGF more
than 15 years ago and despite approval to treat patients with
metastatic colon and advanced non-small cell lung cancer in the
past 3 years, we are still years away from fully understanding
how Avastin can best help patients with early-stage disease in
the critical time before their cancer spreads.
The EU Approach to Biosimilars
We are fortunate that the EU has already made substantial
progress in developing and implementing a policy based in good
science and public health, and is consistent with their unique
regulatory and health care framework. We should be able to
leverage that work to have a frank and transparent scientific
debate here in the United States, allowing us to develop a
model which will be compatible with our own regulatory and
health care system.
The key features of the EU process stem from the
recognition of the unique characteristics of biotechnology
derived proteins. Several years ago, EU legislation clearly
distinguished a ``biosimilar'' (the term they use for follow-on
biologics) from a ``generic'' because of the manufacturing
principles for biologics that are discussed above. The EU
legislation did not attempt to define the scientific standards
for approval of biosimilars. Instead, the EMEA, the science-
based body responsible for approving the marketing of drugs in
the EU, was trusted with that task. Furthermore, the EU
legislation did not seek to constrain the ability of the EMEA
to require data to ensure the safety and efficacy of biologics.
The EU legislation clearly distinguished a ``biosimilar'' from
a ``generic'' due to the many scientific concerns discussed
above; the EU also recognized the inherent dangers of
interchangeability.
The EMEA provided a broad regulatory framework, including
the development of guidance documents, which outline the data
requirements necessary to for the approval of these products.
They pursued a science-based, transparent and open process to
establish concept papers and draft guidances, starting first
with basic principles for all biosimilars. This was followed by
more specific guidances, which enumerate testing requirements
on a product class-by- product class basis. This transparent
process included public scientific workshops in which all
parties were invited to offer input. The EU testing
requirements do allow for abbreviations in testing where
science and safety permit; however, clinical testing,
immunogenicity testing, and post-marketing safety surveillance
are all critical parts of those requirements. In fact, those
requirements were deemed essential to minimize the risk to
patients. The EU pathway strives to achieve follow-on biologics
that are truly highly similar to a reference product while
acknowledging that important clinical differences may still
exist upon market approval, making post-marketing clinical
studies and safety surveillance important.
In conclusion, I sincerely hope that the experiences and
principles I have discussed have informed this debate. It is my
hope that as you examine proposed legislative pathways for
follow-on biologics, you will pursue a scientifically driven
public debate to ensure that public policy is well- founded in
science and supports the development of follow-on biologics
that are safe and effective. We must ensure that we pay the
appropriate attention to the principles of patient safety that
are being discussed in this country and in these halls right
now.
It is my hope, and that of BIO and Genentech, that a
transparent public process leveraging known scientific
considerations will provide a framework and pathway for the
approval of follow-on biologics in the United States--a pathway
that has an overriding concern for patient safety and well-
being. It is also critical that such a framework appropriately
provide incentives for innovation so that the promise of new
and innovative biologic therapies will be realized for
generations of patients to come.
Again, I thank you for the opportunity to submit testimony
for this hearing, and look forward to answering any questions
you may have.
----------
Mr. Pallone. Thank you. Dr. Allan.
STATEMENT OF GEOFFREY ALLAN, PH.D., PRESIDENT, CEO, CHAIRMAN OF
THE BOARD, INSMED, INCORPORATED
Mr. Allan. Good afternoon, Chairman Pallone, and members of
the Health Subcommittee. Thank you for the opportunity to
testify today.
I am Geoffrey Allan, president, CEO, and chairman of the
board for Insmed, Incorporated, a small biotechnology company
whose goal is to provide therapeutic products for metabolic and
endocrine disorders. I am here this afternoon, to urge Congress
to pass legislation that defines a practical, science-driven
approval pathway for biogenerics based on the key principles
that timely approval and timely commercialization of
biogenerics will create savings to publicly financed healthcare
programs and will accelerate research and development of new
and improved lifesaving medications.
As a pharmacologist, I have spent 27 years in drug research
and development at both mature pharmaceutical companies and
early-stage companies like Insmed. I entered this field because
I understand complex molecules and I have dedicated my work at
Insmed to helping patients with rare disorders. It is now my
mission to utilize the scientific experiences and capabilities
of our industry to bring medicines to patients where there is
an unmet medical need. My goal is to extend our mission to
include working with the backbone of the biotech industry, the
researchers, the contract manufacturers, and like-minded small
research and development companies to unleash our scientific
expertise for the development of biogeneric molecules.
In 2005 Insmed received FDA approval for a drug called
IPLEX. This drug is an orphan drug to treat children with a
rare growth disorder. It is a recombinant protein molecule and
it is similar in complexity to many of the recombinant protein
products that are the topic of discussion regarding
biogenerics.
We believe our experience with the development and approval
of IPLEX has positioned us to successfully manufacture
biogenerics. We have developed the infrastructure for the
manufacture, the preclinical and clinical evaluation for
recombinant protein products, and we now want to leverage that
expertise for the development of generic recombinant proteins.
As I said, we have the scientific and technical experience, the
personnel, and the facilities to produce safe and affordable
generic biologics. I believe our experience with IPLEX is very
illustrative of the scientific and technical issues that
confront biogeneric drug developers, issues such as
comparability testing, the nature of clinical data needed to
support the characterization of a biogeneric product. Given our
experience of the manufacturing and clinical development of
IPLEX and including structurally characterizing proteins,
ensuring potency and purity, I believe the scientific expertise
and capability exists for many companies to manufacture safe
and affordable biogeneric products.
In an effort to provide scientific insight into our
experiences, Insmed implemented several manufacturing changes
during the production of IPLEX. We changed cell lines, we
changed locations, we changed overall facilities. We still
maintained the purity, the consistency of the product. The
impact of the manufacturing changes was assessed by
comparability testing in which we used extensive analytical
tests and short-term clinical studies to determine if any
changes to the product resulted. Our experience with IPLEX gave
us the expertise also in longer term clinical outcome studies
and in the assessment of the immunogenicity which measures the
potential antibodies to the IPLEX product.
One might ask how our expertise in the production of one
recombinant protein product would allow us to develop any
generic protein. Although the manufacture of each product is
unique, they all share the same types of manufacturing
processes, the same internal quality control systems are used
to monitor these processes. The manufacturing procedures for
different proteins have actually more in common than they are
dissimilar. The same basic technologies and principles are
applied to fermentation, expression, and purification of any
recombinant protein product produced. We would not need
information on the manufacturing methods used for the brand
product but instead would use our own expertise and tailor it
to the specific generic protein of interest.
In fact, some of the exact test methods or specifications
set by the innovator company that were to standardize the brand
product may well be outdated. Analytical technology has
advanced considerably over the last 20 years, and therefore
there is a real possibility that generic protein drugs will
have a more robust characterization than the innovator product.
Brand companies have been quick to point out that sometime
things can go wrong during the manufacture of a recombinant
protein product. That is true. I do not know of any industry
where occasional errors do not happen. However, it is critical
to understand that there are safeguards that prevent any
potential errors from ever affecting the safety of the product.
Patient safety is paramount, and I believe we enforce good
manufacturing practices that manufacturers do follow, as well
as the process and the testing, the evaluation that is
conducted by the Food and Drug Administration in order to
obtain approval, whether the product is brand or generic. There
is no reason to believe that a generic biologic would be of a
lesser quality and less safe than a brand product. The FDA has
only one single standard to approve safe and effective
products.
You have heard that the science now exists to allow for the
safe production----
Mr. Pallone. Doctor, if you can summarize, you are about a
minute over.
Dr. Schenkein. I apologize. The summary is essentially we
know that the science is here, we would like to be involved in
the development of these products, and I would like to thank
you very much for the testimony this afternoon.
[The prepared statement of Mr. Allan follows:]
Statement of Geoffrey Allan
Good morning Chairman Pallone, Chairman Dingell, Ranking
Members Deal and Barton, and Members of the Health
Subcommittee. Thank you for the opportunity to testify today.
I am Geoffrey Allan, president, CEO and chairman of the
board of Insmed Incorporated. I testify before you this morning
as Chairman of the Coalition for Biotechnology Innovation
(CBI), and it gives me great pleasure to announce the launch of
this newly formed organization to give a voice to small
biotechnology companies that are being brought together by a
shared interest in advancing innovation in the biotechnology
industry. Our primary goal is to pass legislation in the 110th
Congress that defines a practical, science-driven approval
pathway for biogenerics. Collectively, members of CBI will
stand together on the key principle that timely approval and
timely commercialization of biogenerics will create savings to
publicly-financed health care programs, and will accelerate
research and development of new and improved life-saving
medications.
As a pharmacologist, I have spent 27 years in drug
research and development at mature pharmaceutical companies in
combination with my experience at an early-stage company like
Insmed. --I entered this field because I understand complex
molecules, and I have dedicated my work at Insmed to helping
patients with rare disorders. The scientific advancement in the
biotechnology field has been tremendous, and as the CEO of a
small biotechnology company whose goal is to provide
therapeutic products for metabolic and endocrine disorders, it
is my mission to utilize the scientific experiences and
capabilities of our industry to bring medicines to patients
where there is an unmet medical need. My goal is to extend our
mission to include working with the backbone of the biotech
industry the researchers, contract manufacturers, and like-
minded small research and development companies to unleash our
scientific expertise in developing biogenerics.
As I learned about Congress' interest and role in creating
a biogenerics market, I felt compelled to contribute to the
creation of a platform for our coalition to educate Congress
about the burgeoning interest among smaller biotechnology
companies to compete in a biogenerics market. I believe we all
agree that when a generic version or multiple versions of a
therapy are available, competition will drive down overall cost
of these life saving medicines. --The development of
biogenerics will create an explosion of both investment and
innovation in the biologics market.
Innovation is at the core of biotechnology and solving the
mysteries of disease is the goal of our industry.
Unfortunately, protecting monopolies and the financial bottom
line has had an impact on this mission. Our hope is Congress
will allow the FDA to evaluate biogenerics on the basis of
scientific facts and not the politics of the bottom line. In
addition, small biotech companies often face financial hardship
due to the high cost of development, but with the ability for
small biotech to compete in the biogeneric market, they will
have a source of revenue to invest into research and
development of new and improved therapies.
In 2005 Insmed received FDA approval for the drug, IPLEX,
to treat children with a rare growth disorder. IPLEX is a
recombinant protein product that is similar in complexity to
many of the recombinant protein products that are the topic of
discussion regarding biogenerics.
We believe our experience with the development and
approval of IPLEX has positioned us to successfully manufacture
biogenerics. Insmed has developed the infrastructure for the
manufacture, preclinical and clinical evaluation and approval
of recombinant proteins that we now want to leverage for the
development of generic recombinant proteins. We have the
scientific and technical experience, the personnel, and the
facilities to be able to produce safe and affordable generic
biologics. I believe our experience with IPLEX is very
illustrative of the scientific and technical issues confronting
biogeneric drug developers, issues such as comparability
testing and the nature of clinical data needed to support
characterization of a biogeneric product. The same scientific
approach we applied to the development and approval of IPLEX
can be applied to the development of biogenerics.
I believe the scientific expertise and capability exist
for many companies to manufacture safe and affordable
biogeneric products. During the development of IPLEX, Insmed
gained valuable experience in the manufacture and clinical
development of recombinant protein products. We have developed
expertise in all aspects of the manufacture of a protein
product and in the many analytical assays that are used to
structurally characterize proteins and ensure potency and
purity. Insmed implemented several manufacturing changes during
the development of IPLEX, including a change in the cell line
used to produce IPLEX. The impact of the manufacturing changes
was assessed by comparability testing in which extensive
analytical tests were used to determine if any changes to the
product resulted.
Insmed also developed several clinical approaches to
establish safety and efficacy during the development of IPLEX.
These included pharmacokinetic studies to determine the level
of product in the blood and how long it lasts and
pharmacodynamic studies that were short-term to determine the
effect of the product on a specific relevant clinical marker.
Pharmacokinetic studies, and in some cases pharmacodynamic
studies can also be useful to assess comparability. These
short-term clinical studies were used together with several
analytical tests to determine any potential differences in the
product after a manufacturing change. Our experience with IPLEX
also gave us expertise in longer-term clinical outcome studies
and in assessment of immunogenicity, which measures potential
antibodies to the IPLEX protein.
One might ask how our expertise in the production of one
recombinant protein product would allow us to develop any
generic protein. Although the manufacture of each product is
unique they all share the same types of manufacturing processes
and the same internal quality control systems are used to
monitor these processes. The manufacturing procedures for
different proteins have more in common than they are
dissimilar. For example, the same basic technologies and
principles are applied to the fermentation, expression and
purification of any recombinant protein product. We would not
need information on the manufacturing methods used for the
brand product but instead would use our expertise and tailor it
to the specific generic protein of interest.
There is a similar ability to leverage one's knowledge
regarding structural and analytical characterization of one
protein to the development of a generic protein. While the
types of analytical tests are tailored to each product there
are well established batteries of tests that are common for
proteins. One would not need the exact test methods or
specifications set by the innovator company that were used to
standardize the brand product. In fact, some of the tests used
on the brand product may well be outdated. Since analytical
technology has advanced considerably over the last 20 years,
there is a real possibility that a generic protein drug will
have a more robust characterization than its innovator product.
There is sometimes a misconception that the skill and
expertise of generic manufacturers is less than that of brand
manufacturers. I assure you that at Insmed, our personnel are
highly skilled and have years of experience in manufacturing
recombinant protein products. Many of our employees came from
the brand industry and were involved in the manufacture of the
brand products that are now under consideration as biogenerics.
We retain a highly skilled workforce.
Brand companies have been quick to point out that
sometimes things can go wrong during a manufacture of a
recombinant protein product. That is true and I do not know of
any industry where occasional errors do not happen. However, it
is critical to understand that there are safeguards that
prevent any potential errors from ever affecting the safety of
the product. Patient safety must be paramount. One of these
safeguards is that every manufacturer must follow strict
Federal laws and make their product according to Good
Manufacturing Practices, which mandates multiple internal
controls and the establishment of precise product
specifications. Further safeguards are provided by FDA in that
the FDA thoroughly reviews the manufacturing process, the test
methods and the quality and integrity of multiple batches
before it would approve any product, whether brand or generic.
The FDA also inspects the manufacturing facility before
approval and at regular intervals after approval to assure the
quality and integrity of the product, the manufacturing
facility and compliance with good manufacturing processes.
There is no reason to believe that a generic biologic would be
of a lesser quality and less safe than a brand product. The FDA
has only a single standard to approve safe and effective
products.
