[House Hearing, 113 Congress]
[From the U.S. Government Publishing Office]
EXAMINING DRUG SHORTAGES AND RECENT EFFORTS TO ADDRESS THEM
=======================================================================
HEARING
BEFORE THE
SUBCOMMITTEE ON HEALTH
OF THE
COMMITTEE ON ENERGY AND COMMERCE
HOUSE OF REPRESENTATIVES
ONE HUNDRED THIRTEENTH CONGRESS
SECOND SESSION
__________
FEBRUARY 10, 2014
__________
Serial No. 113-117
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
Printed for the use of the Committee on Energy and Commerce
energycommerce.house.gov
______
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COMMITTEE ON ENERGY AND COMMERCE
FRED UPTON, Michigan
Chairman
RALPH M. HALL, Texas HENRY A. WAXMAN, California
JOE BARTON, Texas Ranking Member
Chairman Emeritus JOHN D. DINGELL, Michigan
ED WHITFIELD, Kentucky FRANK PALLONE, Jr., New Jersey
JOHN SHIMKUS, Illinois BOBBY L. RUSH, Illinois
JOSEPH R. PITTS, Pennsylvania ANNA G. ESHOO, California
GREG WALDEN, Oregon ELIOT L. ENGEL, New York
LEE TERRY, Nebraska GENE GREEN, Texas
MIKE ROGERS, Michigan DIANA DeGETTE, Colorado
TIM MURPHY, Pennsylvania LOIS CAPPS, California
MICHAEL C. BURGESS, Texas MICHAEL F. DOYLE, Pennsylvania
MARSHA BLACKBURN, Tennessee JANICE D. SCHAKOWSKY, Illinois
Vice Chairman JIM MATHESON, Utah
PHIL GINGREY, Georgia G.K. BUTTERFIELD, North Carolina
STEVE SCALISE, Louisiana JOHN BARROW, Georgia
ROBERT E. LATTA, Ohio DORIS O. MATSUI, California
CATHY McMORRIS RODGERS, Washington DONNA M. CHRISTENSEN, Virgin
GREGG HARPER, Mississippi Islands
LEONARD LANCE, New Jersey KATHY CASTOR, Florida
BILL CASSIDY, Louisiana JOHN P. SARBANES, Maryland
BRETT GUTHRIE, Kentucky JERRY McNERNEY, California
PETE OLSON, Texas BRUCE L. BRALEY, Iowa
DAVID B. McKINLEY, West Virginia PETER WELCH, Vermont
CORY GARDNER, Colorado BEN RAY LUJAN, New Mexico
MIKE POMPEO, Kansas PAUL TONKO, New York
ADAM KINZINGER, Illinois JOHN A. YARMUTH, Kentucky
H. MORGAN GRIFFITH, Virginia
GUS M. BILIRAKIS, Florida
BILL JOHNSON, Ohio
BILLY LONG, Missouri
RENEE L. ELLMERS, North Carolina
_____
Subcommittee on Health
JOSEPH R. PITTS, Pennsylvania
Chairman
MICHAEL C. BURGESS, Texas FRANK PALLONE, Jr., New Jersey
Vice Chairman Ranking Member
ED WHITFIELD, Kentucky JOHN D. DINGELL, Michigan
JOHN SHIMKUS, Illinois ELIOT L. ENGEL, New York
MIKE ROGERS, Michigan LOIS CAPPS, California
TIM MURPHY, Pennsylvania JANICE D. SCHAKOWSKY, Illinois
MARSHA BLACKBURN, Tennessee JIM MATHESON, Utah
PHIL GINGREY, Georgia GENE GREEN, Texas
CATHY McMORRIS RODGERS, Washington G.K. BUTTERFIELD, North Carolina
LEONARD LANCE, New Jersey JOHN BARROW, Georgia
BILL CASSIDY, Louisiana DONNA M. CHRISTENSEN, Virgin
BRETT GUTHRIE, Kentucky Islands
H. MORGAN GRIFFITH, Virginia KATHY CASTOR, Florida
GUS M. BILIRAKIS, Florida JOHN P. SARBANES, Maryland
RENEE L. ELLMERS, North Carolina HENRY A. WAXMAN, California (ex
JOE BARTON, Texas officio)
FRED UPTON, Michigan (ex officio)
(ii)
C O N T E N T S
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Page
Hon. Joseph R. Pitts, a Representative in Congress from the
Commonwealth of Pennsylvania, opening statement................ 1
Prepared statement........................................... 2
Hon. Michael C. Burgess, a Representative in Congress from the
State of Texas, opening statement.............................. 3
Hon. Frank Pallone, Jr., a Representative in Congress from the
State of New Jersey, opening statement......................... 4
Hon. Marsha Blackburn, a Representative in Congress from the
State of Tennessee, opening statement.......................... 5
Hon. Fred Upton, a Representative in Congress from the State of
Michigan, prepared statement................................... 55
Hon. Henry A. Waxman, a Representative in Congress from the State
of California, prepared statement.............................. 57
Witnesses
Marcia Crosse, Director, Health Care, Government Accountability
Office......................................................... 6
Prepared statement........................................... 8
Answers to submitted questions............................... 59
Douglas C. Throckmorton, Deputy Director of Regulatory Programs,
Center for Drug Evaluation and Research, Food and Drug
Administration, Department of Health & Human Services.......... 21
Prepared statement........................................... 23
Answers to submitted questions............................... 71
Submitted Material
Chart, ``Number of active drug shortages,'' 2007 to June 30,
2013, Government Accountability Office analysis of University
of Utah Drug Information Service data, submitted by Mr. Shimkus 48
EXAMINING DRUG SHORTAGES AND RECENT EFFORTS TO ADDRESS THEM
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MONDAY, FEBRUARY 10, 2014
House of Representatives,
Subcommittee on Health,
Committee on Energy and Commerce,
Washington, DC.
The subcommittee met, pursuant to call, at 2:00 p.m., in
room 2123, Rayburn House Office Building, Hon. Joseph R. Pitts
(chairman of the subcommittee) presiding.
Members present: Representatives Pitts, Burgess, Shimkus,
Blackburn, Guthrie, Griffith, Ellmers, Pallone, Dingell,
Barrow, and Christensen.
Staff present: Clay Alspach, Chief Counsel, Health; Gary
Andres, Staff Director; Sean Bonyun, Communications Director;
Matt Bravo, Professional Staff Member; Noelle Clemente, Press
Secretary; Paul Edattel, Professional Staff Member, Health;
Sydne Harwick, Legislative Clerk; Carly McWilliams,
Professional Staff Member, Health; Katie Novaria, Professional
Staff Member, Health; Heidi Stirrup, Health Policy Coordinator;
John Stone, Counsel, Health; Josh Trent, Professional Staff
Member, Health; Tom Wilbur, Digital Media Advisor; Ziky
Ababiya, Democratic Staff Assistant; and Eric Flamm, Democratic
FDA Detailee.
Mr. Pitts. The subcommittee will come to order. The Chair
will recognize himself for an opening statement.
OPENING STATEMENT OF HON. JOSEPH R. PITTS, A REPRESENTATIVE IN
CONGRESS FROM THE COMMONWEALTH OF PENNSYLVANIA
In recent years, we have seen a dramatic increase in the
number of drug shortages in the United States, particularly
with generic sterile injectable drugs. While the number of new
shortages dipped in 2012 and 2013, the total number of ongoing
shortages has continued to increase. This is unacceptable.
Numerous drugs have remained on FDA's shortage list for some
time. What is the Agency doing to help address these
situations?
Recent news reports have highlighted shortages of oncology
products, parenteral nutrition products and even common, yet
critically important, saline solutions. Such shortages lead to
delays in treatment, rationing of care and higher costs. They
can also pose greater risks to patients in the form of
medication errors and as providers are forced to seek
alternative treatments. Drug shortages are a very challenging
problem and it is clear that there is no simple solution. We
recognize the complicated nature of this issue as well as the
severity.
Last Congress, the subcommittee took action by including a
section on drug shortages in the Food and Drug Administration
Safety and Innovation Act, FDASIA, which was signed into law on
July 9th, 2012. Title 10 of FDASIA sought to address drug
shortages by giving new authorities and responsibilities to the
Food and Drug Administration and placing expanded requirements
on drug manufacturers to notify FDA of an interruption or
discontinuance in production. Among other provisions, under
FDASIA, the Secretary of Health & Human Services is required
to, one, maintain a publicly available up-to-date drug shortage
list; two, establish a task force to implement a strategic plan
to prevent and mitigate drug shortages; and three, submit
annual reports to Congress, including relating actions taken by
the Agency. FDASIA also required GAO to examine the cause of
drug shortages and formulate recommendations on how to prevent
or alleviate drug shortages.
