[House Hearing, 110 Congress]
[From the U.S. Government Publishing Office]
FDA'S FOREIGN DRUG INSPECTION PROGRAM: WEAKNESSES PLACE AMERICANS AT
RISK
=======================================================================
HEARING
BEFORE THE
SUBCOMMITTEE ON OVERSIGHT AND INVESTIGATIONS
OF THE
COMMITTEE ON ENERGY AND COMMERCE
HOUSE OF REPRESENTATIVES
ONE HUNDRED TENTH CONGRESS
SECOND SESSION
__________
APRIL 22, 2008
__________
Serial No. 110-107
Printed for the use of the Committee on Energy and Commerce
energycommerce.house.gov
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COMMITTEE ON ENERGY AND COMMERCE
JOHN D. DINGELL, Michigan, Chairman
HENRY A. WAXMAN, California JOE BARTON, Texas
EDWARD J. MARKEY, Massachusetts Ranking Member
RICK BOUCHER, Virginia RALPH M. HALL, Texas
EDOLPHUS TOWNS, New York FRED UPTON, Michigan
FRANK PALLONE, Jr., New Jersey CLIFF STEARNS, Florida
BART GORDON, Tennessee NATHAN DEAL, Georgia
BOBBY L. RUSH, Illinois ED WHITFIELD, Kentucky
ANNA G. ESHOO, California BARBARA CUBIN, Wyoming
BART STUPAK, Michigan JOHN SHIMKUS, Illinois
ELIOT L. ENGEL, New York HEATHER WILSON, New Mexico
ALBERT R. WYNN, Maryland JOHN B. SHADEGG, Arizona
GENE GREEN, Texas CHARLES W. ``CHIP'' PICKERING,
DIANA DeGETTE, Colorado Mississippi
Vice Chairman VITO FOSSELLA, New York
LOIS CAPPS, California STEVE BUYER, Indiana
MICHAEL F. DOYLE, Pennsylvania GEORGE RADANOVICH, California
JANE HARMAN, California JOSEPH R. PITTS, Pennsylvania
TOM ALLEN, Maine MARY BONO, California
JAN SCHAKOWSKY, Illinois GREG WALDEN, Oregon
HILDA L. SOLIS, California LEE TERRY, Nebraska
CHARLES A. GONZALEZ, Texas MIKE FERGUSON, New Jersey
JAY INSLEE, Washington MIKE ROGERS, Michigan
TAMMY BALDWIN, Wisconsin SUE WILKINS MYRICK, North Carolina
MIKE ROSS, Arkansas JOHN SULLIVAN, Oklahoma
DARLENE HOOLEY, Oregon TIM MURPHY, Pennsylvania
ANTHONY D. WEINER, New York MICHAEL C. BURGESS, Texas
JIM MATHESON, Utah MARSHA BLACKBURN, Tennessee
G.K. BUTTERFIELD, North Carolina
CHARLIE MELANCON, Louisiana
JOHN BARROW, Georgia
BARON P. HILL, Indiana
______
Professional Staff
Dennis B. Fitzgibbons, Chief of Staff
Gregg A. Rothschild, Chief Counsel
Sharon E. Davis, Chief Clerk
David L. Cavicke, Minority Staff Director
_____
Subcommittee on Oversight and Investigations
BART STUPAK, Michigan, Chairman
DIANA DeGETTE, Colorado ED WHITFIELD, Kentucky
CHARLIE MELANCON, Louisiana Ranking Member
Vice Chairman GREG WALDEN, Oregon
HENRY A. WAXMAN, California MIKE FERGUSON, New Jersey
GENE GREEN, Texas TIM MURPHY, Pennsylvania
MIKE DOYLE, Pennsylvania MICHAEL C. BURGESS, Texas
JAN SCHAKOWSKY, Illinois MARSHA BLACKBURN, Tennessee
JAY INSLEE, Washington JOE BARTON, Texas (ex officio)
JOHN D. DINGELL, Michigan (ex
officio)
(ii)
C O N T E N T S
----------
Page
Hon. Bart Stupak, a Representative in Congress from the State of
Michigan, opening statement.................................... 1
Hon. Joe Barton, a Representative in Congress from the State of
Texas, prepared statement...................................... 4
Hon. John D. Dingell, a Representative in Congress from the State
of Michigan, prepared statement................................ 6
Hon. John Shimkus, a Representative in Congress from the State of
Illinois, opening statement.................................... 7
Hon. Michael C. Burgess, a Representative in Congress from the
State of Texas, opening statement.............................. 9
Hon. Gene Green, a Representative in Congress from the State of
Texas, prepared statement...................................... 55
Witnesses
Andrew C. von Eschenbach, M.D., Commissioner, Food and Drug
Administration................................................. 11
Prepared statement........................................... 15
Marcia G. Crosse, Director of Public Health and Military Health
Issues, U.S. Government Accountability Office.................. 65
Prepared statement........................................... 68
Gail H. Cassell, Ph.D., Vice President, Scientific Affairs and
Distinguished Lilly Research Scholar for Infectious Diseases,
Eli Lilly and Company.......................................... 93
Prepared statement........................................... 97
William K. Hubbard, Former FDA Associate Commissioner and Current
Senior Advisor to the Coalition for a Stronger FDA............. 100
Prepared statement........................................... 102
Carl R. Nielsen, Retired Director of the Division of Import
Operations, Office of Regulatory Affairs, Food and Drug
Administration, U.S. Department of Health and Human Services... 105
Prepared statement........................................... 107
Benjamin L. England, Esq., Benjamin L. England & Associates, LLC,
and FDAimports.com............................................. 117
Prepared statement........................................... 120
Submitted Material
Slides accompanying Mr. Stupak's opening statement............... 146
Subcommittee exhibit binder...................................... 154
FDA'S FOREIGN DRUG INSPECTION
PROGRAM: WEAKNESSES PLACE AMERICANS AT RISK
----------
TUESDAY, APRIL 22, 2008
House of Representatives,
Subcommittee on Oversight and Investigations,
Committee on Energy and Commerce,
Washington, D.C.
The subcommittee met, pursuant to call, at 11:00 a.m., in
room 2123, Rayburn House Office Building, Hon Bart Stupak
(chairman of the subcommittee) presiding.
Present: Representatives Stupak, Melancon, Green, Dingell
(ex officio), Shimkus, Burgess, and Barton (ex officio).
Staff Present: Chris Knauer, John Sopko, Kevin Barstow,
David Nelson, Kyle Chapman, Calvin Webb; Alan Slobodin, Peter
Spencer, and Whitney Drew.
OPENING STATEMENT OF HON. BART STUPAK, A REPRESENTATIVE IN
CONGRESS FROM THE STATE OF MICHIGAN
Mr. Stupak. This meeting will come to order. Today we have
a hearing titled ``FDA's Foreign Drug Inspection Program:
Weaknesses Place Americans at Risk.'' Each member will be
recognized for an opening statement of 5 minutes. I will begin.
Today's hearing will once again explore the question of
whether the Food and Drug Administration, FDA, is adequately
regulating the overseas manufacture of pharmaceutical products.
As this subcommittee has reported before, a significant and
still growing quantity of pharmaceutical products used by
Americans are now manufactured with ingredients obtained
overseas from countries on almost every continent. With exact
quantities and sources for these drugs difficult to determine,
the general consensus is that at least 80 percent of all active
pharmaceutical ingredients, APIs, used by U.S. manufacturers to
produce drugs are imported. More importantly, much of this
production occurs in regions that lack robust regulatory
systems, such as China and India. China alone has more firms
registered to export drugs to the U.S. than any other country,
posing major challenges to the FDA. As was noted by former FDA
Commissioner David Kessler in a major news production, I quote:
``China is `as close to an unregulated environment as you can
get.' In fact, it is a lot like the U.S. was in 1906, he says--
'That's why we developed an FDA.'''
The U.S. Food and Drug Administration is the Agency
responsible for overseeing the safety and effectiveness of all
human drugs marketed in the U.S. As part of its effort to
oversee the safety and quality of these products, FDA's policy
is to physically inspect foreign establishments that ship drugs
to the American market.
Last year this subcommittee asked the Government
Accountability Office, GAO, to undertake a comprehensive audit
of FDA's foreign drug regulatory system. The preliminary
findings of that audit were presented at a hearing before this
subcommittee on November 1st of last year. The GAO reported
that a substantial lack of human and economic resources,
weaknesses in databases in IT systems used by the FDA to track
inspections and drug imports, and a lack of permanent
operational support in foreign locations were major challenges
facing the program. GAO also found that many of the FDA
databases used to track foreign firms that export to the United
States contain substantial material inaccuracies that have yet
to be reconciled by the Agency.
More specifically, a lack of resources was determined to be
a major factor undermining FDA's drug inspection program. For
example, while current law requires FDA to inspect domestic
firms once every 2 years, which FDA is managing to do roughly
every 2.7 years, GAO reported that FDA only has enough
resources to inspect foreign firms about once every 13 years.
In China, one of the largest producers of active pharmaceutical
ingredients for the U.S. market, FDA only inspects about 10 to
20 firms each year against an inventory of more than 700 firms.
At this rate, the FDA can only inspect each Chinese firm about
once every 30 to 40 years. Worldwide, GAO concluded that on an
annual basis, the Agency only has enough resources to inspect
about 7 percent of existing foreign plants, which amounts to
inspecting one plant every 13 years. Given that these
inspections are the most important tool the FDA has to ensure
firms are meeting U.S. drug safety regulations, these rates are
unacceptable.
FDA's IT systems for managing inspections and prioritizing
risk was another major concern highlighted at the November 1st
hearing. GAO testified that this system was antiquated, not
designed for this purpose, and fraught with duplicative and
inaccurate data. Such flaws made it difficult for the Agency to
assess risk and prioritize inspections. Further, FDA could not
determine how many foreign firms were subject to FDA
inspections or where they were located. One database suggested
that there were 3,000 foreign firms registered with FDA to
market drugs in the U.S., and yet another database seemed to
show 7,000 firms actually shipped products to the United
States.
How can there be any confidence that the FDA is adequately
regulating foreign drug firms when the FDA has no idea who's
making what, where they are physically located, and when they
were last inspected? These problems highlighted 10 years ago
still plague the Agency today.
If the GAO and Subcommittee findings were not enough to
demonstrate that the FDA's regulatory systems are broken, allow
me to provide more evidence. In December of last year, a
specially formed committee for the FDA submitted a
comprehensive 2-year study entitled, ``FDA Science and Mission
at Risk: Report of the Subcommittee on Science and
Technology.'' This Science Advisory Board report assessed the
Agency's ability to support a variety of existing and future
regulatory operations. The special subcommittee that concluded
this review was comprised of nearly 3 dozen external experts
who represent industry, academia, and other governmental
agencies.
This subcommittee held a hearing on January 29th, 2008, to
explore both the general concerns raised by the Science Review
Board and their implications for food and drug import issues.
The report advisors, including Chairperson Dr. Cassell, who
will testify again today, provided alarming testimony regarding
FDA deficiency in meeting its regulatory responsibilities. The
panel is particularly troubled by the multitude of IT issues
affecting the entire agency, including those related to foreign
drug inspection program.
With regard to the scarcity of resources for conducting
foreign drug inspections at the Agency, the report states:
``Although approximately 80 percent of the active
pharmaceutical ingredients used in our prescription drugs are
imported from abroad, and foreign imports of drugs and active
pharmaceutical ingredients were valued at more than $42 billion
in 2006, FDA conducted only 361 foreign drug and biological
product establishments in 2006. Only 32 field inspections were
made in India and 15 in China, the two largest sources of
pharmaceutical exports to the United States. Millions of
shipments of FDA-regulated products are now imported into the
country each year from foreign facilities that have never been
inspected by FDA, and, with current appropriations, never will
be.''
The FDA Commissioner was present at the January 29th
hearing. During his testimony the Commissioner agreed to
consult further with the Subcommittee to explore ways to
resolve the many problems identified in the Science Advisory
Board report and address a multitude of concerns raised by the
GAO, the Subcommittee, and others related to food and drug
imports. Almost immediately on the heels of the January
hearing, the FDA was quickly overwhelmed by the very type of
crisis these reports and audits predicted would occur:
contaminated heparin from China.
As we are now familiar, in late 2007 and early 2008, FDA
began noticing hundreds of reports of adverse reactions to
heparin, including vomiting, breathing difficulties, low blood
pressure, and as many as 81 deaths. We would learn that tainted
heparin was imported from China, and that the Chinese facility,
Changzhou SPL, which made the active ingredient, had never been
inspected by the FDA because of multiple internal failures.
Laboratory testing revealed that a foreign ingredient called
oversulfated chondroitin sulfate had somehow been added into
the heparin production chain. While investigation into the
origin of this contaminant continues, this tragic episode
underscores the vulnerabilities in the current system used to
regulate foreign drugs.
We have spent almost a year investigating the nature and
extent of failures in FDA's foreign drug inspection program.
After several hearings, the findings of the GAO, FDA's own
Science Board, countless press articles, and the Subcommittee's
own work, there are enough red flags to suggest to this
Chairman, it is time to act and fix this program. GAO said it
perfectly in last year's testimony, and I quote: ``Until FDA
responds to systemic weaknesses in the management of this
important program, it cannot provide the needed assurance that
the drug supply reaching our citizens is appropriately
scrutinized and safe.'' To date, FDA has been unable to assure
the public these products are safe because they do not address
the numerous systemic weaknesses many of us have identified.
Because GAO and others will report today that many of the same
problems we identified last year are still with us today, I can
only conclude that American lives are unnecessarily being
placed at risk.
I look forward to hearing from the Commissioner today.
However, given the current nature of his agency's foreign drug
inspection program, I think it is incumbent upon him to lay out
a credible plan that demonstrates what steps the FDA has or
will take to close these gaps and what resources or regulatory
tools he needs to do the job.
Last year, this Nation's regulatory failure resulted in
dead dogs and cats. This year, it has tragically led to the
deaths of people. If we don't make rapid progress on fixing the
foreign drug inspection program, the next melamine or heparin
tragedy will soon be upon us.
With that, I next recognize the Ranking Member of the
Committee, Mr. Shimkus from Illinois, for an opening statement.
Mr. Shimkus. Thank you, Mr. Chairman. I'd like to yield my
time to the Ranking Member of the full committee, Mr. Barton,
for an opening statement.
Mr. Stupak. Mr. Barton, please, for an opening statement.
OPENING STATEMENT OF HON. JOE BARTON, A REPRESENTATIVE IN
CONGRESS FROM THE STATE OF TEXAS
Mr. Barton. Thank you, and I apologize for going out of
order. I have another meeting upstairs that I'm going to go to
after the statement and then I will come back down for the
questions.
I want to commend Chairman Stupak and Ranking Member
Shimkus for holding this hearing. It continues the bipartisan
tradition of oversight work to ensure that the FDA is policing
the safety of our drug supply. I want to commend Dr. von
Eschenbach for attending, as he said he would when we had a
hearing on this subject several months ago. It shows that he is
a man who keeps his word and is willing to come before the
Subcommittee when necessary.
We're all very concerned about the safety of our imported
food and drugs. And we're even more concerned that many of
those are coming from China, which has a spotty record of
regulating its products which are sold for export. There is a
long history of counterfeit products from China, shoddy
manufacturing. Sometimes those shoddy manufactured products and
counterfeit products cause real problems in our country. The
American people deserve better, and there is something very,
very wrong with our system if we can't decide on a collective
basis, cooperative basis with the administration and the
Congress, what to do about it.
This subcommittee has done outstanding work over the years
in revealing the weaknesses in our current inspection program,
both domestically and foreign. The risk from imported drugs has
increased quite simply because the number of imported drugs
have increased almost exponentially. And we haven't given the
FDA the resources to handle the increased scope of activity.
And it is quite probable--if it's not probable, it's at least
possible that the FDA's regulatory scheme has not been up to
the task in terms of overseas inspections.
I was under the impression, until preparing for this
hearing, that an active drug--a new active drug ingredient if
it is from an overseas plant--had to have preapproval, and that
required inspection. Apparently that's not the case because
we've got evidence that the FDA has allowed foreign facilities
to go uninspected or barely inspected. It would seem that that
would be one change that we need to make and we need to make
immediately.
Another issue before us is, I believe that the ability of
the FDA to refuse products to come into this country needs to
be put into statute. I thought again in preparation, not for
this hearing but a previous hearing, that we had the statutory
authority to give to the FDA that if they felt like a facility
or particular drug or base ingredient wasn't safe, they could
refuse its admittance to the United States market. Apparently
that's not the case. It is an authority that the Secretary of
Health and Human Services, Secretary Leavitt, has asked for. It
is an authority that I support giving the FDA, and hopefully
it's an authority we can put into statutory law on a bipartisan
basis later this year.
It is clear that the FDA needs some new thinking in how to
deal with the 21st century in the global commercial market that
we have today. We don't have the luxury that we had even 50
years ago of just staying here, snug as a bug in a rug, in our
home country, and blocking out the rest of the world in terms
of drug imports and things like that. We have to come up with a
system that makes sense both from an economic standpoint, from
a regulatory and manpower standpoint, but also from a safety
and efficacy standpoint. And that is the bottom-line purpose of
this hearing.
The agency needs congressional approval to clarify its
jurisdiction to warrant criminal conduct outside the United
States that threatens the health and safety of the United
States population--again, that's something I hope we can give
the FDA in statutory authority later this year. The FDA needs a
foreign inspection program with many, many more full-time
inspectors overseas and with the availability to go into these
foreign plants and conduct the inspections in overseas plants
like they are allowed to conduct the inspections in domestic
United States plants. Foreign inspections, unfortunately, are
the neglected stepchild of the FDA's drug inspection program
and that simply cannot continue.
I am told Commissioner von Eschenbach has several good
ideas to share with us in this hearing about how to make those
changes. Again, I want to welcome the Commissioner and welcome
the panelists on the other panels. This is an important hearing
and hopefully, while it's an oversight hearing, will lead to
some legislative action that this committee takes to help
remedy this problem in this Congress.
With that, Mr. Chairman, I yield back.
Mr. Stupak. Thank you, Mr. Barton.
Mr. Dingell for opening statement, please.
OPENING STATEMENT OF HON. JOHN D. DINGELL, A REPRESENTATIVE IN
CONGRESS FROM THE STATE OF MICHIGAN
Mr. Dingell. Sir, I thank you for holding this very
important hearing. Today we are here to again explore whether
this administration is adequately able to protect American
citizens from unscrupulous or incompetent foreign manufacturers
of pharmaceutical products or whether they have the will to get
the money and the resources necessary to do so.
Given the findings of this subcommittee of the recent
disturbing events surrounding tainted heparin, I believe that
FDA is clearly not up to the test, or cannot or will not
undertake the reforms needed to protect Americans from this
threat from abroad, or get the resources that they need to
carry out the business that they are charged with. Indeed, they
don't even tell us what their needs are to meet the challenges
that are imposed upon them by their important responsibilities
of protecting the health and safety of American people.
Now, let's summarize some of the Committee's key findings
from its investigation so far. and then let us ask the
Commissioner to defend the indefensible.
First, significant and growing amounts of pharmaceutical
products are used by Americans that are manufactured overseas.
At least 80 percent of all active pharmaceutical ingredients
are now imported, much of it from countries lacking competent
regulatory systems, such as China and India. Current U.S. law
requires FDA to inspect domestic manufacturing firms once every
2 years. But there is no law requiring the same for foreign
firms. And it is to be observed that FDA cannot and does not
investigate foreign firms sending these kinds of substances
into the United States.
While FDA is able to investigate and inspect domestic firms
about once every 2.7 years, the inspection rate for foreign
firms is once every 13 years or more. In fact at this time, FDA
is able to only inspect about 7 percent of existing foreign
firms shipping drug products to the United States annually.
Now, what does this mean? More than 700 Chinese firms are
currently ``registered'' to export drug products to the United
States. But FDA can only inspect about 10 or 20 of them per
year. In other words, it would take FDA more than 30 years to
inspect each Chinese firm a single time, assuming that no new
firms are added to the list.
The information technology system, or IT system, that FDA
uses to track and manage data on foreign manufacturers and the
drugs they export to the United States is archaic and fraught
with inaccuracies. As a matter of fact, FDA has pointed out to
the Committee or to the public that a recent inspection of one
of the firms involved in the heparin question was the wrong
firm because it had a similar name.
FDA is unable to tell us how many foreign firms are subject
to inspection globally, or where they are located. GAO reports
that FDA cannot determine how many firms are exporting drugs to
the United States. And we are imposing upon American
manufacturers duties to produce safe, effective commodities and
to do so under proper manufacturing practices. No such
imposition is going on with regard to foreign firms, simply
because FDA can't inspect them or tell us that these
requirements are being put in place.