You have heard that the science exists to allow for the
safe production of biogenerics. I have told you that Insmed,
like many other companies, currently has the expertise and
capability to produce biogenerics. What is lacking at this time
is legislation that provides the regulatory pathway. We need a
pathway for biogenerics that gives the FDA authority and
flexibility. The FDA can determine the scientific issues and
the amount of data required for the approval of biogenerics on
a case-by-case basis.
We expect the FDA to issue general guidance documents at
some time regarding biogenerics, but guidance documents are not
absolutely necessary. Furthermore, we would not wait for the
issuance of guidance before submitting applications to the FDA.
Insmed believes that close interaction and dialog with the FDA
on a case by case basis would allow a more robust approval
process than would result from a broad guidance system. At
Insmed, we have shown that we can successfully work with the
FDA and plan to continue to work closely with the FDA during
the development of future biogeneric products.
In summary, we have seen that the science is there for
biogenerics. The expertise and capability also exists for the
manufacture of biogenerics. However, the regulatory pathway is
not available and we are asking you to support legislation that
would create such a regulatory pathway. This would allow not
only Insmed to make safe and affordable biogenerics available
to the American public but would open the floodgates for all
the small biotech firms with the drive, technology, and know
how necessary to create a new and competitive biogenerics
industry that will generate savings and new innovation for all.
----------
Mr. Pallone. Thank you. Mr. Kingham.
STATEMENT OF RICHARD F. KINGHAM, PARTNER, COVINGTON & BURLING
Mr. Kingham. Thank you very much, Mr. Chairman. I am a
partner in Covington & Burling. I am assigned to both the
Washington and London offices, and my practices involves
regulation of biologics and biotechnology products under both
U.S. and European community law.
I submitted a prepared statement that discusses in detail
the criteria that ought to be applied in establishing a
legislative pathway for follow-on biologics and also summarizes
the European community experience with establishing a system
for so-called similar biological medicinal products.
In my time now, I would like to focus on a single criteria
that I believe any such system should satisfy and that is the
need for a substantial period of non-patent data exclusivity.
Now, this is a period of time during which follow-on applicants
may not rely on the safety and effectiveness data submitted by
an innovative manufacturer in support of a reference product.
Every developed nation in the world has such a period of time
that it allows for medicinal products. Data exclusivity serves
a different purpose from patents. Patents protect inventions,
any sort of invention, and they are available for any type of
product and indeed for things that are not even products.
Innovative medicines present a special societal issue, and that
is the need to do lengthy, expensive and commercially risky
studies to demonstrate their safety and effectiveness to meet
FDA approval requirements. Today it takes about 15 years from
the time of the original invention to bring a new biotechnology
product to market, and the fully allocated costs of research
and development are estimated to be about $1.2 billion per
product. Even with all this, there is no guarantee that a
particular product will get to market or that it will recover
R&D costs if it does. Investments and risks of this magnitude
are I think unique to the pharmaceutical industry. Whether or
not patents are available to protect products of this kind,
society has a profound interest in assuring that there are
adequate incentives to do the studies necessary to bring these
products to market.
Now everything I have said up to now is applicable really
to all pharmaceutical products, though some of the figures for
timing and cost may be greater for biotechnology drugs. But
there are special issues posed by biotech products which I
believe more clearly justify a substantial data exclusivity
period.
Under the Hatch-Waxman Act as applied to small-molecule
drugs, a generic product for which an abbreviated new drug
application, or ANDA, is filed must contain an active
ingredient which has demonstrated to be the same as or
identical to that of the referenced drug upon which it relies.
This means that if there is a patent for that active ingredient
and that patent is valid, it is likely that that applicant will
run head on into the patent which protects the referenced
product and therefore the referenced product will enjoy a
period of effective market exclusivity equal to the life of
that patent.
But under any legislative pathway, and I refer not simply
to the one that Representative Waxman has proposed, but any
scientifically reasonable approach to the issues presented by
follow-on biologics, it will in fact be necessary to allow FDA
the discretion to consider applications for products which are
similar to but not identical to the referenced products. Dr.
Woodcock explained the scientific reasons why that is true, and
that means that the possibility exists for different processes
and different structures to be used in producing the active
ingredients of follow-on products so that they will avoid the
protection of both product and process patents that protect the
innovator. This creates the real potential for patents not to
serve the same protective market purpose that is served by
patents for small-molecule drugs under Hatch-Waxman.
Now that is the biggest point, but there are subsidiary
points. Increasingly, for example, the Patent and Trademark
Office and the courts have required that the patent
applications, the claims for biotechnology products be even
more narrowly drawn than in the past, thereby increasing the
plausibility that people can make small changes in the
structure of follow-on products and avoid the patents for the
innovative product. And even if a patent contains claims which
cover a wide variety or an extensive variety of molecular
structures, if patent term restoration is granted, it will
apply only to the specific molecule that was approved by FDA,
not to the other structures that may be covered by broader
patent claims. And of course, we saw only last Monday in KSR
against Teleflex that the Supreme Court is increasingly
scrutinizing that patents should be granted at all and applying
a tougher standard with respect to what constitutes a
significant innovation that warrants protection under the
patent laws.
Now, these are all very legitimate issues for patent
lawyers to be concerned with and for policy discussions to be
held about. But whatever we decide with respect to the scope of
patents, there remains an overwhelming need of society to
provide the incentive for the studies necessary to develop
these products. What is the period of time that should be
provided? Well, the Congress said in 1984 that an effective
patent life of 14 years a period of market exclusivity
guaranteed by the patent life of a drug was the appropriate
time. If patent protection is not fully adequate, and I think
it may not be, then I think the period of 14 years is still the
right number.
Thank you very much.
[The prepared statement of Mr. Kingham follows:]
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Mr. Pallone. Thank you, Mr. Kingham. Mr. Downey.
STATEMENT OF BRUCE DOWNEY, CHAIRMAN OF THE BOARD, GENERIC
PHARMACEUTICAL ASSOCIATION, CHAIRMAN AND CEO, BARR
PHARMACEUTICALS, INCORPORATED
Mr. Downey. Thank you, Mr. Chairman. Thank you, Ranking
Member Deal for inviting me to testify today. I have prepared a
written statement and I ask that it be accepted into the
record, and I would like to expand on that in just a few
points.
First I would like to say that while I am chairman of the
GPHA, the Generic Trade Association, I am actually appearing
today in my capacity as CEO and chairman of Barr
Pharmaceuticals, a company that is a member of the Generic
Association and one that aspires to make generic biologics
which are the subject of this hearing.
I note at the outset that we are at a historic time, and I
was thinking as I came over this morning it is a 23-year cycle.
In 1938, the Food, Drug, and Cosmetic Act was amended to
require drugs be proven to be safe. Actually 22 years later,
the Kefauver amendment required they be proven to be effective.
Twenty-two years after that the Hatch-Waxman bill adds a
pathway for generic pharmaceutical products, and we are here in
2007, 23 years later we hope to add a pathway for generic
biologics.
And I think we have reached an amazing consensus over the
last 2 or 3 years hearing members of the committee on both
sides of the aisle, the number of organizations listed by
Congressman Waxman in his statement, there really is an
emerging consensus that it is not whether there should be a
pathway but what that pathway should look like and what other
provisions it should contain. I think we all agree or could
agree that safety is the number one issue, and we as a
potential manufacturer of generic biologic product certainly
want to manufacture safe and effective products. So we don't
disagree with that at all. And we think FDA is the proper
arbiter of what safety standards should be applied.
We also think there should be a balance between those in
the innovator industry and those in the generic industry, a
balance similar to the one struck in the Waxman-Hatch Act. And
there were two provisions in that Act that dealt with
exclusivities and rights of innovators. One was the patent term
restoration component which as a formula to add patent life to
products were lost in regulatory review, and I point out that
that patent term restoration provision not only applies to
pharmaceutical products but applies to the biologic products
developed by innovators. So they have already got the
prepayment on the biologic side of the patent term restoration
features of Hatch-Waxman.
Now, Hatch-Waxman also included a 5-year exclusivity--and I
personally don't object to that period. I certainly will
disagree with the 14-year period but 5 years I think is an
appropriate number and one that I could certainly support. I
can't again speak for my trade association on that point. And
the third is we all want to ensure that innovation is
protected, and I would argue and I think correctly argue that
the pathway for generic pharmaceuticals was the greatest boon
to pharmaceutical innovation in history because it forced brand
manufacturers to replenish their products in the face of
generic competition.
And so you look at the statistics, and I didn't prepare it
for today but I certainly could and submit it if the committee
wants, the rate of investment in R&D in the brand industry
skyrocketed post Hatch-Waxman because of the threat of generic
competition. And I think the same will happen here in the
biologics business. If there is a generic pathway, you will see
increased innovation and increased spending on R&D.
I would like to quickly, in my last 90 seconds, cover three
points. One is that in the pathway that I think we should
follow, the same standard for BLA, that is innovator biologic
products, NDA's, ANDA's, and that is a pathway that is sponsor-
initiated, we propose the product, we propose the clinical
trial, and the FDA responds and it adds requirements or agrees
as they see proper. I think that provides the great level of
safety that we all seek. It also provides an efficient and
flexible system that can deal with different products in
different ways.
Second, I think we need to have a provision that would
permit resolution of intellectual property disputes in advance
of launching the product. These are very contentious issues.
Many of these products do not have one or two patents, but 30,
40 patents and there are disagreements about whether we
infringe or if they are valid, and there needs to be a
mechanism that allows those issues to be decided before there
is a launch of the product that allows both innovator and
generic companies to manage the risks that they confront and it
also allows for the earliest lawful entry of the product and
doesn't allow the litigation post-exclusivity period, post-
patent to delay the launch of a product.
And then finally I think we need to have the flexibility
for the FDA to establish the requirements on an individual
product basis, and I urge we reject the idea of this public
hearing with all the comments and first to get a draft guidance
and refine it once it is out. I think that simply delays the
process, and the process currently followed where your sponsor
initiated products are presented it to the FDA, the FDA
comments, we carry it out, has provided safety and efficacy
over all sorts of pharmaceutical and device products and would
work very well here. It works for the innovators in the
biologic area, and I would point out that H.R. 1038 has all
three of these features and I would urge that whatever
legislation comes out has them also. Thank you very much.
[The prepared statement of Mr. Downey follows:]
Testimony of Bruce L. Downey
Chairman Pallone, Ranking Member Deal and members of the
House Energy and Commerce Committee Subcommittee on Health. I
am Bruce Downey, the chairman and chief executive officer of
Barr Pharmaceuticals, a leading global generic pharmaceutical
company.
I want to thank you for convening this hearing and for
allowing me to express my company's views on issues so vital to
the continued success of the generic pharmaceutical industry--
an industry that saves consumers and taxpayers literally
billions of dollars each year in prescription drugs costs.
Indeed, no other industry has made, or continues to make, a
greater contribution to affordable health care than the generic
pharmaceutical industry.
While my testimony today is on behalf of Barr
Pharmaceuticals, I also serve as chairman of the Generic
Pharmaceutical Association, which represents more than 100
generic manufacturers, distributors and suppliers of bulk
active pharmaceutical chemicals worldwide. I mention my role in
GPhA because it is important to note that the issue we address
today--that of generic biological medicines--is at the top of
the association's priority list of legislative and policy
initiatives.
Mr. Chairman, this Congress holds the key that will open
the door for generic and other manufacturers to provide
affordable access to many of the life-saving biological
medicines used in the treatment of diabetes, cancer, rheumatoid
arthritis, HIV/AIDS and other diseases. Today, the cost of
these treatments can put them out of reach of many consumers.
The rheumatoid arthritis and psoriasis treatment Enbrel, for
instance, costs an average of $16,000 a year per patient.
Biological drugs for multiple sclerosis range in price from
$16,000 to $25,000 a year. Neulasta, used to correct
chemotherapy-induced white blood cell deficiency, costs an
average $3,500 per chemotherapy cycle.
What becomes frightening from the cost perspective is that
not only are the costs of biological treatments getting more
expensive each year, but the utilization of these medicines is
growing, as well. These two factors coupled together yields
exponential growth in the amount we are spending on biologics
every year.
According to the 2006 Drug Trend Report released in April
by Express Scripts, biotech drug spending increased 21 percent
last year, even as growth in traditional prescription drug
expenditures slowed. The report showed that growth hormone
deficiency spending rose nearly 23 percent in 2006 due to a
10.7 percent increase in utilization, coupled with the increase
in product cost.
This dual impact of higher prices and greater utilization
presents a recipe for disaster which will end in price
controls. The alternative, as we are seeing in the chemical
drug sector, is competition.
Thus, creating a pathway that allows for the introduction
of safe and affordable generic alternatives to these medicines
is vital. It not only will save consumers and taxpayers
billions of dollars a year, but, again, will allow more
patients access to these important medicines.
This committee is well aware of the role traditional
chemical generic drugs play in helping consumers, insurers, and
the government in achieving billions of dollars in savings each
year. Generic drugs filled more than one-and-a-half billion
prescriptions in the U.S. last year. That is nearly 55 percent
of all prescriptions dispensed nationwide. Considering that the
average cost of a generic prescription is less than $30, while
the average cost of a brand prescription is close to $95, it is
easy to see how the Congressional Budget Office estimates the
savings generated by generic drug use to be between $8 billion
and $10 billion each and every year.
As this committee knows, Congress made these savings
possible over 20 years ago with the 1984 enactment of the
Hatch-Waxman Amendments to the Federal Food, Drug, and Cosmetic
Act. Hatch-Waxman achieves a critical balance between access to
less costly generics and innovation of new brand-name drugs. I,
and many others, believe that it is time for Congress to take
the next step and let generic companies provide savings in the
biological field. Doing so, however, will require brushing
aside the current political maneuvering that threatens progress
on this issue, and enacting appropriate legislation that would
allow FDA to begin approving safe, effective, and affordable
generic biologics.
Discussion
Today, I want to briefly discuss three points that I hope
this committee will consider as you move forward on generic
biologics legislation:
legislation must provide a regulatory pathway for
approving generic biologics that is free of artificial barriers
and unnecessary roadblocks, as well as a mechanism for allowing
expeditious resolution of patent disputes that would delay
generic market entry;
market competition generated by generic biologics
would unleash incentives for further innovation of newer
medicines, just as Hatch-Waxman did over twenty years ago; and
generic biologics will provide a market-based
mechanism to help manage private and Federal expenditures and
achieve significant savings.
I. Legislative Framework
Effective generic biologics legislation must include two
parts: a regulatory pathway that allows FDA to expeditiously
approve safe and affordable generic biologics and a mechanism
for allowing generic companies to resolve certain patent
disputes without delaying FDA approval. I will discuss some
important aspect about both of these issues.