Last October, FDA issued its strategic plan for preventing
and mitigating drug shortages. Further, we now have FDA's first
annual report on drug shortages, though it only covers the
first three quarters of 2013. And today, GAO released its final
report pursuant to FDASIA.
While drug shortages continue to plague our health care
system, statistics do indicate progress on some fronts. I am
pleased to see that legislation coming out of this subcommittee
has had a positive impact.
I would like to welcome our witnesses, Marcia Crosse,
health care director at GAO, and Douglas Throckmorton, deputy
director of regulatory programs at the FDA.
I would particularly like to thank GAO for their
comprehensive report and the time they have spent with my staff
on this issue.
[The prepared statement of Mr. Pitts follows:]
Prepared statement of Hon. Joseph R. Pitts
In recent years, we have seen a dramatic increase in the
number of drug shortages in the United States, particularly
with generic sterile injectable drugs.
While the number of new shortages dipped in 2012 and 2013,
the total number of ongoing shortages has continued to
increase. This is unacceptable. Numerous drugs have remained on
FDA's shortage list for some time. What is the agency doing to
help address these situations?
Recent news reports have highlighted shortages of oncology
products, parenteral nutrition products, and even common, yet
critically important saline solutions.
Such shortages lead to delays in treatment, rationing of
care, and higher costs. They can also pose greater risk to
patients in the form of medication errors and as providers are
forced to seek alternative treatments.
Drug shortages are a very challenging problem and it is
clear that there is no simple solution. We recognize the
complicated nature of this issue as well as the severity. Last
Congress, the subcommittee took action by including a section
on drug shortages in the Food and Drug Administration Safety
and Innovation Act (FDASIA), which was signed into law on July
9, 2012.
Title X of FDASIA sought to address drug shortages by
giving new authorities and responsibilities to the Food and
Drug Administration and placing expanded requirements on drug
manufacturers to notify FDA of an interruption or
discontinuance in production.
Among other provisions, under FDASIA, the Secretary of
Health & Human Services is required to: (1) maintain a publicly
available, up-to-date drug shortage list; (2) establish a task
force to implement a strategic plan to prevent and mitigatedrug
shortages; and (3) submit annual reports to Congress including
relating actions taken by the agency.
FDASIA also required GAO to ``examine the cause of drug
shortages and formulate recommendations on how to prevent or
alleviate such shortages.''
Last October, FDA issued its ``Strategic Plan for
Preventing and Mitigating Drug Shortages.'' Further, we now
have FDA's first annual report on drug shortages, though it
only covers the first three quarters of 2013.
And, today, GAO released its final report pursuant to
FDASIA.
While drug shortages continue to plague our healthcare
system, statistics do indicate progress on some fronts. I am
pleased to see that legislation coming out of this subcommittee
has had a positive impact.
I would like to welcome our witnesses, Marcia Crosse,
Health Care Director at GAO, and Douglas Throckmorton, Deputy
Director of Regulatory Programs at the FDA. I would
particularly like to thank GAO for their comprehensive report
and the time they have spent with my staff on this issue.
Mr. Pitts. I will yield the remainder of my time to Vice
Chair Dr. Burgess.
OPENING STATEMENT OF HON. MICHAEL C. BURGESS, A REPRESENTATIVE
IN CONGRESS FROM THE STATE OF TEXAS
Mr. Burgess. Thank you, Mr. Chairman.
You know, when doctors don't have the essential tools, they
are restricted in what they can do for their patients. Members
of this committee have taken the lead and made major strides in
working to reduce drug shortages by passing the Food and Drug
Administration Safety and Innovation Act of 2012. In addition,
I have worked very closely with Chairman Upton and Chairman
Pitts on several of the provisions contained therein, and
things have gotten better, but the problems have not completely
gone away.
As recently as last week, the Food and Drug Administration
listed sodium chloride injection bags as a drug shortage. Now,
sodium chloride is not a particularly esoteric or exotic
molecule, so if we are having that much trouble with salt, it
only makes you wonder what other more difficult molecules may--
the shortages that we may encounter there.
The Food and Drug Administration has a role in addressing
drug shortages, but it is a complex issue. In 2010, over 240
drugs were in short supply or unavailable, and more than 400
generic equivalents were back ordered. In fact, many generic
lines operate at margins so tight, that when production becomes
corrupted, the company simply cannot afford to continue its
manufacture. This inevitably leads to one of the more than
3,000 backlogs of generic applications.
Physicians are still faced with having to tell patients
that they can't receive the care they need, not because there
is no treatment but because a product is simply not available.
I thank the chairman for holding this hearing so we can
learn more about the progress that is being made on the
Nation's drug shortage problem. I am pleased that the
Government Accountability Office report is being released and
look forward to hearing from them on their findings. The law is
aimed to ensure that providers have the tools they need to
alleviate suffering, the suffering of every patient, and
certainly, I am anxious to hear the testimony today.
I yield back to the chairman.
Mr. Pitts. The Chair thanks the gentleman.
Now yields 5 minutes for opening statement to Mr. Pallone.
OPENING STATEMENT OF HON. FRANK PALLONE, JR., A REPRESENTATIVE
IN CONGRESS FROM THE STATE OF NEW JERSEY
Mr. Pallone. Thank you, Chairman Pitts. I am glad we are
having the hearing today on this critical issue of drug
shortages.
Over the past several years, we saw an alarming trend of
increases in drug shortages, and we all know the devastating
effects this can have on patients, potentially prolonging
disease or causing permanent disability or even death. This is
an issue I and many of my colleagues on the committee have long
been concerned about. Congress took action to provide the Food
and Drug Administration with tools to help address this problem
through provisions in the Food and Drug Administration Safety
and Innovation Act, or FDASIA, which passed on a strong
bipartisan basis in the summer of 2012.
In FDASIA, we asked the Government Accountability Office to
review several factors related to drug shortages, updating work
it had done previously, and they released that report today.
And I am glad Dr. Crosse is here to discuss it further with us.
I also want to take a moment to highlight some of the other
aspects of FDASIA that addressed the drug shortage problem. In
its 2012 report on drug shortages, the GAO recommended and we
heard this from other stakeholders, too, an early notification
requirement for potential shortages so that FDA can work with
manufacturers sooner to take steps to prevent or mitigate
shortages. We included such a requirement in FDASIA, and it is
encouraging that the number of new drug shortages declined in
2012 compared to the previous 2 years and that partial data
from 2013 indicates that the trend is continuing.
The FDA has cited this and other FDASIA drug shortage
provisions as contributing to their ability to prevent, by
their calculation, 140 drug shortages in the first three
quarters of 2013.
We also heard from stakeholders the need for faster review
times for generic drug applications and to reduce the
significant backlog of pending applications, and the generic
user fee agreement that was passed as parts of FDASIA was
important in getting FDA the resources it needs to make that
happen.
We have learned that it can be important to have multiple
manufacturers, especially for the most medically important
drugs, to help alleviate drug shortages. As we heard from FDA a
few months ago, the Agency has been aggressively hiring FTEs
for its generic drug program, meeting hiring goals in the law
as part of its efforts to tackle the backlog and speed up
review times.
And these are just some of the steps that have been taken
to address drug shortages, which is, of course, a complex
problem. As I am sure we will hear today from our witnesses,
drug shortages remain high and remain a problem. Many of the
shortages are still of sterile injectable drugs, and I am aware
that these types of drugs face unique challenges, because they
are technically difficult to manufacture. And each drug is
often manufactured by one or a small number of companies,
making it difficult for other companies to be able to fill the
need if any one company develops manufacturing problems.
So it is clear that while we have made progress in some
areas, our work is not over. I thank our witnesses from FDA and
GAO for being here today to continue our discussion on the
topic of drug shortages, and I look forward to learning more
about what we can do to further prevent them. Thank you very
much.
Thank you, Mr. Chairman. I yield back.
Mr. Pitts. At this time, the Chair recognizes the vice
chair of the committee, the gentlelady from Tennessee, Mrs.
Blackburn, for 5 minutes for opening statement.
OPENING STATEMENT OF HON. MARSHA BLACKBURN, A REPRESENTATIVE IN
CONGRESS FROM THE STATE OF TENNESSEE
Mrs. Blackburn. Thank you, Mr. Chairman.
And I want to welcome our witnesses. I thank you all for
being here. And I thank the chairman and the vice chairman of
the committee for their attention to this issue.
As you all know, 2011, 2012, we held hearings, we have
looked at this process and what the factors are that are
causing the drug shortages, and we know that they have
increased in recent years. And I am one of those I believe
let's get to the root cause and to the root problem so that we
are solving this. And I continue to talk with those health
professionals in the community in Tennessee and get their input
on this.
We did take a bipartisan action, as the chairman and the
ranking member have mentioned, and that was to address through
FDASIA the shortages. And FDASIA did provide FDA with the
authority that they needed. It put new requirements on the
manufacturers to help prevent and to mitigate the shortages, or
supposedly, on paper, that is what they are to do.