The last time the Commissioner of Food and Drugs was here,
he promised to return and give us the details of how he was
going to fix this sorry mess. I hope that his testimony today
will not resemble what he told the Senate appropriators last
week, which appeared to be extraordinarily short on substance
and heavy on bureaucratic buzz words. I'm hoping that the
Commissioner will finally tell us what additional resources he
needs.
The President's 2009 budget does little, if anything, to
close the gap in foreign inspection rates. To this point,
neither I nor the American people have any reason to believe
that the administration is protecting us or is serious about
protecting us from dangerous foreign-made drugs or raw
materials from which these drugs are made. Frankly, until the
Commissioner honestly tells the Congress what new regulatory
tools are needed and what it will take to fix the broken IT
systems, and how many personnel it will take to inspect foreign
firms with meaningful frequency, I fear that we are going to
continue to see contaminated products entering both our food
and our drug supply, while FDA sits helplessly by watching
calamities impend upon the safety and security of the United
States.
This is an intolerable situation and this committee intends
to address this with legislation this year. We hope that the
Food and Drug Administration and this administration will do
something about these matters. If they will cooperate and help,
it will make it easier; but if they won't, we will do it to
them anyway.
Thank you, Mr. Chairman.
Mr. Stupak. Thank you, Mr. Dingell.
Mr. Shimkus for an opening statement, please, sir.
OPENING STATEMENT OF HON. JOHN SHIMKUS, A REPRESENTATIVE IN
CONGRESS FROM THE STATE OF ILLINOIS
Mr. Shimkus. Thank you, Mr. Chairman. Today's hearing
revisits the question of great and urgent importance to the
American public and that is, What must the Food and Drug
Administration do or be able to do to assure the safety of
drugs in bulk drug ingredients imported into the United States?
Part of the answer, of course, involves assuring a sufficiently
robust foreign drug inspection program.
This committee explored the foreign drug inspection program
in some detail at a hearing this past November. As was
established at that hearing, the present situation doesn't make
sense. We have an agency that has focused a majority of its
facility inspections on domestic firms, when most of the
facilities involved in supplying drug product to the American
public are now situated overseas. A good portion of these
facilities are in countries like India and China. And we have
an agency that has not implemented the IT systems and
informational tools to identify fully and rapidly the risks
confronting us from abroad, let alone identify all the foreign
facilities that should be subject to inspection.
We have already heard the numbers that show the imbalance
in risk priorities, with most domestic firms inspected about
every 2 years, about literally hundreds of foreign firms that
have not seen an inspection, if at all, in a decade. Clearly
these priorities need to be brought closer into balance.
The Subcommittee also established that frequent
surveillance inspections are important for assuring good
manufacturing practices in foreign facilities. Good
manufacturing practices and related safeguards over the supply
chain reduce the risk that dangerous impurities in substandard
products will turn up in U.S. medicine cabinets. Weak quality
assurance safeguards have tragic effects. As Mr. Whitfield
noticed in November, a bulk product that contains an impurity,
something spot-testing may not detect, can cause injury or
death to numerous people.
We saw this with Chinese imports of gentamicin in the late
1990s. We worry that the same may have occurred with heparin
contamination in recent months.
The main reason for today's hearing is for the FDA
Commissioner von Eschenbach to lay out for us his strategy for
improving the Agency's foreign inspection program. He is here
this morning to respond to findings by this subcommittee, and
the GAO as well as the FDA Science Advisory Board. That panel's
subcommittee report painted a picture of the FDA struggling to
fill its public health mission. It described resource
shortfalls, deficient information systems and structural
problems at the Agency that we should address.
I very much appreciate the Commissioner's willingness to
step once more into the Subcommittee's fire, but it is very
important to hear its plans to address the problems we see. We
will hear this morning some positive actions; but are these
actions enough? Is the Agency using all the tools at its
disposal to orient itself fully to the realities of foreign
imports?
For example, we know there are informational tools at the
FDA's disposal, such as pilot Predict system, that promise
large advances in realtime risk assessment. Predict has been
pilot-tested, but we have yet to see this deployed widely. Why
the hold-up? And what does this say about the Agency's
commitment to modernize? More disturbing is the Agency's policy
to waive inspections, even in countries such as China, for
reasons that have nothing to do with the facility risk or
location. This ad hoc waiver may be driven by resource
constraints, but it raises questions about the Agency's policy
priorities as well.
As we move through the hearing today, I think it is
important that first we develop good information about what the
Agency is doing now to improve its information systems and
foreign posture. We should learn how quickly it can bring some
balance between its domestic and foreign inspection priorities.
We should discuss what authorities FDA needs regarding overseas
criminal conduct. This should help us improve our discussions
about what Congress can do legislatively.
And second, as we discuss what more needs to be done, I'm
hopeful we can also discuss where we want the Agency to be 10
years out. Do we want an agency structured as it is today, just
with more people; or can we find some agreement that we need a
smarter, more agile agency, using all the best and integrated
information technology that can tackle the challenges of global
commerce more cost effectively than the current model?
Mr. Chairman, the Subcommittee has done great work to
identify the Agency's weaknesses as they exist today. Let us
gather some facts and perspective to develop a vision for this
agency's future as well. I yield back the balance of my time.
Mr. Stupak. I thank you.
I want to ask Mr. Melancon for an opening statement,
please.
Mr. Melancon. Thank you, Mr. Chairman. I'm going to waive
an opening statement and reserve my time for future use. Thank
you.
Mr. Stupak. Mr. Burgess.
OPENING STATEMENT OF HON. MICHAEL C. BURGESS, A REPRESENTATIVE
IN CONGRESS FROM THE STATE OF TEXAS
Mr. Burgess. Thank you, Mr. Chairman, and thank you for
holding this hearing today. I think it's timely and, as the
heparin story unfolds, we have no choice but to be more
proactive in our safety measures abroad.
Mr. Chairman, I'm a physician before I came to Congress,
and I know that I have to trust what I'm prescribing for my
patients. I have to trust that it is not adulterated, that it
has not been mislabeled. I have to trust that someone with
criminal intent has not adulterated the medication. The reason
I trust the medicine is because the Food and Drug
Administration approved it.
If it is acceptable that we do not know exactly who
manufactured the ingredients of the drug, or if those
ingredients are safe or not, or if the factories have even been
inspected, then that whole system comes into question.
Pure and simply, doctors rely on the Food and Drug
Administration to approve drugs that keep the American public
safe, and they've done a great job over the years. That safety
is generally stipulated when a patient comes into a doctor's
office and a prescription or treatment is recommended.
Today, we are very fortunate to have a physician at the
helm of the Food and Drug Administration. Therefore, he can
relate to my concerns about the trust that physicians place in
this Federal agency. I certainly would like to thank Dr. von
Eschenbach for once again appearing before us to continue this
important dialogue on the Food and Drug Administration's
inspection program.
In addition to Dr. von Eschenbach's testimony, we will also
hear from the Chair of the Science Board. When we had our
hearing earlier this year on the report, I was very disturbed
at some of the findings. Dr. Cassell's testimony today will
hopefully shed more light on how the report relates to a Food
and Drug Administration foreign drug inspection program. With
the significant increase in imports, I think this program
should be one of the most crucial programs we have at the Food
and Drug Administration. So, Dr. Cassell, thank you for being
with us today as well.
And I would be remiss if I did not welcome Dr. William
Hubbard. You have provided this committee with great insight,
and I thank you for your commitment to making what I believe is
arguably the most important Federal agency in the United States
better and stronger.
We heard the Chairman--I'm sorry, the Ranking Member of the
subcommittee--Ranking Member of the full committee, rather,
talk about the ability to stop dangerous food imports from
entering our country. H.R. 3967, the Imported Food Safety
Improvement Act that was introduced earlier this year, that
bill came largely as cooperation and instruction and advice
from Al Hubbard, Dr. Hubbard, to our office. And we need the
same authority now for the active pharmaceutical ingredients
that are manufactured in other countries coming into our
country.
Mr. Chairman, we are here today to better understand the
Food and Drug Administration's foreign drug inspection program.
And, unfortunately, we all realize the Food and Drug
Administration has real problems in ensuring that our Nation's
food, drugs, and devices are safe and effective. What is not
clear is how the Agency has responded to these shortcomings,
and how effective these measures have been, and how Congress
could actually be helpful in getting the FDA to make the
necessary changes.
According to the GAO report that we will hear about today,
some changes are being made as to how the FDA handles drug
importation. But these changes will require widely invested
resources and firm leadership in order to have the
accomplishments that we all so much desire.
The former Speaker of this House of Representatives, Newt
Gingrich, says, time and time again, real change requires real
change. New technology is desperately needed to help integrate
the databases and modernize the recordkeeping.
Apparently there is talk of starting FDA field offices
overseas, a measure that I would likely support. However, the
mission of these new offices is still not clear in establishing
that clarity should be crucial for receiving the support of
this subcommittee. Meanwhile, we are still consuming drugs from
factories that have never been inspected, are possibly
completely unknown, and we have people dying from these
affected medicines.
The heparin story is still evolving, Mr. Chairman. It is
interesting that no test, no test available would have detected
the hypersulfated chondroitin present in the contaminated
product that came into this country, the very contaminant that
is thought to cause the adverse heparin reactions.
With that, the FDA is trying to improve, and I believe is
trying to improve, under the leadership of Dr. von Eschenbach.
Change and progress is occurring, but these improvements
require resources that have been denied for many years.
Now, the Chairman of the full committee asked a question, a
rhetorical question, I assume: What additional resources the
FDA needs to protect the American people. He questioned the
administration's sincerity about protecting the American
people. I think realistically anyone who has watched this full
committee over the past several weeks would have to wonder
about congressional intent and whether or not that's also
suspect, with the ill-advised bill we had a few weeks ago to
have the FDA take on an entirely new venture to regulate
tobacco. And the lead editorial in today's Wall Street Journal
finishes with the observation, ``congressional priorities are
rarely so grotesque.'' And I would agree with that.
Mr. Chairman, it is not just dollars. We've heard from the
Science Subcommittee the personnel report, and the training of
those personnel are important. The policy and procedures within
the Food and Drug Administration are critical, the lack of
information technology infrastructure prevents--truly prevents
the development of a 21st century system that's needed to
protect Americans. And after all, at the end of the day, that's
what we are all after, providing Americans with the protection
that they have grown to give, that knowledge that they have
grown to accept from the Food and Drug Administration that that
protection is just a given, it is just assured.
With that, Mr. Chairman, I yield back the balance of my
time.
Mr. Stupak. I thank the gentleman.
Seeing no other members, we will call our first witness.
That concludes the opening statements by members of the
subcommittee, and I call our first panel witness to come
forward. Our first panel, we have the Honorable Dr. Andrew von
Eschenbach, Commissioner of the Food and Drug Administration.
It is the policy of this subcommittee to take testimony under
oath. Please be advised that you have the right under the rules
of the House to be advised by counsel during your testimony. Do
you wish to be represented by counsel?
Dr. von Eschenbach. No, sir.
Mr. Stupak. OK.
[Witness sworn.]
Mr. Stupak. Let the record reflect the witness replied in
the affirmative. Doctor, you are now under oath, we will hear
your opening statement. You may submit a longer statement for
inclusion in the record. Commissioner, your opening statement,
please.
STATEMENT OF ANDREW C. VON ESCHENBACH, M.D., COMMISSIONER, FOOD
AND DRUG ADMINISTRATION, WASHINGTON, D.C.
Dr. von Eschenbach. Thank you very much, Chairman Stupak,
Ranking Member Shimkus, members of the Committee, and Chairman
Dingell. Over the past 2\1/2\ years, everytime I have appeared
before this committee my message has been the same: The FDA is
immersed in a rapidly and radically changing world and we must
make radical and rapid changes if we are going to continue our
record of excellence as the world's gold standard regulatory
agency for food and medical products for both people and
animals.
I have consistently endorsed the fact that this would
require additional resources, and over three budget cycles have
presented requests for those additional resources to the
Administration and to Congress. Most importantly, I've
presented to this committee plans and proposals to use current
and future resources wisely and strategically to achieve our
mission to protect and promote the health of every single
person in the country and, in fact, around the world.
Globalization, increased product complexity, and other
market developments, are placing tremendous strains on our
import safety system. These trends are not new and were
anticipated years ago in a report by the GAO. The agency's
response has been deliberate, but nowhere adequate in
proportion to the growth of the challenge.
[Slide shown.]
Dr. von Eschenbach. The first slide I share with you just
demonstrates the volume of FDA-regulated products that are
entering into this country. The data demonstrate that
inspection at our borders for this volume of products could
never be an adequate barrier that would assure protection to
patients and consumers.
[Slide shown.]
Dr. von Eschenbach. The next slide shows the number of
establishments producing drugs outside the United States for
import and, just looking at drugs, there are over 1,300 sites.
And you can multiply this many-fold if you consider active
pharmaceutical ingredients, biologics, medical devices, and
generic drugs. No matter how we arrived at this point, if we
address the challenges of this reality, the solution is not
simply to just do more of what we have done in the past, but we
must do things differently.
[Slide shown.]
Dr. von Eschenbach. The next slide indicates that FDA must
not just be a gatekeeper, but must be involved across the full
life cycle of the products that we regulate, from their very
production to consumption, by imposing strategies that
encompass prevention, intervention, and response across the
entire supply chain, both domestic and foreign.
As you mentioned this morning, Mr. Chairman, at the core of
this systems approach to this total engagement and product life
cycle is the need to create a state-of-the-art information
technology infrastructure with data management systems that are
capable of acquiring the complex and diverse information from
multiple sources with integration and analysis of that
information that defines risks, and targets appropriately FDA's
regulatory resources and actions.
At the last hearing I discussed with you our vision for our
enhanced information technology infrastructure and the progress
we are making along a trajectory toward a total renovation of
this infrastructure by 2010. But information management that
provides comprehensive information about the regulated product
is only one component of what is required. We must assure that
quality is built into these products at the very source of
production, and that all parties involved in the entire supply
chain are held accountable for maintaining that quality. FDA
must be proactive.
In that regard, today, I describe to you a major initiative
of quality assurance: FDA's Beyond our Borders Initiative. This
addresses imported products with a systems-based approach to
the systemic problem of the Agency's regulation of food,
cosmetics, and medical products. The initiative includes a
number of broad activities, including increased collaboration
with foreign regulators, use of third parties to provide
information about regulated industry compliance with FDA
standards, and also providing additional direction to the
regulated industry for their global activities.
Beyond our Borders presents and builds on the very
extensive and successful collaboration we have already
established with foreign counterparts, including more than 70
cooperative agreements and 30 confidentiality agreements with
trusted foreign regulators, many of which provide the
possibility of sharing inspection reports. These relationships
provide a strong foundation for more extensive collaborations
to prevent failure and quality, to intervene earlier when
standards are not being met, and respond more rapidly and
efficiently to signals of adverse outcome.
The increasingly global nature of product development and
production requires our continuous and intensive interaction
beyond our border. This plan includes the establishment of FDA
offices in China, India, Latin America, Europe and the Middle
East. I have been engaged in direct discussions in each of
those areas to obtain support and a welcome for a U.S. FDA
presence, and that progress is well underway, especially to
establishing our first office in China.
FDA can rely in part on these efforts in making important
risk-based decisions regarding imports. Permanent overseas
offices, especially in China, will allow greater access for FDA
inspectors and, very importantly, greater interactions on an
ongoing basis between FDA staff and Chinese officials and
manufacturers to help assure that products that are being
shipped to the United States meet FDA standards for safety and
manufacturing quality.
Another component of Beyond our Borders leverages private
sector resources. As recommended in the President's action plan
for import safety, FDA is pursuing expanded use of third-party
certification by foreign producers to verify compliance with
U.S. safety and security standards with FDA oversight and
verification. These third parties can include foreign
government agencies as well as independent agencies accredited
by the FDA. And they can provide helpful information about
compliance with FDA's requirements. FDA certification will not
supplant our inspectional responsibilities or our regulatory
activities, but will simply complement them and expand our
affect.
To help increase information about foreign facilities, we
will also engage external nongovernmental organizations with
foreign offices to conduct onsite verification of registration
data, product listing information, and the information so
necessary in our ability to understand the source of these
products. We would also be visiting foreign firms and verifying
and documenting that information on a continuous ongoing basis.
Assisting foreign regulators to be able to understand,
implement, and embody FDA standards is another essential
component of this initiative to build capacity beyond the FDA
to a global effort at product safety.
My written testimony about our prevention intervention
response strategy provides more specific information about
Beyond our Borders Initiative and our efforts are underway to
enhance our oversight of imported products. Important of these
is the request of new authorities that will help ensure that
foreign manufacturers of drug products are in compliance with
U.S. law.
We have requested Congress to provide statutory authority
for FDA to require certification by third parties, in certain
circumstances that incoming products must meet U.S. importing
standards; that we can refuse admission of products for which
FDA encounters undue delay, limits, or denials of access for
inspection of foreign manufacturing sites; that we have the
authority to expedite destruction of certain unsafe medical
products and authority to seek asset forfeiture remedies for
criminal offenses regarding fraudulent or counterfeit products.
I appreciate the opportunity to once again be with you
today, and I look forward to answering your questions about the
details of these proposals that will enhance and strengthen
FDA's ability to ensure Americans of the quality of the
products they consume, irrespective of where they are made.
Thank you, Mr. Chairman.
Mr. Stupak. Thank you, Mr. Commissioner.
[The prepared statement of Dr. von Eschenbach follows:]
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
Mr. Stupak. Mr. Commissioner, appreciate you being here
today, and thank you for taking the time to come to the
hearing. We invite you to stick around for our second panel's
testimony. The witnesses on our second panel represent more
than 100 years of working experience with the FDA in the
pharmaceutical industry, as well as significant oversight
experience at the GAO. So while we welcome your testimony, we
think their testimony would also be valuable in assisting you
in making changes at the FDA, and I think it would be
worthwhile for you to listen to it.
I'm going to yield my time for questioning at this point in
time and turn to the Chairman on the full committee, Mr.
Dingell, for questions, please.
Mr. Dingell. Mr. Chairman, you are most kind and
considerate, for which I thank you. Yes or no to these
questions, Mr. Commissioner, because I have very little time.
Isn't it true that in 2007 there were 3,200 foreign firms
registered with FDA to ship drug products into the United
States?
Dr. von Eschenbach. I believe that number is correct, sir,
yes.
Mr. Dingell. Now, is it also true that according to a GAO
audit, you inspect only about 2- to 300 of those foreign
establishments each year?
Dr. von Eschenbach. That's correct, sir.
Mr. Dingell. At current inspection rates, that it will take
FDA more than 13 years to inspect each foreign establishment
once?
Dr. von Eschenbach. Yes, sir. And that's why we need a
systemic approach.
Mr. Dingell. Now, GAO estimates that there are 714 drug
manufacturing establishments in China registered with FDA;
isn't that true? Yes or no.
Dr. von Eschenbach. I believe that to be true, sir. I would
have to check that number.
Mr. Dingell. Now, of these 700 and more firms in China,
isn't it also true that you'd inspect an average of 10 or 20 of
these each year?
Dr. von Eschenbach. Yes, sir.
Mr. Dingell. GAO tells this committee the Agency inspects
each domestic drug manufacturing firm once every 2.7 years. If
FDA is inspecting each foreign firm once every 2 or 3 years,
each domestic firm once every 2 or 3 years, how can you justify
not inspecting foreign firms at the same rate?
Dr. von Eschenbach. Mr. Chairman, we are completely in
agreement that we need to extend our ability to provide
regulatory oversight to firms.
Mr. Dingell. So you're telling me that that situation is
indefensible; is that correct?
Dr. von Eschenbach. It is unacceptable for the future, yes,
sir.
Mr. Dingell. OK. Now let us address your budget. GAO
reports across 41- to 44,000 for each foreign inspection; is
that correct?
Dr. von Eschenbach. I cannot verify that number, sir. We
have slightly different numbers, but----
Mr. Dingell. According to GAO, if FDA were to inspect each
foreign establishment once every 2 years, as is required for
domestic forms--firms, it would cost FDA approximately $70
million. Have you seen these figures?
Dr. von Eschenbach. Yes, sir, I have.
Mr. Dingell. Do you agree with them?
Dr. von Eschenbach. That figure may be somewhat higher than
our estimates, but it is a reasonable number.
Mr. Dingell. It is within the ballpark.
Now, to inspect Chinese firms at the same rate FDA inspects
U.S. firms, it would then cost FDA about $16 million if we use
the estimates of GAO; is that correct?
Dr. von Eschenbach. Approximately; yes, sir.
Mr. Dingell. Do you differ with those?
Dr. von Eschenbach. Well, Mr. Chairman, I think it is
important for me to point out----
Mr. Dingell. Yes or no.
Dr. von Eschenbach [continuing]. That I believe we need to
look not just at the cost of inspections but the entire system
that we're using for inspections, and that may require
different cost.
