[Pages S10655-S10658]
From the Congressional Record Online through the Government Publishing Office [www.gpo.gov]

FDA APPROVAL OF BUPRENORPHINE/NALOXONE

Mr. LEVIN. Mr. President, last week, the fight against heroin
addiction took a major leap forward after a decade of struggle. On
October 8, 2002, the Food

[[Page S10656]]

and Drug Administration, FDA, announced the approval of a new anti-
addiction drug, buprenorphine/naloxone, which, followed with the
directives of a new law I authored along with Senators Hatch and Biden,
makes a dramatic change in the way America fights heroin addiction.
This new anti-addiction drug, developed under a Cooperative Research
and Development Agreement, CRADA, between the National Institute on
Drug Abuse, NIDA, and a private pharmaceutical company, has been the
subject of extensive successful research and clinical trials in the
United States. The new law, the Drug Addition Treatment Act of 2000,
permits, for the first time, such anti-addiction medications to be
dispensed in the private office of qualified physicians, rather than in
a centralized clinic. That change can have a revolutionary reduction in
the number of addicts, the crimes some of them commit, and the heroin
related deaths which have occurred.
This newly approved anti-addiction medication has already been in use
in France, where significant success has been achieved in getting
patients off of heroin, reducing drug-related crime and reducing
heroin-related deaths. For example, user crime in France and arrests
are down by 57 percent and there has been an 80 percent decline in
deaths by heroin overdose.
It is estimated that there are approximately 1 million individuals in
the U.S. who are addicted to heroin. The new office-based system is a
revolutionary change and will make our communities better and safer
places to live. It will open the door to tens of thousands of
individuals to get rid of their addiction, but are now unable to or are
reluctant to seek medical treatment at centralized methadone clinics,
where their appearance amounts to an announcement of their addiction
and which for many addicts are difficult to get to for their once or
twice a day use. According to a report by the Department of Health and
Human Services, many individuals who want to get rid of their addiction
will not go to centralized clinics, ``. . . because of the stigma of
being in methadone treatment. . . .'' The report went on to say that
HHS was:

. . . especially encouraged by the results of published
clinical studies of buprenorphine. Buprenorphine is a partial
mu opiate receptor agonist, in Schedule V of the Controlled
Substances Act, with unique properties which differentiate it
from full agonists such as methadone or LAAM. The
pharmacology of the combination tablet consisting of
buprenorhine and naloxone results in . . . low value and low
desirability for diversion on the street. Published clinical
studies suggest that it has very limited euphorigenic
affects, and has the ability to precipitate withdrawal in
individuals who are highly dependent upon other opioids.
Thus, buprenorphine and Buprenorphine/naloxone products are
expected to have low diversion potential . . . and should
incerase the amount of treatment capacity available and
expand the range of treatment options that can be used by
physicians.

The compelling need for this new system of treatment is borne out in
some astonishing data. A recent study by the U.S. Office of National
Drug Control Policy, ONDCP, released in January of this year, shows
that illegal drugs drain $160 billion a year from the American economy;
and that the majority of these costs, $98.5 billion, stem from lost
productivity due to drug-related illnesses and deaths, as well as
incarcerations and work hours missed by victims of crime. The report
found that illegal drug use cost the health-care industry $12.9 billion
in 1998. Commenting on the release of the study, ONDCP Director John P.
Walters said:

Drugs are a direct threat to the economic security of the
United States . . . and results in lower productivity, more
workplace accidents, and higher health-care costs, all of
which constrain America's economic output. Reducing substance
abuse now would have an immediate, positive impact on our
economic vitality. When we talk about the toll that drugs
take on our country, especially on our young people, we
usually point to the human costs: lives ruined, potential
extinguished, and dreams derailed. This study provides some
grim accounting, putting a specific dollar figure on the
economic waste that illegal drugs represent.