So this is a wonderful opportunity for us to look at the
GAO report, to question you, to hear from you and to continue
to try to look at this systemically, holistically and to get to
the root causes of solving this problem.
And, Mr. Chairman, I yield back to you for further
yielding.
Mr. Pitts. The Chair thanks the gentlelady. That concludes
the panel's--or members' opening statements.
On the panel today, we have two witnesses: Dr. Marcia
Crosse, Director of Health Care, U.S. Government Accountability
Office, and Dr. Doug Throckmorton, Deputy Director for
Regulatory Programs, Center for Drug Evaluation and Research,
U.S. Food and Drug Administration.
Thank you for coming. Your written testimony will be made
part of the record. You will have 5 minutes to summarize your
opening statement.
And at this time, the Chair recognizes Dr. Crosse for 5
minutes for her summary.
STATEMENTS OF MARCIA CROSSE, DIRECTOR, HEALTH CARE, GOVERNMENT
ACCOUNTABILITY OFFICE, AND DOUGLAS C. THROCKMORTON, DEPUTY
DIRECTOR OF REGULATORY PROGRAMS, CENTER FOR DRUG EVALUATION AND
RESEARCH, FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH &
HUMAN SERVICES
STATEMENT OF MARCIA CROSSE
Ms. Crosse. Chairman Pitts, Ranking Member Pallone and
members of the subcommittee, I am pleased to be here today to
discuss our work on drug shortages.
As you know, prescription drugs are a critical part of
medical care, but over the last decade, there has been an
increase in the number of drugs that are in shortage. This has
included drugs to stabilize trauma victims, to control pain
during surgery, to treat heart disease and cancer, and to
provide nutritional support to premature infants.
Today, GAO released our report on drug shortages, a study
you mandated in the FDA Safety and Innovation Act, and I am
happy to discuss our key findings. We found that the number of
drug shortages remains high and that providers experience
challenges responding to shortages without adversely affecting
patient care. Beginning in 2007, the number of new drug
shortages increased each year until 2012, when the number of
new shortages declined, and that downward trend appears to have
continued through 2013, based on the partial year data we
analyzed.
However, while the number of new drug shortages has begun
to decline, the total number of shortages active during a given
year, including both new shortages and ongoing shortages that
began in a prior year, has continued to increase, because many
shortages are prolonged, with some spanning multiple years. The
majority of shortages are of sterile injectable drugs,
particularly generics.
Shortages of medically necessary drugs can have a range of
negative effects. A drug shortage may require providers to
delay or ration care, create difficulties finding alternative
drugs, increase the risk of medication errors, lead to higher
costs, reduce time for patient care, and result in the hoarding
or stockpiling of drugs in shortage. For example, providers may
have to ration care by prioritizing the patients who have a
greater need for the drug.
The immediate cause of a drug shortage can generally be
traced to a manufacturer halting or slowing production to
address quality problems, triggering a supply disruption. Other
manufacturers have a limited ability to respond to supply
disruptions due to constrained manufacturing capacity.
We also identified potential underlying causes specific to
the economics of the generic sterile injectable drug market,
such as that low profit margins have limited infrastructure
investments or led some manufacturers to exit the market.
Although there are few studies of underlying causes, among the
issues that have been examined are that purchasers focus
primarily on price rather than quality, reducing incentives for
manufacturers to invest in maintenance or quality improvements;
that group purchasing organizations negotiate reduced drug
prices on behalf of hospitals and other providers, lowering
profit margins for manufacturers that win contracts and leading
losing manufacturers to exit the market; and that a 2005 change
in Medicare Part B drug reimbursement policy for outpatient
providers decreased both demand and prices for generic drugs.
The stakeholders we met with, which included manufacturers
and group purchasing organizations, had mixed views on these
potential underlying causes, with no general agreement on the
role such factors may play.
In examining FDA activities, we found that the Agency has
prevented more potential shortages and improved its ability to
respond to shortages in the last 2 years. The new requirement
that manufacturers must notify FDA in advance of a potential
shortage has allowed FDA to take steps to prevent and mitigate
shortages sooner. For example, it has expedited application
reviews and inspections, exercised enforcement discretion, and
helped manufacturers respond to quality problems.
These steps are important to respond to some of the
immediate causes of shortages. However, some of the underlying
causes we identified are beyond the Agency's authority, as FDA
does not have control over private companies' business
decisions. For example, the Agency is unable to require
manufacturers to start producing or continue producing drugs or
to build redundant manufacturing capacity, regardless of the
severity of a shortage.
Nonetheless, FDA can take steps to maximize the Agency's
use of the information it has to address drug shortages. We
identified shortcomings in its management and use of the
Agency's drug shortage data. In our report, we made
recommendations to FDA to improve its database and to conduct
routine analyses, and the Agency has agreed with these
recommendations.
In summary, while FDA has made progress in preventing
potential drug shortages and responding to actual shortages,
the number of shortages remains high and many persist for
months and even years. The large number of potential shortages
reported to the Agency suggests the market is still at risk of
supply disruptions. As a result, patients and providers will
continue to struggle as essential and life-saving medications
remain in short supply.
Mr. Chairman, this completes my prepared statement, and I
would be happy to respond to any questions you or other members
of the subcommittee may have.
Mr. Pitts. Thank you.
[The prepared statement of Ms. Crosse follows:]
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
Mr. Pitts. The Chair now recognizes Dr. Throckmorton, 5
minutes to summarize his opening statement.
STATEMENT OF DOUGLAS C. THROCKMORTON
Mr. Throckmorton. Mr. Chairman and members of the
subcommittee, I am Douglas Throckmorton, Deputy Director of
FDA's Center for Drug Evaluation and Research. Thank you for
the opportunity to speak with you today about the work FDA is
doing to address drug shortages.
I would like to begin by discussing their causes. Drug
shortages, as others have said, are usually preceded by a
disruption in manufacturing of a product. Some product
disruptions are manufacturer controlled, such as decisions to
permanently discontinue production of a drug that is no longer
profitable. Other factors are outside the manufacturer's
control, such as natural disasters or the unavailability of
materials needed for manufacturing, a particular problem when
materials are only available from one supplier.
Most often, however, shortages are the result of quality
failures within manufacturing facilities, such as failing to
follow proper sterilization procedures that allow bacteria to
grow in a sterile product. Quality failures can also result
from failures to maintain a manufacturing line: For example,
poorly maintained, old equipment has led to the introduction of
iron particulates in injectable products. Preventing these
supply disruptions requires the manufacturer to commit to
quality manufacturing.
Turning to drug shortages in the U.S. today, while work
remains, progress has been made in the prevention and
resolution of drug shortages in the United States. The Agency
is well positioned to work with manufacturers to find ways to
prevent or reduce a shortage's impact on patients, provided we
are aware that there is the potential for a shortage. Early and
timely notification by manufacturers has been aided importantly
by the Executive Order of the President as well as by passage
of FDASIA and has enabled FDA and manufacturers to prevent 170
shortages in 2013.
We are also seeing fewer new shortages. The number of new
drug shortages in the United States rose steadily from 60 in
2005 to an all-time high in 2011 of 251 new shortages. After a
series of interventions, the number of new drug shortages has
fallen to a low of 44 in 2013.
There do, however, continue to be shortages that persist
for longer periods. Here, while progress is being made, the FDA
is tracking and working to resolve 97 total shortages that
began in 2013 or earlier. This work has been accomplished by
FDA working closely with manufacturers, and some of the tools
we have applied include identifying manufacturers who are
willing and able to increase production of a drug in shortage;
expediting FDA inspections and reviews of submissions, both
from manufacturers that are currently producing as well as
manufacturers who are interested in starting new production of
a drug in shortage; and, finally, exploring risk mitigation
measures for products initially not meeting established
standards to allow them to remain available safely.
While FDA's standards of safety, efficacy and quality do
not change in a shortage situation, FDA does balance our
standards with the needs of patients for particular products,
especially patients with limited treatment options. FDA makes
certain that drug shortages are considered before taking
enforcement actions or issuing warning letters. In appropriate
cases, temporary exercise of regulatory flexibility is an
important tool in ensuring access to needed drugs.
As a part of FDA's work on drug shortages in 2013, the FDA
released its strategic plan, as called for in FDASIA. The goals
of the plan are to improve the Agency's response to drug
shortages and to advance longer-term approaches for addressing
the underlying causes of shortage.
First, to improve how we address imminent or existing
shortages, FDA is focusing on three areas: First, we are
improving communications within CDER within the FDA to ensure
that our decisions are efficient and appropriate. Second, we
are improving our databases related to drug shortages, creating
a dedicated drug shortage data system to improve how we track
drug shortages and allow us to better assess progress on
prevention and mitigation of those shortages, including the
work we do to produce the annual report to Congress required
under FDASIA. Third, FDA continues to work to improve timely
and accurate communication about drug shortages to patients and
caregivers.