Mr. Dingell. My time here--my time here is much limited,
and I do apologize, but I've got--quite frankly, I'm going to
be honest with you, I'm establishing that you don't have the
resources and you can't do your job.
Now, GAO reveals the most curious finding, in which the FDA
has dedicated only $11 million for fiscal year 2008 and $13
million for fiscal year in 2009 to conduct all foreign
inspections, and this includes food as well. Are you aware of
that finding?
Dr. von Eschenbach. Yes, sir.
Mr. Dingell. Do you agree with it or disagree with it?
Dr. von Eschenbach. I agree with the finding.
Mr. Dingell. Pardon?
Dr. von Eschenbach. I agree with the finding.
Mr. Dingell. All right. In light of these numbers, does the
FDA need more resources to conduct inspections of foreign drug
manufacturers? Yes or no.
Dr. von Eschenbach. Yes, sir; I've asked for more
resources.
Mr. Dingell. All right. So is it fair for me to say, then,
using FDA's estimate--rather, using GAO's estimate of $16
million just for Chinese firms, your resources here under the
budget request of $11 million and 13 million are not adequate;
isn't that right?
Dr. von Eschenbach. They are not in--they are not in
concurrence with GAO's estimates; that's correct.
Mr. Dingell. OK. Are you telling me that these are adequate
or not?
Dr. von Eschenbach. I'm telling you that we are putting
those to appropriate use. I have requested additional resources
to do more, but I'm trying to make the point that in addition
to doing more, we have to do it differently.
Mr. Dingell. You know, I've been in this business a long
time, and I've had Food and Drug Commissioners constantly tell
me, oh, we're going to have a new means of doing this and we're
going to do this, we're going to be leaner and meaner. It turns
out that they are leaner and poorer and weaker and less capable
of doing their job. And all these promises that I get from
commissioners of Food and Drug about how they are going to do
better turn out to be nothing more or less than, quite frankly,
hooey.
Dr. von Eschenbach. Mr. Chairman, if you will allow me in
the dialogue----
Mr. Dingell. It is very----
Dr. von Eschenbach. Heparin----
Mr. Dingell. I've been talking to Food and Drug
Commissioners for 40 years. You're not the first fella I've had
to skin for not doing his job and coming up here and defending
an indefensible situation. So I want to maintain any respect
for you, but I can't maintain my respect for you if you keep
toe-dancing around the hard facts that curse you with the
inability to do your job because you don't have the resources.
Dr. von Eschenbach. Mr. Chairman, I agree with you that we
need more resources, but I think the point of the story is, the
heparin situation indicated that, even if we had done the
inspection, we would not have detected that contamination.
That's why I'm trying to make the point to you that in addition
to resources for more inspections, which I agree with----
Mr. Dingell. Well----
Dr. von Eschenbach [continuing]. That we also have to
change the system.
Mr. Dingell. How much--let's come right down to the nut-
cutting stage here and let's get a hard answer. How much money
do you really need to carry out your responsibilities? In
regard to foreign inspection, foreigners are not compelled by
absence of inspections by FDA to carry out good manufacturing
practices. American manufacturers are. How much money do you
need to see to it that you put your treatment of foreign
manufacturers of prescription pharmaceuticals and foods in the
same position that you put U.S. manufacturers, because you
inspect U.S. manufacturers on an adequate level and you do not
inspect foreign manufacturers in the same way? How much money
do you need to do the job that you have to have? Now, give me
an answer to that question.
Dr. von Eschenbach. Well, sir if you took the $45,000 for
inspection and multiplied it by the number of facilities----
Mr. Dingell. Mr. Commissioner, just tell me how much do you
need? I'm rather tired of all this toe-dancing. You cannot do
your job, you are not doing your job. How much money do you
need to do it?
Dr. von Eschenbach. Mr. Chairman, that would require me to
present to you a business plan. You gave a figure of $45,000
per inspection, if we were to inspect everything every 2
years----
Mr. Dingell. How much money do you need to do your job if
you do the job on foreigners that you do on Americans? Simple
question. I'm sure you----
Dr. von Eschenbach. It would be the number of facilities.
Mr. Dingell. Repeat it. How much money do you need? You are
carrying water for an administration that is not giving you the
resources that you need. This committee wants you to have the
resources that you need to do the job that you have to do to
protect the American people. Sixty-two people died because of
bad heparin. Hundreds of others were made sick. You presided
over this, because you do not have the resources to do the job
that you need to do.
How much money do you need to do the job that you are
supposed to do to see to it that Americans are safe? You are
the Commissioner of the Food and Drug Administration. You are
presiding over an intolerable situation. How much resources do
you need?
Dr. von Eschenbach. Mr. Chairman, I would like to have the
resources that will enable us to do a systemic overhaul of the
entire process, not a figure that's related to the cost per
inspection times the number of facilities.
Mr. Dingell. I don't want--just how much money do you need,
on the basis of what I have described is going on, to do the
job that you have to do to see to it that good manufacturing
practices are conducted in places like China so as to protect
the American consumers against unsafe commodities? You have one
fine scandal going on, you have others going on with regard to
fish and fish products. And you simply are absolutely incapable
of addressing your responsibilities.
Dr. von Eschenbach. Well, Mr. Chairman, if you wanted an
answer to that question just for drugs, given the formula----
Mr. Dingell. Well, please answer just for drugs.
Dr. von Eschenbach [continuing]. $45,000. It is $45,000 per
inspection times 3,000 facilities, just for drugs. What I am
attempting to do is respond to your question.
Mr. Dingell. I don't want to hear about how you're----
Dr. von Eschenbach. Bigger than that.
Mr. Dingell. Going to have new methodologies and how you're
going to have a new regime for dealing with the Chinese. I just
want you to tell me how much it takes you to provide the same
necessary inspection for Chinese manufacturers of
pharmaceuticals that you have now going on with regard to
American manufacturers, so that you can insist that there be
good manufacturing practices carried forward in China like they
are carried forward in America.
It makes about no sense American manufacturers are getting
raw materials in from China that put American citizens at risk.
So how much do you need to do your responsibility of inspecting
those foreign firms in China to see to it that they carry out
their proper responsibilities of giving us good manufacturing
practices to assure the safety of the American consuming
public? Simple question. How about an answer?
Dr. von Eschenbach. If there are 3,000 facilities in China
at $45,000 per inspection, that would be the figure.
Mr. Dingell. What did he say? What did you say?
Dr. von Eschenbach. If the estimate is that it costs
$45,000 per inspection and there are 3,000 facilities, that
would be the figure. But I'm trying to discuss with you the
fact that I don't believe that is the solution to the problem.
I believe it is much more complex and the solution needs to be
much more comprehensive than simply inspecting a facility.
Mr. Dingell. Well, all right. How do you propose to assure,
then, that good manufacturing practices are carried forward
without inspecting these people?
Dr. von Eschenbach. Well, they need to be inspected. I'm
not precluding that----
Mr. Dingell. All right.
Dr. von Eschenbach [continuing]. This doesn't----
Mr. Dingell. How are you assured that the facilities are
safe? How are you to be assured that they are clean? How are
you to be assured that there are not adulterants added? You
just have a fine fuss going with the Chinese about whether they
are adding illegal components. It is here in the newspaper. Are
you aware of this?
Dr. von Eschenbach. One thing, Mr. Chairman----
Mr. Dingell. Are you aware of this article, Commissioner?
Dr. von Eschenbach. One thing, as I pointed out in my
opening statement, is that we cannot do this on an episodic
basis of going and coming. We have to have offices that are
physically present in these countries where these products are
being produced; engaged in an ongoing continuous presence that
involves inspections and enhancement of our inspection, at the
same time building capacity within those countries.
Mr. Dingell. See, if I can simplify this and get rid of the
toe-dancing here, you've got $45,000 per investigation, you've
got 3,000 firms, that comes to $70 million, am I right?
Dr. von Eschenbach. Yes, I will trust your math, sir.
Mr. Dingell. I note, with apology to you, Mr. Chairman,
that my time has expired. I want to get back into these matters
at a time later.
Commissioner, I have nothing--no ill will towards you. I
have ill will of the most gross sort towards the fact that you
come up here and defend a situation that is indefensible, and
that you are not soliciting the resources that you need to do
your job to protect the American people the way the law says
you should, and that you are tolerating an administration which
is allowing this kind of situation to obtain, because they are
too damn tight to see to it that the American people have the
funds that are necessary to protect them against wrongdoing in
foreign countries.
I yield back the balance of my time.
Mr. Stupak. I thank the Chairman.
Mr. Shimkus for questions, please.
Mr. Shimkus. Thank you, Mr. Chairman.
Dr. von Eschenbach, it is--we knew it would be an
interesting morning, so it is good to have you here. Let me
just put this out just to start with. Did you attempt through
the budgetary process to solicit additional funds to address
some of these funding constraints that the chairman tried to
raise?
Dr. von Eschenbach. Yes, sir, I did.
Mr. Shimkus. Can you say that again?
Dr. von Eschenbach. Yes, sir. I'm sorry. I did.
Mr. Shimkus. Thank you. One of--the success of elected
officials, hopefully, is to try to take the complex and make it
simple for folks to understand. And I think that is where the
frustration comes, because we're not trying to manage an
unwieldy bureaucracy. If we had a dime for every outsider who
came in to reform the Federal bureaucracy with all the great
ideas and then left really being tamed by the bureaucracy, not
able to really develop--and there are some people, and we're
going to hear it from other panelists later on.
Some of the questions that we pose is, how do we remake the
Agency in a new world, in a new era? How do we--some people say
dismantle it. If we were to start over from scratch, what would
we do?
I'm not convinced that more money is always the solution. I
think there is an argument that--more resources in this case.
But, based upon the whole budget and other priorities, as I
will address to the other members of the panel, if you have a
producer, a manufacturing facility in the United States that
has operated 10 years straight, been investigated every 2
years, 5 times, with zero defects, that may call for
readjusting priorities and saying, well, you have clearly got
this down. We are going to come once every 3 years, and then
you can shift to areas that we know need to be inspected.
I like charts and slides, and I can't put this up like you
did. But the reality is, you just have a factory, And we have
got raw materials coming in, and we produce a product, and it
gets to the consumer. And right here in the factory is where
everything happens. And in good manufacturing practices, under
ISO standards or under any type of thing, they test the raw
materials coming in. You test the product that is going out--
you should--and you watch the chain inside the factory to make
sure there is no contamination and you have--you have a
process.
Constitutionally, I know the President proposes a budget.
We always get folks to come up here and complain--it doesn't
matter what administration--they are cutting one side to give
money to another. And we always respond--I always respond what
the President proposes and we dispose.
Constitutionally, all spending begins in the House. So, you
know, as much as we have identified a resource issue--you have
mentioned that you have asked for more resources. It is up to
the House of Representatives in our appropriation process, if
there is a shortfall, for us to do that. And there may be
proposals that come through that will end up doing that. But
the military acronym that we used in the infantry, keep it
simple. There is another one. There are actually 2 S's, but it
is not politically correct to say the second S. Keep it simple.
So based upon the opening statements of your testimony, we
have got a resource concern, and we--that--we also know it is a
manufacturing evaluation in these factories, and we have
technological hurdles that many of us would have hoped we would
have been before and seen a little bit more progress than what
we think we are at. And so that is kind of the analysis that I
have.
We have this chart, the majority put up another one using
the country of China and the United States. But it basically
has the domestic inspections versus--the inspectors versus the
facilities, and there we have foreign, and there is a big gap.
The question is, how do we fix that gap? Can you just--and that
is the whole premise of this whole hearing, is how do we fix
that gap? Tell me how we would do this as simply as possible,
because we are all basically simple people up here.
Dr. von Eschenbach. The answer to your very important point
of looking at this and arriving at a conclusion is the fact
that if we were just simply to increase the number of
inspections, which we need to, but that in itself would not
solve this problem, that--no greater example of that than the
heparin situation in which inspection would have not detected
that contaminant.
And so what I have been attempting to do and what I tried
to share with Chairman Dingell is that, in addition to
addressing the need to increase our inspections, we also need
to overhaul the entire system, everything from the creation of
an information technology infrastructure to working with our
foreign components and other regulatory agencies in other
governments, to working with the private sector in terms of
good manufacturing processes and hold them accountable for
building quality at the outset.
Mr. Shimkus. Because my time is short, get through--I think
we'll build on these.
In the second panel, GAO will testify on the next panel
that, although the Agency has made positive progress in its
databases and in steps to improve foreign inspections, it is
not enough, as I said, to close the gap.
And you've already started talking about commenting. We
have established in good manufacturing that good manufacturing
practice surveillance inspections are critical to assure
quality of the drug supply and that more surveillance of
foreign firms is needed. And I think you would agree with that.
How quickly do you believe it will take us to close this
inspection gap, the gap that I just raised in the first
question?
Dr. von Eschenbach. I believe that trajectory is going to
be limited by our resources and authority and capacity to
absorb the change.
Mr. Shimkus. So tell us the authority and follow up with
the chairman's question on what resources. That's what we need.
Dr. von Eschenbach. The information technology
infrastructure could be in by 2010 to 2012 at the very latest.
The expansion of the workforce and enhancement of our capacity
in our overseas presence could be done again within a matter of
2 to 3 years. So I think the timelines for modernization for
the FDA are relatively in a 5-year frame.
Mr. Shimkus. We will examine heparin next week more
closely. But given the broader implications, would good
manufacturing practices surveillance inspection of the SPL
plant, which did not occur, have provided information that
would have helped in the current investigation? Now, that is a
different question than what you have stated before.
Dr. von Eschenbach. Mr. Shimkus, I cannot answer for that
question as authoritatively today. I don't believe it would
have, based on our current understanding of this investigation
and our findings. But it is ongoing. It is an ongoing
investigation, and I think the final answer is not yet
determined.
Mr. Shimkus. Yesterday, FDA released a warning letter on
the Chinese-based heparin firm that supply the contaminated
product, which said violations cause the heparin to be
considered adulterated. If it wasn't for the heparin recall,
how long do you think this plant would have shipped adulterated
product before it was inspected?
Dr. von Eschenbach. I cannot give you a time on that, sir.
Mr. Shimkus. Its U.S. client apparently didn't catch the
violations. Wouldn't an earlier FDA surveillance inspection
have kept adulterated product off the product?
Dr. von Eschenbach. Well, again, this contaminant was not
detectable by the routine analytical methods. So the answer is
no.
Mr. Shimkus. Well, that's going to be the debating point.
It's not detected. But other aspects of a good manufacturing
product evaluation might have highlighted flaws in the process
where--I concur. I think that under current inspections--see,
we're talking about two things, and I had to learn this. One is
getting the product after it has been produced, smashing it up,
and testing it to see if the efficacy and if it has been
adulterated and all those other things. But the whole process
of the manufacturing processes is watching as the production
line is moving forward. And that is where it is just not
testing the end product, it is testing the production of the
product.
Dr. von Eschenbach. Correct. There is no question that,
based on our inspection, that particular facility would have
come under our regulatory intervention and for other reasons,
and that in itself, perhaps, would have shut down that
particular source. It is my understanding that there are other
factories, other sources whose good manufacturing practices
were quite appropriate and acceptable, yet the contaminant was
still occurring.
So, again, it is the issue of that particular facility had
problems. We would have detected those. But that doesn't mean
we would have detected this contamination of the heparin
supply, because that is much more ubiquitous and would not have
been detected by our routine analysis.
Mr. Shimkus. Yes. And I'll end on this. Mr. Chairman, thank
you for the time.
Our concern is that the possible deviation of the good
manufacturing processes, and I--that's where we want to keep
these issues and highlight that point.
Thank you, Mr. Chairman.
Mr. Stupak. Thank you, Mr. Shimkus.
Mr. Commissioner, on page 4 of the GAO testimony it
states--and I quote--``the regular inspections of manufacturing
establishments are an essential component in ensuring drug
safety,'' end of quote. Do you agree with that?
Dr. von Eschenbach. Yes, sir, I do.
Mr. Stupak. Mr. Commissioner, you keep saying that the
inspection would not have detected the heparin contamination.
You don't know that. You don't know that because you don't know
what you would have found if you would have inspected that lab
or that plant because you didn't inspect them until after we
had these deaths.
In fact, Mr. Commissioner, the opposite can also be true,
can it not, that your lack of inspections, like 30 years in
China, actually encourages manufacturers to do substitutes like
they did in this case here. If I'm not going to be inspected
for 30 years, instead of using the pig intestines that you're
supposed to use, why not use a sulphate chondroitin? No one is
going to catch it, right? So why not use it?
The same thing with melamine. We want to get a higher
protein for this industrial food. Why not put melamine in
there? They're not going to inspect us. It's going to take 30
years, so you'll never catch us.
So one could easily argue that the lack of inspections
actually encourages a less safe product in some of these
plants, is that not true?
Dr. von Eschenbach. That is certainly one possibility, sir.
Mr. Stupak. Sure. So the only definitive answer we can give
is, look, we didn't inspect. It is wrong. We are supposed to
inspect. We inspect in this country every 2 to 3 years. We must
inspect every 2 to 3 years for that deterrent effect that
inspections cause, whether it is in the United States or in
China or anywhere else in the world, correct?
Dr. von Eschenbach. We need to inspect appropriately. And
what I have been trying to express is the fact that we need----
Mr. Stupak. OK. Before you go there, before you go there--
--
Dr. von Eschenbach [continuing]. The number of inspections
or the frequency but the kind of inspections that we're doing.
Mr. Stupak. I'm willing to go there with you, but you have
to agree with me an inspection is a deterrent.
Dr. von Eschenbach. I'm sorry, sir. I didn't hear.
Mr. Stupak. Sure. You would agree with me that the
inspection is a deterrent?
Dr. von Eschenbach. It can be, yes, sir.
Mr. Stupak. I mean, in the short time we have been here,
toothpaste with the antifreeze, DEG, the cough syrup with the
DEG, the melamine, the mixed protein, and now we have the
heparin with chondroitin. So inspections actually act as the
deterrent.
Now, you want to talk about other ways to do inspections.
Our last hearing, I had mentioned in the opening, was January
29th, and you were at that hearing. I know you sat through it,
and we appreciated the fact that you did.
And you're talking about setting up--in fact, Kyle, if you
can put that pyramid up that the inspector had. He has his FDA
on top, FDA presence; and then you have these agreements. You
have this pyramid here. It looks at the very top you have the
FDA, but on the bottom where the work is being done you're
relying on third parties to do it. Is that sort of correct?
Dr. von Eschenbach. No. It is just a little graphic.
Mr. Stupak. Third-party certification program, foreign
competent authority inspections----
Dr. von Eschenbach. That is intended to show that
everything channels up to the FDA as the final authority. But,
actually, you could turn it the other way around and say the
FDA is the foundation for all of that.
Mr. Stupak. Right. And you were talking--when Mr. Dingell
was asking questions, are there other ways to do inspections,
you're talking about third parties and having third-party
certifications, right?
Dr. von Eschenbach. That's one other addition, yes, sir. It
expands our effectiveness and our influence across a wider
horizon.
Mr. Stupak. In one of your earlier slides you show, besides
drugs, we have medical devices, animal food, biologics all
coming into this country from foreign countries, right?
Dr. von Eschenbach. Yes, sir.
Mr. Stupak. January 29th, when you were in a hearing, we
had a the GAO, and they talked about your third-party
inspection programs and--especially on medical device
manufacturing. Your third-party inspection program has been
around since 2004, and it is called the accredited persons
inspection program, the pilot multipurpose audit program. And
it shows that over a 4-year period only 5 inspections had been
accredited by these organizations, these third-party
organizations. And the GAO concluded that the small number of
inspections completed to date by accredited third-party
organizations raises questions about the practicality and
effectiveness of establishing similar programs that rely on
third parties to quickly help FDA fulfill its responsibilities.
So you are saying this proposal you're talking about, even
in your testimony, so far at least in medical devices, it is
not going to work, it is not effective, there is too few of
them. In 4 years, you had 5 inspections only from third
parties. So why is this going to be different?
Dr. von Eschenbach. That's correct. And I have spoken to
the people in CDRH about what some of those barriers were for
acceptance of that third party. There are opportunities, I
think, to improve upon that substantially.
The other thing is, of course, what we define by a third
party. That could also, of course, be other foreign regulatory
agencies which have their own jurisdictions. So it is a much
broader scope.
Mr. Stupak. Sure. But even the FDA says, even in looking at
your Beyond the Borders program, the one you talk about in your
testimony, we are lacking specific implementation steps. What
are the associated time frames would this be on our borders
that--there is a lot of talk about this, but it will have
little impact to reduce the interval between inspections. The
FDA will have to--how do you plan on doing it?
Dr. von Eschenbach. Well----
Mr. Stupak. I mean, you talk----
Dr. von Eschenbach. First of all, it is a multi-pronged
approach. In addition to establishing these FDA Beyond Our
Borders initiative----
Mr. Stupak. OK. What is the main prong? You said this is a
multi-pronged approach. What is the main one?