Another recent study, released in September of this year, determined
that the majority of drug offenders in our State prisons have no
history of violence or high-level drug dealing. The study found that of
the estimated 250,000 drug offenders in state prisons, 58 percent are
nonviolent offenders. The authors concluded that these nonviolent
offenders ``. . . represent a pool of appropriate candidates for
diversion to treatment programs . . . .'' They went on to say that
``The `war on drugs' has been overly punitive and costly and has
diverted attention and resources from potentially more constructive
approaches.''
Of the juveniles who land behind bars in State institutions, more
than 60 percent of them reported using drugs once a week or more, and
over 40 percent reported being under the influence of drugs while
committing crimes, according to a report from the Bureau of Justice
Statistics. Drug-related incarcerations are up and we are building more
jails and prisons to accommodate them, more than 1000 have been built
over the past 20 years. According to the July 14, 1999 Office of
National Drug Control Policy Update, ``Drug-related arrests are up from
1.1 million arrests in 1988 to 1.6 million arrests in 1997--steady
increases every year since 1991.''
In a September 3, 2001 interview with the New York Times, then-Drug
Enforcement Administration nominee Asa Hutchinson underscored the need
for drug rehabilitation for nonviolent offenders, saying that we are
``not going to arrest [our] way out of this problem.''
I believe that the system that we have finally put in place will
effectively put America on the right road to fighting and winning the
heroin addiction war. It has been a long and difficult road for over a
decade. First, in providing the resources to help speed the development
and delivery of anti-addiction drugs that block the craving for illicit
addictive substances. Second, authoring a law that would allow for such
medications to be dispensed in an office-based setting rather than
centralized clinics, by physicians who are certified in the treatment
of addiction. In 1996, the Senate adopted my amendment to the budget
resolution to steer $500 million over 6 years to the National Institute
on Drug Abuse, which resulted in substantial increases in funding for
research conducted by the National Institute on Drug Abuse. Then, in
1997, when Senator Moynihan and Senator Bob Kerrey joined me in
convening a panel of experts to present their expert views at a Drug
Forum on Anti-addiction Research, in an effort to assess the level of
progress and needed support to expedite new anti-addiction discoveries.
In October, 2000, the Drug Addiction Treatment Act, was enacted into
law. Today, we are taking a giant step forward with the Food and Drug
Administration's approval of this new anti-addiction drug, which will
allow for the appropriate and long awaited, conventional, office based
approach to addiction treatment in this country.

The protections in the new law against abuse are as follows:
Physicians may not treat more than 30 patients in an office setting;
appropriate counseling and other ancillary services must be offered.
Under this legislation the Attorney General may terminate a physician's
DEA registration if these conditions are violated and the program may
be discontinued altogether if the Secretary of HHS and Attorney General
determine that this new type of decentralized treatment has not proven
to be an effective form of treatment.
This great success would not have been possible without the
scientific genius, leadership and steadfast support of many
individuals, including, Dr. Alan Leshner, who, during his 7-year tenure
as Director of NIDA, energetically led the government initiated
partnership that produced buprenorphine/naloxone for the treatment of
heroin addiction; Dr. Frank Vocci, a brilliant scientist who heads up
Medications Development at NIDA and whose tutoring has led me to a
better understanding of the science of addiction; Dr. Charles Schuster
of Wayne State University, a past director of NIDA who has conducted
clinical trials on buprenorphine/naloxone, the results of which have
been presented in testimony before Congress. Dr. Schuster has been my
resource and my guide on this issue from the very beginning and his
advice and expertise continues today; Dr. James H. Woods, Director of
Drug Addiction Research Projects at the University of Michigan, has
long been a progressive force in the area of addiction research, and
has been an effective voice in the formulation of legislative policy in
the area of addiction