Recognizing that drug shortages commonly begin with the
supply disruption related to product quality, FDA's long-range
efforts include a focus on preventing supply disruptions and
shortages by encouraging and sustaining improvements in
manufacturing quality. For over a decade, FDA has been working
with academics and industry experts to stimulate the
development of novel manufacturing technologies which can help
prevent drug shortages linked to manufacturing quality.
In conclusion, progress has been made in efforts to prevent
and mitigate important drug shortages, aided by early
communications with sponsors about potential shortages.
Shortages do continue to occur. FDA will continue to work to
address them. Importantly, FDA will continue to work with
others to support the pharmaceutical industry in their long-
term efforts to modernize drug manufacturing to prevent
shortages. By working together, we can prevent drug shortages
from occurring, address them when they do occur, and provide
patients with access to medicines when they are in critical
need.
I am happy to answer any questions that you have.
Mr. Pitts. The Chair thanks the gentleman.
[The prepared statement of Mr. Throckmorton follows:]
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
Mr. Pitts. That concludes the opening statements of the
panel. We will now begin questioning, and I will recognize
myself for that purpose for 5 minutes.
Dr. Throckmorton, while FDASIA required that the report be
submitted by no later than December 31st, 2013, FDA's first
annual shortages report was submitted to the committee on
February the 5th and with data from only the first three
quarters of 2013. You notice in your testimony that 170 new
shortages were prevented in 2013. This is up from 140 in the
report FDA submitted to the Congress. I assume that means that
FDA claims to have prevented 30 shortages in the fourth quarter
of the year. Is that correct?
Mr. Throckmorton. We do have our full-year data available
now, and we would be happy to share that with you, Mr.
Chairman.
Mr. Pitts. All right. Well, let's use that smaller sample
size for sake of discussion. It would be helpful to have more
detailed information about how FDA prevented these shortages.
What specific actions did the Agency take? Which drug products
would currently be in shortage if not for the Agency's actions?
Mr. Throckmorton. I can get you some specific information,
but I can give you a general sense of some of the activities
that we took in this last year, if that would be helpful.
Mr. Pitts. All right.
Mr. Throckmorton. One issue regards something called
regulatory flexibility. So these are places where we have
either expedited additional actions that otherwise would have
taken a bit longer or taken a review under hand and done
additional work on it. And last year, we had 76 instances of
regulatory flexibility that we exercised, affecting a total of
68 products.
There is another way of thinking about the actions that we
have taken recently to try to speed the development of products
or assure that products that potentially go into shortage
remain available; that is by looking at the kinds of expedited
reviews that my review staff do. So several of the offices
receive applications from sponsors for new factories, for new
lines within a factory. Last year, my Office of Generic Drugs
expedited 118 applications, involving a total of 62 accelerated
new drug applications, so an important number of products where
we worked hard to make certain that they were more quickly
reviewed than normal. Our Office of New Drug Quality, which is
another office looking at supplemental applications to approve
drugs, approved innovator drugs, looked at 52 supplemental
applications in an expedited forum last year. And then finally,
my Office of Biologic Products, which looks at new biologic
products, obviously, a very important issue in terms of
therapeutics and therapeutic development, they expedited seven
reviews last year.
I think, so, in total, those things reflect the kind of
commitment that my center has to looking at these things,
expediting wherever we are able to devote our resources to do
it.
Mr. Pitts. OK. Now, you mentioned the Office of Generic
Drugs expedited 118 applications, including 62 abbreviated new
drug applications. ANDA, is that what you call it?
Mr. Throckmorton. Yes.
Mr. Pitts. In order to prevent or mitigate a shortage, how
many of those applications were actually approved?
Mr. Throckmorton. You know, I would need to get back with
you about that information. Obviously, we are applying our
usual standards, but 118 applications, I think, speaks to the
level of effort that we undertook.
Mr. Pitts. On average, how long did it take FDA to approve
an ANDA that was given expedited review status? Do you know?
Mr. Throckmorton. It is a good question, and I will get
back with you with that information.
Mr. Pitts. OK. And I would like to know more about what
expedited review means in this situation. Does an ANDA
referencing a product in shortage go to the top of the queue?
Is there a special team within the Office of Generic Drugs
responsible for moving them through the review process faster?
Mr. Throckmorton. This will be a longer conversation. As I
am sure you are aware, we have new resources under GDUFA, under
the Generics Drugs User Fee Act. As a part of those resources,
we have reorganized the Office of Generic Drugs. We are
elevating it in terms of its importance within the Center for
Drugs, and as a part of that action, we are looking to be as
efficient as we possibly can. So to answer your question, I am
going to need to get back and look at the kinds of changes that
that office has made about the review staff.
Mr. Pitts. All right.
Dr. Crosse, did you have any discussions with FDA review
staff about what it means for a shortage product to receive
expedited review status within OGD?
Ms. Crosse. We did talk with FDA about this. We actually
are continuing our work looking at drug shortages where we are
planning on taking a more in-depth review of the number of drug
shortages that have been expedited and how that relates to the
number of applications that are sitting in the queue for drugs
that are in shortage. One issue, of course, is that even when
you expedite an application, if it is approved, that doesn't
mean that the manufacturer is ready to begin production that
day. And there is some concern that approving one ANDA may
displace another drug within that manufacturer's facility if
you are trying to move very quickly to move something to the
top of the line without the sort of normal planning time, so
that is something we heard about, but we are looking further to
try to get some statistics for you on how frequently FDA is
moving on these applications and what proportion of the
applications are getting moved on.
Mr. Pitts. Yes. And I would also be interested in how FDA
works with the manufacturer to address their targets to assess
when production capacity and output has addressed the shortage.
My time has expired.
The Chair recognizes the ranking member, Mr. Pallone, 5
minutes for questions.
Mr. Pallone. Thank you, Mr. Chairman.
I wanted to start with Dr. Throckmorton. I would like to
know how helpful you are finding the drug shortage provisions
in FDASIA, and whether there are other things that you think
Congress should do to help address drug shortages. And I would
also like to hear more about FDA's strategic plan for
preventing and mitigating drug shortages. I was pleased to see
that it was released last October, in fulfillment of one of
your FDASIA obligations.
So essentially three questions: Would you update us on how
things stand today with regard to drug shortages and the
Agency's plan to address them? And now that FDA has some
experience with FDASIA, are there parts of the law that don't
work as intended or, you know, as well as they should? And
then, third, are there other areas we should be thinking about
to help address the shortages?
Mr. Throckmorton. Well, thank you. So, first, let me just
say the provision of FDASIA that expanded the notification that
manufacturers have been providing for us has been enormously
helpful. It is hard for me to overstate that. We are learning
about shortages earlier than we had previously, and it is
giving us the opportunity to talk with manufacturers in ways
that we hadn't had an opportunity before, and we have been able
to prevent shortages as a result. So, unquestionably, that
aspect of FDASIA has been useful from the FDA's perspective. We
continue to make use of it. As you know, we are continuing to
write rulemaking and things related to it, but it is
fundamentally a valuable aspect of the work that we are doing
that is very useful.
The other aspects of FDASIA, I think, have also been useful
for us as well. The requirement to produce an annual report, I
think, is valuable, because it does give us an opportunity on
an annual basis to look back and assess whether there are
things that we need to continue to work on or where progress
has been made. That is a piece that we were able to provide to
you recently for three quarters of the year's data. We,
obviously, need to update you with the full-year data, because
we think that gives a fuller picture of the activities that the
FDA--that the--that FDA has conducted. And so, fundamentally,
FDASIA has been valuable to us from a shortage prevention
strategy.
Now, you asked us whether additional things were identified
in the strategic plan that needed also to be done, and the
short answer is yes. So there are many things that we can do
internally. There are things that we need to do from a process
perspective to make sure that the FDA continues to improve our
responses to the drug shortages issue, and that--those relate,
many of them, to process. So I chair the task force that has
been steering our response to drug shortages since FDASIA's
passage. That task force is made up of individuals from across
the Agency, so not just simply my center, but also the Center
for Biologics, the inspectional branch of the FDA. All of us
are coming together to talk about the things we need to do, the
things that we need to communicate about better, to be able to,
you know, basically do the job more efficiently and more
appropriately.
We also recognize we need to improve our communications.
The communications we place on the Web site are looked at
hundreds of thousands of times by individuals looking for
information about shortages. We heard loud and clear when we
talked to our stakeholders what needed to be improved, so that
the information was easier to find, so that topical information
was easier to identify, that the normal saline shortage, for
instance, was at the top of the queue, when you opened up that
Web page, that you could get that information quickly. We have
heard those kinds of comments, and we are doing what we can to
improve those communications.
Separately, however, there are things that are, as Dr.