A. Approval Pathway
Effective biologics legislation must include a regulatory
approval pathway that does not impose unnecessary barriers to
prompt market entry. Hatch-Waxman was largely successful in
achieving this goal for generic drugs regulated under the
Federal Food, Drug and Cosmetic Act, and this legislation
should do the same for biologics regulated under the Public
Health Service Act. An adequate abbreviated pathway must
include, for example:
clearly defined comparability criteria;
provisions giving FDA discretion to require the
needed tests--and only the needed tests--to make safety and
effectiveness determinations;
provisions setting forth the circumstances under
which FDA can deny approval;
provisions setting forth the contents of an
abbreviated biological application;
the ability to obtain an interchangeability
rating that is immediately operative;
no unique names for generic biologics, which is
fully consistent with FDA's position that unique biologic names
should not be used to differentiate products with the same
active ingredient(s) when credible scientific data demonstrate
that no pharmacologically relevant differences exist;
a timely review process that allows a company to
discuss with the FDA research and testing and to know when
action on the application can be anticipated; and
an approval process that gives FDA flexibility as
to what should be required on the label.
Equally as important, effective biologics legislation must
not include provisions like those advocated by groups such as
BIO--provisions that would unnecessarily delay approval and/or
prevent consumers from receiving the biggest benefit from
generic biological products. For example, legislation should
not include:
a requirement that all generic applications
include full clinical and human trials, or any clinical trials
other than those that FDA deems necessary to the relevant
scientific issues;
further legislation, or Congressional
authorization/oversight or FDA regulations or guidances before
the agency can give an interchangeability rating to a generic
product;
unique names for generic biologics, which would
impede interchangeability findings and thus prevent the
substitution of generic for brand that is essential for cost
savings;
provisions requiring agency-issued guidance or
notice and comment rulemaking, which can take years and years
to complete, before FDA can accept or approve a generic
biologic application; and/or
provisions requiring the generic company to have
an identical label to the reference product, particularly where
the brand has patented certain labeling information.
There is no justification for provisions like these, which
will delay generic market entry and the interchangeability
rating needed for consumers to benefit most from generic
competition. They are entirely unnecessary to ensuring approval
of safe and affordable generic biologics.
For example, while today clinical data may be needed for
most biological products, Congress should not impose rigid
requirements for such testing in all circumstances. Rather,
Congress should give FDA the ability to draw on its decades of
experience with these compounds by granting the agency the
discretion to require such tests only when it determines that
such clinical studies are needed.
It is significant that FDA agrees. FDA Deputy Commissioner
Janet Woodcock addressed this during Congressman Waxman's
Oversight & Government Reform Committee hearings last month,
testifying that the ``use of human subjects for trials that are
not needed but are simply to check a box on a regulatory
requirement is not desirable.'' Dr. Woodcock added that the
ability to physically characterize protein molecules and other
complex substances ``has evolved and is continuing to evolve''
and that ``flexibility in enabling FDA to incorporate the new
science into the regulatory process...is in the best interest
of the public as well as the agency and the industry.''
Congress has entrusted FDA to make scientific judgments
regarding drugs and biologics. This scientific advice from the
agency should be headed.
Barr urges Congress to pass a regulatory framework for
approving generic biologics that is free of unnecessary
barriers and roadblocks in the form of artificial requirements,
such as clinical studies and agency guidances. Such a framework
will give FDA the flexibility it needs to approve safe and
interchangeable generic biological products as quickly as
possible.
B. Patent Provisions and Other IP Provisions
A key part of effective generic biologics legislation is a
mechanism that allows the generic company to resolve certain
patent disputes without that litigation impacting FDA approval.
This was also a goal of Hatch-Waxman, although the brand
industry has found ways around the law's intent, which was that
patent disputes be resolved early, so that the generics can
enter the market at the earliest time after valid and
applicable patents have expired. Barr submits that any bill
providing a pathway for generic biological products should take
into account what we have learned from our 20-plus years of
experience with the Hatch-Waxman patent provisions and improve
upon that system in order to ensure that affordable biological
products reach the public as quickly as possible. Thus, an
effective generic biologic bill must, at the very least,
contain patent provisions like the following:
First, companies need patent certainty prior to
marketing. Without it, companies will not invest in bringing
affordable, comparable products to market prior to patent
expiration because doing so could subject them to enormous
patent infringement damages. Thus, effective legislation must
include provisions that allow a generic company to obtain the
required certainty--through litigation if necessary--while FDA
is reviewing the application.
Second, equally as important, however, is the
fact that generic companies not be forced to litigate every
patent relating to the brand product in order to obtain the
patent certainty needed to launch. Thus, a biological patent
system should provide a mechanism for litigating only those
patent disputes that the generic company believes would delay
its launch. There will be other patents--for example patents
applicable to manufacturing processes that the generic company
is not using--for which the only effect of early litigation
would be unnecessary delay. I am not suggesting that the brand
company should forever be foreclosed from asserting its
patents. The brand company should have that opportunity, just
not before the generic company markets its product.
Accordingly, the system that will allow for the most
expeditious generic market entry is one that permits the
generic company to select the patents that will be litigated
pre-product launch. This system also protects the brand
company's intellectual property by allowing for suit on any
patent that can reasonably be asserted after the generic
company begins marketing.
Third, generic companies need to be able to
resolve patent disputes without those disputes delaying the FDA
approval process, as we now experience with small molecule
drugs under Hatch-Waxman.
Fourth, generic companies must be able to
litigate patent disputes quickly and efficiently. This will
only happen if the generic company is permitted to designate a
forum that would allow for more efficient litigation
resolution. Right now, the brand company has the ability to
bring suit against an ANDA applicant in virtually any district
court in the country. Brand companies increasingly have brought
suit in districts with the longest time to trial. In some
courts, its takes from three to five years just to get to
trial. Where certainty is essential, this means more delayed
market entry.
Fifth, if a brand company refuses to participate
in the patent process, as increasingly happens with small
molecule applications, the generic company must be allowed to
enter the market without risking potentially massive damages.
Under proposals such as those found in H.R. 1038, generic
companies have some protection in the event that the brand
company refuses to participate in the patent process. Brand
companies have complained that this takes away substantive
patent rights and forces them to give what amounts to a
compulsory patent license. Not true. These provisions only
apply if the brand company violates its statutory obligation to
participate in the patent process. If the brand company follows
the law, all of its patent rights would remain intact.
Finally, part of the so-called IP discussion surrounding
generic biologics is the idea of exclusivity. On the generic
side, the issue is clear: consumers and taxpayers, without
question, will see the most significant savings from
interchangeable products. Thus, it is essential that any
generic biologics bill incentivize generic companies to do the
work necessary to achieve an interchangeability rating from
FDA. At present, no such incentive currently exists and,
therefore, will need to be included in the legislation.
On the brand side, the issue also seems clear: lengthy,
new exclusivity periods for brand companies are not necessary
because the law currently provides more than enough incentive
to continue innovating. For example, brand companies already
get significant incentives, including multiple provisions
allowing for patent term restorations, orphan drug exclusivity,
and various tax credits. If the brand companies disagree, they
are free to come forward and present data to support their
argument. Indeed, Representative Waxman has invited discussion
on this issue. However, the brands have not yet come forward
with any concrete data that would suggest that additional
incentives are necessary. It is my view that only if they do
come forward with such evidence should Congress consider
enacting new exclusivity periods.
II. Generic Competition Will Spur Innovation
There is a misconception that market competition from
generic biologics would diminish the incentive for originators
to innovate new biologics. Generic competition will not slow
innovation. In fact, just the opposite would be true. Market
competition generated by generic biologics would accelerate
further innovation of new biological products, while at the
same time lowering the cost of treatment with existing
medicines.
For example, Dr. Scott Gottlieb, recently the FDA Director
of Medical Policy Development and Deputy Commissioner for
Medical and Scientific Affairs, has explained: ``Legislation to
expose today's biologics to easier competition, after
legitimate patents have expired, is going to accelerate
development of improved products, not just lower-cost. Those
making static assumptions .--.--. about how much savings this
legislation is likely to bring are losing sight of the
competition and progress it will have unleashed.'' [Forbes 4/
17/07 edition (emphasis added)]. Similarly, the January 2007
study released by the Pharmaceutical Care Management
Association concluded that increased competition from generic
biologics would not only create pressure to reduce the cost of
these products, but also produce added incentives for further
innovation. Thus, generic biologics legislation would provide
the dual benefit of increased savings and advancements in
medical treatments.
III. Savings
No one can legitimately dispute that generic biologics
will provide a market-based mechanism to help manage private
and Federal expenditures and achieve significant savings. And
no one can dispute that the American health care system has
ever needed those savings more than it does today.
As the use of life-saving biological drugs continues to
increase, so does the amount consumers and taxpayers spend.
Indeed, spending on biotech drugs increased 21 percent in 2006,
to approximately $40 billion, according to the 2006 Drug Trend
Report. Spending in this sector is expected to grow to $100
billion over just the next four years. By 2010, biological
medicines will account for 26 percent of total drug spending in
the U.S. It is particularly important to note that Medicare
spending for biological drugs continues to escalate
disproportionately to Medicare funding. To put things in
perspective, Medicare and Medicaid will spend $2.5 billion this
year on just one biological drug--the anemia treatment Epogen--
which is a half-billion dollars greater than the entire fiscal
year 2007 budget of the Food and Drug Administration.
The solution to managing this spending is, of course, the
use of safe and effective, lower-cost generic biologics. Just
as generic chemical drugs have saved billions of dollars so,
too, will generic biological drug products. A study released by
Express Scripts in February 2007 showed that generic biologics
would save payors $71 billion over 10 years. An Engel & Novitt
study in January 2007, as well as other independent economic
analyses we have seen, show that generic biologics would
generate significant savings for Medicare Part B reimbursed
medicines. Now, the brand companies take issue with some of
these studies. Significantly, though, they do not take issue
with the fact that generic biologics will save billions of
dollars. They only take issue with how many billions will be
saved. But in the end, whether the number is $71 billion or
$7.1 billion, we simply cannot afford to lose the savings that,
without question, would be achieved through use of generic
biological medicines.
Congress should act now and pass legislation giving FDA
authority to review abbreviated applications for generic
biologics. The agency would be able to begin reviewing those
applications as soon as they were submitted and the public
would be assured that when the FDA approves a generic version
of a biological product, just as has been the case with
traditional drugs over the past 30 years, it will be safe,
effective and have the same performance as the innovator
product.
Chairman Palone and Members of the Committee, Barr always
has been deeply committed to providing the public with
affordable, safe generic drug products, and to do so as
expeditiously as possible under the circumstances. That is why
Barr has joined with consumer groups like AARP, Consumers
Union, Families USA; employee unions life AFL-CIO and AFSCME;
major corporations like Caterpillar, Ford, GM, and Kodak;
healthcare providers Aetna, Blue Cross Blue Shield and Kaiser
Permanente; pharmacy leaders like CVS/Caremark and the National
Association of Chain Drug Stores; and no less than 18 of the
nation's governors in calling on Congress to pass legislation
creating the framework for the approval of safe, effective and
lower-cost generic biological drugs.
Congress has the opportunity this year to create--a huge
win for patients, for taxpayers and for employers alike.--
Indeed, effective generic biologics legislation very well could
be the most important piece of consumer legislation enacted
this year. We urge Congress to move forward in this effort.
Thank you, Mr. Chairman. I am happy to respond to any
questions you and the committee may have.
----------
Mr. Pallone. Thank you. Ms. Hoffman.
STATEMENT OF RUTH HOFFMAN, EXECUTIVE DIRECTOR, THE
CANDLELIGHTERS CHILDHOOD CANCER FOUNDATION
Ms. Hoffman. Chairman Pallone, Ranking Member Deal, and
members of the committee, I sincerely thank you for giving me
the opportunity to testify on an issue of great importance to
the childhood cancer community and to me personally.
I am here today to explain the crucial role of biologics in
the ongoing war on childhood cancers. Children with cancer have
unique needs. They are not simply little adults; children have
their own biological systems and unique tumor
characterizations. Current toxic therapies that have proven
effective for adults aren't a solution for children with
cancer. In fact, these treatments are causing secondary cancers
in the children who do survive to adulthood.
The best hope for children with cancer rests in the
research and development of new and targeted biologics. So
please don't deprive children with cancer future cures by
depriving the biotech industry of incentives to innovate.
My name is Ruth Hoffman, and I am the executive director of
the National office of Candlelighters Childhood Cancer
Foundation. Candlelighters was founded in 1970 by concerned
parents of children with cancer, and today we have a membership
of over 50,000 families at the national office and more than
100,000 families across the country.
Advocating for children with cancer is my job, but I am
also the mother of eight children, including a 20-year survivor
of childhood cancer.
On July 10, 1987, my world changed forever. My 7-year-old
daughter had been sick for 9 months. She had been diagnosed by
her family physician as having a bug bite, a virus, an
infection--she was on antibiotics; ear infections--she had
tubes put in; tonsillitis, she had her tonsils and adenoids
removed; and a neurotic mother, who is me. Despite these
attempts to explain her failure to thrive, Naomi continued to
deteriorate to a mere 32 pounds. So in shear desperation, I
carried her to the emergency ward of our local Children's
Hospital and it was on that day in July that I heard the words
that seared my heart and my soul forever, my daughter had
cancer.
Naomi was diagnosed with acute myelogenous leukemia, M5,
the bad leukemia. Her prognosis was poor. Few survived AML in
1987. Fortunately, bone marrow transplants were just beginning
as a potential therapy to treat children with AML, and her 9-
year-old brother was a perfect donor match. Her treatment
included IV chemotherapy for 5 days on, 24 hours a day,
followed by 3 weeks off, and that continued for 5 months. This
was followed by high-dose chemotherapy and total body
radiation. After 9 months of living in a complete bubble
environment where for many months she never was able to get off
her bed, Naomi was considered cured.
What I didn't know then but I sadly know now is that
childhood cancer is for life. The 5-year survival rate used to
determine adult cancers as ``cured'', has little meaning to
children who complete treatment at 8 years of age. We are
treating children with intensive toxic therapies at a time in
their lives when they have growing bodies and developing
brains. You can't treat a young child's body with these kinds
of invasive therapies and not impact their overall health for
the rest of their life.
Naomi did not emerge from her treatments unscathed, either.
She has cataracts, heart damage, endocrine dysfunction, and is
sterile. Then 2\1/2\ years ago, I received a second call that
made my life stand still once again. Naomi was diagnosed with
papillary thyroid carcinoma, metastatic to her lymph and bones,
a second cancer but this was caused directly by the total body
radiation that she received as a little girl to treat her first
cancer.