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both at home and abroad. Dr. Herbert Kleber, Professor of Psychiatry at
Columbia University and one of the Nation's foremost experts on drug
addiction and treatment, provided invaluable assistance to me in
putting together this new system of treatment. Dr. Chris-Ellyn
Johanson, President-elect of the College on Problems of Drug Dependence
and Professor in the Department of Psychiatry and Behavioral
Neuroscience at Wayne State University, has made major contributions to
understanding the basis of the buprenorphine therapeutic effects in the
treatment of heroin abuse and dependence; and Dr. Stephanie Meyers
Schim, former president of the Michigan Public Health Association, who
has helped us to understand that drug addiction is a public health
problem that is in crisis and that our health policies should reflect
this reality.
In closing, I would like to thank those who too often go unnoticed,
the Senate staff members who kept this legislation on track despite the
many twists and turns and the unforeseen challenges along the way. My
Deputy Legislative Director Jackie Parker, whose commitment and
diligence in moving this issue was characteristically unwavering. Bruce
Artim, who serves Senator Hatch on the Judiciary Committee and Marcia
Lee of Chairman Biden's Subcommittee on Crime and Drugs were undeterred
in their resolve to move all obstacles that came in the way of making
this new system of treatment a reality.
Finally, I ask unanimous consent that the remarks of Dr. James H.
Woods of the University of Michigan, Dr. Chris-Ellyn Johanson and Dr.
Charles R. Schuster of Wayne State University, and Dr. Herbert Kleber
of the New York State Psychiatric Institute, along with a list of
participants, be printed in the Record.
There being no objection, the material was ordered to be printed in
the Record, as follows:

Dr. James H. Woods, University of Michigan, Press Conference on Food
and Drug Administration (FDA) Approval of Buprenorphine/nx (BUP),
October 9, 2002

There are a variety of reasons for the scientific and
medical excitement today celebrating the approval of
buprenorphine for the pharmacotherapy of narcotic abuse. It
fits in what I hope will be a succession of new therapies for
drug abuse that will be employed under The Drug Addiction
Treatment Act to change the way we view addictions and how
they may be treated.
There are, of course, many different groups of individuals
who are responsible for this important day. We need to show
our considerable appreciation to Senators Levin, Hatch, and
Biden for their support for The Drug Addiction Treatment Act.
Having worked most with Sen. Levin, I know that he has been
long interested in the important problem of drug abuse. He
has visited us at the University to see firsthand what we
were up to in evaluating different, novel approaches to
pharmacotherapy of drug abuse. He has kept the problems of
developing these therapies in mind and has worked long and
hard to bring this legislation into being. I know the Senator
believes fervently that buprenorphine's approval is going to
produce some major changes in the treatment of narcotic abuse
because of the ways that it will be used in conjunction with
The Drug Addiction Treatment Act. I wholeheartedly agree and
I hope what we are seeing today with buprenorphine will be
replicated with increasing frequency in the future.
In my opinion, we will see the individual physician taking
an increasingly important role in dealing with narcotic
addiction in a different way. They will be dealing with
individuals who would not otherwise present themselves for
the kinds of treatment currently available. Those who prefer
the privacy of individual physician treatment can be allowed
that privilege with this new medication for it is very, very
safe. When we consider that 5 of 6 narcotic abusers are not
in treatment, it is clear that this new approach to therapy
is sorely needed.
We need to show our appreciation to the National Institute
on Drug Abuse and their efforts toward medications
development. Were it not for their support in developing
buprenorphine, we would not be having this meeting today.
They have supported strongly both the effort to move
buprenorphine along towards this drug abuse indication, and
related research toward the development of other much needed
therapies in the field of drug abuse. Thus, knowing a bit
about what they have in mind for the future, I think we will
be seeing more of these meetings.
We need to thank the firm, Reckitt Benckiser, for
sponsoring buprenorphine. It was clear early in the study of
buprenorphine that it might have potential as a
pharmacotherapy. This has been demonstrated quite well. The
drug has been fascinating to opioid pharmacologists ever
since it was made public, and its interesting pharmacological
properties were described. Though some of its pharmacology
remains elusive to us, it is clear that we may have happened
upon just the right molecule for opioid abuse treatment. Our
Narcotic Center Grant at the University, funded by NIDA for
some 30 years, has had the objective of improving upon some
of the effects of buprenorphine. We have made and studied
extensively hundreds of chemical relatives and found many
compounds comparable to buprenorphine, but none superior to
it in safety or duration of action. Thus, we believe that
buprenorphine is a substance that will be the best of its
kind for this type of therapy.
I appreciate the concert of effort that it takes to bring
this new type of attention to the problem of drug abuse. It
is only with the combined legislative, governmental,
pharmaceutical, and scientific efforts that these problems
will be dealt with effectively.
____