Crosse said, outside of our scope, outside of the things that
the FDA is able to undertake. There are things that the
manufacturers, we believe, have a role to explore, and there
are other things that other stakeholders could explore as well
that have great potential, I believe, in addressing the
underlying causes of shortage. Happy to talk with you about
those if you are interested.
Mr. 1Pallone. All right. Let me just get into one more
question, because my time is almost gone here. One of the GAO's
recommendations is that FDA conduct routine analysis of its
drug shortage database to identify trends, and that seems like
a reasonable suggestion. Seems like FDA already does this to
some extent but perhaps not in as formalized a process as the
GAO.
Can you just tell us a little more on the problems of the
current FDA databases and what you hope the improvements will
accomplish, and does FDA believe that performing analysis such
as GAO recommends would help it come up with the
recommendations for avoiding shortages?
I think you will have 15 minutes--15 seconds.
Mr. Throckmorton. Fundamentally, we agree with the
recommendations that the GAO has made. We understand that the
quality of the decisionmaking that we can have with regards to
shortage depends on the quality of the data. So we are putting
in place a new drug shortage data system that is going to make
the data more robust, make it more standardized and improve our
assessment of those data.
Mr. Pallone. OK. All right. Thanks a lot.
Thanks, Mr. Chairman.
Mr. Pitts. The Chair thanks the gentleman.
Now recognize the gentlelady from Tennessee, Mrs.
Blackburn, 5 minutes for questions.
Mrs. Blackburn. Thank you, Mr. Chairman.
And, again, I thank each of you for being here with us.
I want to--I have got just a couple of questions. I know
that the FDA report said, you know, the number of reported new
shortages has declined in 2012 and for the first three quarters
of 2013, but then GAO says the total number of active shortages
continues to be high. So do you each agree with that?
Dr. Crosse?
Ms. Crosse. Yes, we do agree. The number of new shortages
has decreased, and we think that the FDASIA early notification
has been very helpful in that regard, but a number of shortages
have persisted across time.
Mrs. Blackburn. OK.
Ms. Crosse. I think we present that information in our
report.
Mrs. Blackburn. Yes, you do.
Dr. Throckmorton, do you continue to--do you agree with
that, that the shortages continue to be too high?
Mr. Throckmorton. Absolutely. I mean----
Mrs. Blackburn. OK. Just want to be sure everybody is in
complete agreement on that, because what I am hearing from the
providers in Tennessee, they agree with the GAO report.
And, Dr. Throckmorton, they look at yours, and it is kind
of a head scratcher, because they are not seeing the amount of
improvement that your report would lead people to believe is
there. And we continue to hear about the shortages with the
generic sterile injectable drugs, the IV fluids, the
medications for anesthesia, some of the cancer therapies. So
these are problems, and you might be making some progress, but
it is not coming fast enough.
And so let's talk about FDA implementing the system and
preventing--getting to the point that they can prevent new
shortages and decrease the backlog of the current shortages.
So, Ms. Crosse, give me the couple of things that we need
to be holding them responsible for doing. What is going to
speed this up, because we can't do this where we are saying 10
years from now, we are going to have this in place?
Ms. Crosse. Well, we do continue to look at some of the
underlying causes. You know, I think we need to look a little
more closely at those generic drug applications that are
sitting at FDA and the extent to which FDA has been able to
expedite the applications, which could be something that would
help, but----
Mrs. Blackburn. OK. Let me.
Ms. Crosse [continuing]. There are still a number of----
Mrs. Blackburn. If I can engage you right there for just a
minute.
Ms. Crosse. Sure.
Mrs. Blackburn. So Dr. Throckmorton, you said you expedited
118 this year.
Mr. Throckmorton. Generic applications, yes.
Mrs. Blackburn. OK.
Dr. Crosse, what would be a better number? What--if you
were setting a goal for him, how many should they be expediting
every year? Two hundred?
Ms. Crosse. I don't know.
Mrs. Blackburn. You don't know.
Ms. Crosse. I don't know. And I think there is a concern
that if you expedite too many, that then you are creating a
clog at the top.
Mrs. Blackburn. OK.
Ms. Crosse. It is difficult. You need--you know, there--
even within the priorities----
Mrs. Blackburn. Thank you. So----
Ms. Crosse [continuing]. There are priorities.
Mrs. Blackburn [continuing]. It may be approved, but then
they can't put it straight into manufacturing.
Ms. Crosse. Right. So there needs to be conversations with
the manufacturers about how quickly they could come on line.
Mrs. Blackburn. So they need to be engaging them on the
front end rather than the back end----
Ms. Crosse. Yes.
Mrs. Blackburn [continuing]. Or at the point of approval.
Would predictability in this process with the review
system, because as I talked to some that are working in the
generic space, the bio-therapeutic space, the unpredictability
at the FDA seems to be a problem?
Dr. Crosse, would that help?
Ms. Crosse. You know, that is not something that we heard
from the manufacturers----
Mrs. Blackburn. OK.
Ms. Crosse [continuing]. Particularly. I think that, you
know, certainly that is always an issue in any review process
for the applications, but it is not something that they
particularly pointed to here, because of the unpredictability
of when a shortage might occur.
Mrs. Blackburn. OK.
Dr. Throckmorton?
Mr. Throckmorton. I want to try to draw a distinction
between the numbers of ongoing shortages, those that last
extended periods of time, which are important--and that is one
group of shortages that I think we know less about than we need
to, I think that is a group that bears additional exploration--
and the numbers of new shortages and the numbers of new
shortages prevented. So when I answered your question that
there are too many shortages, I--there are too many shortages
because they are shortages that impact on human access to drugs
in the U.S. I mean, that is--
Mrs. Blackburn. Sure.
Mr. Throckmorton [continuing]. We would have to do away
with those before there would not be too many shortages.
Having said that, however, I think we have to acknowledge
that there has been work that has been important, that has been
able to prevent new shortages from adding onto that pile, if
you were. We are able to prevent shortages that matter. Our
next important task, a task that I think we need to undertake,
is to understand those longer duration shortages, those
shortages that mean no product is in the marketplace at all;
there is no manufacturer willing and interested in
manufacturing the product.
Mrs. Blackburn. My time has expired. I thank you for that
additional explanation.
Mr. Chairman, as I yield back to you, I do want to take a
moment and wish happy birthday to Congressman Guthrie.
Yield back.
Mr. Pitts. The Chair thanks the gentlelady and, well----
Mr. Guthrie. You didn't say which birthday.
Mr. Pitts [continuing]. Wishes Mr. Guthrie a happy
birthday.
At this time, the Chair recognizes the ranking member
emeritus of the full committee, Mr. Dingell, 5 minutes for
questions.
Mr. Dingell. Mr. Chairman, I thank you for your courtesy
and for holding this important hearing. I am pleased the
committee is turning again to the important topic of drug
shortages. There are many causes for this: the availability of
raw materials, complexity of manufacturing, certain treatments,
sudden increases in demand. We have also got a significant
problem in adequate funding for FDA and an adequate number of
personnel to properly address the business of that Agency.
While we have made some progress in this area, such as the
passage of the FDA Safety and Innovation Act, which improved
communication and reporting of drug shortages, we all agree, I
think, that there is more work to be done. So I hope our
witnesses will answer the questions yes or no.
Dr. Throckmorton, the last time this committee held a
hearing on drug shortages, the situation was dire. Is it
correct that the number of new drug shortages quadrupled from
2005 to 2011, yes or no?
Mr. Throckmorton. Yes.
Mr. Dingell. Now, Doctor, is it correct that there are only
44 new drug shortages in 2013 compared with 117 during the year
2012, yes or no?
Mr. Throckmorton. Yes.
Mr. Dingell. Now, Doctor, is it correct that FDA
successfully prevented 170 drug shortages in 2013, yes or no?
Mr. Throckmorton. Working with manufacturers, yes.
Mr. Dingell. Now, Dr. Crosse, although GAO used slightly
different metrics, did your Agency also find a decrease in new
drug shortages during 2012, yes or no?
Ms. Crosse. Yes.
Mr. Dingell. Dr. Throckmorton, did the new authorities
provided in the--to the Agency in FDASIA help FDA to reduce the
number of new drug shortages, yes or no?
Mr. Throckmorton. Yes.
Mr. Dingell. Would you submit for the record additional
changes that need to be made to further reduce the delays and
the shortages when they occur?
Mr. Throckmorton. Yes.
Mr. Dingell. I also would like to know, would more
personnel and more money assist FDA in terms of addressing
these questions?
Mr. Throckmorton. We are devoting resources we need to this
problem.
Mr. Dingell. And so, Doctor, would you submit us a short
monograph on that----
Mr. Throckmorton. Yes.
Mr. Dingell [continuing]. To assist the committee?
Dr. Throckmorton, does FDA need additional authorities to
help combat both existing and future drug shortages, yes or no?
Mr. Throckmorton. Existing authorities are providing us
important tools.