Treatment for children with cancer really hasn't changed
much since Naomi was originally diagnosed in 1987. Today all
children with cancer continue to be treated solely, and I say
solely with highly toxic cancer drugs that were developed 20 to
30 years ago. Only one new drug has received marketing approval
by the FDA for childhood cancer in the last decade. That drug
too was not a new class of smart drugs or biologics, it too was
another toxic chemotherapy agent.
These traditional chemotherapy drugs have not provided a
cure for many childhood cancer tumor types. Cancer remains the
No. 1 disease killer of America's children, more children still
die from cancer than cystic fibrosis, muscular dystrophy,
asthma, and AIDS combined.
Those who do survive face lifelong late effects including
severe drop in IQ, heart damage, sterility, deafness, severe
growth deficits, and most shockingly, secondary cancers. What
is even more disturbing is that these mortality rates have not
changed in the last decade. I want to repeat that. Toxic
chemotherapy and radiation treatments have not increased the
survivorship of children within the last 10 years. We have
reached a plateau with survival rates, and we have reached a
limit of toxicity from current chemotherapy drugs and radiation
treatments that we can give our children. I can't offer hope to
any more families whose children are diagnosed with cancer
today than I could 10 years ago.
Is there hope for these youngest cancer patients in this
country? Absolutely. We stand at the threshold of a new era in
the genetic treatment of disease. Large research initiatives
are underway to identify the genetic fingerprints of many types
of adult cancers, but funding for targeted therapeutic research
for childhood cancer is minimal. What kids need is increased
incentives for industry to develop new types of targeted
therapies to treat children with cancer, not fewer incentives.
Children with cancer need treatment breakthroughs. They
need new molecular-based therapies that will kill the cancer
and not the kid. Biologic drugs have proven to be an effective
weapon in the war on cancer for adults.
Today you are considering the important issue of allowing
for abbreviated approvals of biosimilar products. We fully
support increasing access to affordable drugs, but what kids
with cancer really need most is access to drugs that can truly
treat and truly cure their disease. Please don't create
legislation that reduces costs by reducing incentives for
biotech companies to develop targeted therapies for cancer. For
me and for the parents I represent, lifesaving trumps cost
saving any day.
My daughter Naomi draws her inspiration from something
Ralph Waldo Emerson wrote: ``Do not go where the path may lead,
go instead where there is no path and leave a trail.'' We are a
nation of trailblazers and innovators. I want to thank
Representatives Inslee, Baldwin, and Green for introducing
legislation that will enable this tradition of innovation to
thrive in service to our Nation's children with cancer.
Candlelighters' motto is ``...because kids can't fight
cancer alone!'' and I urge the members of this committee to
think hard about the impact of your decisions on young lives.
Kids can't fight cancer alone. They rely on adults like you and
me to offer them hope so that they too may live a long a
healthy life.
[The prepared statement of Ms. Hoffman follows:]
Testimony of Ruth Hoffman
Chairman Pallone, Ranking Member Deal, and members of the
subcommittee, I sincerely thank you for giving me the
opportunity to testify before you today on an issue of great
importance to the childhood cancer community, and to me
personally.
I'm referring to the crucial role of biologics in the
ongoing war on childhood cancers. Children with cancer have
unique needs. They are not simply ``little adults;'' children
have their own biologic systems and unique tumor
characterizations. Current toxic therapies that have proven
effective for adults aren't a solution for kids with cancer--in
fact, these treatments are causing secondary cancers in some of
the children who survive to adulthood. The best hope for
children with cancer rests in the research and development of
new and targeted biologics. I am here today to explain to the
committee how important it is that you not deprive children
with cancer of future cures by depriving the biotech industry
of incentives to innovate.
My name is Ruth Hoffman, and I am the executive director of
the national office of Candlelighters Childhood Cancer
Foundation. Candlelighters was founded in 1970 by concerned
parents of children with cancer. Our mission, then and now, is
to provide information and awareness for children and
adolescents with cancer and their families, to advocate for
their needs, and to support research so every child has the
opportunity to survive and lead a long and healthy life. Today
we have a membership of over 50,000 members of the national
office and more than 100,000 members across the country linked
to our 37 affiliate offices in 28 States.
Advocating for children with cancer is my job as Director
of Candlelighters. But I am also the mother of a 20-year
survivor of childhood cancer.
Twenty years ago, on July 10, 1987, my world changed
forever. I was 31 years old, had a 9-year old son, a 7-year old
daughter (Naomi), a 1-year old son--and I was 5 months pregnant
with identical twin boys. My daughter Naomi had been sick for 9
months. She had been diagnosed by our family physician as
having a bug bite, virus (put on antibiotics), ear infections
(had tubes put in), tonsillitis (tonsils and adenoids removed),
and a neurotic mother--me! Despite these attempts to explain
her ``failure to thrive,'' Naomi continued to deteriorate to a
mere 32 pounds. She was no longer able to walk. So in sheer
desperation, I carried her to the emergency ward of our local
Children's hospital. It was on that day in July that I heard
the words that seared my heart and my soul forever: ``Your
daughter has cancer.''
Naomi was diagnosed with Acute Myelogenous Leukemia (M5)--
the ``bad'' leukemia. Her prognosis was poor. Few survived AML
in 1987. Fortunately, bone marrow transplants were just
beginning as a potential therapy to treat children with AML,
and her 9-year-old brother was a perfect donor match for Naomi.
Her treatment included I.V. chemotherapy for 5 days on, 24
hours a day, followed by 3 weeks off, for 5 months. This was
followed by high dose chemotherapy and total body radiation.
After 9 months of living in a complete bubble environment,
Naomi was considered ``cured.'
What I didn't know then, that I sadly know now, is that
childhood cancer is for life. The 5-year survival rate used to
determine adult cancers as ``cured'' has little meaning to
children who complete treatment at 8 years of age. We are
treating children with intensive toxic therapies at a time in
their lives when they have growing bodies and developing
brains. You can't treat a child's young body with these kinds
of invasive therapies and not impact their overall health for
the rest of their life.
Naomi did not emerge from her treatments unscathed. She had
cataracts, heart damage, endocrine dysfunction, and was
sterile. But she had her life, and she was determined to live
it to the fullest. Then, 2\1/2\ years ago, shortly after Naomi
graduated from college, I received the call that made my life
stand still once again. Naomi was diagnosed with papillary
thyroid carcinoma, metastatic to her lymph and bones--a second
cancer--but this one was caused directly by the total body
radiation that she received to treat her first cancer.
Naomi just keeps living her life and doing her best to
invest it with meaning. She currently works at Children's
National Medical Center here in Washington, DC, where she's
employed as a clinical trial coordinator for a study of boys
with Duchenne Muscular Dystrophy. She volunteers as a camp
counselor for children with special needs including cancer, and
she recently attended the Lance Armstrong Summit in Texas,
where she represented and advocated for survivors of childhood
cancer.
Naomi lives every day with the fact that, in all
likelihood, cancer will end her life prematurely. But she
hasn't given up hope. On the contrary, she's more committed
than ever to making her life matter--not just to herself, but
to other young people with cancer. She's so committed to the
search for new molecular-based therapies for children with
cancer that she is organizing her own fundraiser this November.
Naomi's Hope for a Cure will raise money for research towards a
genomic characterization of pediatric AML.
Treatment for children with cancer hasn't really changed
much since Naomi was originally diagnosed in 1987. Today, ALL
children with cancer continue to be treated solely with highly
toxic cancer drugs that were developed 20 to 30 years ago. Only
one new drug has received marketing approval by the FDA for
childhood cancer in the last decade. That drug was not a new
class of ``smart drugs.'' It too was another toxic chemotherapy
agent.
These traditional chemotherapy drugs have not provided a
cure for many childhood cancer tumors, and they leave those
children who do survive facing lifelong late-effects, including
severe drop in IQ, heart damage, sterility, deafness and--most
shockingly--secondary cancers. As a result, cancer remains the
number one disease killer of America's children--more children
still die from cancer than Cystic Fibrosis, Muscular Dystrophy,
Asthma, and AIDS combined.
Every day I get calls from frantic parents around the
country, looking for guidance and for hope. Just last week, I
got a call from a young father whose 10-day old son, Jack, had
just been diagnosed with a brain stem tumor. My job was to tell
him that all doctors can offer infants like Jack is
chemotherapy--they can't radiate children under three. What I
did not want to tell him was that even with treatment there's
only a 10 percent chance that Jack will survive to see his
second birthday. Jack is not alone. Only half of children
diagnosed with metastatic bone cancer will survive 5 years.
Even today, half of children and teens diagnosed with Naomi's
original cancer--acute myelogenous leukemia--will die within 5
years.
What is even more disheartening is that these mortality
rates have not changed in the last decade! I want to repeat
that: the toxic chemotherapy and radiation treatments that we
are giving our children with cancer have NOT increased
survivorship in the last 10 years! We have reached a plateau
with survivorship rates, and we have reached the limit of
toxicity for current chemotherapy drugs and radiation
treatments. I can't offer any more hope to families whose
children are diagnosed with cancer today, than I could 10 years
ago.
As director of Candlelighters, I've come here to tell you
that the status quo is not good enough for children with
cancer. As Naomi's mother, I'm asking you: ``Can't we do better
for our children?''
Is there hope for this youngest cancer patients? The answer
is a resounding YES! We stand at the threshold of a new era in
the genetic treatment of cancer. Large research initiatives are
underway to identify the genetic fingerprints of many types of
adult cancers--but funding for targeted therapeutic research
for childhood cancer is minimal, and lagging behind today's
adult cancer research initiatives. What kids need is increased
incentives for industry to develop new types of targeted
therapies to treat children with cancer.
Children with cancer need treatment breakthroughs. They
need new molecular-based therapies that will ``kill the cancer,
not the kid.'' Biologic drugs have proven to be an effective
weapon in the war on cancer for adults, and one of the most
promising treatments for the future. Because conventional
chemotherapy and radiation treatments are so dangerous to
children, young cancer patients are depending on innovative
biotech companies to continue to develop more effective and
targeted treatments in the future.
At this critical moment when targeted therapies are finally
bearing the fruit of decades of research and providing new hope
for cancer patients and their families, it is essential that we
not undermine the development of these life-saving biologic
agents.
Today you are considering the important issue of allowing
for abbreviated approvals of biosimilar products. We fully
support increasing access to affordable drugs. But what kids
with cancer need most is access to drugs that can treat and
cure their disease. A policy that produces more copies and less
innovation will not help the children and their families living
with cancer. Please don't create legislation that reduces costs
by reducing incentives for biotech companies to develop
targeted therapies for cancer. For me, and for the parents I
represent, life-saving trumps cost-saving any day.
Elizabeth Edwards said in her statement to the press upon
her relapse of breast cancer, ``Femara didn't exist 5 years
ago. I don't expect to get yesterday's medicine. If I can help
it, I'd like to get tomorrow's medicine.'' Don't our children
with cancer deserve the promise of tomorrow's drugs as well?
The R&D pipeline for new biologics is a lifeline of hope for
these kids and their families. Please don't shut it off.
My daughter Naomi draws her inspiration from something
Ralph Waldo Emerson wrote: ``Do not go where the path may lead,
go instead where there is no path and leave a trail.'' We are a
nation of trailblazers and innovators. I want to thank
Representatives Inslee, Baldwin, and Green for introducing
legislation that will enable this tradition of innovation to
thrive in service to our Nation's children with cancer. And I
want to thank the committee for recognizing that the future of
biologics can't be measured in dollars and cents alone--that
the bottom line for patients and their families is the
priceless currency of life, health, and hope.
Candlelighters' motto is ``... because kids can't fight
cancer alone!'' I urge the members of this committee to think
hard about the impact of your decisions on young lives. Kids
can't fight cancer alone. They rely on adults like you and me
to offer them hope, towards a healthy adult future of their
own.
----------
Mr. Pallone. Thank you, Ms. Hoffman, and thank you for
telling the story about your daughter and implications that you
think it has for the legislation. We appreciate it.
Dr. Weisbart.
STATEMENT OF ED WEISBART, M.D., CHIEF MEDICAL OFFICER, MEDICAL
AFFAIRS, EXPRESS SCRIPTS, INC.
Dr. Weisbart. Thank you. First I want to just tell you how
sorry I am for the problems in your family.
I am Dr. Ed Weisbart. I am the chief medical officer at
Express Scripts, and I am a practicing physician; and I am
delighted to be here today to talk about the issue of
biogenerics from the perspective of a leading pharmacy benefit
management company. Express Scripts would like to thank you and
the committee for consideration of this historic policy which
we believe will fundamentally improve health outcomes by giving
people access to lower-cost biologic alternatives.
Express Scripts is one of the Nation's largest pharmacy
benefit managers. We monitor prescription drug trends and
expenses for 1,600 clients including large, self-insured
nationwide employers; Government payers; unions; and across the
sector health insurance companies, with over 50 million
American lives. We work every day on behalf of our clients and
their patients to make prescription drugs safer and more
affordable. It should come as no surprise that with the rise in
cost of biotech pharmaceuticals that our clients are looking to
us for advice on how to manage this ever-increasing biotech
drug spend. In fact, our clients are demanding that we help
deal with this issue.
I would like to make three main points today. First,
specialty drug spending, especially in biologic agents, is
growing at an alarming rate. Second, pharmacy benefit managers
have developed many highly effective tools to manage the
increasing cost of prescription drugs, and third, we are eager
to apply these tools to biogenerics with the potential benefits
to patients, plan sponsors, and the certainly to the
Government.
Spending on pharmaceuticals is now 11 percent of total
healthcare spending. Within pharmaceuticals are specialty drugs
which are mostly the highly priced biologic agents we have been
discussing. As spending for non-specialty pharmaceuticals now
slowed to single-digit growth, specialty drug spending is now
up to 26 percent increase in 2006.
In 2006, spending on specialty drugs was $54 billion,
representing 20 percent of the pharmaceutical spending. In
2010, spending for specialty drugs will nearly double as we
heard today to almost $100 billion. This rate of increase is
the second highest rate of increase in healthcare today,
exceeded only by diagnostic imaging tests, the second largest
today.
As I said, Express Scripts represents 1,600 clients,
managing the pharmacy benefit for over 50 million Americans. We
have sophisticated tools such as formularies, tiered co-
payments, step therapies, and a variety of other drug
utilization management programs, just to name a few. These
tools promote the most clinically sound and cost effective use
of pharmaceuticals.