Dr. Chris-Ellyn Johanson, Wayne State University, Press Conference on
Food and Drug Administration (FDA) Approval of Buprenorphine/nx (BUP)

My name is Chris-Ellyn Johanson and I am a professor in the
Department of Psychiatry and Behavioral Neurosciences at
Wayne State University and the incoming president of the
College of Problems of Drug Dependence. When I joined the
Wayne State faculty in 1995, I was fortunate enough to become
a part of a research center at the University of Michigan,
headed by Dr. James Woods and funded by the National
Institute on Drug Abuse. This center is devoted to the
development of safer and better opiate drugs and has been
continuously funded by the National Institute on Drug Abuse
for over 30 years. My research has focused on trying to
understand how buprenorphine exerts its therapeutic effects
in the treatment of heroin abuse and dependence.
I have been fortunate to work in collaboration with Jon-Kar
Zubieta, also from the University of Michigan, using state-
of-the-art neuroimaging techniques in conjunction with
behavioral measures to understand the biobehavioral basis of
the therapeutic efficacy of buprenorphine. Our studies have
clearly demonstrated that because buprenorphine's unique
pharmacology as a partial mu agonist, it can block the
dependence-related effects of heroin-like drugs and in many
ways combines the characteristics of the agonist treatment
agent methadone and the antagonist treatment, naltrexone.
Further, its pharmacology makes it a drug with a long
duration of action and a remarkable margin of safety.
So I am very pleased to be here today to welcome
buprenorphine into the armamentaria for the treatment of
heroin addiction. Not only will buprenorphine allow the
expansion of treatment options for clinicians, but because of
the legislation sponsored by Senator Levin to allow office-
based practice for drugs such as buprenorphine, this option
will be available to an increased number of opiate-dependent
patients. I want to personally thank Senator Levin and his
staff for their efforts in promoting more rationale treatment
for heroin addiction. The Drug Abuse Treatment Act of 2000,
which allows qualified physicians to treat opiate addicts in
their office, brings the treatment of heroin addiction into
mainstream medicine. This will not only increase the
availability of treatment but will as well destigmatize it.
Without this legislation, buprenorphine's unique advantages
could not be effectively utilized.
I would also like to thank Senator Levin and his staff on
behalf of the College on Problems of Drug Dependence. One of
the major goals of this scientific organization, which has
been in existence since 1929, is the development of safer and
more useful medications for the treatment of addiction,
including heroin dependence. Most of the scientists who have
been responsible for the development of buprenorphine are
members of this organization and have presented their
findings with buprenorphine at its annual scientific meeting.
Because of this, CPDD has been very involved in pushing for
the approval of buprenorphine and has been appreciative of
the help of Senator Levin in getting approval.
____

Dr. Charles R. Schuster, Wayne State University

My name is Charles R. Schuster and I am a Professor of
Psychiatry and Behavioral Neuroscience at the Wayne State
University School of Medicine.
I am extremely excited by the news that the Food and Drug
Administration has approved the marketing of two
buprenorphine preparations, Subutex and Suboxone, for the
treatment of opiate dependence. These products are the first
to be available in a new model of office-based treatment of
opiate dependence allowed under the Drug Abuse Treatment Act
of 2000. We can thank Senator Levin for his incredible
thoughtfulness and tenacity in fighting to get this
legislation through Congress.
One of the major advances that has been made in the past
several years by a joint effort between Reckitt-Benckiser
Pharmaceutical company and the National Institutes on Drug
Abuse/NIH is the development of buprenorphine for the
treatment of opiate addition. I am privileged to have had a
role in the development of this safe, effective treatment
both during my tenure as the Director of NIDA and
subsequently as a NIDA