Dr. von Eschenbach. Enhancing our current inspections.
Mr. Stupak. Enhancing your current inspections. What data
are you going to have to enhance current inspections done by?
Dr. von Eschenbach. We did more foreign inspections this
year than in the history of the FDA. We can do even more next
year in targeting----
Mr. Stupak. Even with $13 million and each one costs
$45,000, you're going to do more?
Dr. von Eschenbach. We are targeting 500 foreign
inspections next year in addition to creating a foreign
presence.
Mr. Stupak. Five hundred at $45,000. I wasn't a math major.
That would be about $200 million you're going to need, and you
ask for $11 million. How is that going to jive?
Dr. von Eschenbach. There is already an inherent--it is up
to 500. We are up to 350, approximately.
Mr. Stupak. OK. So I wasn't a math major. That would be $20
million, not $200 million. So, either way, $20 million is about
half of what you have asked for. So how do you get there?
Dr. von Eschenbach. Well, there is also the capability of
leveraging what we already had in play.
Mr. Stupak. Leveraging with who? Who is going to do the
inspections if you're not doing them? How are you leveraging?
Who is doing them?
Dr. von Eschenbach. We have inspectors in the Agency----
Mr. Stupak. Sure.
Dr. von Eschenbach [continuing]. And we'll need to detail
them to the foreign inspections that we are targeting.
Mr. Stupak. I see. So----
Dr. von Eschenbach. One of the things that is more
efficient----
Mr. Stupak. Your IT system is broken. You don't--how are
you going to prioritize it? The GAO says you can't even tell us
what is being produced and sent to the United States.
Therefore, it is hard to prioritize what is most significant to
prioritize your inspections. So once you start with your IT
system so you know who is out there, what are they sending?
What is the right of the American people?
Dr. von Eschenbach. Yes, sir. And we started that 2 years
ago. That's in midcourse. We anticipate----
Mr. Stupak. When will it be done, your midcourse?
Dr. von Eschenbach. Pardon me?
Mr. Stupak. Your midcourse, when will it be done? Two more
years?
Dr. von Eschenbach. Two more years.
Mr. Stupak. So 2 more years before we have an IT system
that can tell us what is out there, who is producing what, and
then be able to prioritize our inspection. So we have got to
wait 2 more years before we can even prioritize?
Dr. von Eschenbach. It is incremental. It is improving
consistently and constantly, but it won't be at full maturation
until 2 years. The data center, for example, at White Oak at
our consolidated facility is expected to open up in early '09.
Mr. Stupak. Early '09.
OK, it is my understanding that you proposed but not yet
implemented a Foreign Vendor Registration Verification Program.
When is that program going to start? I understand it is
supposed to help improve the accuracy of the information in
your databases. And the way I understand the program, your
Foreign Vendor Registration Verification Program, the FDA is
going to contract with an external organization to physically
conduct site verification on the registration data of the firms
shipping drugs and other FDA-regulated products of the United
States. When is that going to start? Have you began the Foreign
Vendor Registration Verification Program? It sounds to me like
you're saying we can't do it internally, so let's get someone
externally to do it. Have you begun that process?
Dr. von Eschenbach. No. It is a matter of leveraging where
those verifications are occurring for multiple purposes. We can
benefit from that. Because, as you pointed out in the data
system, there is a lot of redundancy. There are, in fact, firms
that registered and are no longer shipping to the United
States, and that is what created that discrepancy in the
database.
Mr. Stupak. Right. So you're going to have this Foreign
Vendor Registration Verification Program. When is that going to
start? Have you contracted with anyone to do this? That's what
I'm asking.
Dr. von Eschenbach. That is in process, And I cannot tell
you when that will be fully implemented. But it is in process.
Mr. Stupak. '09?
Dr. von Eschenbach. I would have to get back to you about
that, sir.
Mr. Stupak. Do you have any money in the budget to
implement a Foreign Vendor Registration Verification Program?
Dr. von Eschenbach. These are parts of the planning of the
budget, yes.
Mr. Stupak. But do you have in '09--is there a line in
there for a Foreign Vendor Registration Verification Program?
Dr. von Eschenbach. I cannot specifically speak to a line
item for that.
Mr. Stupak. OK. Shouldn't we really assign, in fact, some
of the legislative proposals have indicated a unique
identification number to every foreign establishment that makes
a drug and that have all databases, including those used by
FDA, Customs, track activities such as inspection, products
alert? Shouldn't we have that?
Dr. von Eschenbach. Yes, sir.
Mr. Stupak. Do you have that program ready to be
implemented where every establishment----
Dr. von Eschenbach. That is being done in collaboration
with the other agencies that you have talked about.
Mr. Stupak. But you can't give them a foreign inspection
number until you know what firms are out there, right? You have
got to establish the firms first before you can give them a
foreign inspection number, right?
Dr. von Eschenbach. Correct.
Mr. Stupak. OK. So it sounds like you're verifying what is
out there first, correct?
Dr. von Eschenbach. Well, it is a combination of both. It
is through registration and our verification.
Mr. Stupak. OK. My time has expired. Mr. Burgess for
questions.
Mr. Burgess. Thank you, Mr. Chairman.
Dr. von Eschenbach, welcome again to our humble little
subcommittee. Since most of the reason for this hearing today,
at least in my opinion, revolves around the heparin story
coming out of China, let's stay on that for just a minute. What
is the culprit there that is making people sick?
Dr. von Eschenbach. It was a compound that was added to the
heparin that you alluded to earlier, the hypersulfated
chondroitin sulfate.
Mr. Burgess. When you say ``added,'' did Baxter add this?
Dr. von Eschenbach. No, sir. This appears to be coming from
the source in China.
Mr. Burgess. Well, of course, the counter from--at least my
understanding from reading the papers today, the Chinese say,
well, it may have been added in the United States. So we have a
fair degree of certitude that that contaminant was in the
product before it was ever imported to this country?
Dr. von Eschenbach. Yes, sir.
Mr. Burgess. Well, how would someone get it in there?
Dr. von Eschenbach. We haven't determined that at this
point, sir.
Mr. Burgess. We're reasonably sure that this hypersulfated
chondroitin sulfate is the culprit?
Dr. von Eschenbach. Yes, sir.
Mr. Burgess. What are the tests used to detect that?
Dr. von Eschenbach. Well, upon noticing the adverse events
and searching for what the offending component was within the
heparin the patients were receiving, the routine analytical
methods did not detect any abnormality. It wasn't until we did
very sophisticated testing with nuclear magnetic resonance and
a variety of other very sophisticated strategies in highly
specialized laboratories that we were able to detect the
presence of something that shouldn't have been there. And then
that was subsequently identified as this particular compound.
Mr. Burgess. Now, did the Food and Drug Administration
decide to start doing the nuclear magnetic resonance testing on
the compound?
Dr. von Eschenbach. Yes, sir. We launched that
investigation. We engaged both within the FDA as well as
outside the FDA the appropriate scientists. And then, once we
identified the compound, we actually developed an assay that
could be used for routine screening to be able to find that
contaminant in heparin; and that was distributed essentially
worldwide so that many agencies around the world are now using
our assay and evaluating their own heparin supplies.
Mr. Burgess. But in December of 2007, no one, including the
FDA or any of the manufacturers--or the importers, rather, or
any other country would have been using that test?
Dr. von Eschenbach. No, sir. It didn't exist.
Mr. Burgess. It didn't exist. So it would have been
impossible, even had you--we have heard all the stories about
perhaps the wrong manufacturing location was selected for
inspection. But even had all of the inspections--even if we had
had an inspector at every plant in every foreign country,
likely as not this contaminant could have found its way
through?
Dr. von Eschenbach. Yes, sir.
Mr. Burgess. In fact, it seems very likely that this
contaminant would have found its way through.
Mr. Stupak brings up a good point about we have got the
melamine in the dog food and now we have got hypersulfated
chondroitin sulfate in the heparin. And you do have to wonder,
is this just a very unscrupulous merchant with its thumb on the
scale or is someone actively trying to do us harm? And,
obviously, I wouldn't ask you to speculate since I'm doing that
for you, but it does raise those very big questions.
So what ability do we have--now, we--I realize the dog food
wasn't your purview. But what ability do we have to anticipate
the next level of larceny or terrorism--if I can use that
word--that might come our way in our food or the active
pharmaceutical ingredients that are coming from overseas?
Dr. von Eschenbach. Well, our ability to protect and
promote the public health is going to be dependent upon the
information that we have to act upon. And what I am suggesting
in this system's approach to our ability to now deal with
products that are coming from all over the world, have an
extraordinarily diverse complexity, that we have to be able to
be much more present at the source of the production of those
products.
Mr. Burgess. Not only that, you have got to think like a
thug and have the same type of simulations and--you could not
intuitively have known that this product was going to enter the
pipeline. I mean, none of us----
Dr. von Eschenbach. No.
Mr. Burgess [continuing]. Fat, dumb, and happy last
Christmas would have had any idea that this was about to happen
to our pharmaceutical industry.
I guess what I'm asking is, is there a room of guys over--
or men and women over at the FDA, one of whom who thinks like
criminals, one of whom thinks like terrorists, and they try to
run these simulations? Where is our new vulnerability----
Dr. von Eschenbach. And, in fact--in fact, that has been a
model that we've benefited from as we looked at our food
protection plan. Because we had been approaching food from the
perspective of food defense as it related to intentional
contamination, as well as food safety as it related to the
unintentional contamination that could come from bacteria, et
cetera, and chemicals; and we appreciated the opportunity to
integrate that into a cohesive system that is based on
important intelligence as well as modern scientific analytical
tools. And that's a concept that we have extended to all of the
products that we regulate, and it is inherent in this
prevention/intervention response strategy.
Mr. Burgess. One of the things that really was striking
when we had our food safety hearings earlier this year was the
fact that there is no communication between the various
commercial interests that are overseas importing food back to
our country. There was no communication between them if they
had a bad supplier or they got something that was contaminated
within their shop, that they didn't communicate I guess largely
because of competitive concerns with their counterparts.
But really even more disturbing is that they wouldn't
communicate with the Food and Drug Administration; and it just
seems like now, with the melamine in the dog food and the
hypersulfated chondroitin sulfate in heparin, that there are
some minds out there that require that we be so vigilant that
we are willing to give up some competitive influence or, if
nothing else, the Food and Drug Administration may need to
require that people be forthcoming with this information lest
we get a bucket of chicken wings full of polonium over here
someday, which none of us would like to see.
Dr. von Eschenbach. And to that point, Dr. Burgess, we have
consistently enhanced our dialogue in collaboration with other
Federal agencies, importantly, our relationship with Homeland
Security.
Mr. Burgess. Now, earlier--well, actually, I guess it was
last year--I introduced H.R. 3967. Mr. Hubbard helped us a
great deal with that. And the whole idea there was to have the
ability to stop something from coming into the country if we
knew it was wrong, if we knew it was bad. Right now, it doesn't
seem like we have the tools at our disposal, and Ranking Member
Barton mentioned that in his opening statement, that we don't
have a way to stop this stuff from coming in. And that is--
going forward, that just seems to me to be something that is so
critical that we need to incorporate that into whatever plan
you come up with or we come up with.
The whole concept of equivalence came up when we talked
about food safety, the equivalence standard that the United
States Department of Agriculture has for about 20 percent of
the jurisdiction that it has over imported food; and the Food
and Drug Administration has an 80 percent jurisdiction over
imported food but doesn't have that same equivalency standard
that, even though the manufacturing is in a different country,
it has got to be equivalent to what the manufacturing process
would be in this country. And it is my understanding we don't
even have that equivalence standing for the production of
active pharmaceutical ingredients.
Dr. von Eschenbach. One of the points of FDA Beyond Our
Borders is to work effectively with our foreign counterparts so
that these products meet our standards before they are able to
come into this country. And there is a dialogue in--that I
think we need to find for harmonization.
I convened the first meeting of all of the international
regulators from mature regulatory agencies around the world,
all 27 of them--24, I believe--that came to the meeting 2 years
ago to begin this dialogue, and we've had 3 meetings since.
Mr. Burgess. Well--but it seems like the standards already
set by the USDA would be--again, that equivalency standard
would be one that would be pretty easy. We talk about
harmonization. That is great. But we have a standard out there
that works reasonably well for the 20 percent jurisdiction that
is out there. And at least for the active pharmaceutical
ingredients, it seems like that is something that we should be
quick to pick up.
Dr. von Eschenbach. There may be some issues with regard to
the individual products that may or may not create unique
concerns about equivalence, but it is an area we are
discussing.
Mr. Burgess. Do you have--does this discussion we are
having about heparin right now--and I realize that heparin
would not fall into the debate about bio-similars or bio-
identicals. But just the fact that we have got the story out
there with an adulterated product, does this affect the debate
on the so-called generic biologics--bio-similar products that
this committee--Health Subcommittee of this full committee is
investigating?
Dr. von Eschenbach. Well, again, I think, Dr. Burgess, it
reflects the important testimony that you heard from our
scientific advisory board at a previous hearing and that one
other component of this systematic modernization of the FDA is
that we have a really robust and strong scientific
infrastructure that will give us the modern tools of science
and technology to make discriminating decisions about these
complex and very difficult products to understand but to do
that in a way that gives us greater insight from a scientific
perspective about those products. And I think whether it is
the--dealing with the complexities of bio-equivalence or
understanding the components of a drug that is causing an
adverse reaction, building the scientific infrastructure is one
other pillar to this new FDA.
Mr. Burgess. Let me just ask you one other question
quickly, because it is about money, and Chairman Dingell went
to some lengths to talk about money. We have heard about the
administration's budget. Of course, Congress has--April 15th
has come and gone, and we have not passed a unified budget
resolution. Clearly, it is up to the House. It is up to House
leadership. In fact, it is up to the Speaker of the House to
work--initiate the work on those appropriations bills, those
critical appropriations bills that you're going to depend upon
to get your funding.
The stories that I'm hearing are likely that we will not be
able to do that work this year. The environment is just too
toxic and too contentious. As a consequence, there will be a
continuing resolution at the end of the fiscal year, which
essentially will leave you at level funding.
So although it is great to go into some sound and fury
about budget numbers, the reality is, the reality for your
agency, is what is being handed to you by the Speaker of the
House is you're likely to have level funding this next year,
this next fiscal year; and how is that going to impact your
ability to do all of these things that we have talked about
this morning?
Dr. von Eschenbach. Well, I believe it has been my
responsibility in the 2\1/2\ years I have been at the FDA to
critically assess the status of the Agency, to bring multiple
partners together to begin to define a strategic plan for what
the Agency needed to accomplish and how it needed to change and
what those initiatives would be that would require support,
would require resources, would require new authorities, and we
have done that across the wide spectrum. Everything from our
food protection plan to now addressing issues----
Mr. Burgess. But in order for you to do our job and for us
to do our job--and, unfortunately, right now, that does not
seem to be the case.
I will yield back the balance of my time.
Mr. Shimkus. You have no time to yield back.
Mr. Stupak. Mr. Melancon for questions, please.
Mr. Melancon. Thank you, Mr. Chairman.
In listening to Mr. Burgess--and we're talking about the
level funding and trying to blame the Speaker, I think we can
go back about a couple of years and blame the previous Speaker
and the majority. So if you want to put blame where it stands
looking at GAO, this decline started sometime back if I recall.
Not trying to put any blame on anybody, but the article
today in the New York Times, one of the things that catches my
attention is Chinese imports--you've had exported poisonous
toothpaste, lead-painted toys, toxic pet food, tainted fish,
and now contaminated medicine. It seems to be getting worse
rather than better. I mean, with all this that is surrounding
us, did you not expect that maybe we would be talking about
heparin or some other medication that is coming from China
today?
Dr. von Eschenbach. I believe what has occurred is not
necessarily things are getting worse. I think what we have done
is systematically uncover what has been a significant set of
issues, and we're addressing them systematically in an effort
to resolve them. I believe even--if you'll give me a moment--
when we first encountered the problem with melamine in pet
food, our ability to interact and work with our Chinese
counterparts at that time was nowhere near as effective as this
most recent episode with heparin, where we had immediate and
rapid access into the country. We worked directly with our
counterparts at the SFDA, sharing specimens, engaging in
analytical processes. So I believe we're making progress, but
the problems are substantial, and they require substantial
effort.
Mr. Melancon. Well--and I hear what you are saying. But
then when you suggest that the heparin was contaminated in
China, the Chinese are saying it got contaminated over on our
side. Isn't there some memorandum of understanding or agreement
that is supposed to be going on between the two countries or is
this just pointing the fingers at each other?
Dr. von Eschenbach. No. There was a scientific dispute, if
you will, about an analytical methodology; and we're engaged in
the discussion of that. We believe the analytical methodologies
that we have applied and are being applied by others are the
correct ones.
Mr. Melancon. Well, it appears to me that this memorandum
of agreement is more like a memorandum of let's disagree. And
it is just--it is a growing tension, I think, between the two
countries. You know, I think what I read in the article, that
there was less pointing of fingers between the Germans and the
Chinese than between the United States and the Chinese over
this heparin issue.
Given China's fundamental difference and understanding of
science used to assess what is causing the tainted heparin
problem, can we trust the Chinese to adequately regulate our
drug supply, since it appears that FDA isn't willing to do it?
Dr. von Eschenbach. Well, the FDA is working very directly
with our counterparts in China. They are engaged, I think, in a
very conscientious effort to improve their entire system within
the country. I have met with their Minister of Health who
believes this is as important to the health and welfare of the
Chinese people as it is to the rest of the world.
Mr. Melancon. What is it that they have done that you can
document?
Dr. von Eschenbach. Well, as part of the memorandum of
understanding, we have really engaged, as I just pointed out
with the heparin situation, in an opportunity for us to work
directly with them, specimen sharing and the ability to get to
the bottom of product----
Mr. Melancon. That's why I concern myself with this
memorandum of misunderstanding or disagreement in that they are
immediately saying it is your fault, it isn't our fault. I
mean, do we not work through the process of how the science is
going to be done on these products so that we'll know?
Dr. von Eschenbach. Yes, sir. We convened an international
meeting at which they were present, and the scientists
internationally have been engaged in this discussion, and we
are continuing that.
Mr. Melancon. Let me go back to the--when we started. GAO
is showing that, in the beginning of '02, we started a decline
in inspectors. Do you have any numbers that go back past '02
that shows that--the budgetary and the number of inspections or
inspections that were done overseas as opposed to inspections
that are done here? I'm trying to see if there was a trend or
if this just started at a certain period of time and is it all
budgetary.
Dr. von Eschenbach. I cannot give you specific numbers. My
recollection of what I evaluated when I looked at this, coming
to FDA, was that the number of foreign inspections had remained
relatively flat, while the number of products and firms that
were producing things and coming into the United States was
growing almost exponentially. So the gap was substantially
widening. And we obviously need to keep pace. So the--I don't
know that the inspections went down as much as stayed flat,
while the demand substantially increased.
Mr. Melancon. So as we've exported all our manufacturing to
other countries we have not kept up with the overseeing of the
manufacturing of these products?
Dr. von Eschenbach. That's correct. We've not kept up with
the globalization that has occurred in the marketplace.
Mr. Melancon. And we're outsourcing again. Maybe we can
outsource people to go out there and do them.
I've had some conversations with some company
representatives. They seem to be opposed to any form of charge
by the Department to pay for the inspections, and I understand
that they don't want to have any cost--any additional cost
incurred. How do we pay for this since we don't have the money,
since we are left with a huge deficit and a huge problem?
Dr. von Eschenbach. I'm sorry.
Mr. Melancon. It's OK.
Dr. von Eschenbach. Well, I have, again, consistently
proposed that the FDA need--should and is on a broad base as
far as its resource infrastructure. Budget appropriations are
an important part of that. User fees have also been a part of
our budget when applied appropriately and segregated
appropriately so that they're not influencing our regulatory
decisions. And I think user fees are an alternative mechanism
of support.
Mr. Melancon. Did someone in the Department, you or someone
within the Department that can make decisions, surely saw this
problem coming toward us, did they not?
Dr. von Eschenbach. I'm sorry, sir.
Mr. Melancon. The inspection problem or the ability to not
inspect, to have the manpower to have the money, no one saw
this coming? Did we just wake up last month and say----
Dr. von Eschenbach. No, sir. When I arrived at FDA 2\1/2\
years ago, I set 5 strategic priorities, one of which was
globalization. And that was an effort to recognize what was
occurring and what had been pointed out by others and to really
begin a very aggressive, systematic, and systemic approach to
being able to address the complexity and the magnitude of the
problem. And what we have been discussing are the parts and
pieces of that.