One of the most potent tools we have is the promotion of
generic medications. Generic medications are time-tested,
proven to be clinically effective, and have highly
characterized safety profiles. An additional advantage, of
course, is that they are the most affordable option for
patients and plan sponsors. Because of the affordability and
the other reasons, patients actually have higher compliance
rates with generic medications than with the newer brand
medications. Using these programs, our company leads the
industry in filling as many as 60.3 percent of all
prescriptions with generic drugs. If I had more time, I would
be delighted to tell you of the success we have had lately in
promoting the adoption of generics in the statin category last
year. In that category alone, we saved over $230 million for
our clients and their members, just since January 2006.
Reducing costs safely, while preserving clinical outcomes and
not shifting costs to patients is our core competency as a
pharmacy benefit manager.
The money spent on biologics is increasing at an alarming
rate. The legislation before you would allow for a pathway for
FDA for companies to bring to market generic versions of these
important medications. We have the tools today to assist
patients in transitioning to these more cost-effective
biogenerics. In fact, our transitioning tools would be even
more effective in this market because of the limited number of
patients involved, a limited number of prescriptions, and the
limited number of treating physicians, not to mention the
enormous potential savings. Our plan sponsors, our clients, are
extremely motivated to have us help pursue each and every one
of these savings opportunities.
Regardless of whether the FDA deems a product
interchangeable or comparable, we will be quite effective at
working with prescribing physicians to help patients receive
the most effective and clinically appropriate care. Many
studies, including a detailed one by Express Scripts, have
sought to demonstrate the potential savings associated with the
FDA's ability to approve biogeneric products. They each differ
in methodology assumptions but what is clear about each one of
these studies is that the Federal Government as well as all
payers stand to find savings in the billions of dollars. That
is billions with a B, not a number you can ignore in healthcare
today.
In closing, this historic legislation will allow patients,
payers, physicians, and PBM's to work together to make these
wonderful therapies more available with frankly improved health
outcomes and tremendous savings.
Thank you for allowing us to talk about this.
[The prepared statement of Dr. Weisbart follows:]
Testimony of Ed Weisbart, M.D.
Good Morning Chairman Pallone, Ranking Member Deal and
other distinguished members of the committee.
I am Dr. Ed Weisbart, chief medical officer at Express
Scripts, and I am pleased to be here today to discuss the issue
of biogenerics from the perspective of a leading pharmacy
benefit management company. Express Scripts would like to thank
the Chairman and committee for their consideration of this
historic policy issue which we believe will fundamentally
improve health outcomes by giving patients access to lower-cost
biologic alternatives.
Express Scripts is one of the Nation;s largest pharmacy
benefit managers. We monitor prescription drug trends and
expenditures for 1,600 clients including large, self-insured
employers, government payers, unions and health insurance
companies with over 50 million lives. We work every day on
behalf of our clients and their patients to make prescription
drugs safer and more affordable. It should come as no surprise
given the dramatic rise in the cost of biotech pharmaceuticals
that our clients look to us for advice on how to manage this
ever-increasing biotech drug spend. In fact, they have been
demanding action to make these therapies more affordable.
In my testimony today, I want to make three basic points:
First, specialty drug spend, especially biologic
agents, is growing at an alarming rate;
Second, pharmacy benefit managers have developed
many tools to manage the increasing cost of prescription drugs;
and
Third, how we would apply these tools to
biogenerics and the potential benefit to patients, plan
sponsors and the government.
I. Trends in Specialty Spend
Spending on pharmaceuticals now represents 11 percent of
total health care spend. Within the pharmaceuticals are
specialty drugs, which are mostly the high priced biologic
agents being discussed today. As spend for non-specialty
pharmaceuticals has slowed to single-digit growth, specialty
drug spend increased 21 percent in 2006. \1\
---------------------------------------------------------------------------
1 Express Scripts, Inc., 2006 Drug Trend Report, www.express-
scripts.com/ourcompany/news/outcomesconference
---------------------------------------------------------------------------
In 2006, spending on specialty drugs was $54 Billion,
representing 20 percent of the pharmaceutical spend. In 2010,
spend for specialty drugs will almost double to $99 billion.
This rate of increase is the second highest in health care
field, exceeded only by diagnostic imaging tests.
II. Tools of PBMs
As I said, Express Scripts represents 1,600 clients,
managing the pharmacy benefit for over 50 million individuals.
To this end, we have developed sophisticated tools, such as
formularies, tiered copayments, step therapies and drug
utilization management programs to name a few. These tools
promote the most clinically sound and cost effective use of
pharmaceuticals.
One of the most potent tools we have is the promotion of
generic medications. These therapies are time-tested, proven to
be clinically effective, and have well characterized safety
profiles. One additional key advantage is that they are the
most affordable option for patients and plan sponsors. For
these reasons, patients achieve higher compliance rates with
these therapies. Utilizing these programs, our company leads
the industry in filling as many as 60.3 percent of all
prescriptions with generic drugs.
When a particular drug comes off patent and can be filled
with a generic, that fill rate climbs to about 96 percent. An
example of this would be when simvastatin came onto the market
as a generic version of Zocor.
Where there is considerable patient monitoring needed, such
as the case in preventing transplant rejections, what we call a
narrow therapeutic index, physician prescribing patterns are
more cautious and we see a generic fill rate of 83 percent.
These generic fill rates are based on empirical drug spend
data.
It is important to recognize that all of our programs for
promoting the use of generics, or less expensive branded
medications, are reviewed by our external Pharmacy and
Therapeutics committee. This independent self-governing
committee is made up of both primary care and sub-specialty
physicians and pharmacists, none of whom are employed by
Express Scripts.
III. How We Would Apply PBM Tools to Biogenerics
As we have stated, the money spent on biologic agents is
increasing at an alarming rate. This legislation will allow for
a pathway at FDA for companies to bring to market generic
versions of these important medications. PBMs have the tools to
assist patients in transitioning to the more cost-effective
biogenerics. In fact, our transitioning tools will be even more
effective in this market because of the limited numbers of
patients, prescriptions and treating physicians, and the
potential enormous savings. Our plan sponsors will be very
motivated to have us pursue each and every savings opportunity.
Regardless of whether the FDA deems a product as
interchangeable or just comparable, we will be quite effective
at working with the prescribing physician to aid patients in
receive the most cost effective and clinically appropriate
therapy.
To use a non-biologic example, Express Scripts' P&T
Committee reviewed the potency of drugs called statins to
determine the degree that they lowered LDL or ``bad''
cholesterol. Our independent P&T Committee concluded that three
statins were in the ``high-potency'' category.
In this case, statin A had a much higher price than statin
B. So, we educated consumers and physicians about the lower
cost alternative brand product. We successfully moved 49
percent of market share to the preferred brand product within 6
months, and the outcomes for the patients are equally
successful.
At the same time, statin B's product went generic. And,
Express Scripts simultaneously moved 96 percent of market share
to the preferred generic agent within 3 months, resulting in
$230 million of savings since January of 2006 in the area of
anti-cholesterol drugs alone.
While they have remained a relatively small percentage of
prescriptions, biologics are the single, largest segment of
drug spend, with an additional 400 to 700 biologics in the
pipeline. The average cost per day of a biopharmaceutical is
$45 compared with $2 per day for a traditional medicine. In the
traditional drug market, generic medications decrease prices
60-90 percent as compared to branded oral-solid medications.
Many studies--including a detailed one by Express Scripts--
have sought to demonstrate the potential savings associated
with the FDA's ability to approve biogeneric products. What is
clear about each of these studies is that the Federal
Government--as well as all payors--stands to find savings in
the billions of dollars.
In closing, this historic legislation will allow patients,
payers, physicians and PBMs to work together to make these
wonderful therapies more available, with improved health
outcomes and tremendous savings.
Mr. Chairman and Members of the Committee, thank you for
allowing me to testify before the Committee on this important
issue. I would be happy to answer any questions you may have.
----------
Mr. Pallone. Thank you, Doctor. We will now go to questions
from the members, and I will start. I am recognizing myself for
5 minutes.
I wanted to ask Mr. Kingham, as you heard, Dr. Woodcock--
well, I don't know if you were here when she testified,
presumably.
Mr. Kingham. Yes, I was.
Mr. Pallone. She, at least I think she said, that clinical
trials should not be mandated or required for the approval of
follow-on biologics. She argued that FDA should have the
flexibility to require different levels of testing depending on
the complexity of the follow-on product and that while clinical
trials might be required for the more complex molecules today,
that could change with advancements in science. Now that seems
to be at odds with your written testimony which states that
clinical trials should be required for all products, and my
question really is if the FDA is telling us that clinical
trials shouldn't be mandated and we shouldn't have flexibility,
why should we disregard that and require them? Aren't they the
real experts that we should be listening to?
Mr. Kingham. Well, first of all, Congress has told FDA what
to do with respect to the data to support applications for
drugs on a number of occasions, so it is not unprecedented. And
then the FDA has to do what you tell them to do. You did that
in 1962 when you required proof of efficacy by only one type of
clinical trial, not just clinical trials adequate and well-
controlled clinical investigations. And in the legislation that
Representative Waxman cosponsored in 1984 that Congress
specified a particular type of comparative clinical trial, a
bioequivalent study to demonstrate that generic drugs should be
approvable.
So you have done it many times. But the fact is that at the
present time, both in Europe and the United States, nobody has
seen a protein product of the type that we are dealing with
under section 351 that can be approved without some use in
humans. I think as a matter of basic science and policy, it is
entirely reasonable to require some experimentation, some
clinical use of a product before it is introduced into medical
practice in those circumstances. I am quite happy that the FDA
has substantial discretion as to the exact testing that is
required. Right now where they have that discretion they are
requiring substantial clinical tests, not minor ones but major
clinical tests lasting months and involving substantial numbers
of patients.
Mr. Pallone. So you think there should at least be some
trials, it is just a question of what they would do?
You give flexibility in what they do but----
Mr. Kingham. I think the thing that disturbs me in at least
one of the bills that is before this committee, H.R. 1038, is
that while the legislation does ultimately give the FDA the
power to require a clinical trial, it segregates the clinical
trial issue from other types of data and attaches to it a sort
of warning to the agency that they better not require
duplicative or unethical tests. Now, I have never seen anything
like that in a bill directed to the FDA before, but the message
that it clearly sends is you shouldn't really be doing this.
The message I heard from Dr. Woodcock was most of the time,
probably all the time for the foreseeable future, for the types
of proteins that are regulated under section 351, some form of
clinical testing is going to be necessary.
Mr. Pallone. I will admit that it wasn't totally clear what
she was saying. I would like to ask Dr. Allan. When Hatch-
Waxman was enacted in 1984, his detractors claimed that it
would stifle innovation, yet the number of new technologies
developed in the last 20 years, particularly in biologics, has
been staggering. You noted in your testimony that the pending
legislation would be a positive step for the biotech industry
and would continue to fuel the cycle of innovation. You want to
just elaborate on that a little if you could? Now, I am talking
about Mr. Waxman's legislation.
Mr. Allan. Yes. I think the innovation that would be
stimulated by an act of this type would be enormous in the area
of analytical methodology to characterize proteins, there would
be an absolute rush to the door for people to develop this
methodology, to assist in the development of these novel
protein products. We were hearing this morning that science
might be many years away. I would absolutely guarantee that if
the incentive was provided to the scientists out there in both
research laboratories within universities or biotech companies
that there would be an enormous leap in our knowledge of how to
characterize proteins efficiently and effectively.
Mr. Pallone. OK.
Mr. Allan. And this argument would disappear.
Mr. Pallone. OK. Thank you. Ms. Hoffman, I appreciate your
being here and what you said. But the way I see it, innovators
have a virtual monopoly on the market now and aren't
necessarily doing the research and development that you say is
needed. So I guess what I don't understand is how the approval
of the follow-ons which we are talking about today would
dramatically change the playing field. In other words, if we
approve a pathway for follow-ons, then why would that mean that
there would be any less innovation along the lines of what you
suggest or what you think is needed?
Ms. Hoffman. I guess I was saying that in terms of orphan
diseases--diseases like childhood cancer, it doesn't appear
that there is enough incentive to be producing biologics and
new treatments and new therapies for these patient populations;
and I can't see that by reducing any sort of incentive that
that is going to make things better.
So my proposal is that anything to cut back on incentives
is going to make things even worse. I mean, we are already at
zero, but we have no hope, none at all, to even get on the
playing field. And I mean, it is not just childhood cancer, it
is all orphan diseases, whether it is muscular dystrophy or
other children's diseases, it is a huge issue. And if we take
that incentive away from biotech companies, I just don't see
that there will be cures that come down.
Mr. Pallone. I understand your concern. You want to make
sure that we don't eliminate incentives.
Ms. Hoffman. Yes.
Mr. Pallone. Thank you. Mr. Deal.
Mr. Deal. Thank you. I want to thank all the witnesses. You
have been very helpful, very informative and your written
testimony elaborates even further than your 5 minutes did. I
thank you for that.
Mr. Kingham, let me ask you specifically some questions so
I can clarify some terms here and thank you for refining your
testimony down to talking about the issue of exclusivity. I do
believe that is one of the two, in my opinion, major areas. The
other big major area I would classify would be the overall
safety issue, and I want to talk to some of you about that in
just a second.
Let me first of all understand: patent extension currently
extends to biologics, does it not?
Mr. Kingham. Yes, it does, sir.
Mr. Deal. OK. In your literature and in your attachment in
particular, the terms market exclusivity and data exclusivity
are used. Are they the same information? Is it the same term?
Does it mean the same thing?
Mr. Kingham. No, not necessarily. Market exclusivity is a
term for a period during which there is not competition because
of some regulatory or other legal protection. It can be a
patent, it could be orphan exclusivity under the orphan drug
amendments, something like that. Data exclusivity is the period
during which someone cannot rely upon your data to get a
follow-on product approved. Data exclusivity does not preclude
another company that is prepared to do research and development
and do its own clinical trials from obtaining approval of a
competitive product. That is why we have multiple biologic
products in a number of therapeutic categories today because
different companies did the work to support their products.
Mr. Deal. So when you were talking about the 14 years, you
were talking about market----
Mr. Kingham. That is correct. What I am saying is that I
believe Congress made a judgment in 1984 that that was a
reasonable period to provide the incentives needed to do the
research and development.
Mr. Deal. OK. Now, in terms of data EE, that comes to the
issue of how much can a follow-on piggyback onto what FDA
currently has submitted by the original innovator, am I
correct?
Mr. Kingham. That is correct.
Mr. Deal. All right. Are you advocating a period of data
EE?
Mr. Kingham. Yes, I am.
Mr. Deal. How long?
Mr. Kingham. Of 14 years and the reason for that is that I
believe that with all the various problems I identified, we
cannot be sure that patents will provide a certain period of
market EE. I would propose that that be provided with data EE.
Mr. Deal. If we are talking about market exclusivity being
different than patent protection which I understood you to
advocate, why would you also need data EE?