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grantee. Under the auspices of a NIDA funded treatment
research project I have utilized buprenorphine as a
maintenance therapy and have been very impressed not only
with its effectiveness in curtailing heroin use, but as well
with its acceptance by patients who would not have considered
treatment with methadone. Thus this medication may reach
opiate addicts who currently are resistant to enrollment in
opiate maintenance programs that use ORLAAM and methadone. I
have letters on my desk from patients whose lives have been
turned around by the buprenorphine maintenance treatment we
have provided them. I have even more letters from opiate
addicted people who are asking where they can find such
treatment. Because of the approval by the FDA of two
buprenorphine preparations and the passage of the Drug Abuse
Treatment Act of 2000, it is now possible to give the answer.
Find a qualified physician in your area of the country and be
seen as a regular patient in their office receiving a
prescription for buprenorphine. Tragically, I see young
people every day who are in need of medications to ease their
need for heroin so that they can become invested in
rehabilitation activities that can return their life
trajectory to a normal, productive and fulfilling course.
Currently the available medications, methadone and ORLAAM,
are extremely useful but ensnared in regulations that grossly
limit their potential effectiveness. Having a safe, effective
narcotic preparation like buprenorphine that can be used by
qualified physicians for the treatment of opiate addition
that is unfettered by the methadone regulations is a major
advance in our ability to provide badly needed services in a
cost effective manner.
I am very proud as a resident of the state of Michigan to
have Senator Levin as my representative in the United States
Senate. He and his staff have worked tirelessly to secure the
passage of the Drug Abuse Treatment Act of 2000. This
landmark legislation represents a major shift in policy in
how we view and treat the problem of opiate addition. This
advance in our policies regarding the treatment of opiate
addition has been a long time in coming. But thanks to the
efforts of Senator Levin, it has finally arrived. I join in
celebrating this achievement which has the potential for
providing significant help to those attempting to overcome
the ravages of opiate addition. Individuals seeking help for
their opiate addition do not have much political power and
are rarely heard in drug abuse policy debates. Fortunately
for them they have a compassionate and steadfast advocate in
Senator Levin.
____

Remarks of Dr. Herbert Kleber at Press Conference on FDA Approval of
Buprenorphine/NX