Mr. Melancon. Well, the difficulty I have with an
aggressive approach is that 2\1/2\, 3\1/2\ years later we are
here; and we are getting dumped on with chemicals and bad drugs
and such as that. Did you come to the Congress? Did you go to
the White House? Did you say to somebody, look, we need to have
the money. Either give it to us in user fees, inspection fees
or set up a mechanism where the companies can send people over
there to inspect the products that are going to be part of
their final products? Did we do any of that?
Dr. von Eschenbach. Yes, sir. For the period of time I have
been at the FDA, I have consistently and continuously requested
increases in the budget. That trajectory is continuing. I have
consistently attempted to bring forward plans of initiatives
that I believed would be demonstrated to have impact and for
which we could be held accountable for outcomes. We have talked
on multiple occasions, just even this morning, about the
transformation of our IT infrastructure.
Mr. Melancon. So you requested the White House for the
increase of the budget over the periods of years?
Dr. von Eschenbach. Yes, sir.
Mr. Melancon. And they have rejected that. How much more
did you ask for for the inspectors from the White House?
Dr. von Eschenbach. While I was going through the budget
presentations and made my request to the Department, that
subsequently went on to the administration and then recommended
to the Congress.
Mr. Melancon. How much? What was the dollar amounts that
you asked for to make sure that we were adequately supervising
overseas manufacturing of our products?
Dr. von Eschenbach. Well, I asked for additional resources;
and I cannot give you that specific number today.
Mr. Melancon. If you could get that back to us so that we
could have that as part of the record, I would sure appreciate
that.
In this changing world that everybody has been talking
about for the last 10 years, surely people have looked to the
future of where the jobs are going to go, or maybe they didn't
look to where the jobs are going to go and where the
manufacturing was going to be done. If we were friends with
everybody in the world, I probably wouldn't be sitting here
having this conversation. But, as Mr. Burgess contemplated,
there are some people that don't really like us, and this may
be an avenue for them, through terrorism, to come after us, and
that is the last thing we need. And so, I would wish that you
would impose upon the administration the importance of food
safety to this country's security.
I think my time is out. I yield back my time, if I have
any.
Mr. Stupak. I thank the gentleman.
Mr. Green for questions, please.
Mr. Green. Thank you, Mr. Chairman.
I would like to welcome Dr. von Eschenbach back.
Mr. Chairman, I apologize for not being here for opening
statements. I ask unanimous consent to have my full statement
placed into the record. I just want my full statement----
Mr. Stupak. Without objection.
[The prepared statement of Mr. Green follows:]
Statement of Hon. Gene Green
Mr. Chairman, thank you for holding this hearing today on
the FDA's foreign drug inspection program. I think this a very
important topic.
As we know from previous hearings in this subcommittee and
the FDA's self assessment report, ``Science and Mission At
Risk,'' the Agency is underfunded and does not have enough
employees or resources to protect the country against unsafe
drugs, medical devices and food.
The inadequacies of the FDA's foreign drug inspection
program were most recently highlighted with the blood thinning
drug heparin.
Initially, the tainted heparin was believed to be an
isolated incident and the active ingredient in the drug was
traced back to a Chinese facility that had never been inspected
due to confusion in the FDA because the name of the facility
was confused with another plant with a similar name.
However, further investigations found the contaminated
heparin products have been found in at least 10 countries, not
including the United States, and have been linked back to 12
different Chinese companies that were somehow involved in the
tainted heparin. A man-made chemical is believed to be
responsible for the adverse reactions and 81 deaths associated
with the drug.
We should not be surprised by the lack of inspections in
foreign drug establishments by the FDA.
According to the GAO in FY07, there were 714 drug
establishments in China, but only 13 inspections were conducted
over the entire year. As another example, India had 410 drug
establishments and only 65 inspections were conducted.
What is alarming is the fact that eighty percent of the
active pharmaceutical ingredients of drugs consumed in the
United States are manufactured abroad and most of those drugs
are manufactured in China and India. And, the FDA has publicly
acknowledged that some foreign facilities may never be
inspected.
Clearly, the FDA foreign drug inspection program needs to
be changed and has some hurdles to overcome.
The FDA currently does not have the authority to conduct
inspections at will overseas and must be invited to a plant in
order to conduct inspections and the FDA often warns plant
officials before they are inspected.
Additionally, the FDA does not rely on end product testing
with drugs as they do with food products, which can detect
contamination in a final product. Also, the FDA does not have
one system to track and monitor foreign drug inspections.
The FDA needs resources including more employees, an IT
system, and appropriate funding. In short, the foreign drug
inspection program needs a complete overhaul in order to ensure
product safety, which I know is something we all want.
Thank you Mr. Chairman, I yield back my time.
----------
Mr. Green. Mr. Chairman, this is not necessarily a question
for our FDA Commissioner, but I find it ironic, because in our
full committee and even our Health Subcommittee over the last
few years, particularly after the 2003 Medicare Prescription
Act or even before, we have had a number of hearings by our
committee concerned about my constituents going on the Internet
and importing pharmaceuticals, whether it be from Canada or
Europe or whatever, because they don't really know where they
come from. And the argument we heard many times is that we
don't know where they come from. We don't know if you're
ordering it from a Canadian pharmacy, or you are maybe ordering
it from a China pharmacy, or somewhere else.
And yet now it seems like what we're hearing is our drugs
that are approved, that 80 percent of the ingredients are
imported. And, you know, we have learned that there is no
oversight over that, or I guess very little, if any.
I guess my concern, if I was in the business of producing a
pharmaceutical, just like if I was in the business of producing
any other product, the responsibility for that assures the
oversight with the FDA but also with that person or that
company who is importing that ingredient, whether it is active
or inactive, is part of something we are putting in our body
that is a pharmaceutical.
Has there been any discussion on what the pharmaceutical
companies--I know our next panel will hear that. Has the FDA
looked and said, OK, did you all go to this plant in China to
look for these ingredients? What--let me see your track record
of what you did. Because you are importing that product to put
it in something that you're putting your name on.
Dr. von Eschenbach. You make a very, very important point,
Mr. Green, that the corporate responsibility is an integral
part of this whole effort and the safety; and FDA holding them
accountable for that has been a part of this. It is required
that they carry out their own quality assurance and are
vigilant in the screening of their materials, and so I do
concur with you that that is an important part of the effort,
and FDA holds them accountable and that secures our supply of
drugs.
Mr. Green. Is there any information you can give the
Oversight Committee, for example, on heparin or whatever else
that may come along? When this developed, did the FDA go to
that company and say, OK, let's see what you did on the quality
of this product that you're selling to our constituents?
Dr. von Eschenbach. Right. When a company imports an
ingredient to--an active pharmaceutical ingredient to
incorporate in the development of a finished product, they are
responsible and accountable for assuring the quality of that
product, and they have to assess it and test it. I think the
point we were making earlier is, with regard to the contaminant
in heparin, none of the conventional tests could detect that
contaminant. So it was something that was beyond our ability to
recognize using conventional testing.
Mr. Green. And I think what you are going to hear from most
of us is that the FDA is the traffic cop, and you need more
resources to do that. And I appreciate you asking the
administration.
It is also our job as Members of Congress. Although when
the Chairman miscalculated $200 million to $20 million--that's
why we are not the Appropriations Committee. But if we were, we
would probably be--what we've heard for a number of months--we
would probably be saying, yes, we need to upgrade and provide a
lot more funding so you can do your job as the traffic cop but
not take away the corporate responsibility.
Because I am speeding down the road, and I have an
accident, sure, if there had been a policeman there to stop me,
I wouldn't have had that accident, but it is still my
responsibility for speeding down that road. And, Mr. Chairman,
I think that's what we need. Maybe the next panel will explain
the corporate responsibility along with our effort to try and
make sure the FDA does their job as a traffic cop.
I yield back.
Mr. Stupak. Thank you.
Mr. Barton for questions, please.
Mr. Barton. Thank you, Mr. Chairman.
Dr. von Eschenbach, my understanding is that recently the
FDA has announced some of its preliminary results in the
heparin investigation, and it is my understanding that your
agency has indicated that you have traced the contaminated
material to China. Is that right?
Dr. von Eschenbach. Yes, sir, that's correct.
Mr. Barton. OK. Now it is also my understanding that the
Chinese authorities don't accept the FDA's findings. Is that
correct?
Dr. von Eschenbach. It is my understanding that the one
difference is that they believed that there was product with
which there were adverse events associated, but they could not
find the contaminant in that product and, therefore, they were
refuting the causal link. Our assay, our methodologies, which
are much more sensitive, did in fact find the contaminant in
that product. So that's where there is a very specific
difference----
Mr. Barton. Where do we go from here?
Dr. von Eschenbach. Well, I think what--where we are at
this point is we have assured that the supply of heparin in
this country today is safe. We have prevented any further
import of product coming from China from--through an import
alert, from companies that are in question. And everything that
is coming is being tested before it is allowed into the United
States to be sure it is free of the impurities.
Mr. Barton. So you--under current law, the FDA has the
authority in this case to prevent any product manufactured in
China of that name from coming into the country? So even if the
Chinese don't agree, it really doesn't matter, because the FDA
can say you can't bring it in?
Dr. von Eschenbach. That's correct. We deemed it
adulterated.
Mr. Barton. OK. Now, do we--my understanding is that you
and Secretary Levitt have indicated that you do think that the
FDA needs explicit authority in terms of foreign imports and
foreign inspections to categorically prohibit certain products
when you have found defects in them. Is that correct?
Dr. von Eschenbach. What we've requested, Mr. Chairman, if
I can be explicit, is we can deny a product entry into this
country if we deem it adulterated. What we'd like to do is
extend that to not allowing a product to come in if we haven't
had the opportunity or been given the opportunity to inspect
facilities from which that is coming. So the very fact we have
been denied access to the facility in itself would allow us----
Mr. Barton. So you've got the authority under existing law
to prohibit adulterated material. What you want is the
authority to say, if they refuse to allow U.S. FDA inspectors,
then you can also prohibit the material?
Dr. von Eschenbach. Exactly. Yes, sir.
Mr. Barton. Now, when Chairman Dingell--I wasn't here, but
when Chairman Dingell was asking questions, my understanding is
that he wanted you to give some assurances in terms of numbers
of increased inspectors and in numbers of increased dollars and
assets that you would need in the FDA to instigate these
overseas inspections. Now you told me in my office that you
want to locate FDA inspectors permanently overseas, is that
correct?
Dr. von Eschenbach. Yes, sir, that is correct.
Mr. Barton. All right. Do you have an estimate yet as to
how many inspectors and how much additional resources in terms
of dollars that you would need to implement this kind of
general plan that you have talked to me about?
Dr. von Eschenbach. With specific reference to the first
initiative in China, we would anticipate placing 13 FDA
personnel. Eight of them would be FDA coming from the United
States, and five would be local residents that we would employ.
The approximate cost of that--that would also include our
presence in Beijing, Guangzhou, where there is major food
production, and Shanghai, where the largest exports are
occurring, and the approximate cost of that operation is about
$13 million.
Mr. Barton. $13 million. Now, in that specific case, have
the Chinese authorities been in consultation with you and your
staff?
Dr. von Eschenbach. I apologize, Mr. Chairman. May I
correct that? It is 13 people, but $3.1 million. I apologize.
Mr. Barton. That is a better number. So long as it is an
adequate number. Have you or your staff consulted with the
Chinese authorities about this specific case?
Dr. von Eschenbach. Yes, sir.
Mr. Barton. If so, are they supportive, neutral, in
opposition to it?
Dr. von Eschenbach. They have been very supportive across a
number of their ministries, but we are awaiting approval from
their foreign office. That is still outstanding. But in our
interactions with counterparts and their regulatory agencies,
as well as their export agency, AQSIQ, and the Ministry of
Health, they recognize this is an important opportunity to
enhance capacity.
Mr. Barton. Now, if this plan materializes, will the
inspectors in China have the same authorities as the inspectors
in the United States? In other words, can they go into any
facility at any time or do they have to go through some
procedure that would make it possible to let there be a cover-
up before they were able to actually undertake the inspection?
Dr. von Eschenbach. No, we will anticipate they would have
the same authority as if they were coming from the United
States.
Mr. Barton. OK. On a slightly different topic, it has been
suggested that inspections overseas, facilities overseas that
the U.S. FDA does inspect, that they be inspected on the same
timetable as domestic facilities, i.e., at least once every 2
years. Our GAO friends are going to testify later today that if
we implemented that system, it would cost at least $70 million
a year just for China--no, $70 million a year in total, and of
that cost $17 million would be in China by itself. One, do you
agree with those numbers? And, two, if you do agree with those
numbers, is this funding level something that the FDA can
digest without too much of a growing pain?
Dr. von Eschenbach. Well, to be clear, I don't disagree
with the numbers per se. What I have tried to explain to
Chairman Dingell was I really think the conversation has to be
broadened beyond just the number of inspections and their
frequency. I believe that it needs to be a tiered approach.
There are some facilities that, quite candidly, need to be
inspected more frequently and more intensively than that and
others, by the very nature of their product and their history
on a risk-based approach, may very well be able to be inspected
less frequently than that with oversight by FDA, by having
information and intelligence that comes from other regulatory
agencies who are also doing inspections and by having also
local information from our local counterparts and the producers
and suppliers.
So I was trying to explain to Mr. Dingell that, rather than
simply responding to a formulaic number, that what I really
think we need to do is create a much more strategic system of
inspections that is tiered, that is risk-based, and that is
focused on the particular issues of the product and its source.
Mr. Barton. Well, that system that you just outlined, do
you do that in the United States?
Dr. von Eschenbach. Not to the degree that we need to and
this is all consistent with what is really an integrated
program.
Mr. Barton. So this idea is something that would be
relatively novel if implemented?
Dr. von Eschenbach. Well, I think it is the modern FDA and
it is based also on the importance of having an information
technology infrastructure that supports all this.
Mr. Barton. OK. Well, it is worth pursuing.
My final question, Mr. Chairman. Republican staff have been
noodling some with their pencils and come up to do the foreign
inspections that we think need to be done, we being Republican
staff from the Subcommittee of Oversight and Investigation. It
is going to take about 500 FDA inspectors additionally. Do you
agree or disagree with that number and if you agree with it,
how long do you think it would take to find and train those
inspectors and get them in place overseas?
Dr. von Eschenbach. I can't----
Mr. Barton. That is just on a--that is not an official
estimate. That is Mr. Shimkus' and my staff's best guess. It is
not from some think tank that tens of millions of dollars went
into to come up with.
Dr. von Eschenbach. I can't refute the number. But it would
have to be a phased-in approach to bring the number of people
of that magnitude, more importantly, those skill sets.
Mr. Barton. The number is in the ballpark?
Dr. von Eschenbach. I am going to accept it is in the
ballpark, yes.
Mr. Barton. And do you have a time frame? You were getting
ready to answer that and I cut you off. Two years, 5 years, 3
years?
Dr. von Eschenbach. I believe that could be accomplished,
as I indicated earlier, in an overall time frame of five at the
outset. That particular process could be accomplished as early
as perhaps three.
Mr. Barton. My final question, are there any other
countries that do foreign inspections like we are contemplating
asking, directing the FDA to do? Do the Europeans have foreign
inspections in place----
Dr. von Eschenbach. Yes.
Mr. Barton [continuing]. In China.
Dr. von Eschenbach. Other--not necessarily do they have
offices abroad, but they engage in foreign inspection.
Mr. Barton. Thank you, Mr. Chairman.
Mr. Stupak. Thank you, Mr. Barton.
Mr. Commissioner, are you familiar with the program that
was put in late 1990s with Europe, the mutual recognition
agreement that they attempted to put in?
Dr. von Eschenbach. I am aware of it, sir, but I am not
familiar with all the details.
Mr. Stupak. And what happened to that program?
Dr. von Eschenbach. I apologize, I cannot answer that for
you today.
Mr. Stupak. I was on a committee for a while and it was
under--Mr. Barton actually was the chairman and then we had a
hearing in 1998 on it and basically it didn't work. This was
with Europe, European Union, where we are supposed to do mutual
inspections. In fact, it says under this arrangement the EU
member states will be taking the place of FDA when it comes to
inspections for good manufacturing practices.
Dr. von Eschenbach. Yes.
Mr. Stupak. Now if that program in the late 1990s didn't
work with Europe, which is probably closer to us in culture and
same standards and regulatory system, how on God's green Earth
will it ever work in China, where we have very little in
common? If Europe doesn't work, how is it going to work in
China?
Dr. von Eschenbach. Because I believe fundamentally the
world is a lot different in 2008 than it was in 1998 and
peoples' thinking is different. I've just recently even met a
few days ago with growers.
Mr. Stupak. Well, wouldn't we want to try to get back with
Europe then?
Dr. von Eschenbach. Pardon me.
Mr. Stupak. Wouldn't it be easy to implement this agreement
in Europe and in China? Why wouldn't we go back there and then
the inspectors we are using in Europe we can use them in China
and get to that 500 number that Mr. Barton talked about?
Dr. von Eschenbach. One of the places that is included in
FDA beyond our borders is Europe and working with our European
counterparts----
Mr. Stupak. So do you have an agreement like that in
Europe?
Dr. von Eschenbach [continuing]. Part of this effort. We
haven't established the office in Europe but it is part of the
plan.
Mr. Stupak. Part of the plan, which hasn't worked yet and I
don't see how it is going to work now.
Now let me ask you this, and I don't mean to be
argumentative, draft legislation sent to your office a draft of
our committee--latest copy of our food and drug inspection
legislation. Have you seen this?
Dr. von Eschenbach. Yes, sir, I have.
Mr. Stupak. We sent it to your office. Are you prepared to
comment on it at all?
Dr. von Eschenbach. We are looking forward to working with
you and Chairman Dingell and others on the Committee.
Mr. Stupak. Yes, you say that all the time but you never
comment on our legislation. We are trying to help you out here
so----
Dr. von Eschenbach. Well, my staff has had multiple
interactions with the staff of the Committee, and we look
forward to those continuing with the specifics of the bill.
Mr. Stupak. We would like to know where the FDA stands on
the bill, OK? It is going to be moving quickly, so--in fact one
of the parts in there--let me just ask you a quick question.
Isn't it true that foreign drug manufacturing firms can
register with the FDA even if the firm does not intend on
shipping products to the United States?
Dr. von Eschenbach. Yes, sir.
Mr. Stupak. And in order to do that you have to do an
inspection and everything it costs us taxpayers, right? If you
apply for--you go and do a pre-inspection, right?
Dr. von Eschenbach. I believe that is correct, yes.
Mr. Stupak. OK. According to the GAO, some of these
manufacturers will register with the FDA as a marketing tool
because the FDA registration might be seen as an endorsement of
that plant by the FDA in some foreign markets. Are you aware of
that?
Dr. von Eschenbach. I have heard that alluded to.
Mr. Stupak. And therefore, as in our legislation, wouldn't
the sizable registration fee ensure that foreign establishments
who register with the FDA are serious about actually exporting
drugs to the United States? In other words, a sizable
registration fee, would it weed out those firms who wish just
to register so they can market products elsewhere and not to
the United States?
Dr. von Eschenbach. I can't comment whether that would be
an adequate deterrent or not, sir.
Mr. Stupak. They are gumming up your databases, aren't
they, these firms that applied to get the U.S. certification,
but they never ship; they are sitting in your database or just
gumming up the IT system that we are having so much trouble
with, are they not?
Dr. von Eschenbach. Well, there may be important
intelligence information about those firms that could be
helpful to us. I don't know that it is gumming up the system,
but they shouldn't--
Mr. Stupak. What important intelligence information would
be in the database?
Dr. von Eschenbach. Pardon me.
Mr. Stupak. What important intelligence information would
be beneficial by having them sitting in your database that they
never ship drugs to the United States?
Dr. von Eschenbach. Well, maybe we would learn something
about them that we would never want them to ship drugs into the
United States.
Mr. Stupak. Well, after you pre-approve them and they are
registered, you would never know, because you don't go back and
check them because they are not shipping to the United States.
Dr. von Eschenbach. But by recognizing we might be able to
cross-reference them with other databases that exist in our
other counterparts around the world.
Mr. Stupak. How many man-hours and the amount of resources
have we spent on this heparin investigation, do you know?
Dr. von Eschenbach. How many man-hours are spent what, sir?
Mr. Stupak. On this heparin investigation thus far by the
FDA. You have gone over and done an inspection over there, you
have a couple reports on the 483, we got letters. How much time
have you spent?
Dr. von Eschenbach. I can't give you an exact hourly
figure.
Mr. Stupak. Give me a guesstimation. How many inspections
could we have done if we would have--we have 90,000, 100,000
more?
Dr. von Eschenbach. I couldn't give you that estimate, sir.
Mr. Stupak. OK.
Dr. von Eschenbach. Because I don't think they are exactly
equivalent.
Mr. Stupak. Well, if you had gone over and done the
inspection which was never done in this plant before, you
already did one inspection there, right, on heparin, that is
approximately $45,000, you have a couple of people over there
doing that, right?