Mr. Kingham. You need it because the patents may not
protect the products under a system of----
Mr. Deal. But if you got a statutory market EE, that gives
you the protection, does it not?
Mr. Kingham. Yes, sir, if the provision of the law were
similar, for example, to what is in the orphan drug amendments
of 1983 which provides a period of time during which a
competitive product cannot be approved without regard to
patents, without regard to data and so forth. That would
achieve the same purpose.
Mr. Deal. OK. The data exclusivity to me comes under my big
category of the safety issue as to how much can you use in
determining the safety of the follow-on product. In that
regard, I have been intrigued by some indications of people who
suggested that we look at the FRFRA provisions of the EPA as it
relates to the regulation of pesticides. They have some unique
statutory provisions there. Have you had any occasion to ever
look at those?
Mr. Kingham. Well, I have. Of course, the pesticide law led
to some very serious constitutional problems back in the 1970's
when the Environmental Protection Agency under instructions
from Congress sought to use the data that had been submitted by
innovators in order to approve follow-on pesticide products,
but they had actually assured people who filed data under the
previous application system that the data would not be used in
that manner. That led to a significant constitutional issue and
very complicated questions concerning how and if to compensate
people for the use of their data which brought down the whole
registration system for a number of years.
Mr. Deal. My reading of the Ruckelshaus case in 1984 that
was supplemented by the Thomas v. Union Carbide case of 1985
seems to have approved at the Supreme Court level those
statutory schemes, and in that regard I need to ask you this
question before time runs out.
Mr. Kingham. OK.
Mr. Deal. Part of that was all based on I think what the
language was, reasonable investment backed expectation that the
information submitted to a Government agency would not be
violated or remain invalid.
Mr. Kingham. That is correct.
Mr. Deal. Is there anything as you see it under current law
that gives to current innovators of biologics a reasonable
investment-backed expectation that the information would not be
shared? If so, is it stated or is it simply implied?
Mr. Kingham. Well, in 1974, the Food and Drug
Administration said in the Federal Register that they would not
use the safety and effectiveness data filed under an
application under section 351 of the Public Health Service Act
to approve competitive products. It was very clearly stated
that they would not approve generic products on the basis of
data that were submitted by innovators.
Mr. Deal. Other than that, is there anything that you think
is there?
Mr. Kingham. Well, that has been the continuous course of
conduct since then. The agency has never taken that back, and
the regulation that it promulgated on the basis of that legal
approach remains in effect today. It is a bit complicated
because it has to do with the implementation of the Freedom of
Information Act, but the representation has existed since 1974
that data will not be used to approve other people's products.
Mr. Deal. Thank you.
Mr. Pallone. Mr. Waxman?
Mr. Waxman. Mr. Chairman, with all due respect, Mr. Kingham
is a lawyer and he is presenting to us his understanding of the
law, but perhaps we ought to have lawyers from the generic
industry as well. I certainly can't substitute for them, but I
can tell you I wrote these laws. And I think that the gentleman
has made some statements that are incorrect.
There is a patent, and the patent is for 20 years. When you
go into FDA, there is a period of time in which FDA takes to
review it. Sometimes there is a delay at FDA because of FDA,
sometimes there is a delay at FDA because of the manufacturers.
The argument in the mid-1980's was in addition to the patent,
there ought to be exclusivity for some of the time lost at FDA
for approval. So the bill is the restoration of some of that
time. The law didn't guarantee 14 years, it said up to 14
years. That was the maximum. Now, what we have presented to us
from the industry, the bio industries, they ought to have a
minimum of 14 years.
Now, we also provided some other exclusivities. We provided
exclusivity of only 5 years for the most innovative new
molecular entity, because we wanted to encourage the companies
to look for new uses for some of the drugs that were out there,
and we said we will give you 5 years of exclusivity. Well, that
was 5 years for something really worthwhile. If it weren't so
dramatic, we gave them 3 years.
I also wrote the Orphan Drug Act. The Orphan Drug Act was
to give an incentive to develop drugs that weren't profitable,
so we provided a term of exclusivity in the Orphan Drug Act.
Now we have the testimony from Mr. Kingham that we ought to
give them what was given under the Orphan Drug Act, but these
are companies that are making biological drugs that are
profitable. Nobody is going to want to make, by the way, a
generic version of a non-profitable biologic drug. So the
question then should be should they have the same kind of
exclusivity that was given to the orphan drug act which was to
make up for the fact that they probably weren't going to get a
big windfall. By the way, many of them did. You can never take
back exclusivity. You can never take back some of that period
of time.
So if I were looking for the wish list of the biotech
industry, since they now take the position, well, we ought to
have a pathway, my wish list would be as follows. Let us give
the companies that are already on the market and may be on the
market with new products as much exclusivity as possible, and
that is certainly what they are arguing. It is in their
economic interest to argue for that position. I would also
argue, Mr. Schwieterman, if I were in the biotech industry that
argues that any legislation should rule out the possibility of
establishing interchangeability because ``it is not possible in
the present state of science and technology to treat them as
interchangeable.'' Do you agree that it is impossible given the
current state of science to devise studies necessary to
determine whether two biologics are interchangeable?
Mr. Schwieterman. No, I don't agree. I don't agree that it
is impossible. The use of the term interchangeability is a term
that connotes confidence in data and the science and the use of
a product in a particular patient that provides a particular
effect. It is to me a term that actually is science-driven and
data-driven, and I think it fully possible in certain settings
where the data exists and in the context of the application an
indication that you could, in fact, in those----
Mr. Waxman. In fact, the terms in my bill is lack of
significant clinical difference in the safety of effectiveness.
So in effect, you can have an interchangeable provision. Well,
if I were I guess from the bio industry, I would say, well, I
certainly don't want this to be considered equivalent in this
way because it will be substituted. That is how we get our big
savings is we substitute a generic drug.
Mr. Downey, a number of proposals would require FDA issue
guidance to classic cases of biologics before the agency may
approve a generic biologic. You have experience with the agency
both as a generic manufacturer and as a company that sells some
brand-name products. Would requiring a guidance for a class of
generic biologics be consistent with current FDA policy and
would it make sense?
Mr. Downey. Well, no, it is not consistent with FDA policy
today. Even the innovative biologic products are not subject to
a guidance. They propose their own product and their own
guidelines, and the FDA comments. That is precisely what
happens in BLA's, new drug applications, abbreviated drug
applications, and that is what we think should happen here.
Mr. Waxman. Well, if I were from BIO and I was trying to
figure out how do I extend my exclusivity period, I would also
want to complicate things by several years making me have to go
through this rigmarole.
Mr. Downey. I believe if we had that process the first
generic biological would extend beyond the career horizon of
the current executives in the bio industry.
Mr. Waxman. Then you make them do more clinical trials.
That also would postpone the competition. So you want more
exclusivity and if that doesn't protect you to make maximum
profits, then you want more obstacles before you get the
competitor out there.
All of the wish list is in the other bill that is before
this committee. I think we all agree there ought to be a
pathway and there needs to be a balance. But we need incentives
not only for new products, we need incentives for generic
products as well; and before the Hatch-Waxman Act was adopted
over 20 years ago, there was no generic industry. In fact, the
only thing the generic guys did was reproduce the drugs for the
brand-name companies. The brand-name companies said, well, they
don't know how to do this sort of thing. Well, they were
actually making the drugs but the brand-name companies were
selling them for whatever the monopoly would allow.
We want that balance for both sides, and I would submit
that the bill that Mr. Inslee introduced is one that I would
want us to walk through very carefully and make sure that that
balance is achieved.
Thank you for that.
Mr. Pallone. Thank you. Dr. Burgess.
Mr. Burgess. Thank you, and thank you all for being with
us. It really has been an informative panel.
Dr. Schenkein, if I could ask you, you heard the line of
questioning that Mr. Waxman was just following. Is that period
of EE, is that something that you feel is important to the
continued development of breakthrough and innovative products?
Dr. Schenkein. I do. I believe it is critically important.
As we look at the development of biologics, particularly as
they have a better efficacy-to-safety ratio, they are safer,
they appear to be more effective, we move them into the agavent
setting. By doing so, we need to wait for the pivotal studies
to first be done in the metastatic setting. So the timing by
which we can move these medicines up to the agavent setting
where we believe they will have the biggest impact and
potential possible cures, particularly in malignancies, and
transform other illnesses, takes a long period of time. It can
be as long as a decade after the original approval to complete
or design those studies.
Mr. Burgess. Let me see if I understand that concept
correctly. You are developing these products that are used in
individuals with fairly advanced disease, stage IV metastatic
cancer, and as you develop the expertise of the comfort level
with those products, they are then possibly going to be
investigated as agavent therapy for someone with early stage
disease to prevent recurrents and extend life at an earlier
stage of a similar cancer, is that----
Dr. Schenkein. That is absolutely correct, and that period
takes a long period of time.
Mr. Burgess. Is it possible to make some of these difficult
compounds, is it possible to make them so that they are just
absolutely identical? We heard the testimony from the gentleman
from Express Scripts about the symptostatin story and no doubt
that someone can make an exact replica of that molecule, with
some of the things that you work with, is it going to be
possible to make an exact replica of the molecule?
Dr. Schenkein. At this point the science that we have
available today, it is not possible for us to say that these
are the same.
Mr. Burgess. How do you even then extrapolate that to the
individuals where we are going to treat their lymphocytes and
give them back those? I mean, how do you do a study when your
population is one and it is either effective or it is not?
Dr. Schenkein. That raises the complexity even to the next
level above the standard proteins or antibodies that are being
processed now. So it will become even more complicated than
that setting.
Mr. Burgess. But as we get into the realm of personalized
medicine of individuals, that is going to be critical, is it
not?
Dr. Schenkein. I believe so.
Mr. Burgess. And it will be expensive, will it not?
Dr. Schenkein. It is too early yet. We don't know. We know
that these innovative----
Mr. Burgess. Let me rephrase that. Even if it is expensive,
it is very likely to be worth it, is that a fair statement?
Dr. Schenkein. After careful testing, if it determines
safety and efficacy, then that will be a therapy that will be
useful.
Mr. Burgess. What about the doctor who writes a
prescription for someone to go to the drug store and fill it
with recombinant DNA--in your experience would it be OK for
someone just to substitute something different from what the
doctor has established as the product that he wants his patient
to receive?
Dr. Schenkein. As a physician, I think it is critically
important that I have that relationship with my patients so I
know exactly what that patient is receiving when I prescribe
it. I am making challenging decisions at every point about a
variety of different medicines I can use. And unless the
product is exactly the same, which we are not talking about in
the case of follow-on biologics, I need to have the ability to
make a decision with that patient on which medicine I want to
give them.
Mr. Burgess. Is that a big enough difference to be a
difference? Could that affect the critical outcome of a
patient?
Dr. Schenkein. It is certainly possible. When I make a
decision to use a therapy, I base that decision on clinical
evidence, large-scale clinical trials that have been published
and presented. If that is not available for another molecule, I
factor that in the decision. It is a totally different level of
evidence to be able to base an important decision with a
patient.
Mr. Burgess. If I could, I would like to ask a question. I
would like both you and Mr. Kingham to respond and anyone else
if you feel so moved. When I first heard of this issue of
generic biologics or follow-on biologics, I thought that has to
be a pretty small universe. We talk of savings, again the
gentleman from Express Scripts talked about with statins. That
is a huge universe. But when we talk about follow-on biologics,
and maybe it is just an era that is just beginning, but
realistically, what kind of savings can we expect, should we
expect if we were to pass say the Waxman bill through Congress
this year?
Dr. Schenkein. So again, as a physician and an oncologist
designing clinical trials, I don't think that is my best area
of expertise to comment on cost savings.
Mr. Burgess. Well, then Mr. Kingham, do you have an opinion
about----
Mr. Kingham. Well, I can't give you a precise number but I
think there are a number of reasons why the number will be
smaller than many advocates of the legislation suggested.
Studies that I have seen assume that there aren't any effective
patents for any major products where as there are. They assume
that the legislation and regime would be in place immediately
and drugs would be improved within months or a very short
period of time after the law was passed. The European
experience doesn't support that. They have had a system in
place for 3\1/2\ years and they have approved two products.
It assumes that a number of products that present very
complex issues for approval, like monoclonal antibodies and so
forth, would be in the groups of products that will get
approved and will compete. I think it is going to be a long
time before the science is there, much less the patent
situation. It assumes tradition or something very similar to
traditional substitution patterns for generic drugs.
Quite apart from the scientific issues of interchange,
these drugs aren't administered and dispensed in the same way
so that the patterns of substitution that apply with
prescriptions taken to the drugs store won't be relevant. And
it assumes price differentials that I think may be greater than
the price differentials that will actually occur based on
experience in markets outside the United States. There are a
lot of assumptions that have been set into these projections. I
suspect we are talking about savings, and there would be some
for sure that are a small fraction of the savings that have
been suggested.
Mr. Burgess. Thank you, Mr. Chairman.
Mr. Pallone. Thank you, Dr. Burgess.
Mr. Downey. I would like to respond to----
Mr. Pallone. OK. But let me just tell everybody what we are
going to do here. We have to vote on the Iraq supplemental, and
we only have 13 minutes. So we will ask Mr. Downey to respond,
and then we are going to have Ms. DeGette and then we will go
and vote.
Mr. Downey. There is only one aspect to Mr. Kingham's
response that I agree with and that is there will be very few
approvals in the first 5 years because it takes a longer time
to bring the generic versions to market than a generic
pharmaceutical. But today, the Taxpayers Against Government
Waste issued a report where they said after the first 5-year
period, the next 10 years will result in $43 billion in savings
and I don't think that is an unreasonable estimate. And I do
strongly disagree we won't achieve the same substitution rates.
I know that we believe that we achieve those rates in the
hospital setting for other pharmaceutical products, we will
achieve them here. I know that the drug benefit managers like
Express Scripts do an excellent job of educating patients and
physicians about the benefits of generic products, and I am
sure they will carry that expertise into the biologic areas and
we will achieve those substitution rates and we will achieve
that level of savings.
Mr. Pallone. Thank you. The gentlewoman from----
Dr. Weisbart. May I?
Mr. Pallone. Well, I just don't want to run out of time. If
you want to be quick, go ahead.
Dr. Weisbart. I will be very brief. A couple quick points.