Mr. Dingell. Would you please submit a detailed response to
the record, including the resources needed by the Agency?
Mr. Throckmorton. Yes.
Mr. Dingell. Dr. Crosse, GAO's report on drug shortages
makes two recommendations to FDA. Specifically, you recommend
that the Agency use its drug shortage database in a more
proactive manner to identify trends and patterns to help
prevent shortages before they occur. Is that correct?
Ms. Crosse. Yes.
Mr. Dingell. Now, Dr. Throckmorton, does FDA agree with
this recommendation?
Mr. Throckmorton. Yes.
Mr. Dingell. Would you please both submit a detailed
response for the record regarding how FDA could use this
database more proactively and whether you need more resources
to implement the recommendations?
Mr. Throckmorton. Yes.
Ms. Crosse. Yes.
Mr. Dingell. Now, I am pleased with the progress made in
preventing drug shortages since the passage of FDASIA. We need
to take a step back and look at the big picture. Fundamentally,
drugs are in shortage because we simply aren't making enough of
them. As you know, many current shortages are of generic
sterile injectable drugs.
Dr. Throckmorton, does FDA believe there is sufficient
incentives to enter this market today, or are more needed?
Mr. Throckmorton. Important question. I can't answer it
without a fuller discussion with other stakeholders.
Mr. Dingell. Would you submit a proper analysis, then, in
response to this?
Mr. Throckmorton. Yes.
Mr. Dingell. Now, I think it is time to start thinking
outside the box about how we can continue to make progress on
preventing these drug shortages and combating existing
shortages. We need new and new innovative ideas to help solve
the problem as well as cooperation from all stakeholders. I
look forward to working with my colleagues on the committee,
the FDA and all stakeholders on this critical issue moving
forward.
Mr. Chairman, I thank you and I yield back the balance of
my time.
Mr. Pitts. The Chair thanks the gentleman.
Now yields 5 minutes to the vice chairman of the
subcommittee, Dr. Burgess, for questions.
Mr. Burgess. Thank you, Mr. Chairman.
Dr. Throckmorton, you know, we had the Executive order from
October of 2011 and then, of course, Food and Drug
reauthorization in July of 2012, but for the casual observer to
this problem of drug shortages, can you kind of just give us a
thumbnail of what is being done to deal with the existing drug
shortages?
Mr. Throckmorton. We have a number of things. First off, I
would say existing drug shortages, especially those that have
lasted for a prolonged period of time, are hard. They are hard
to resolve, because the factors that have led to them have
meant manufacturers have left that space entirely, so resolving
those is going to require finding tools to encourage a new
manufacturer to decide to add a product to a manufacturing
line, make a decision that that is a product that they can make
a profit at, decide to design that line and get approvals and
things. So that--those long-term shortages are things I think
we need to explore further than we have to date to now.
Mr. Burgess. Hold that thought for just a second. Let me
just ask you, have the manufacturers been responsive?
Mr. Throckmorton. Manufacturers understand this issue. We
have been in close discussion with many of the manufacturing
organizations, ISPE and PDA and other groups. They have
identified this group, these groups of longer-term shortages as
things that we need to continue to talk about, absolutely.
Mr. Burgess. You know, Dr. Crosse talked about enforcement
discretion and you talked about exercise of regulatory
flexibility. Can you give us some practical examples of where
that exercise of regulatory flexibility--I mean, for example,
the anesthetic drug propofol, has there been any? Is there
anywhere where regulatory flexibility may help in that
particular shortage?
Mr. Throckmorton. Let me give you a slightly different
example, and then we can return to propofol if it isn't useful,
but let's talk about total parenteral nutrition, or the
nutritional supplements that were in critical shortage recently
that are used in newborn infants, where it is just really life
or death for them to be able to get access to these medicines.
Those products were in limited availability because the
manufacturers are having a hard time producing enough
sufficient materials. FDA expedited any and every review,
expedited all of our inspectional activities to make certain
that whatever the manufacturer was able to provide, we were
able to make certain was available to serve the infants, the
newborns as quickly as possible.
We have had other examples where particulates have been
found, examples of drugs in shortage where particulates have on
surface required cessation of manufacture, cessation of
distribution of the product. Because of their critical nature,
we worked with the manufacturers, we have worked to find
filters that could be placed in line when that product is
administered to the patient, allowing them to continue to be
used. Even though that there is this product defect, these
particulates that exist, we have determined they have to be
made available to the patients, we have worked with the
manufacturers to make that happen. So----
Mr. Burgess. And so that has been successful. Talk about
propofol, though, because I get a lot of questions about that.
I mean, lack of an anesthetic, a reliable, safe anesthetic drug
is a--I mean, it is a big deal.
Mr. Throckmorton. Absolutely. And propofol's a slightly
different situation, because there the issue is a large
fraction of the propofol comes from outside the U.S. Well over
90 percent of the propofol is imported into the country, and
there have been some concerns about importation as--because of
some use of propofol in unapproved uses.
The FDA's interest, the focus that we have had, has been to
make certain that the propofol is available for patients who
are using it on label as indicated, as you said, in outpatient
settings for anesthesia and those things. So our work there has
been to work with the sponsor to do anything we needed to make
sure the patients received it when it was indicated for them; 5
million units, dosages a month or something, it is an
enormously important product that we are paying very close
attention to.
Mr. Burgess. Well, and it has revolutionized outpatient
surgery because the recovery time is so abbreviated with that
as opposed to the other compounds that were previously
available in days gone by.
Mr. Throckmorton. Absolutely. And we know that when in the
past, there was a propofol shortage a few years ago, and what
we learned in that shortage was that when physicians moved from
propofol to other products that they were less familiar with,
you know, mistakes occurred, because they were not as familiar
with the dosage and how to monitor patients and things like
that. So making certain that that product is available is
something that is very important for the U.S.
Mr. Burgess. Just very briefly, I have heard anecdotally
that difficulties getting proper amounts of Tamiflu during this
last flu season and that the cost for Tamiflu had really
exponentially increased. Can you speak to that at all?
Mr. Throckmorton. I haven't heard that the cost of Tamiflu
has spiked. There are other increases in pricing that we have
been hearing about, although that is not something that the FDA
normally, you know, has the statutory authority over. And while
there were some spot shortages with Tamiflu, we think at
present we are able to produce the needed--the necessary
amounts of Tamiflu necessary.
Mr. Burgess. Thanks, Mr. Chairman.
I have some additional questions I will submit in writing,
but I thank you for the courtesy.
Mr. Pitts. The Chair thanks the gentleman.
Now recognize the gentlelady from Virgin Islands, Dr.
Christensen, for 5 minutes for questions.
Ms. Christensen. Thanks, Mr. Chairman. And I want to thank
you and the ranking member for this hearing today.
While I am very happy to hear that the drug shortages are
reducing, as everyone has said, they still remain too high, and
we know that rural areas, communities of color, territories
like my district will be some of those where we will feel it
the most when there is a drug shortage.
I have a question that sort of digs a little deeper into my
colleague from Tennessee, the vice chair's question, I think.
And I am asking both--I will start with Dr. Throckmorton, but
also ask Dr. Crosse to comment. One of the explanations I have
heard for the increase in drug shortages was that FDA was
forcing manufacturers to come up with the state-of-the-art
manufacturing practices, even though the old tried and true
were completely adequate to ensure safety and effectiveness.
The argument went that to meet the new standards, some
companies had to shut down their lines to upgrade their
facilities, resulting in the shortages.
I have also heard something that is almost the opposite
argument, that FDA had been telling some companies for years
that their facilities were in decline and needed to be upgraded
to avoid problems in the future, even though the facilities
were currently meeting inspection standards, and eventually,
those warnings, unfortunately, came through.
So, Dr. Throckmorton, can you comment on these two
different perspectives? You mentioned in your testimony that
FDA is trying to encourage industry to adopt new technologies
but, at the same time, that FDA is not raising the bar, is not
raising the bar on standards for existing appropriate
technologies. That seems a very nuanced point. Could you just
elaborate for me?
Mr. Throckmorton. Absolutely. So there are a set of
standards that are in place right now for manufacturing, for
sort of quality manufacturing that we would expect a firm that
is making propofol, a firm that is making a tablet form,
whatever, a set of standards that they have in place that would
guide, you know, the manufacture of a product so that it is
sufficiently safe and efficacious in quality manufacturing.
Those things are working, and we are not changing those
standards at all.
What we also see is that there are more efficient ways to
be manufacturing products, especially products that are very
complicated, products that are like sterile injectables or
products that are biologics, places where you want to use the
state-of-the-art manufacturing processes. We have been working
for over a decade now trying to identify those manufacturing
processes to help guide drug manufacturing and then make
recommendations in the form of guidance in ways that
manufacturers can look at to do better than the current.