Dr. von Eschenbach. Well, the point--I thought the point of
the question you asked me was what was the effort expenditure
across FDA. The effort expenditure----
Mr. Stupak. Correct.
Dr. von Eschenbach [continuing]. Across FDA involved a
whole host of people in a variety of places within the FDA.
That wouldn't necessarily translate into those people doing
inspections.
Mr. Stupak. I see. But to give you more money to do things.
Let me just change gears here for a minute. FDA's primary
goal here is to protect the public health. And let me ask you a
question or two and then I'll--if anyone else wants to ask a
question they can on any issue.
But this bisphenol A, BPA, OK, it is the chemical used in
baby bottles and has terrible side effects. The National
Toxicity Program at NIH has determined BPA may cause neural and
behavioral problems as well as effects in the prostate gland,
mammary gland at an early age for puberty in females. The
Canadian Government has declared BPA to be toxic. The FDA
continues to maintain that it is safe.
While the FDA has undertaken a formal transparent
reassessment safety of BPA, to include those in Federal
Register public comment and expert advisory panels, when do you
expect to have some decision on BPA?
Dr. von Eschenbach. Well, upon learning of the new data,
new information, we immediately convened an interagency task
force to address that new data scientifically, and that is in
process and that will render our opportunity to make a
decision. The Canadians are continuing their process of
assessment with a commentary period. So we will be working with
them, other counterparts, and our own internal scientific
process, which is underway.
Mr. Stupak. When do you expect to have a decision?
Dr. von Eschenbach. I cannot tell you exactly when that
decision will be made, because I don't know what the complexity
of the analysis will involve, but it is underway.
Mr. Stupak. Well, the Canadian Government has already
pulled BPA as being toxic, as they labeled it in their country,
so why has it taken us so much longer to get at this?
Dr. von Eschenbach. I think again, Mr. Stupak, it is going
to be based on what the science dictates and what the science
tells us, and until we have that analysis----
Mr. Stupak. Are you saying the Canadian Government wasn't
based on science?
Dr. von Eschenbach. What I am saying is that FDA is going
to assess the science and make its own independent decision
taking into account the information that is available from
other sources like Canada.
Mr. Stupak. Well, we would like some decisions soon on BPA.
Our subcommittee is working on it and----
Dr. von Eschenbach. We are acting upon this as we speak.
Mr. Stupak. I have heard so many of those promises and they
never come true. So I just want to make sure we have some date
certain that you can give us when we could expect a decision on
BPA.
Any questions, Mr. Shimkus, Mr. Burgess?
Mr. Burgess. Yes, I could--just a couple of follow-ups on
the line of questioning that you were pursuing, Mr. Chairman.
Now, Dr. von Eschenbach, again we will cover the same ground,
but inspectors in every location and every port in the People's
Republic of China wouldn't have found that goop that got into
the heparin, would it?
Dr. von Eschenbach. No, sir.
Mr. Burgess. Because we didn't know it was there. We didn't
test for it. We didn't know to test for it.
Dr. von Eschenbach. Correct.
Mr. Burgess. Now the chairman also talks about how he is
concerned that all of these extra applications coming into the
IT systems are going to gum up the works. Are you at all
concerned--when you think about gumming up the works that might
be a little concern, but are you at all concerned about what we
just did to the Agency with dumping tobacco in your lap?
Because this is a huge new regulatory authority taken over by
your agency that quite honestly we see that we are having
trouble keeping up with what we are supposed to keep up with,
and now we have got a product that when used as directed kills
400,000 people a year and you are going to certify that it is
safe and effective? I mean, it is beyond goofy to think that
that legislation makes sense with the crisis mode that the Food
and Drug Administration is in right now. Again, it is our
premier Federal agency and we are treating it with extreme
disrespect by adding that regulatory requirement to what you
are already doing.
And I don't expect you to answer that because I know that
you are too smart to, but in today's Wall Street Journal you
are quoted: The Food and Drug Administration Commissioner Andy
von Eschenbach told Congress in October that the $5 billion in
user fees over the next decade was not enough to kickstart a
tobacco division, and the Food and Drug Administration may have
to divert funds from its other programs.
Is that--did the Wall Street Journal get it right? Is that
essentially correct?
Dr. von Eschenbach. Well, I think the point of that was
that the monies were not coming to the FDA. They were going to
the general treasury with the idea that you have pointed out--
is that our resources and authorities have to be commensurate
with our responsibilities, so that if we don't have the
capability of carrying out those responsibilities then we will
fail in our mission.
Mr. Burgess. Again, your core mission is to--things have
got to be safe and effective. So can we ever do that with
tobacco? Can we ever say it is safe?
Dr. von Eschenbach. Well, as a physician I know that there
is no way that you can define a tobacco product as being safe.
If used as directed, it produces the result of disease and
death.
Mr. Burgess. Well, now there was, I thought, a very
insightful amendment offered during the markup process that
would have allowed the Food and Drug Administration the
authority to either ban tobacco outright or require that
tobacco manufacturers produce a zero milligram nicotine
cigarette. If you are going to have this authority, would you
not think those two tools in your toolbox would be essential
for securing the public health?
Dr. von Eschenbach. Well, I believe there is a need for a
lot of discussion about what tools are in the toolbox. As you
pointed out, the significant issue of nicotine being the most--
one of the most addictive substances that humans are exposed
to, especially during development as teenagers are, that if you
eliminated that completely you would eliminate the problem of
addiction.
Mr. Burgess. Thank you, Mr. Commissioner. I yield back the
balance of my time.
Mr. Stupak. Thanks. Mr. Melancon or Mr. Green? Mr. Shimkus.
Mr. Shimkus. Just have unanimous consent that I may submit
some questions for the record and just for the statement say
that if--I think a lot of the basic premise here is that if
people want to sell goods and products to our citizens they
need to meet our standards. And if you want to sell goods and
services to our citizens, I think you ought to be willing to
pay for that opportunity since we are the market everybody
wants to get to. And, you know, it shouldn't be the burden
placed upon taxpayers.
I also believe in trust, but verify when you have
international agreements, and also that management by walking
around or inspecting by walking around is still a basic
practice that we all should observe and in this case that is
our concern about not being involved in the factory.
Thank you, Mr. Chairman.
Mr. Stupak. Thank you. You will be happy to know our
legislation does include in there registration fees so
taxpayers aren't paying for it. Please look at it. We are
moving that legislation quickly.
Dr. von Eschenbach, thank you for your time. I hope you
will stay for the next panel. As indicated earlier, they have
100 years of experience in these areas, and hopefully we can
all benefit from their expertise. Thank you again for your
time, sir.
Dr. von Eschenbach. Thank you, Mr. Chairman. Just let me
close by expressing I know what you share and other members of
the Committee share. And that is, although we are talking about
the many important changes that have to occur at FDA, some of
the things that we must always preserve is the caliber and the
quality of the incredible people that make up that agency.
There are--half of the Agency are involved in our field
activities and they are doing heroic work, as you just alluded
to with regard to our ability to immediately mitigate the
problems associated with contaminated heparin. And so I thank
you for our opportunities to present to you a vision for the
future, and I appreciate your recognition of the incredible
efforts that the people of FDA are making on behalf of the
American people.
Mr. Stupak. I agree with you, and the best way we can honor
their work is to give them the resources they need so they can
fully do their job.
Dr. von Eschenbach. I agree with you. Thank you.
Mr. Stupak. I would like to call up our second panel of
witnesses and ask them to come forward here in a few moments.
Gail Cassell, Vice President, Scientific Affairs and
Distinguished Lilly Research Scholar for Infectious Diseases at
Eli Lilly and Company. Dr. Marcia Cross, Director of Public
Health and Military Health Care Issues at the U.S. Government
Accountability Office. Mr. William Hubbard, former FDA
Associate Commissioner and current Senior Advisor to the
Coalition for a Stronger FDA. Mr. Ben England of Benjamin
England & Associates and FDAImports.com. Mr. England previously
held several senior level regulatory positions at the FDA. And
Dr. Carl Nielsen, retired Director of the Division of Import
Operations within the Office of Regulatory Affairs at the FDA.
We will give everybody a minute or two here to assemble
before we do the oath. It is the policy of the subcommittee to
take all testimony under oath. Please be advised that witnesses
have the right under the Rules of the House to be advised by
counsel during their testimony. Do any of you wish to be
represented by counsel? A shaking of the heads indicate no.
Therefore, let's take the oath.
[Witnesses sworn.]
Mr. Stupak. Let the record reflect that witnesses replied
in the affirmative. You are now under oath.
We will now hear a 5-minute opening statement from each of
our witnesses on the second panel. You may submit a longer
statement for inclusion in the hearing record.
Dr. Cross, for the Government Accountability Office, shall
we start with you, please?
STATEMENT OF MARCIA G. CROSSE, DIRECTOR OF PUBLIC HEALTH AND
MILITARY HEALTH CARE ISSUES, U.S. GOVERNMENT ACCOUNTABILITY
OFFICE
Dr. Crosse. Thank you, Mr. Chairman.
Mr. Chairman, members of the subcommittee, I am pleased to
be here today as you examine FDA's foreign drug inspection
program. I testified before this subcommittee last November on
this topic. At that time I discussed how FDA's programs were
not keeping up with the globalization of drug manufacturing. I
testified about weaknesses in FDA's data systems, difficulties
in prioritizing foreign establishments to inspect, infrequent
inspections and challenges unique to conducting foreign
inspections.
Slide, please. I have a slide. This slide shows the large
mismatch between the number of foreign drug establishments and
the number of inspections performed. As you can see, the
largest mismatch is in China. Since the hearing in November,
FDA has announced a number of initiatives to address these
concerns, as we have heard today from the Commissioner. You
asked that we examine these and the extent to which they will
fill the gaps we identified.
FDA's initiatives have the potential to strengthen FDA's
foreign drug inspection program, but they do not fully address
the weaknesses.
Let me discuss in turn the four key areas of concern we
previously raised.
I testified in November that FDA's databases did not
provide an accurate count of foreign establishments and provide
widely divergent counts, with the result that FDA does not know
how many foreign establishments are subject to inspection.
One recent FDA initiative is to require electronic
registration to reduce inaccuracies in its registration
database. However, this will not prevent erroneous registration
by firms that do not manufacture for the U.S. market. Another
initiative aimed at reducing duplication in its import database
is a proposal that FDA has supported to change the data it
receives from Customs and Border Protection on products
entering the United States. However, the implementation of this
proposal is not certain and would require actions from multiple
Federal agencies in addition to FDA.
FDA has also begun efforts to integrate its various
databases. This could provide FDA with a more accurate count of
establishments subject to inspection, but it is too early to
tell how much it will help and this effort has not been fully
funded. In fact, FDA officials told us that implementation has
been slow because the Agency has been forced to shift resources
away from the improvements in order to maintain the current
systems.
Next I testified that gaps in information weaken FDA's
processes for prioritizing the inspection of foreign
establishments that pose the greatest risk to public health.
FDA lacks key information on many foreign establishments. This
limits its ability to use its risk-based approach to select
establishments for inspection.
To address this, FDA has discussed obtaining useful
information such as inspection reports from foreign regulatory
bodies. However, the Agency already has a number of such
agreements in place and it has faced challenges in using these
arrangements in the past. For example, FDA had difficulties in
determining whether the scope of other countries' inspections
met its needs and inspection reports were not always readily
available in English. FDA also told us that complete reliance
on another country's inspection results is risky. The result
has been that FDA only used its existing arrangements six times
in the past year. This raises concerns about some of the
proposals the Commissioner has discussed to rely on inspections
from others.
I also testified in November that FDA inspected relatively
few foreign establishments each year. And at the current rate
it would take FDA more than 13 years to inspect all foreign
establishments just once. FDA slightly increased the number of
foreign drug inspections in fiscal year 2007, but the Agency
still inspects foreign establishments at a substantially lower
rate than domestic establishments.
The foreign inspections shown in the figure are the largest
number that FDA has ever conducted. FDA's budget calls for
incremental increases in funding for foreign inspections. FDA
dedicated about $10 million to foreign drug inspections in
fiscal year 2007 and plans to dedicate about $11 million to
such inspections in fiscal year 2008. However, it would cost
about $70 million per year to perform biennial inspections of
foreign establishments, as is already required for domestic
establishments. The $11 million FDA plans to spend this year
for all foreign drug inspections falls short of the $16 million
that would be needed each year just to conduct biennial
inspections in China.
Finally, I testified that FDA faced certain logistical and
staffing challenges unique to conducting foreign inspections,
including reliance on volunteer inspectors and a lack of
translators. FDA has proposed establishing a dedicated cadre of
staff to conduct foreign inspections, but the overall time
frame associated with this initiative is unclear.
FDA has also announced plans to establish offices overseas
with an initial eight FDA staff to be based in China and five
Chinese nationals to provide translation and logistical
support. However, the impact that these offices will have on
the foreign drug inspection program is unknown because these
staff would be responsible for all FDA regulated products.
In China, in addition to the estimated 714 drug
establishments, there are an estimated 675 medical device
establishments and many more firms manufacturing food and other
FDA-regulated products subject to inspection. The agreement
with China is not finalized and plans for other countries are
still in development.
In conclusion, Americans depend on FDA to ensure the safety
and effectiveness of the drugs they take. The recent incident
involving heparin underscores the importance of FDA's
initiatives. FDA's actions, if fully implemented, could address
some of the concerns we identified. Given the growth in foreign
drug manufacturing for the U.S. market and the relatively few
foreign inspections conducted by FDA, the Agency will need to
devote considerable resources to this area if it is to increase
the rates of inspections. However, FDA's incremental increases
will have little impact in the near future to reduce the
interval between inspections for these establishments.
In addition, many of FDA's initiatives will take several
years to implement and require funding and certain interagency
or intergovernmental agreements that are not yet in place.
Taken together, FDA's plans represent a step forward in filling
the large gaps in FDA's foreign drug inspection program, but do
little to accomplish short-term change.
Mr. Chairman, this concludes my prepared remarks. I will be
happy to answer any questions that you or other members of the
subcommittee may have.
[The prepared statement of Dr. Crosse follows:]
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
Mr. Stupak. Thank you, Doctor.
Dr. Cassell.
STATEMENT OF GAIL H. CASSELL, PH.D., VICE PRESIDENT, SCIENTIFIC
AFFAIRS AND DISTINGUISHED LILLY RESEARCH SCHOLAR FOR INFECTIOUS
DISEASES, ELI LILLY AND COMPANY
Dr. Cassell. Mr. Chairman, members of the subcommittee, I
am Gail Cassell, Vice President for Scientific Affairs and
Distinguished Research Scholar for Infectious Diseases at Eli
Lilly and Company. Of relevance to my testimony today, I have
previously been a member of the advisory committees of the
Directors of both Centers for Disease Control and the National
Institutes of Health. And in 1994-95 I also cochaired the
congressionally mandated review of the NIH Intramural Program.
I appear before you today as a member of the FDA Science Board,
Advisory Committee to the FDA Commissioner. I served as Chair
of the Subcommittee on Science and Technology of the Science
Board, which authored the report that you have heard referenced
today by Chairman Stupak, the ``FDA Science and Mission At
Risk.''
By way of background I just remind you that in December of
2006, the Commissioner charged the Science Board with
establishing a subcommittee to assess whether or not FDA's
current science and technology can support the Agency's
statutory mandate to protect the Nation's food and drug supply.
You have already also heard Mr. Stupak allude to the
composition of the Committee. I would just emphasize that this
committee was made up of a very distinguished group of 30
experts, including former deputy--our former Chief Counsel to
the FDA, as well as knowledgeable experts, some of whom had
worked in FDA. Over 14 members of the 30--of the 33-member
committee were members of the National Academy of Sciences, and
we had one Nobel laureate.
The record of the proceedings of the meeting in which we
presented the results of this report will show that the full
report was accepted by the full Science Board and, in fact, the
full 33-member committee adopted the recommendations of the
report.
For over a year this group of experts worked intensively
conducting their review. It became rapidly apparent that the
FDA suffers from serious scientific deficiencies and is not in
a position to meet current or emerging regulatory
responsibilities. It is agency-wide and not limited to a single
program or center. Since every regulatory decision must be
based upon the best available scientific evidence in order to
protect the public's health, we concluded that American lives
are at risk and that there is an urgent need to address these
deficiencies.
Of relevance to the topic that we have at hand today, which
is that of foreign inspections, especially for drugs, I might
add that many aspects of food and drug manufacturing also
should be based upon the latest, very latest science and
technology, including scientific methods and technologies that
are the latest as far as specificity and sensitivity for
detecting not only chemical contaminants but also microbial
contaminants, and that we should have investigators in the
field performing those manufacturing inspections that in fact
are qualified in terms of quality control and scientific
expertise.
The level of concern by all of the members of our
subcommittee of the Science Board was and remains high, and
thus the intensity of our commitment to the review and their
insistence that define our findings be broadly communicated.
Quite simply, what we found is that FDA resources have not
increased, while the responsibilities have increased
extraordinarily, and you have heard that from many different
individuals today and you'll hear further from others.
We also found that the Agency has not adapted in order to
maximize existing resources by capitalizing upon scientific
resources in the academic community and other government
agencies; i.e., leveraging their resources. The specifics of
our finding was the subject of a hearing, as you have heard Mr.
Stupak refer to this morning, on January the 29th. So I will
not discuss all the findings in detail, but I would rather like
to focus upon those aspects of our review that are most
relevant to the topic of today's hearing on foreign inspection.
Number one is the area of growing disparity between
responsibility and resources; two, gaps in scientific capacity
and capability, information technology and to a lesser extent
organizational structure.
With regards to growing disparity between FDA
responsibility and resources, there is no more quintessential
governmental responsibility than the protection of basic
commodities of American life, such as our food and drugs. The
Science Board emphasizes that the need for an effective FDA is
greater today than ever before since the FDA regulates 80
percent of the Nation's food supply, plays a critical role in
assuring the safety of therapeutics and vaccines and devices,
and regulates a vast number of other consumer products, and
historically has been the Agency to which governments around
the world look to for determinants of the safety of products.
Moreover, something that hasn't been mentioned today, I
would like to emphasize that FDA is increasingly important to
the Nation's economic health, as it regulates a quarter of
consumer expenditures, and the industries that it regulates are
innovative leaders in science and technology and among the few
American industries with a positive trade balance with other
nations. Further, FDA will be a critical component in combating
bioterrorism. That has been alluded to this morning but not to
any great extent. It is something that certainly should be of
great concern to all of us as we talk about potential for
intentional contamination of the food and drug supply as it
relates to bioterrorism.
The Science Board concluded that FDA is slowly being
hollowed out by a progression of budget cuts and inattention to
the Agency's needs. That deterioration in turn means that not
only can the Agency not fulfill its public health mission, but
that the safety of the citizens and the well-being of our
country are undermined. Furthermore, as the Agency falls
further and further behind, the public is increasingly losing
confidence in the government's ability to protect them.
The demands upon the FDA have soared. As we have already
said, the metrics alone are daunting, 125 new statutes added to
the FDA's workload by Congress in the past two decades, most
without resources. And in reference to the number of
establishments we were told during our review that there were a
total of 375,000 establishments outside the United States
making products coming into the United States and in effect
that these were on all continents and over 100 countries.
In addition, there has been a tripling in a decade of R&D
and drugs and medical devices; an exponential increase in drug
adverse reaction reports and the emergence of extraordinarily
new health threats that threaten contamination of products,
including mad cow disease, E. coli 157, et cetera.
But perhaps most emblematic of the trend is the tenfold
increase in the past decade of imports from other countries.
Today, as you know, 15 percent of our food supply is imported
from more than 100 nations, along with over half the drugs. Yet
FDA has been given virtually no new authorities nor resources
to address such a dramatic change in the sourcing from products
made overseas often in developing countries with little or no
tradition of scientific rigor.
What about gaps in capacity and expertise? FDA's resources
have not only not kept pace with responsibilities, many
critical agency programs have sustained actual cuts. I won't go
into the cuts as it relates to food, but certainly that was one
of our areas of biggest concern.
Although one FDA function, new drug and device review, has
received additional funding from industry paid user fees, it is
important for you to realize that the Agency as a whole has
lost a thousand people over the past decade that perform
critical function. Some of them relate to, of course, the
foreign inspection that we are talking about today. This loss
in scientific capacity has resulted in loss of personnel to
perform not only the inspection associated with marketed
products, but is equally important in that it has resulted in
loss of individuals in critical areas of scientific expertise,
and we will come back to that in a minute.
Innovations and advancements in science are outstripping
FDA's capacity to understand and regulate them, and I would
contend that this applies both with regards to manufacturing of
those new products as much as it does to pre-approval of those
new products.
We are on the cusp of another revolution in therapeutics,
breakthroughs in human, animal, and microbial genomics,
molecular biology, nanotechnology, computational mathematics,
imaging, et cetera, that will revolutionize not only medicine
and food production, but also drugs for animal health. Yet FDA
is not and does not have the capacity to prepare for these
breakthroughs, whether it be again in the pre-approval process
or the post-marketing surveillance or manufacturing inspection.