Your decisions will determine how much the savings is. Your
decisions will determine that. If you decide to follow some of
those recommendations, you will have very little savings. If
you decide to pay attention to the wisdom of Mr. Waxman and
yourself just a minute ago, your savings are potentially
enormous. Clients are pressing us to do this. They are not that
many prescriptions, they are all handled through specialized
pharmacists with a few physicians we know how to reach them. If
you think of the savings I just talked about for Simvastatin
for a $40 or $80 change of prescription, these are hundreds of
dollars. Our clients are very motivated to have us do
everything we are doing today and way more to make these
savings happen. In terms of the timing of this, that is up to
the courts. As we know, there are lots of drugs that come off
patent protection for which generic drugs reach market years in
advance of when the brand manufacturers--but the 10K filing
would make you think that is the not case.
And last, a large part of the savings early on are due to
erythroproteins which a large percentage of it comes to the
Federal Government. So the savings that are potential here are
savings for the Federal Government in large part. It is a huge
opportunity. That is soon if you introduce legislation.
Mr. Pallone. All right. Thank you. I recognize the
gentlewoman from Colorado for 5 minutes.
Ms. DeGette. Thank you, Mr. Chairman. I am a little nervous
because I do want to vote on the supplemental.
Mr. Pallone. You have 11 minutes left. If you take 5 we
will still get there.
Ms. DeGette. I want to ask you, Dr. Shenkein, as we have
been hearing this testimony, the view of all of the
representatives at BIO who are here is that because biologics
are so complex, it would be very difficult to create a generic
version; and what we have heard from several of the witnesses
is BIO seems to be supportive, employing a biosimilar pathway
similar to the one in the EU which relies heavily on clinical
trials. So if that is the case, do you think we will ever have
a situation where biosimilar will not have to go through pretty
much full clinical trials before approval?
Dr. Schenkein. I can't obviously predict what will happen
in the future. All I know is right now, the science in the
foreseeable future, we don't have the ability to be able to
determine that these molecules are the same.
Ms. DeGette. So your answer would be in all probability
these follow-on biologics would need to go through a full
clinical trial, correct?
Dr. Schenkein. Yes.
Ms. DeGette. Well, then my next question, and I am going to
also ask Mr. Downey that question, too, is we have several
proposals in front of us to create these pathways to approve
follow-on biologics, and I haven't signed on to any of these
approaches because like most of us, I am still trying to figure
out the right balance. But all of the approaches are predicated
on the belief that the FDA is going to handle increased
responsibilities for the process. So my question is given the
fact the FDA is continuing to struggle to meet its current
obligations with fewer and fewer resources, what would that
agency need to be able to oversee a whole new pathway for
biosimilars? I want to start with Dr. Schenkein, and then I
want you to answer.
Dr. Schenkein. So we do believe it is critically important
that with any policy that moves forward that it doesn't
distract the FDA from the ability to review and approve
innovative drugs that are advancing the field forward. That has
to be the primary focus. I can't comment on what the FDA would
require to be able to----
Ms. DeGette. Do you think they would need substantial
additional resources to do this job adequately?
Dr. Schenkein. I can't really comment.
Ms. DeGette. OK. What about you then Mr. Downey?
Mr. Downey. House bill 1038 provides user fees to support
the generic biologic program at FDA and----
Ms. DeGette. Some of us have real concerns about user fees,
too.
Mr. Downey. Well, you asked how it would be funded.
Ms. DeGette. OK.
Mr. Downey. At least in 1038 it contemplates user fees, and
I would support that because I think the FDA does need
additional resources and that is a place from which they can
come and there will be great savings achieved by it. On the
clinical trials, I disagree with the comments that were made.
In terms of mandating clinical trials in the statute, that is
not required for an original innovator BLA. Those requirements
are all imposed by FDA on a product-by-product basis with
product relevant clinical testing. That is handled in the drug
area, it is handled in the innovator biologic area, and what we
believe is appropriate for generic biologics. And I think also
if you recall Dr. Woodcock's testimony, she said they have
approved products with limited clinical studies and those that
have required more clinical studies.
Ms. DeGette. But all of them needed clinical studies.
Mr. Downey. For today.
Ms. DeGette. So I think for today we have to go on that
assumption.
Mr. Downey. I would disagree. I think you need to think as
I talked about it earlier, it is 20-year cycles. This is the
bill that I think will last 20 years, and as you all know it is
very difficult to reopen these very contentious and difficult
issues; so I believe we should provide FDA the flexibility and
the resources to handle this issue for a long period of time.
And if you look at the products, I do disagree with some of the
testimony here today. I think simple proteins, like insulin,
can be fully characterized and they don't really require the
clinical trials. Now, I realize that FDA is probably going to
disagree with me on that, but I do believe that science is
advancing so fast and it is so clear that in a very short time
we will be able to have very minor clinical trials, if any.
Ms. DeGette. I will say, I don't disagree with what you are
saying, but I do think it is probably a little naive to say we
will just do user fees and that will cover the cost. I am
really going to look forward to working with Mr. Waxman and Mr.
Pallone to make sure that whatever we do here, we give the FDA
adequate resources to do this. I myself have a 13-year-old
daughter who is insulin-dependent. I am not going to use a
generic insulin with her unless I am pretty darn well sure. Ms.
Hoffman, mother of eight, is sitting here nodding, too. We are
just not going to do that unless we are sure.
Mr. Pallone. I am going to have to stop you. I appreciate
it because we want Mr. Inslee to have a little time, but there
is only 5 minutes left on the vote. You are at your own peril
here. You might have missed the vote.
Mr. Inslee. Regarding data exclusivity we have a couple of
numbers that have been suggested so far, one is zero and one is
14 years. And the previous incarnation which I appreciate Mr.
Downey, he called it the Waxman-Hatch bill. That is
appropriately honoring the House.
Mr. Downey. I try to remember which house I am in.
Mr. Inslee. I appreciate that. It had between a 5- and 14-
year data exclusivity as opposed to paying--is there any reason
that any of you could articulate to go backwards to zero on
that if indeed there was a societal purpose to protect data
exclusivity for the reasons Mrs. Hoffman has talked about, to
have an incentive for innovation. Is there any reason to have
gone backwards? For instance, is it easier to do a follow-on
biologic for instance and some of the other chemical or is the
FDA much faster than it used to be so that you don't need that
much protection? Is there any reason to go backwards to zero?
Can anyone articulate any reason?
Mr. Pallone. Let me just indicate we are going to have
about a minute to answer the question and then we got to go
because otherwise we are going to miss the vote.
Mr. Kingham. Well, I would just say quite simply no, I
can't conceive of any reason for a zero.
Mr. Inslee. That is the right answer. I have to go vote.
Thank you very much.
Mr. Pallone. Thank you. Thank you, gentlemen and lady. We
appreciate your input. This was a very good hearing I feel, and
I got a lot of insight. It is a very difficult and complex
problem, so we thank you very much. You may get additional
questions in writing from us within the next 10 days which we
would like you to respond to, and without further ado, this
hearing is adjourned.
[Whereupon, at 2:30 p.m., the subcommittee was adjourned.]
[Material submitted for inclusion in the record follows:]
Statement of Priya Mathur, California Public Employees' Retirement
System
On behalf of the California Public Employees' Retirement
System (CalPERS), I appreciate the opportunity to provide
testimony for the hearing record on the high cost of
biopharmaceuticals and the need to establish a safe pathway for
the approval of biogenerics. As vice-chair of Health Benefits
for the Board of Administration of CalPERS, I was elected by
400 thousand public sector members to serve on the board of
CalPERS to invest their $230 billion of retirement assets and
to manage their multi-billion dollar health benefit program.
The high cost of biopharmaceutical products presents an
unsustainable challenge to CalPERS and to our entire health
care system. At a time when our state is trying to expand
health insurance coverage to more Californians, slow the rate
of growth in health care costs, and make our health care system
more efficient, we cannot afford the status quo. I commend
Chairman Pallone for his leadership in this area. In addition,
I would like to thank the sponsors of the bipartisan Access to
Life-Saving Medicines Act, introduced by Representatives
Waxman, Emerson, Pallone and others.
CalPERS Background
CalPERS was established by state law in 1932 to provide
retirement benefits for California public sector employees. In
1962, state law authorized CalPERS to provide health benefits
to their members. Our mission is to advance the financial and
health security for all who participate in the System.
CalPERS' health program covers 1.2 million active and
retired state and local government public employees and their
family members. Of that total, approximately two-thirds are
active members and one-third are retirees. Notably, CalPERS is
the third largest purchaser of employee health benefits in the
Nation--behind the Federal Government and General Motors
Corporation--and is the largest purchaser of health benefits in
California.
This year, CalPERS will spend almost $5 billion on health
benefits--or $13.4 million per day. Of that amount, CalPERS--
for the first time--will spend over $1 billion on our members'
prescription drugs.
Slowing the Rate of Growth in Health Care
Recognizing that we have a fiduciary responsibility to
constrain cost growth and ensure healthcare value, CalPERS has
long been a leader in implementing cost-effective programs.
These initiatives include consumer-friendly managed care,
aggressively negotiating favorable contracts with insurers by
leveraging our pool of enrollees, state of the art hospital
purchasing and quality assurance arrangements. In addition, we
have instituted innovative prescription drug benefit cost-
sharing designs to maximize the use of generics and
therapeutically appropriate brand drugs. We have also provided
incentives for the use of over-the-counter and mail-order
medications and mail-order, particularly for the treatment of
chronic diseases.
CalPERS has enjoyed tremendous success in controlling
prescription drug costs through the use of generics. This has
been possible thanks to the efforts of this Committee, and
particularly Mr. Waxman, whose efforts two decades ago led to
the enactment of the ``Drug Price Competition and Patent Term
Restoration Act of 1984,'' better known as Hatch-Waxman.
As members of this committee well know, Hatch-Waxman gave
the Food and Drug Administration (FDA) the authority to provide
an abbreviated approval process for those products deemed
equivalent to an innovator product once a product's patent had
expired. For multi-source drugs in our self-funded PPO, which
covers about a quarter of our members, our generic substitution
rate is approximately 96 percent. Without generic substitution,
we estimate that our costs would be about 60 percent higher--
saving our enrollees and our state taxpayers hundreds of
million of dollars annually.
In spite of all of our cost-containment efforts, we are
experiencing double-digit increases in health care spending
over time. Since 2002, CalPERS has seen an average annual
increase of about 13.5 percent for our HMOs and PPOs, and a 12
percent average annual increase in our association member
plans.
Increasing Cost of Biopharmaceuticals
Because of the complex delivery requirements of many
biopharmaceuticals, it is exceedingly difficult to break out a
stand-alone spending line for these products. However, we
believe that our spending on so-called ``specialty drugs'' is a
good proxy because biotech products make up the great majority
of spending in this category. CalPERS spending for these
products is distressingly substantial and rising at a rate that
is significantly higher than traditional pharmaceuticals.
Total spending for specialty drugs was $83.7 million in
2006, up from $67.4 million in 2004. Spending on these
prescriptions increased by 16.9 percent in 2005--compared to a
5.4 percent increase in traditional prescription drugs. On
average, spending for biotech products was at least $55 per
day--compared to traditional drugs at only $2 per day.
Promise of Biogenerics--Competition and Lower Cost
CalPERS supports a competitive health care marketplace
that leads to innovation and further development life-saving
medicines. Today, biopharmaceutical manufacturers enjoy
monopoly positions. Today, unlike traditional pharmaceuticals,
no competition is created in the marketplace once a patent has
expired on a brand name biopharmaceutical. Competition does not
exist because the FDA has held that it does not have the
authority to approve biogeneric products. CalPERS supports
giving the FDA explicit authority to approve biogeneric
products that are safe.
It is imperative that Congress take action this year to
enact bipartisan legislation to give FDA the authority to
approve safe biogenerics. Today's biotech companies are
benefiting long after patents expire and are profiting at the
expense of all Americans. No employer, labor organization or
health plan can continue to offer affordable coverage without
competition in the biopharmaceutical industry. Without the
ability to access less expensive, comparable, and
interchangeable biopharmaceuticals, CalPERS ultimately will be
forced to increase prescription drug co-pays or increase
premiums, shifting the increasingly unaffordable costs onto the
individuals who can least afford them.
Finally, I would like to address the issue of safety.
Opponents of this legislation--primarily the biotech industry--
are claiming that those who support the Access to Life-Saving
Medicines Act are ignoring the safety threat of bringing
biogenerics to the marketplace. I want to be clear--the safety
and health of our members comes first in any decision we make
about any policy. That is why we strongly support providing FDA
with full discretion to make the ultimate decision about
whether and when any prescription drug product, whether it be
brand or generic, comes to market. The Access to Life-Saving
Medicines Act does provide the FDA with that discretion.
CalPERS is proud and honored to add our support to the
growing list of workers, seniors, patient groups, businesses,
health plans, health care providers, pharmacy benefit managers
and countless others who support the Access to Life-Saving
Medicines Act to open the door to biogeneric competition. We
stand ready to work with the Committee to pass legislation to
give FDA the authority to approve safe and effective
biogenerics as a means to providing consumers with affordable
alternatives to high-cost biopharmaceuticals. Thank you for the
opportunity to provide testimony for the hearing record.
----------
Statement of Coalition for a Competitive Pharmaceutical Market
Thank you Chairman Pallone, Congressman Deal, and members
of the Subcommittee on Health. The Coalition for a Competitive
Pharmaceutical Market (CCPM) appreciates the opportunity to
submit this statement to the hearing record. We commend you for
holding this important hearing on the need to establish a
workable, safe and science-based regulatory pathway within the
Food and Drug Administration (FDA) for the approval of
biogeneric products.
Background
CCPM is an organization of employers, health plans,
pharmacy benefit managers, chain drug stores, generic drug
manufacturers, and others committed to a competitive
pharmaceutical market that expands access to affordable
prescription medications. To achieve this outcome, we believe
we must remove barriers to competition and choice that generic
drugs bring to the market. We also need to develop new pathways
to bring that same competition to the marketplace as it relates
to biopharmaceuticals. Monopolies, such as what currently exist
in this arena, are not only detrimental from a consumer and
business perspective, they actually remove incentives for
innovation. This helps explain our commitment to the
establishment of a workable pathway for biogenerics.
As employers, including some of the Nation's largest
manufacturers, it is imperative that our employees have access
to safe and affordable prescription medications for two
reasons. First, a healthy and productive workforce is critical
to our ability to compete in a global economy. Second, the high
cost of health care is limiting our ability to compete with
other nations, and pharmaceuticals are the single fastest
growing segment of overall health care costs. As health plans
and pharmacy benefit managers, access to safe and affordable
prescription medications is critical to our ability to slow the
rate of growth in health insurance premiums for businesses and
consumer out-of-pocket costs. As chain drug stores, we are on
the front line as witnesses to the impact of high-cost
prescription drugs on consumers. Finally, as generic drug
manufacturers, we are committed to producing safe and
affordable generic alternates to employers and consumers. Our
membership is diverse, but we are united in our belief that a
definitive regulatory pathway for the approval of biogenerics
is critical to improving our Nation's health and controlling
prescription drug costs.