Today marks an important milestone in the treatment of
substance dependence disorders. Buprenorphine, both in the
combined form with antagonist naloxone and in the mono-form,
have just been approved by the Food and Drug Administration,
the first therapies approved for in-office prescribing under
the Federal Drug Addiction Treatment Act of 2000. The path
has been a long and at times torturous one but a careful one.
It can hardly be described as a rush to market: my first
research paper on buprenorphine was published in 1988 and
colleagues had published earlier. During this decade and a
half we have learned much about this agent and it's potential
for the treatment of narcotic addition. I am very grateful
for the help from certain key senators, both in passing the
Drug Addition Treatment Act and for their continued
encouragement during this long and difficult process. Senator
Carl Levin of Michigan has been a special stalwart in this
process but the effort has truly been a bipartisan one with
Senators Orrin Hatch of Utah and Joseph Biden of Delaware
both playing active roles along with Senator Levin.
The importance of this day, however, is much more than the
particular medications involved. Buprenorphine to be sure
should help in combating opioid dependence in formerly
underserved communities. It is estimated that there are up to
1 million opioid dependent individuals in the United States
of whom less than 200,000 are in treatment. The annual cost
to society of opioid addiction is more than 20 billion
dollars. Buprenorphine may increase the likelihood of people
who have not currently sought out treatment to do so, thus
reducing the enormous toll, both in health and in crime, that
addiction takes on society. Injecting drug users and their
sexual partners, for example, have become the largest new
group of individuals becoming HIV positive. While
buprenorphine is neither a panacea nor a magic bullet, it
has major advantages in terms of safety, duration of
action, and ease of withdrawal in comparison to existing
medications on the market. That plus the ability to be
treated in the privacy of the doctor's office are all
important advances.
The major importance of the FDA approval and the Drug Abuse
Treatment Act, however, go well beyond the particular
medications and instead to how we think about addiction.
Papers by myself and my colleagues have emphasized that
opioid dependence as with other addictions is a chronic
relapsing disorder, not a character flaw, failure of will, or
lack of self-control. These drugs change our brains, changes
that can persist long after the individual has stopped taking
the drug and lead frequently to relapse. When a patient who
cannot stop smoking on his own seeks help from his physician,
he is seen as a patient who needs help and the physician will
respond with a variety of medications and behavioral
interventions. Likewise, it is my hope that with the advent
of these medications the treatment of opioid dependence will
be able to be mainstreamed. Individuals who are dependent
either on street opioids like heroin or on prescription
opioids will be able to receive help in doctors' offices and
medical clinics. They will hopefully one day be treated with
the same dignity with which we treat the patient trying to
give up smoking or the diabetic or the hypertensive, all
individuals that have chronic relapsing disorders involving
both physical and behavioral components.
Addiction is initiated by a voluntary act but this initial
voluntary behavior is in many cases shaped by pre-existing
genetic factors and there are early brain changes, which may
evolve into compulsive drug taking less subject to voluntary
control. It is important to recognize, however, that drug
dependence erodes but does not erase a dependent individual's
responsibility for control of their behavior. Many patients
with other chronic illnesses fail to see the importance of
their symptoms and thus may ignore physician's advice, fail
to comply with medication, and engage in behaviors that
exacerbate their illnesses. While such patients may not be as
disruptive, demanding, or manipulative as alcohol or drug
dependent patients, the patterns of denial of symptoms,
failure to comply with medical care and subsequent relapse
are not particular to addiction. One thing, however, that
does separate addiction from other illnesses is the waiting
list for treatment throughout the United States which
contradicts assertions that addicted persons do not want
help.
Compassion or sympathy is not the basis for the argument
that physicians should treat addicted individuals. Medically
oriented treatments can be quite effective. In addition,
addiction treatments have been effectively combined with
legal sanctions such as drug courts and court-mandated
treatments. Medical interventions should be taught in medical
schools and primary care residencies. If physicians develop
and apply the skills available to diagnose, treat, monitor,
and refer patients in the early stages of substance
dependence, there will be fewer late-stage cases.
I have been involved in treatment and research with
substance dependent individuals for over 35 years, initially
at Yale University and the last decade at Columbia
University. In between I spent approximately 2\1/2\ years as
the Deputy Director of the Office of National Drug Control
Policy under Bill Bennett and the first President Bush. The
new era in office-based treatment of opioid dependence is a
worthy successor to efforts made by our Office back in the
early 1990's to expand the number of individuals in treatment
with substance dependence. My appreciation--and that of many
future patients--to the legislators and federal agencies that
made this possible.
Thank you.
____

Press Conference Participants, FDA Approval of Buprenorphine/Naloxone,
October 9, 2002, SR 236

Senator Carl Levin.
Senator Orrin Hatch.
Dr. Frank Vocci, Director of the Division of Treatment
Research and Development, National Institute on Drug Abuse.
Dr. Steven K. Galson, Deputy Director, Food and Drug
Administration's Center for Drug Evaluation and Research.
Dr. Wesley Clark, Director, Center for Substance Abuse
Treatment, Substance Abuse and Mental Health Services
Administration.
Dr. Herbert D. Kleber, Professor of Psychiatry and
Director, Division of Substance Abuse, Columbia University.
Dr. James H. Wood, Professor, Department of Psychology and
Pharmacology and Director of Drug Addiction Research
Projects, University of Michigan.
Dr. Chris-Ellyn Johanson, Professor of Psychiatry and
Associate Director of Substance Abuse Research, Wayne State
University.
Dr. Charles Schuster, Professor of Psychiatry and
Behavioral Neuroscience, Wayne State University.

____________________