Tens of billions of dollars are being spent by both the
public and private sector on the development of such products,
yet FDA has been denied the relatively minor funding necessary
to ensure their rapid and safe entry into the market. At a time
in which U.S. competitors in science, medicine and food
production are under increasing strain from overseas, a weak
and underfunded FDA will be a brake on the very technologies
that the United States is relying on for its medical and
technological future.
It is absolutely critical that individuals involved in
inspection of these products coming in from overseas in terms
of manufacturing inspections have the adequate science and
technology to allow them to do a better job than they are
currently able to do today. They should have the methods to
perform increased sensitivity tests in looking for
contaminants, both chemical and microbial, both in drugs and in
vaccines, biologics, and also food, perhaps even including,
something, as we heard this morning, maybe others would not
call it quite as sophisticated, it is much more practical than
most would admit, but perhaps information technology as well.
I would also be remiss if I did not remind you, however,
that again the FDA's food safety program is one that needs the
greatest support with regards to these new technologies because
they are simply at rock bottom, both in terms of numbers of
scientists but also their scientific capabilities as far as
monitoring the food supply.
The Science Board subcommittee viewed the current
scientific needs of FDA to be extensive and diverse in critical
terms--in terms of critical expertise, infrastructure and
knowledge perhaps, as I have said, across the Agency, and we do
believe that this is a serious impediment.
FDA, in terms of the recent heparin episode, illustrates
just how critical science is at FDA for monitoring of drug
quality. We heard during our review of the Center for
Biologics, for example, that that center mandates that some of
their scientists be present in manufacturing inspections to
play a role in quality control; i.e., so that they can be
assured that the right technologies are being applied to
evaluate the quality of the drugs being manufactured, and I
would submit to you that this should be something that
shouldn't be an exception with regards to biological products
or vaccines, but it also should be true for drugs.
It is commendable that FDA was able to develop a new test
very quickly that has picked up the contaminant in heparin, but
also has certainly shared it around the world, but in fact
perhaps it could have been done more quickly had more sensitive
tests been in operation and in use all along.
Mr. Stupak. Doctor, would you summarize?
Dr. Cassell. Yes, thank you.
In conclusion, FDA can no longer fulfill its mission
without substantial and sustained additional appropriations,
particularly in the area of information technology. Others will
address this in detail. I will in the questioning if asked. The
current situation has developed over years. The question is not
why or how we got here but how we are going to go forward.
The report actually, we would argue, would serve as a
blueprint with regards to that and we recognize that financial
additions to the budget are not the only answer, as we already
heard this morning. While our report focused upon the FDA
organizational structure related most to the scientific
infrastructure, it might well be in light of continuing issues
related to globalization that we should be asking what FDA
organizational structure is needed to protect the public's
health in the 21st century setting of globalization with
rapidly expanding importation of foreign drugs, vaccines, and
biologics. And again, while our subcommittee focused on
organizational structures that related to the scientific
infrastructure, Congress may like to consider requesting, for
example, the Institute of Medicine to perform a more in-depth
study to evaluate overall agency structure as it relates to
food safety and also drug safety.
And with that, because I am out of time I will stop, but
thank you very much for your patience.
[The prepared statement of Ms. Cassell follows:]
Statement of Gail H. Cassell, Ph.D.
Mr. Chairman and Members of the Subcommittee, I am Gail H.
Cassell, Vice President for Scientific Affairs and a
Distinguished Research Scholar for Infectious Diseases of Eli
Lilly and Company. I am also Professor and Chairman Emeritus of
the Department of Microbiology of the University of Alabama
Schools of Medicine and Dentistry. I am a member of the
Institute of Medicine of the National Academy of Sciences and
am currently serving a second term on the governing board of
the IOM. Of relevance to my testimony today, I have previously
been a member of the Advisory Committees of the Directors of
both the Centers for Disease Control and the National
Institutes of Health (NIH). In 1994-95, I also co-chaired the
congressionally mandated review of the NIH intramural program.
I appear before you today as a member of the FDA Science Board,
Advisory Committee to the FDA Commissioner. I served as Chair
of the Subcommittee on Science and Technology of the Science
Board, which authored the report ``FDA Science and Mission at
Risk.''
Background
In December 2006, the Commissioner charged the Science
Board with establishing a subcommittee to assess whether FDA's
current science and technology can support the Agency's
statutory mandate to protect the Nation's food and drug supply.
The subcommittee was comprised of three Science Board members
and 30 other experts. The subcommittee formally presented its
report to the Science Board and FDA on December 3, 2007. The
report was unanimously endorsed by each of the 33 members of
the Subcommittee and the full Science Board. The Science Board
accepted the report as final and dissolved the subcommittee.
The record of the proceedings of that meeting will show that
due to the seriousness of the deficiencies found and the
urgency of the situation, the Science Board was adamant that
the report be broadly disseminated among the public and policy
makers, including posting it in the Federal Register.
The subcommittee review was unique in many respects. First,
it is only the second time in over a century that the Agency
has been reviewed by an external committee reviewing the Agency
as a whole entity. Second, the Committee was composed of
leaders, not from a single sector, but from industry, academia,
and other government agencies. The expertise and level of
accomplishments of the members are almost unprecedented in a
single committee, especially considering their breadth and
knowledge in regulatory science and understanding of the
mission of the Agency.
The subcommittee included expertise ranging from a Nobel
laureate in pharmacology, 14 members of the National Academy of
sciences (including two engineers), a renowned economist and
specialist in workforce issues, a leader in health care policy
and technology assessment, a former CEO of a large
pharmaceutical company, a former Assistant Secretary for Health
and Human Services who also headed global regulatory affairs
within a large company for over 20 years, a former Chief
Counsel for the FDA, and the first under Secretary for Food
Safety at the U.S. Department of Agriculture overseeing the
Food Safety and Inspection Service and coordinating U.S.
government food safety policy.
For over a year, this group of experts worked intensively
conducting their review. It became rapidly apparent that the
FDA suffers from serious scientific deficiencies and is not
positioned to meet current or emerging regulatory
responsibilities. It is agency wide, i.e. not limited to a
single program or Center. Since every regulatory decision must
be based upon the best available scientific evidence in order
to protect the public's health, we concluded that American
lives are at risk and that there is an urgent need to address
the deficiencies. The level of concern by all members of the
Subcommittee and the Science Board members was, and remains,
high, and thus the intensity of their commitment to this review
and their insistence that the findings be broadly communicated.
What we found is, quite simply, demands of FDA have soared
over the past two decades. Resources have not! Furthermore, we
found that the Agency has not adapted in order to maximize
existing resources by capitalizing upon the scientific
resources in the academic community and other government
agencies.
The specific findings of our review were the subject of a
hearing of this Oversight Committee held on January 29, 2008
``Science and Mission at Risk: FDA's Self-Assessment.'' Thus, I
will not discuss all of the findings in detail today but rather
I would like to focus upon those aspects of our review that are
most relevant to the topic of today's hearing on foreign
inspections: 1) Growing Disparity Between Responsibilities and
Resources; 2) Gaps in Scientific Capacity and Capability; 3)
Information Technology; and 4) Organizational Structure.
Growing Disparity between FDA Responsibilities and Resources
There is no more quintessential governmental responsibility
than the protection of basic commodities of American life such
as our foods and drugs. The Science Board report emphasizes
that the need for an effective FDA is greater than ever before:
FDA regulates 80% of the nation's food supply; plays a critical
role in assuring the safety of therapeutics such as drugs,
vaccines, and medical devices; regulates a vast number of other
consumer products, ranging from televisions and cellular
telephones to cosmetics, blood, and pet food; and has
historically been the Agency to which governments around the
world look to make determinations about the safety of new
products. Moreover, the FDA is increasingly important to the
Nation's economic health, as it regulates a quarter of consumer
expenditures, and the industries it regulates are innovative
leaders in science and technology and among the few American
industries with a positive trade balance with other nations.
Further, FDA will be a critical component in combating emerging
threats such as intentional contamination of the food supply
and the threat of chemical, biological and radiological attack-
as well as naturally occurring threats such as SARS, West Nile
virus, and avian influenza.
The Science Board concluded that FDA is being slowly
``hollowed out'' by a progression of budget cuts and
inattention to the Agency's needs. That deterioration, in turn,
means that not only can the Agency not fulfill its public
health mission, but that the safety of our citizens and the
well being of our economy are being undermined. Further, as the
Agency falls farther and farther behind, the public is
increasingly losing confidence in the government's ability to
protect them.
The demands upon the FDA have soared due to the
extraordinary advance of scientific discoveries, the complexity
of the new products and claims submitted to FDA for approval,
the emergence of heretofore unknown health threats, and the
globalization of the industries that FDA regulates. The metrics
alone are daunting, 125 new statutes added to FDA's workload by
Congress in the past two decades, most without resources to
implement them; 375,000 establishments making FDA-regulated
products; a tripling in a decade of R & D in drugs and medical
devices; an exponential increase in drug adverse reaction
reports; and the emergence in recent years of extraordinary new
health threats, such as, E. coli 0157H:7, AIDS, mad cow
disease, and more. Perhaps most emblematic of this trend is the
ten fold increase in the past decade of imports from other
countries. Today, 15% of our food supply is imported from more
than 100 nations, along with over half of our drugs, yet FDA
has been given virtually no new authorities nor resources to
address a dramatic change in the sourcing (and associated risk)
from products made overseas, often in developing countries with
little or no tradition of scientific rigor.
Gaps in Scientific Capacity and Expertise
FDA's resources have not only not kept pace with its
responsibilities, many critical agency programs have sustained
actual cuts. For example, FDA's food headquarters program has
lost 20% of its scientists in just the past three years,
despite an upswing in outbreaks of foodborne disease in the
United States and a steady increase in contaminated seafood,
produce and other foods being imported from foreign countries.
Similarly, FDA has lost several hundred inspectors due to
budget cuts since 2003, leaving the Agency not only incapable
of inspecting domestic manufacturers but also ensuring that
most of the nation's ports have no FDA inspectors. Although one
FDA function, new drug and device review, has received
additional funding from industry-paid user fees, the Agency as
a whole has lost 1000 people over the past decade. This loss in
scientific capacity has resulted in loss of personnel to
perform inspections associated with marketed products but
equally important, it has resulted in significant and critical
gaps in scientific expertise.
Innovations and advancements in science are outstripping
FDA's capacity to understand and regulate them, threatening not
only the safe introduction of new technologies but also
American leadership in pharmaceuticals, vaccines,
biotechnology, and medical devices. The United States is on the
cusp of another ``revolution'' in therapeutics that holds great
promise for effective treatments of cancer, Alzheimer's,
Parkinson's, and other previously incurable conditions.
Breakthroughs in human, animal, and microbial genomics,
molecular biology, nanotechnology, food processing technology,
computational mathematics, in vivo imaging and many more are
likely to change the face of medicine and food production, yet
FDA has not been given the capacity to prepare for these
breakthroughs. Tens of billions of dollars are being spent by
both the public and private sector on the development of such
products, yet FDA has been denied the relatively minor funding
necessary to ensure their rapid and safe entry into the market.
At a time in which U.S. competitiveness in science, medicine,
and food production are under increasing strain from overseas,
a weak and underfunded FDA will be a brake on the very
technologies that the United States is relying upon for its
medical and technological future.
Our Science Board Subcommittee considered the funding
issues to be more acute for the Center for Food Safety and
Applied Nutrition (CFSAN) than for other FDA programs. FDA's
food safety program is characterized as one steadily dropping
in staffing, and in funding for essential functions. Budget
cuts for food safety have brought the Agency from doing 35,000
domestic food inspections in 1973 to fewer than 8000 in 2007
(meaning FDA inspects most facilities on average only every 10
years). The foreign inspection rate is even worse, as the
Agency may manage to inspect a dozen foreign food manufacturers
in 2008, despite the thousands of overseas producers sending
food to our shores. Moreover, as FDA's leadership in food
safety erodes, other countries are presenting themselves as the
appropriate model for food safety standard setting, even though
such standards can be unscientific and disguised trade
barriers, to the detriment of principles of sound science and
to market access for American food exports. A recent GAO report
indicates that less than 7% of foreign drug manufacturing sites
are inspected annually be FDA.
The Science Board Subcommittee viewed the current
scientific needs of FDA to be extensive and diverse in terms of
critical expertise, infrastructure, and knowledge gaps across
FDA. Again, they were particularly critical in CFSAN. The food
industry is rapidly changing both in terms of its global nature
and the sophistication of the technologies used for production,
processing, and marketing. In addition, the hazards related to
food are changing and evolving in concert with changing food
technologies and food production locales. The food regulatory
program lacks sufficient high-quality applied field and
laboratory research data to understand the mechanisms of
contamination and how to mitigate or eradicate the many
pathogens involved in the food production process.
Additionally, CFSAN scientists are limited in their knowledge
of food production, whether in the agricultural or aquacultural
aspects of food production, especially in foreign production
arenas. The capability and capacity of FDA to detect food-borne
viruses and parasites have not kept pace with the emergence of
this public health threat from international sources. It is
essential that FDA have the capability to rapidly detect food-
borne pathogens. Currently they are limited in scope and have
lengthy time requirements. Quick high throughput technologies
are needed. This is a serious impediment to the US food safety
program. Likewise, quick high throughput technologies are
needed for detecting chemical contamination in both food and
drugs. While the FDA was able to develop an assay for screening
of heparin during the recent adverse reactions, the assay needs
to be adapted to high throughput with improved sensitivity and
adoption for field use.
Information Technology Systems
FDA's information technology systems are woefully outdated
and inadequate, posing a concrete threat to the Agency's public
health mission. The report's authors were extremely disturbed
by the state of FDA's IT infrastructure. We found a situation
problematic at best, at worst dangerous. Many of FDA's systems
are far beyond their expected life span, and systems fail
frequently (even email systems are unstable). Emergency back-up
systems are not in place. I heard recently that the newly
established program related to adverse event reporting was lost
due to failure of a back-up system. This has already resulted
in a 6 week delay in implementation and it remains inoperable.
Reports of product dangers are not rapidly compared and
analyzed, inspectors' reports are still laboriously
handwritten, and the system for managing imported products
cannot communicate with Customs and other government systems.
These inadequacies do not only cause inefficiencies and waste,
but more importantly mean that dangers lurking in information
coming to the FDA are simply missed--such as drug adverse
reactions that are duly reported but not flagged for attention
due to incapacities in information management. Data bases and
data mining capabilities for appropriate tracking of
inspections sites has proved to be a major challenge with
existing technology and expertise. Inaccurate data bases and
data bases not easily mined continue to hamper foreign
inspections for drug manufacturing even though some of the
problems were identified by GAO over a decade ago.
Conclusion
FDA can no longer fulfill its mission without substantial
and sustained additional appropriations. The current situation
has developed over many years, the question is not why or how
we got here but rather how do we strengthen FDA going forward?
Our subcommittee strongly believes our report provides the
required blueprint.
The report is unique in yet another important way. It not
only provides an assessment by a rigorous review of the Agency
by a diverse team of experts from the public and private
sectors, but it also includes a simultaneous assessment by
leaders of the FDA (as contained in Appendices L-M). Our
Subcommittee requested staff to not only identify science and
technology gaps but to link each directly to their specific
regulatory mission. This comprehensive external/internal
analysis--done at the same point in time for an entire Agency--
is indeed rare.
We recognize that adequate resources--human and financial--
alone will not be sufficient to repair the deteriorating state
of science at FDA, which is why our committee also recommended
significant restructuring. While our report focused upon the
FDA organizational structure related most to the scientific
infrastructure, it might well be that in light of continuing
issues related to globalization that we should be asking ``What
FDA organizational structure is needed to protect the public's
health in the 21st century setting of globalization with
rapidly expanding importation of foreign drugs, vaccines,
biologics, and food?'' While our Subcommittee recommended that
the Science Board conduct an extensive review of the Office of
Regulatory Affairs and the National Center for Toxicological
Research, Congress may want to consider requesting IOM to
perform a more in depth study to evaluate the overall Agency
structure given the concerns also raised regarding structure
and drug safety. Regardless of the organizational structure, it
is clear that without a substantial increase in resources, the
Agency will be unable to meet either the mandates of Congress
or the expectations of the American public, regardless of
management or leadership changes. Our findings are supported by
many recent GAO reports as you will hear today as well as
recent reports form the congressional Research Service and the
National Academy of Sciences.
On behalf of our Subcommittee, we thank Chairmen Stupak and
Dingell and ranking members Barton and Shimkus for holding this
hearing and for your recognition of the seriousness of the
deficiencies we have identified and the urgency with which they
need to be addressed. The urgency of our advisory is simply
predicated upon the fact that we see signs of an increasingly
chaotic environment descending upon FDA, and the need to
address the deficiencies we identified. Without immediate
action, injuries and deaths from an overwhelmed regulatory
system are certain, and the costs to our society will be far
greater than any dollar figure upon which we all can agree.
----------
Mr. Stupak. Thank you, Doctor.
Mr. Hubbard, please, for your opening statement.
STATEMENT OF WILLIAM K. HUBBARD, FORMER FDA ASSOCIATE
COMMISSIONER AND CURRENT SENIOR ADVISOR TO THE COALITION FOR A
STRONGER FDA
Mr. Hubbard. Thank you, Mr. Chairman. I have written
testimony. I will just make a few opening remarks.
It is ironic but sad that we were here on November 1st
talking about this at the very time when the initial heparin
deaths began to come in in reports, and so I appreciate the
fact that you stayed with this issue because I do think it
needs to be stayed with until we find a solution. And while FDA
can't with absolute certainty associate the contamination from
Chinese sources, the evidence is pretty darn strong, and the
inadequate conditions that the FDA found when it did inspect
the facility in Changzhou is, I think, indisputable.
I can't overemphasize the risk we are putting our citizens
through by continuing to allow these products to come into our
country with no FDA screening.
You referred, Mr. Chairman, in your opening remarks to
Commissioner Cassell's remarks about why the FDA was created. I
think that is a very appropriate analogy for us to consider.
When Congress created the FDA in '06 you had a marketplace
overrun with problems with foods and drugs, and there were
three characteristics. You had widespread substitution of
cheap, but unsafe food and drug ingredients, things like talcum
for flour and sawdust for cereal, an abundant use of all kinds
of chemicals and drugs and products driven more by profit
motive than by quality, and lastly a weak-to-nonexistent
regulatory system. Well, you know, that sounds familiar,
doesn't it? So these factors are very clearly the case now with
our import system.
FDA has found substitutions of cheaper but dangerous
ingredients, and that is often from less developed nations. You
had mentioned melamine, the antibiotics in seafood, saccharine
masking putrid fish, watered-down apple juice. The list is a
fairly long one. And further, foreign producers, as you
referred earlier, Mr. Chairman, can rely on the fact that FDA
is not on the case and that a firm is unlikely to be caught and
then if they are caught they are unlikely to be punished, and
so that the incentives are all in the wrong place.
And then--and then lastly, you have got equally evident
that the governments of these nations are incapable, in my
view, of assuring the safety of the products they send to us.
In fact, they often deny the very existence of the problem. So
we really only have three alternatives. We do nothing, that has
just been the default for many years, and just hope for the
best. We can rely on the assurances of these foreign
governments, but as I said, I just don't think that is
meaningful in this environment. Or we can accept the fact that
we have not taken care of the FDA and given it the means.
So I'll note that we have built a terrific regulatory
authority in this country with over almost a century. We have
built up the FDA, it has wonderful scientists and dedicated
personnel, but we don't use it in protecting us from these
foreign drugs, which I just think is a tremendous lapse. And we
have not given them the tools and resources they need. You know
as consumers we spend a penny and a half a day on the FDA. And
I believe if we just spend 2 or 3 cents a day on the FDA that
we could fix these problems.
And I think if you polled American citizens, they would put
FDA--the things that FDA does--at the top five or six things
that they would want to see their tax funds spent for. And if
we don't do something, Mr. Chairman, I think we are going to be
back here over and over again having these same discussions.
And in fact, these foreign drugs form a string of ticking time
bombs. Heparin's gone off and I think there are going to be
more until we fix this problem.
And so with that, I thank you for your time.
[The prepared statement of Mr. Hubbard follows:]
Statement of William K. Hubbard
INTRODUCTION
Mr. Chairman and members of the Committee, I am William K.