So we are not looking to change the current acceptable
process practices; we are looking to find a way to incentivize
a move toward a more efficient, a more continuous kind of
manufacturing that we think offers a lot of potential for
preventing shortages by improving the overall quality of
manufacturing.
Ms. Christensen. Thank you.
Dr. Crosse, would you like to add anything?
Ms. Crosse. Well, we too heard from industry these--the
same concerns and from FDA the same response. You know, FDA has
moved increasingly and, now under FDASIA, explicitly is moving
to a risk-based inspection decisionmaking process about which
manufacturers they should be inspecting with which frequency.
The drugs that are in shortage, the sterile injectables,
are inherently risky in their manufacture, and so you would
expect there to be a higher level of inspection of those
facilities just because of the risk of the product. We, as part
of the ongoing work I mentioned before, we are going to be
looking at the pattern of inspections that FDA has had across a
number of years of these facilities to see if we are seeing any
change, because it was a concern raised to us by manufacturers,
but the standards, as posed in regulation and guidance, have
not changed.
Ms. Christensen. Thank you. I have a number of other
questions that I will submit for the record, but I have a short
one.
Dr. Crosse, the GAO report doesn't focus on shortages of
medically important drugs. Can you tell us how closely the
shortage characteristics and trends provided in the report are
likely to track with or predict those from medically important
drugs? Is that something you can focus on in the future?
Ms. Crosse. We are very--it tracks very closely. We did use
a different data source. We used information from the
University of Utah Drug Information Service, because they have
had a database for much longer, and so we were able to look at
trends across time. FDA didn't develop its database until 2011,
and we wanted data that would go back to 2007. But the
majority, the vast majority of the data that Utah posts are of
medically necessary drugs. There is a very close alignment
there. There are some differences in the way the two--that FDA
and Utah count the drugs, so the numbers may look different
even though you are talking about the same drug shortage.
Ms. Christensen. And my time is up, so, thank you, Mr.
Chairman.
Mr. Pitts. The Chair thanks the gentlelady.
Now recognize the gentleman from Illinois, Mr. Shimkus, 5
minutes for questions.
Mr. Shimkus. Thank you, Mr. Chairman.
Thank you for being here. And obviously, a follow up to the
GAO report. A few comments before I begin. You know, we are
never going to have enough money to do whatever we want to do,
and more people and more money, sometimes it is just assumed
that is going to make things better, but this really--it is
important for me to always remember the whole budget pie. When
65 percent is mandatory spending, 35 percent is discretionary
spending, if we don't get control of our mandatory spending,
spending stays the same, discretionary keeps shrinking, which
will affect all agencies, the military and the like.
And so, in this budget debate, as people say, and we hear
the discretionary part of the budget, it--we are ill-advised
not to always talk about the problems of mandatory spending.
I would also say that FDA was one of the few agencies that
got additional money through these budgetary fights than a lot
of other agencies.
So, with that, Sydne, can you put up this--because a lot of
the questions, I think, are pertaining to this that is in the
GAO report. And I have it on--that is why I have been playing
around with my iPad, trying to figure out everything that this
chart says, but I think it is very illustrative, whether it is
Marsha Blackburn or John Dingell, I think they have all been
referring to this chart. And the dark blue is ongoing shortages
which began in prior years.
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Mr. Shimkus. Now, I guess the first question I have is, so
like in the 2000, you have 40. Those don't always carry--some
of those must fall off. Is that true?
Ms. Crosse. Yes, that is--that is true. It is not the
same----
Mr. Shimkus. Cumulative.
Ms. Crosse. It is not cumulative of all of them. Some drug
shortages are resolved, and so they drop out. Those that have
not been resolved by the end of the year roll over into our
data for the next year.
Mr. Shimkus. And forgive me if I didn't read the report as
closely as I should have, from 2007, even until what is
projected on the final bar chart, which isn't finished with the
fiscal year, are there pending drugs that follow that whole
time period?
Ms. Crosse. There--I am not aware of any that followed the
entire time period. We do have some that have extended for 5
years, a very small number. Most drug shortages are resolved
within 1 year or 2 years, but there are a very small number of
shortages that have continued across multiple years.
Mr. Shimkus. Thank you. Now--and so then the lighter blue
portion is really kind of, Dr. Throckmorton, that is what you
have been referring to, is that success has been made in the
new shortages, right? So--and we see that on this chart.
And that is--Dr. Crosse, you have concurred with that, too.
There is some--there is progress being made on that, as we can
see from that pending chart. Correct? And that is both in the
testimony.
Ms. Crosse. Yes. Yes, that is correct.
Mr. Shimkus. So I guess the--so that is my kind of
summation. I think this chart is very illustrative in the
report and kind of highlighted what most people had talked
about.
I guess the--a couple years ago, when we have been having
these debates, I always wondered why the market itself doesn't
respond to alleviate these shortages based upon a price signal.
Now, there--Dr. Burgess kind of mentioned, which Dr.
Throckmorton, you may have dismissed that there was a Tamiflu
signal sent. I don't know that. You said you didn't know that.
Why, in my minute left, is there something structurally about
how we, either the government in its coding or its spending
through Medicare and Medicaid or the insurance applications of
purchasing drugs, is there something that distorts the market
signals for shortages?
Ms. Crosse. I am not sure. You know, we didn't really look
at it that way.
Mr. Shimkus. That is fair. Maybe that is something, Mr.
Chairman, to follow up with in another question in the future.
Dr. Throckmorton, what do you think?
Mr. Throckmorton. I think, as others have commented,
economics have got to be playing a role in the decisions that
the manufacturers are making here. I think we know less about
that, at least speaking for myself, speaking for the FDA, than
we might like to, but those are important----
Mr. Shimkus. A lot of these shortages are low-margin
generic drugs, too, so if they are very low margin, they are
making a penny on whatever the application is. And that is hard
to get a price signal on a return on a major if you only have
one plan operating full speed producing all this product.
Mr. Throckmorton. Dr. Burgess' propofol--others would
remember better--someone has said that the profit on a dose is
in the tens of cents.
Mr. Shimkus. Yes, great. Excellent.
Thank you very much. Mr. Chairman, I yield back.
Mr. Pitts. Chair thanks the gentleman.
Now recognize the gentleman from Kentucky, Mr. Guthrie.
Five minutes for your question.
Mr. Guthrie. Thanks. I appreciate what the gentleman from
Illinois is asking because I had a kind of high school reunion
with some friends. A friend of mine is an emergency room
physician in Auburn, Alabama, and he was telling me about the
shortage of drugs. And he said it wasn't the expensive stuff.
And he couldn't do his service properly sometimes because of
that. And, you know, classic price controls in economics--I am
not saying there are price controls, but when there is not
ability to move the price for some reason, it is something to
investigate--then you would say it is going to be a shortage in
quality. That is the two things you mentioned is shortage of
ability and quality, and it seems there is not a price signal,
that the gentleman from Illinois, to allow other people to
enter.
We are not talking about even hundreds of dollars or
thousands of dollars. We are talking about sometimes cents and
sometimes just dollars, and people aren't getting over that.
But, Dr. Crosse, in your testimony, you noted that FDA
officials have told you that FDASIA's requirements that
manufacturers notify the FDA in advance have helped the
situation that they are able to take some steps, but you also
note that while FDA is planning to establish a new information
system to track data, there are significant concerns,
specifically that they are not conducting routine analysis of
existing data, drug shortages in the database to identify or
respond proactively. Can you elaborate, or will you elaborate
on what----
Ms. Crosse. Yes. Well, we did have concerns about what we
call internal controls, the extent to which FDA was ensuring
the accuracy of the information in their database and then the
extent to which they were doing broader analyses to look at
such things as the ongoing shortages, as opposed to using it as
a tool to help them track the status of an individual shortage.
So what we weren't seeing were those kinds of larger analyses
looking at trends. And as time goes on and they have more fully
developed data, we believe it is important for them to engage
in that. And they have agreed with us that that is something
that they plan to start doing now that they have a little more
data for a little longer period of time, that that is something
that they can do.
But, you know, we do talk a little bit, to your earlier
point, about the, kind of, the economics. That is part of what
we are trying to continue to look at. There have been issues
raised to us but no agreement on whether or not there is any
one source of what is holding down those prices.
Mr. Guthrie. OK. Thanks. And so also I noticed, in 2011,
inspections were at their peak. FDA inspections were at their
peak, and also the shortages were at their peak. Has GAO
examined the correlation between inspections and drug
shortages?
Ms. Crosse. We haven't. And that is also part of what we
are going to continue to look at, is to go and see if there was
a change across time in inspections. But as I noted before,
these are high-risk products for the most part. Most of these
are the sterile injectable drugs, and they are high-risk
products where you would expect FDA to be going with some
greater frequency to those facilities than to someplace that is
making, you know, a tablet that has been in operation for a
long time with a good safety record.