View on Prescription Drug Marketplace
CCPM strongly supports a vigorous and competitive
prescription drug market, one in which innovation leads to new
life-saving medicines. Currently competition is limited in the
biopharmaceutical market because the FDA does not have the
clear authority to approve biogeneric products. As a result,
even when a patent has expired on a brand biopharmaceutical,
the lack of a pathway thwarts competition, and keeps
biopharmaceutical prices artificially high. CCPM urges Congress
to find a bipartisan solution to create an appropriate
regulatory route for FDA review of biogenerics. We believe the
solution should grant the FDA the authority to use its
discretion and scientific expertise to evaluate interchangeable
and comparable biogeneric products while ensuring patient
safety.
Hatch-Waxman Law
One of the most important health care laws enacted over the
past 30 years was the Drug Price Competition and Patent Term
Restoration Act of 1984--commonly known as the Hatch-Waxman
law. This landmark legislation broke important new ground in
granting FDA the authority to approve generic versions of
prescription products. Hatch-Waxman also gave FDA express
authority to provide an abbreviated approval process for those
products deemed equivalent to the prior approved product. It is
estimated that this law saves patients and payers billions of
dollars each year. We believe that bipartisan legislation
introduced this year by Representatives Waxman and Emerson,
H.R. 1038, the Access to Life-Saving Medicine Act, is an
important next step in ensuring that biologic prescription
drugs are more affordable and accessible. CCPM supports this
important legislation, which will provide the clear authority
that the FDA needs to approve biogenerics and bring much-needed
competition to the biopharmaceutical market.
Consumers and Purchasers Will Benefit With Greater Innovation and
Greater Competition
Total spending on prescription drugs in 2006 is estimated
at $213.7 billion and is expected to rise to $497.5 billion by
2016. \1\
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1 Poisal, J.A., et al, ``Health Spending Projections Through 2016:
Modest Changes Obscure Part D's Impact'', Health Affairs 26, no. 2
(2007) Exhibit 6.
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The use of biopharmaceuticals is increasing at almost
twice the rate of traditional medicines accounting for
approximately $30 billion in U.S. sales and 12 percent of total
pharmaceutical usage last year. \2\
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2 MedAdNews, November 2006 .
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The reason for the dramatic increase becomes clear when
one examines the cost biopharmaceuticals compared to synthetic
drugs. The average cost of a biopharmaceutical is $45 per
patient per day, versus $1.66 per patient per day for a
synthetic drug. These medicines can and do improve the lives of
millions of patients--but without generic versions, the costs
may keep needed treatments out of the hands of many consumers.
Providers of prescription drug coverage, both in the
private sector as well as the Federal Government through
programs such as Medicare and Medicaid, depend heavily on the
role of generic products to help control costs. The lack of
certainty in the prescription drug marketplace, particularly in
the biopharmaceutical sector, poses great challenges to payers.
Forecasting future health care expenditures remains difficult
because there is no clear timeline for when or even if there
will be lower cost alternatives for biopharmaceuticals. Many of
the biopharmaceuticals on the market today are ``off-patent''
and more than $10 billion worth of biopharmaceuticals are
expected to come off patent by 2010, \3\
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3 Engel & Novitt, LLP, ``Potential Savings That Might Be Realized
by the Medicare Program From Enactment of Legislation Such as The
Access to Life-Savings Medicine Act (H.R. 6257/S. 4016) That
Establishes A New cBLA Pathway For Follow-On Biologics. Table 4a. ,
January 2, 2007 so the sooner these lower cost biogenerics can enter
into the marketplace, the better. Additionally, when exploring avenues
to introduce competition into the marketplace, CCPM urges Congress to
clearly outline a reasonable process for early resolution of patent
disputes to avoid any unintended loopholes and ensure certainty for the
biogeneric marketplace.
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Guiding Principles for Bipartisan Legislation
When considering legislation to provide a clear regulatory
pathway for the approval of biogenerics, CCPM encourages
Congress to consider five key principles:
1. Protect and promote fair and open competition. CCPM
members are leaders within their industries, and highly
competitive. Several Coalition members are patent holders, and
as such, respect and understand the development of innovation
and need for patent protections. However, we strongly believe
that once a patent expires or is successfully challenged,
biogeneric competition should be able to enter the market.
2. Provide a definitive pathway for the approval of
biogenerics. We believe there must be certainty in both timing
and method of the biogeneric approval process. FDA needs the
authority to approve both comparable and interchangeable
biogeneric products. Congressional deference to the FDA's
expert scientific judgment is appropriate. In addition, any
action should permit prescribers and pharmacists to substitute
one biologic for another when appropriate.
3. Encourage consistent and uniform terminology. Whether
the terms are ``comparable,'' ``interchangeable,''
``therapeutic equivalent,'' or ``generic''--we want an
abbreviated process that results in a ``biogeneric,'' meaning a
lower cost alternative to biologic pharmaceuticals.
4. Increase resources for the Food and Drug
Administration.In order to adequately assume these new
responsibilities, the FDA will need adequate resources. We
support additional resources for FDA to secure more staff to
ensure the timely review of biogeneric applications and the
safety of biogenerics for consumers.
5. Include the new legal authority for a biogeneric
pathway in must-pass legislation this year.
We encourage Congress to move quickly to establish a
regulatory pathway for the approval of biogenerics. We are
confident this hearing will affirm the science for comparable
and interchangeable products has arrived. Once the FDA has the
discretionary authority to begin this process, it will drive
innovation that will assist in the identification of similar
and substitutable methods for these off-patent products. Each
day that passes without biogenerics is another day of limited
options. No payer, whether individual or employer, public or
private, can afford unlimited monopoly pricing. CCPM is
encouraged to hear reports that members are committed to
including a workable pathway in FDA Revitalization efforts,
including the prescription drug reauthorization legislation
(PDUFA) and strongly support you in this endeavor.
CCPM is pleased that the Energy and Commerce Health
Subcommittee is considering issues like biogenerics that can
make a positive impact on our health care system. We believe a
bipartisan bill that empowers the FDA to use the best science
to encourage innovation and biogeneric competition should be
passed this year. The Waxman-Emerson-Pallone bill certainly
meets this standard and, as such, CCPM has called for--and is
urging--its passage. However, like the sponsors of this
legislation, we well understand that there will be compromises
to make before any bill is signed into law. What must not be
compromised is safety as well as a workable, science-based
pathway to provide competition and choice to consumers,
employers, health plans and Federal, state, and local
purchasers of pharmaceuticals. The very act of holding this
hearing represents an important step to achieving this outcome
and ending the unsustainable monopoly that currently exists. We
commend you, Chairman Pallone, for taking this step and we look
forward to working with you and all the other members of the
Subcommittee and full Committee on this important issue.
Coalition for Competitive Pharmaceutical Marketplace (CCPM) Membership
April 2007
Aetna Inc, America's Health Insurance Plans, Apotex, Barr
Laboratories, Ben Venue Laboratories, Blue Cross Blue Shield
Association, Caremark, Caterpillar, Inc., DaimlerChrysler
Corporation, Eastman Kodak Company, Express Scripts, Ford Motor
Company, General Motors Corporation, Generic Pharmaceutical
Association, Hospira, Humana, Kaiser Permanente, Medco, Mylan
Labs, National Association of Chain Drug Stores, National
Association of Health Underwriters, Pharmaceutical Care
Management Association, Ranbaxy Pharmaceuticals, Teva
Pharmaceuticals USA, Wallgreens Company , Watson
Pharmaceuticals, Wellpoint
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May 23, 2007
David Schenkein, M.D.
Vice President
Clinical Hematology/Oncology
Genentech
1 DNA Way
South San Francisco, CA 94080
Dear Dr. Schenkein:
Thank you for appearing before the Subcommittee on Health
on Wednesday, May 2, 2007, at the hearing entitled ``Assessing
the Impact of a Safe and Equitable Biosimilar Policy in the
United States.'' We appreciate the time and effort you gave as
a witness before the Subcommittee on Health.
Under the Rules of the Committee on Energy and Commerce,
the hearing record remains open to permit Members to submit
additional questions to the witnesses. Attached are questions
directed to you from certain Members of the Committee. In
preparing your answers to these questions, please address your
response to the Members who have submitted the questions and
include the text of the Member(s question along with your
response. In the event you have been asked questions from more
than one Member of the Committee, please begin the responses to
each Member on a new page.
To facilitate the printing of the hearing record, your
responses to these questions should be received no later than
the close of business Friday, June 1, 2007. Your written
responses should be delivered to 316 Ford House Office Building
and faxed to 202-225-5288 to the attention of Melissa Sidman,
Legislative Clerk/Public Health. An electronic version of your
response should also be sent by e-mail to Ms. Melissa Sidman at
[email protected] in a single Word formatted
document.
Thank you for your prompt attention to this request. If
you need additional information or have other questions, please
contact Melissa Sidman at (202) 226-2424.
Sincerely,
John D. Dingell
Chairman
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Responses to Questions from May 2, 2007, House Energy & Commerce,
Health Subcommittee Hearing, Dr. David Schenkein, Genentech, Inc.
The Honorable Edolphus Towns
A protein that was recently approved under the 505(b) 2
pathway, Omnitrope, contains a rating indicating that FDA has
not evaluated sufficient data to justify a finding of
interchangeability. In addition, you have recently testified it
will take at least another ten years to establish standards of
interchangeability for biological products. Since it appears
that there is a huge gap in our understanding of how to
demonstrate interchangeability of follow-on protein products,
it might be advisable to allow physicians to make decisions
based on their patients' specific clinical situations. Would
you agree?
Yes. Given that follow-on versions of biological products
cannot be identical to or the same as the innovator product
they seek to emulate, only treating physicians should be
allowed to make decisions regarding the interchangeability of
products. They should not substitutable at the pharmacy level.
Given the greater complexities of biologics compared to
smaller molecules, it seems logical that we establish a pre-
approval requirement for clinical data with follow-on protein
products.-- Would you agree that, based on state-of-the-art
science, FDA could not approve a follow-on protein product
without clinical data?
Yes, I agree. Again, given the fact that follow-on
biological products cannot be scientifically the same as the
innovator product, it is necessary to test them independently
in clinical trials to assure their safety and efficacy.
The Honorable Anna Eshoo
Representative Waxman's legislation provides no market
exclusivity to innovator products--zero years. Representative
Inslee's bill provides 14 years of market exclusivity. In the
Senate, one of Senator Kennedy's draft proposals affords 10
years of market exclusivity to innovator products. For
comparison, the European Union allows a total of 11 years of
innovator exclusivity. In the U.S., pharmaceutical drugs
(pills) are allowed 5 years of exclusivity plus 3 years for new
uses of approved drugs under Hatch-Waxman.
What factors (e.g. expense, risk, length of Research and
Development period, patent protections) must Congress take into
account in arriving at the ``right'' number?
All of these factors need to be taken into consideration
for Congress to arrive at the ``right number.'' As you are
aware, the research and development cycle of biological
products is lengthy, costly and risky. In addition, given that
the approval standard for a follow-on biologic will necessarily
be based on ``similarity'' or ``comparability'' and not
``sameness,'' we are concerned that the patent protections
afforded innovators may not be sufficiently protective to
ensure an adequate return on our investment. Specifically,
follow on manufacturers may engineer around our patents, yet
still gain FDA approval for a product that is ``similar'' or
``close'' to the innovator product. If this is the case, then
follow on companies could theoretically piggy back on an
innovator's investment once the innovator product goes to
market. To ensure that companies such as Genentech are able to
continue to invest in researching and developing life-saving
therapies, Congress should construct a system that guarantees a
sufficient amount of time during which our invention and data
are protected. The legislative history of Hatch-Waxman
indicates that Congress contemplated that 14 years is the
intended period of effective patent life for a small molecule,
whether achieved through patent protection, data exclusivity,
patent term restoration, or a combination of all 3. As such, we
believe that the same 14 years should be applicable to
innovator biologics; however, the only true way to guarantee
such time is through data exclusivity.
Genentech has 14 products on the market today. How
important is market exclusivity for the average biotech
company, which typically has only a few, if any, approved
products in its portfolio?
Extremely important. Every company needs the assurance of
an appropriate amount of time during which to recoup the
investment made in R&D.
How does this system affect academic and medical research
centers, such as Stanford University and the University of
California, who are also patent holders? Any final bill must
assure appropriate patent notification provisions to ensure
that academic and medical research centers have sufficient
notice in order to protect their own intellectual property
rights. Without notification procedures, these institutions
could unwittingly be denied the opportunity to protect their
inventions, either through entering into licensing agreements
or through litigation.
Assuring the safety and efficacy of all drugs is my #1
priority in this debate.
Why is it important for a follow-on manufacturer to
conduct post-market studies to ensure the safety of their
products?
Given that follow-on biologic products are, by definition,
different than the innovator product, it is extremely important
that the FDA have the authority to require post-marketing
studies of the follow-on applicant in order to ensure the on-
going safety of the product once it is marketed and available
for use.
In constructing a follow-on biologics pathway, should
Congress limit FDA's ability to impose post-market studies on
follow-on biologics manufacturers?
No. The FDA should have the authority to require post-
marketing studies of both follow-on and innovator companies.
If a generic drug manufacturer were to submit an
application for a follow-on version of a breakthrough cancer
biologic, and that follow-on was not clinically tested:
As a physician, would you be comfortable having your
patients switched from a biological product that you have
prescribed, to a follow-on product? Would you want your mother
or child to receive a follow-on biologic?
No, I would not. Again, given that follow-on products are
by definition different than the innovator they seek to
replicate, it is critical that the follow-on product be
independently tested to assure its safety and efficacy. As a
physician, I would not prescribe a follow on product that had
not been independently tested, as I could not be certain it was
safe to do so.
What types of risks to patient safety does mandatory
interchangeability present with respect to biologics? Do
generic drugs (pills) possess these same risks?
There are significant risks to the patient in the context
of mandatory interchangeability between follow-on and innovator
products. Since the products are not identical, unlike small
molecule generics, they should not be treated as such. Rather,
only treating physicians should be empowered to make decisions
about which drugs to prescribe his or her patients, whether a
follow-on or innovator product. Generic pills (small molecules)
are shown to be identical to their innovator counterpart. As
such, the FDA is able to allow the safe interchangeability of
generics in this context because the innovator counterpart has
been proven to be safe and effective. In this case, the follow-
on and innovator product cannot be the same and should be not
deemed to be interchangeable by the FDA or a pharmacist. Only a
treating physician should make such a determination.