Mr. Guthrie. And then, Dr. Throckmorton, drug shortages
often require practitioners to utilize alternative treatments
that may not be as effective. Does the FDA compile and
disseminate information regarding alternative treatments in
times of shortage for practitioners or patients?
Mr. Throckmorton. We have typically left that to other
groups, particularly the pharmacists and ASHP, for instance,
with their Web site that Dr. Crosse has been using for her data
and things, do identify alternative uses. We are able to
identify other drugs with the same indication, but we recognize
the practice of medicine is such that people look for other
alternative therapies that may or may not be on label, and so
we tend to use the other--where we take advantage of other
people's expertise to have them do that for us.
Mr. Guthrie. Can GAO provide more detail about FDA's
regulatory actions to prevent or mitigate drug shortages based
on your discussions with Agency staff as well as manufacturers?
And bottom line, are FDA's actions or decisions being exercised
consistently?
Ms. Crosse. I don't know that I can speak to whether they
are be exercised consistently. We certainly can provide you
with some additional detail on what actions they have taken.
Mr. Guthrie. Mr. Chairman, I yield back.
Mr. Pitts. The Chair thanks the gentleman.
I now recognize the gentleman from Virginia, Mr. Griffith,
for 5 minutes.
Mr. Griffith. Thank you, Mr. Chairman. I appreciate.
Thank you all for being here today and answering these
questions.
I would be remiss to not remind everybody that drug
shortages, particularly of sterile injectables, led to some
health care providers feeling dependent on the supposedly
sterile compounded drugs that ultimately led to the fungal
meningitis outbreak in 2012 that killed 64 Americans, including
two in my area.
Because these drugs were more difficult to obtain, illegal
manufacturers that called themselves compounding pharmacies,
like NECC, entered the market to fill the need of hospitals and
outpatient clinics for sterile injectables.
Thankfully Congress put the FDA on notice with FDASIA to
deal with the drug shortages, much like Congress did with the
Drug Quality and Security Act with large-scale compounding and
illegal manufacturing.
FDA officials have signalled that the Agency has begun to
identify signals to better predict quality issues at
manufacturing facilities.
Dr. Throckmorton, can you comment on these improvements?
Mr. Throckmorton. Mostly to say that we understand the
importance of getting that right, so identifying what those
metrics are and then having a discussion about how they would
be used is very important. And so part of our ongoing efforts,
efforts this coming year and beyond, are to speak with
manufacturing experts that can talk about the kinds of measures
that a plant uses to follow their own manufacturing quality,
understand those things better, and then talk about how a
purchaser might make use of those kinds of information.
Mr. Griffith. And I appreciate that, and one of the
concerns that I had was that it appeared in that fungal
meningitis outbreak that the lawyers at FDA were not using all
the powers that were available to them to oversee. And while we
don't want too much oversight that stops manufacturers who are
doing the right things from producing their product, I am
hopeful that the lawyers are being more aggressive if they see
something that looks like it is out of line, because while we
want to have a good supply, we want to have a safe supply as
well. Would you not agree with that, and do you think the
lawyers are being a little more aggressive post the outbreak of
the fungal meningitis problem?
Mr. Throckmorton. I would absolutely agree we need to do
anything we can to assure a safe supply.
Mr. Griffith. All right.
Dr. Crosse, GAO recommended that the FDA improve its
databases so the Agency can employ more predictive analyses to
its preventative activities. How did the Agency respond to this
critique, and how far off are they from putting your
recommendations into practice?
Ms. Crosse. FDA agreed with our recommendations, and my
understanding is they are beginning to do it immediately.
Mr. Griffith. All right. Also, the GAO report found that
the FDA lacked policies, procedures and specific training
materials related to management and use of its existing drug
shortage database. What impact does this have on the Agency's
ability to use this database to prevent or mitigate shortages?
Ms. Crosse. Well, we think they do need to have these kind
of standard procedures in place to assure the accuracy of the
data and the understanding on the part of their staff of
exactly how data should be entered and how it should be
analyzed. They also agreed that they would move forward on
those steps.
Mr. Griffith. I appreciate it. What role do you think this
database could play in addressing future drug shortages?
Ms. Crosse. Well, we think it is important for the Agency
to have good information because they need to be able to look
at this more broadly, to look within classes, to look across
time to see, to be able to measure whether or not they are
putting the right steps in place and having the kind of impact
to improve the situation rather than treating these as each
individual kind of situation that has to uniquely be solved.
Mr. Griffith. I appreciate it. Thank you very much.
With that, Mr. Chairman, I yield back.
Mr. Pitts. Chair thanks the gentleman.
I now recognize the gentlelady from North Carolina, Ms.
Ellmers. Five minutes for questions.
Mrs. Ellmers. Thank you, Mr. Chairman, and thank you to our
panel for being here today. In my district, this is a very
specific situation and I am hearing from all of my hospitals.
In particular, I will focus on Wake Med Hospital System. They
are an 870-bed health care system with multiple facilities
around Raleigh, North Carolina. They basically deal with the
three primary vendors for IV infusions. And all three have
experienced quality manufacturing issues as well as holiday
production shutdowns that contributed to the shortage. Wake
Med's pharmacy spent an additional $80,000 in January to stock
up on the drugs in anticipation.
I appreciate the efforts of the FDA to address the
shortage, but it appears that they are only addressing the
symptoms and not the real causes.
I am also concerned about the Medicare reimbursement
system, especially the explosion of the 340(b) discounts, which
is reducing margins for generic manufacturers. This is pushing
them to stop producing low-cost generic injectables, just like
the system is driving community cancer clinics into hospitals.
It also appears that these manufacturers simply don't have the
margins to invest in their manufacturing plans, which is why we
see many of the quality problems.
My question has to do with what is and how are we
addressing these issues right now. I want to focus my questions
today on the FDA's work with the industry to make sure everyone
is working together to find solutions.
Dr. Throckmorton, there remains virtually no transparency
in the process for how drugs that make it onto the shortage
list ultimately get off this list. How does the Agency decide
that a product is no longer in shortage, and is there a
consistent and standardized formula for FDA uses to produce a
product from the shortage list?
Mr. Throckmorton. The short answer is, yes, we do have a
consistent process that we use to apply to drugs to decide when
they come onto the shortage list and when a shortage is no
longer existing and they can come off.
Our focus is on determining whether or not patients in the
U.S. can get the treatments that they need. So it is not
focused on product-by-product shortage, so there may be a
shortage of a buffered aspirin because one manufacturer of a
kind of buffered aspirin may no longer be manufacturing. But
there may be four other kinds of aspirin that are available.
That will not be a shortage from our perspective because the
other products can and will ramp up. That is something our
people know about, talk with those other manufacturers, were
able to assess using prescription data, using other data that
we have access to; we can determine whether those other
manufacturers can fill in for that manufacturer that has made a
decision to not manufacture or needed to stop manufacturing to
improve a plant or improve a product line.
That is slightly different than the kinds of data that the
University of Utah counts, the data that Dr. Crosse is
referring to. We are looking at the totality of the data, the
availability of a given therapy, not an individual product. And
so our numbers are slightly different than ASHP that the
University of Utah have.
We believe fundamentally ours reflect the availability of
the therapy for the patients, which is our public health goal,
if you will. But behind that, we have a process in place to
determine when available production is not able to meet demand
and then work with manufacturers, and when production returns
and is once again able to meet demand, to take something off of
the shortage list.
Mrs. Ellmers. OK.
Also, very specifically, there again, Dr. Throckmorton, the
FDA's inspection of API can remain a barrier and ANDA holder
can market the generic drug. How has the Agency tried to
improve its record on this issue to ensure that the ANDA
holders can market a drug and potentially address a drug
shortage?
Mr. Throckmorton. Two parts to that answer. The first part
would be some of the actions that we have already talked about,
the expedited reviews and some of the expedited inspections
that the FDA is being able to do, particularly in shortage
situations.
There is a second longer term, and it relates to the
passage of GDUFA. So the Generic Drug User Fee Act has provided
us additional resources and additional opportunity to sort of
balance the playing field, if you will, so that we are able to
devote the resources we need to the generics market, which--85
percent of the U.S. drug market is generics now. We are able to
allocate the resources that we need to that area to make
certain they are getting the inspectional attention, the
compliance history, the reviews from our reviewers that they
need to, so that is an important addition for us.
Mrs. Ellmers. Thank you so much.
And I see my time is expired. Thank you, Mr. Chairman.
Mr. Pitts. Chair thanks of the gentlelady.
That concludes the questions of the members who are
present. We will have additional questions we will send to you
in writing. If you would please respond promptly.
I remind members that they have 10 business days to submit
questions for the record, and members should submit their
questions by the close of business on Tuesday, February 25.
Thank you very much for the testimony, the good information,
and we look forward to continued work with you.
With that, without objection, the subcommittee is
adjourned.
[Whereupon, at 3:15 p.m., the subcommittee was adjourned.]
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