Hubbard. Before my retirement after 33 years of Federal
service, I served for many years with the U.S. Food and Drug
Administration, and for my last 14 years was an FDA Associate
Commissioner responsible for, among other things, FDA's
regulations and policy development. Although I remain retired
since my departure from FDA, I serve as an advisor to The
Alliance for a Stronger FDA, a consortium of patient, public
interest, and industry organizations whose mission is to urge
that FDA's appropriations be increased. The Alliance and its
constituent members are greatly concerned that FDA's resource
limitations have hampered the Agency's ability to ensure the
safety of our food and drug supply. Today's hearing is a
further exploration of your recent focus on one of those
concerns--the massive increase in pharmaceuticals being
imported into the United States at a time in which FDA's
capacity to oversee those foreign producers is in serious
doubt. Accordingly, I wish to thank the Committee for inviting
me to testify on that subject today.
BACKGROUND
As you know, Congress created the current regulatory
structure for assuring the safety of human drugs in 1938,
through its enactment of the Food, Drug and Cosmetic Act. That
statute recognized that drugs could be a key component of our
health care system, but that drugs were also powerful chemicals
with the capability to produce great harm if not carefully
regulated. Thus, Congress determined it necessary to create a
relatively pervasive regulatory system, a key part of which is
oversight of the production processes by which our drugs are
manufactured. In carrying out its congressional mandate, FDA
has promulgated regulations that provide specific requirements
for drug manufacturers to meet, known as GMPs (for Good
Manufacturing Practices). These include requirements that
active ingredients of the drug be of a prescribed purity,
strength and quality; that the drug be made in well controlled,
sanitary conditions; that its labeling and packaging be equally
well controlled; and that laboratory tests of the drug be
performed routinely using well established scientific methods
and properly calibrated equipment to confirm that the drug is
always produced in the form approved by the FDA.
GMPs and Domestic Drug Production--A Successful Safety
Record. The result of this regime, established by Congress, and
implemented by FDA and drug manufacturers, has been a domestic
drug supply in which Americans can have great confidence with
regard to quality and safety. Combined with the success of the
user fee program that this committee created, we have access to
new drugs as fast or faster than anywhere else in the world and
we can be assured that our medications produced in the United
States conform to equally high production standards. Moreover,
countries around the world have been able to look to the FDA as
the ``gold standard'' for determining if a new drug should be
approved and for establishing safe manufacturing controls for
marketed drugs. But the investigations you have been pursuing
in recent months with regard to imported drugs point to a dark
side of drug manufacturing that threatens to undercut the hard
work of so many and the traditional safety assurances upon
which we have long relied.
FOREIGN SOURCING OF THE U.S. DRUG SUPPLY
The reason for this concern, of course, is that 80% of the
active ingredients in our drugs are now coming from overseas,
and increasingly the so-called ``finished pharmaceutical''--the
pill we take by mouth or liquid injected into our bodies--is
being produced in other countries as well. Further, the most
rapid growth in foreign drug suppliers has occurred in
developing nations such as China and India, with the prospect
of future suppliers from Vietnam, Thailand, Malaysia, and a
host of African counties. Unfortunately, we know from
experience that drugs produced overseas are not given the same
``special'' treatment that we have given drugs made here in the
United States. In most countries, pharmaceuticals products are
subject to normal arbitrage, which means that drugs move about
much as do electronics, apparel, auto parts and thousands of
other goods. This has meant that drugs are often purchased from
suppliers who have little or no oversight by regulatory bodies;
that key elements of safe drug production are ignored--such as
quality testing, expiration dating, and labeling; and that
producers of substandard and counterfeit drugs have a
relatively easy access to the marketplace. Finally, in less
developed countries, it is abundantly clear that the regulatory
bodies, if they exist at all, are weak and ill prepared to
assure the safe production, distribution, and storage of drugs
being exported to the United States.
DRUG COUNTERFEITING
Further complicating and endangering this situation is the
prevalence of counterfeiting around the world. We, of course,
see counterfeit designer clothing, watches and videos being
sold on street corners across the country. But a fake Gucci bag
is likely to pose little threat to your health, while
counterfeit drugs are reported to cause deaths in the hundreds
of thousand worldwide each year. In some countries, it is
estimated that a patient is more likely to get a counterfeit
drug than a real one, meaning that more than half of that
nation's drug supply is fake. Indeed, drug counterfeiting is
considered to be endemic around the world, with the United
States, until recently, a rare exception. But that may be
changing rapidly. FDA has seen its counterfeit drug caseload
soar in recent years, paralleling the movement of drug
production from domestic to foreign sources.
Perhaps this is coincidental, but certainly China has been
alleged to be a principle world supplier of counterfeit
products. For example, a ``sting'' operation by the The Sunday
Times of London last year set up a phony drug wholesaler, who
was able to buy large quantities of counterfeit drugs from a
Chinese manufacturer, who was reported to make pharmaceutical
ingredients for legal sale by day and fake drugs for illicit
sale by night. The Times reported that counterfeiters are
increasingly turning from fake handbags and currency to drugs,
because the drugs are so easy to make and sell on world
markets.
And the New York Times described recently how counterfeit
glycerin, which has been linked to hundreds of deaths in
children when used in cough syrups and analgesics, was traced
through a pipeline ``from the Panamanian port of Colon, back
through trading companies in Barcelona, Spain, and Beijing, to
its beginning near the Yangtze Delta in a place local people
call `chemical country'.''
FDA AND IMPORTED DRUGS
As this is occurring, what has been the reaction by our
regulatory structure--the FDA? I recognize that you and others
in Congress have been highly critical of FDA's oversight of
drug imports in a number of areas--poor identification of
foreign drug sourcing, little examination or testing of drugs
when they arrive at U.S. ports, and virtually no routine
surveillance of foreign drug manufacturers for adherence to
GMPs. But, as you know, I have often defended the Agency as a
cadre of highly capable, dedicated public servants who are
struggling to keep up with the challenges of a rapidly changing
pharmaceutical supply chain. I contend that we as a nation have
failed to give FDA the tools it needs to carry out the mission
we have assigned to them, such as:
Staff to conduct regular inspections in foreign
facilities as are now done for domestic manufacturing plants;
Modern IT systems that would allow FDA to
effectively track and monitor the production and movement of
imports. The import data system is so old and communicates so
poorly with other FDA information systems that it is difficult
for FDA officials to use risk as a predominant driver of their
compliance;
Registration procedures for foreign drug
manufacturing that would allow us to know who is making drugs
for our market, where they are located, and what they are
manufacturing; and
Port inspectors to examine the almost 20 million
annual shipments of foods, drugs, and other products that FDA
is expected to regulation. For over 400 ports of entry, FDA has
only 450 inspectors, meaning that most ports aren't staffed at
all and many can be staffed only part time.
Irrespective of particular needs, however, we must also
face up to the fact that FDA is asked to regulate these
products with a law whose 70th anniversary is this year--a time
in which there were few drugs being made anywhere in the world,
and none being imported into the United States. To use a
transportation analogy, drug manufacturing has moved in the
ensuing years from automobiles to airplanes to spacecraft, and
FDA is still driving a Ford Model T, at least with respect to
imported drugs. Current law and resource allocations for the
FDA place most of the responsibility for assuring the safety of
imported drugs on the Agency. So, while domestic drug
manufacturers are held to a high standard of drug safety, with
regular GMP inspections, foreign producers often need worry
only about the remote possibility that an FDA inspector at a
border crossing will find a problem and stop the drug's entry.
WHERE DO WE GO FROM HERE?
I recognize that members of Congress on both sides of
Capitol Hill are considering a number of legislative
improvements to address import safety. Making major changes in
the regulatory structure will likely be akin to turning a giant
oil tanker--you can start the turn now, but it will take
considerable time to fully change direction. But I believe
there are some key principles that could be adopted right away,
which have been suggested by the GAO and by FDA's Science
Board:
1) We need to initiate GMP inspections of foreign drug
manufacturing facilities immediately, with a special focus on
drugs made in countries without a safe drug production and
internal regulation. Without such inspections, we essentially
have no oversight of those manufacturers. A GMP inspection is
far more than just a snapshot of that facility the day the
inspector arrives. It is a detailed survey of how that plant
has been operating for months, which allows a realistic
conclusion about whether that facility can and does follow
accepted drug production procedures. Relying on testing by the
FDA or the U.S. drug company that receives the foreign
ingredients is not a substitute for examining the source of
production. The GAO notes that FDA today can allocate only
about $11 million for its entire foreign drug inspection
program. That is far too little an effort for such an important
part of our national safety net, but, unfortunately, says a
great deal about our current commitment to assuring the safety
of those drugs. I urge you to support a level of appropriated
funds that will permit FDA to assure that foreign facilities
are complying with our standards.
2) Upgrading FDA's IT systems should be among our highest
priorities. If we don't even have a system for capturing who's
making these products, where they are, what's coming into our
country, and related critical information needs, we can't hope
to begin the process of improving our coverage of imports. The
IT systems should be configured in a way that allows the Agency
to use a myriad of risk factors, including potential impact on
the public health, to direct its inspectional and import
efforts. The Science Board recommends increased appropriations
of $800 million for FDA's overall IT needs, so there is a long
way to go if FDA is to have state-of-the-art information
systems, but we could at least start with funding an effective
import information system.
3) Institute a vigorous mechanism for testing drugs for
ingredients or contaminants that are not approved for that
compound. History has shown that processors, especially in less
developed countries, can be adept at adding substances to
increase the value of the product or decrease costs of
production. But the danger of doing so, whether it be the
industrial plastic melamine in pet food, the polysaccharide
inulin in apple juice, or the dietary supplement chondroitin in
heparin, is well established, and poses an enormous hole in the
safety net we are trying to maintain. Recent events have shown
that U.S. processors and the public can be victimized alike by
these nefarious activities, and we must find a way to end them.
In conclusion, I believe that the scientists within the
Food and Drug Administration have shown that they can
effectively assure the safety of drug production when given the
tools with which to do so. And U.S. drug manufacturers accept
the need for high standards in drug manufacturing and generally
adopt those standards faithfully, and many go to great lengths
to secure their chain of supply of drug ingredients. Drugs made
in the United States under FDA's rigorous quality control
standards have an extraordinarily good safety record, as
measured by the paucity of manufacturing defects and deaths and
illnesses related to manufacturing deficiencies. But it is
obvious that foreign sources do not share in that record of
success. It does no good to have rules if they are not obeyed,
no good to set high standards if they are not used, and no good
to develop advanced scientific skills if they are not employed.
That countries such as China have a record of serious problems
in drug manufacturing is indisputable. And the disparity in
drug inspections--in which FDA inspects U.S. facilities
regularly and those in China and India almost never--is
indefensible. I urge you to make changing that paradigm one of
your highest priorities for this year.
Thank you again for inviting me to give my views on this
subject.
----------
Mr. Stupak. Thank you, Mr. Hubbard.
Mr. Nielsen, please, for your opening statement, sir.
STATEMENT OF CARL R. NIELSEN, RETIRED DIRECTOR OF THE DIVISION
OF IMPORT OPERATIONS, OFFICE OF REGULATORY AFFAIRS, FOOD AND
DRUG ADMINISTRATION, U.S. DEPARTMENT OF HEALTH AND HUMAN
SERVICES
Dr. Nielsen. Mr. Chairman, members of the subcommittee, I
thank you for another opportunity to discuss FDA's foreign drug
inspection program, and I hope my participation will help the
subcommittee develop effective remedies for a public health and
safety system needing serious attention.
The press has been very active the last couple months
following the contaminated heparin story. FDA had a press call
yesterday and reported there are now 81 deaths associated with
the use of contaminated heparin from China. Truly the heparin
story is a tragedy that seems to keep growing in magnitude.
Because the FDA investigation has not isolated the likely node
in the supply chain where the contamination occurred, FDA is
encouraging all batches of heparin to be tested. Is that
sufficient?
FDA wants to be able to say it would not have made a
difference whether the Changzhou plant was inspected earlier,
that the contamination would not have been discovered. FDA is
responding in its usual react mode to a serious injurious event
after the damage is done, not a prevention mode. Granted, the
mandatory identity test in each batch of API received by the
drug manufacturer would not have identified the contamination,
but facility inspections do help leverage safety. I say that
the Chinese foreign manufacturer and its suppliers had adhered
to good manufacturing practices and control of raw material and
if FDA had inspected the plant to verify good manufacturing
practices were in place, then perhaps 81 lives could have been
saved.
If compliance with the current GMP regulations could not
have reasonably prevented or deterred the contamination of the
heparin, then it may be time to finally update and rewrite the
drug GMP regulations rather than trying to convince industry
through nonbinding guidance documents to enhance scrutiny of
active ingredients and other components.
The vulnerability of the U.S. Drug supply to imported
substandard or counterfeit active pharmaceutical ingredients,
or APIs, is not a new issue before the Agency. Beginning in
1991, my colleague Benjamin L. England, who is also appearing
on his behalf, another FDA investigator and I initiated
numerous international investigations with U.S. Customs related
to APIs from several foreign countries, including China.
In my previous testimony before this subcommittee on
November 1st, 2007, I stated those counterfeit investigations
found evidence that there were deaths associated with the use
of carbamezapine, an anti-convulsant made out of imported
counterfeit carbamezapine active ingredient. Those
investigations also found evidence of imported counterfeit APIs
back to the mid-1980s.
Only one of the counterfeit cases was successfully
prosecuted. In March 1996, in a plea agreement the defendant
admitted the importation of several counterfeit APIs for
several years. In May 1996, while I was a senior special agent
in FDA's Office of Criminal Investigations, I wrote an internal
memorandum to the upper management of the OCI describing the
potential threats of harmful impurities being introduced into
finished drugs by counterfeit APIs and APIs from unapproved
sources, and I suggested several strategies to combat the
threats of counterfeit APIs.
This memorandum was produced to this subcommittee by FDA
during a hearing in June 2000 on the subject of counterfeit
drugs. Ultimately, months after I submitted my memorandum, a
meeting was held in the Commissioner's office in February 1997
and the imported counterfeit drug problem was verbally declared
a top priority. Unfortunately, there was a leadership change at
the Agency within a month and the counterfeit API issue largely
left the Agency's radar scope.
It seems it takes numerous deaths now to generate a call to
evaluate and modify FDA requirements and operations. It has
been 8 years since the 2000 hearing on imported counterfeits
and 17 years since the first imported counterfeit API
investigation. The same regulatory requirements for receiving
and accepting components by finished drug manufacturers remain
the same:identity tests and certificates of analyses provided
by the supplier.
Sadly, when looking at the history of the API problem, it
should not be a surprise that it is possible for the recent
heparin incident to occur.
It is time for a radical change in improvement and
adjustment of agency operations that fits the international
trade paradigm and facilitates the trade of safe products. FDA
must have a credible presence in foreign markets to better
ensure compliance with good manufacturing practices and other
requirements that it assure a supply of safe and effective
drugs.
The heparin incident demonstrates just how internationally
linked we are relative to drug safety. Prescription drugs and
over-the-counter medicines may represent less than 10 percent
of all FDA imported regulated commodities, but the heparin
scenario shows the serious cascading adverse health affects of
the contamination of just one common and old drug.
The FDA can be rebuilt, but it will be expensive. The
public health cost is higher though if no significant
investment is made, as demonstrated by the heparin incident.
Effective post-market surveillance activities are essential to
FDA's public health and safety mission.
There are many great ideas for steering FDA effectively
into the 21st century, but without investment in the integrated
IT, execution of the great ideas are not very likely. If the IT
development is functionally absent from corrective measures,
then we should just plan a 10-year reunion to revisit what
should have been known or done to prevent more deaths from
contaminated drugs.
The foreign firms may not be in immediate reach for
inspection, but the products are. Imported drugs are not going
into a black hole.
I thank you for your time and look forward to answering any
questions you may have.
[The prepared statement of Mr. Nielsen follows:]
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
Mr. Stupak. Thank you and thank you for your testimony. Mr.
England, please, your opening statement, sir.
STATEMENT OF BENJAMIN L. ENGLAND, ESQ., BENJAMIN L. ENGLAND &
ASSOCIATES, LLC, AND FDAIMPORTS.COM, INC.
Mr. England. Thank you, Mr. Chairman and members of the
Committee. I am Benjamin L. England, founder and owner of an
FDA consulting practice called FDAImports.com, practicing
attorney, and I represent foreign and domestic food, drug,
medical device, and cosmetic companies in matters that involve
the FDA.
I am a 17-year veteran of the FDA. My written testimony,
which is supplied for the record, discusses my background in
greater detail. I am not going to belabor it here. I am pleased
that the subcommittee has taken up the initiative to press for
solutions for managing these safety risks associated with
imported products again and to focus today specifically upon
FDA's foreign drug inspection program.
I am troubled that we are again meeting in the shadow of
adverse events that have claimed the lives of American
consumers, and we are still hearing about what FDA is doing
after the fact.
The last time I appeared before you I had made mention of
the counterfeit bulk drug investigations of the 90s as well.
And I might--Mr. Nielsen just recounted his efforts to improve
the FDA's investigation of imported counterfeit drugs which was
most likely, at least in my opinion, quashed at some point in
the Agency. In fact, when Mr. Nielsen left OCI--I am going to
tell a story on him and he doesn't know I am going to do it--
but when he left OCI and eventually reported to his job as the
Director of the Division of Import Operations and Policy, he
indicated to his supervisor, his new supervisor, that he was
looking forward to getting back to finding ways to prevent
counterfeit drugs from other countries into this country, to
which his supervisor asked, what counterfeit drugs?
This heparin incident apparently occurred because of some
human error in deciding inspection had already been conducted
or should be conducted. I believe that we are on the brink of a
series of these events and that waiting for FDA's timeline will
be a mistake. The time for developing strict strategies is long
past.
As I said months ago in the press and to your staff, Mr.
Chairman, this recent case appears to be the close cousin of
the counterfeit drug cases discovered nearly 2 years ago--2
decades ago, excuse me.
At that time, the illegal conduct was discovered through
intensive smart facility inspections and by the efforts of
forward thinking forensic scientists and investigators. This
occurred only because of the intellectual connection between
certain domestic inspections at U.S. facilities by a keen FDA
investigator who had previously conducted the foreign
inspection of the bulk supplier, coupled with follow-up
inspections at the foreign supplier, which were themselves
targeted with knowledge of where evidence of illegal conduct
was likely to be found. It is no different today except that we
now have available to us significantly improved technological
solutions that may prove more useful to more precisely and
efficiently identify, target, and intercept safety risks prior
to the realization in the marketplace.
I will provide now just a summary of six of my
recommendations, and at this stage I believe that they are
basically in the order of priority I would put them at. One, it
is axiomatic that FDA's data systems, operational and
management systems alike, have become the breeding grounds for
potential disasters. Now let me be clear. That is not to say
that all the products being imported or distributed into the
U.S. are dangerous or even high risk. Rather, the relative risk
of any of them is not known by the FDA. The agency can barely
manage to do more on a daily basis than to check for
registration numbers, listing numbers, and on a very good day
some Establishment Evaluation data. When determining whether
imported drugs should enter the country, the systems remain
badly stovepiped or siloed and FDA's proposals will take at
least another 5 years to correct them. FDA's solutions appear
primarily to be to lay a common portal over the systems, which
will not actually integrate the legacy systems.
Number two, FDA does not conduct enough foreign GMP
surveillance inspections to constitute a regulatory force in
the world, even though the prized markets for such articles is
here in the United States. The agency should be required to
conduct foreign good measuring practice inspections at the same
frequency as domestic inspections. Even without additional
funding this would level the relevant risks between domestic
and foreign sources of drugs and would force the Agency to
balance those risks against the two sources.
The cGMP surveillance inspection, when conducted by
competent investigators who have at their disposal integrated
account-based information covering the life cycle of products
manufactured by the facility, remains the single most effective
means for detecting the kinds of activities that have been
prevalent in the counterfeiting of drugs, the production of
articles using unapproved sources of materials, and product
substitution. Without a rigorous foreign inspection program FDA
will never prevent the next product contamination before it
causes illness or death.
Three, throwing more money at FDA without requiring the
resources to be used to produce different outcomes will produce
diminishing returns. In my opinion, I believe the most critical
area for increasing funding is in FDA's IT systems. FDA systems
must be far smarter and must be capable of taking data from a
variety of sources, both internal and external, for comparison
against legacy data. Its operational systems must utilize risk-
based algorithms, designed to predict where an exertion of
agency effort will yield positive and measurable safety and
security results.
Without a major reinvention of FDA's IT systems, even the
hundreds of proposals that were in the 2003 import strategic
plan are of limited value. And following that, I would
dramatically increase the resources in the field inspection
force to include dedicated foreign inspection cadres, funding
to increase laboratory capacity, funding for leveraging State
inspections for FDA's domestic operations, and enhancement of
those few headquarters components that are capable of actually
assisting the field operations.
Four, in order to take the most advantage of enhanced IT
systems, the Agency should begin moving immediately to an
account-based regulatory approach that enables the
interconnectivity of regulatory processes along the entire life
cycle of its products to encompass all steps from application
and approval, where required, to the consumer impact.
FDA could learn a lot by understanding how Customs has
moved from a transaction-only approach to an accounts-based
approach that evaluates the transaction in the context of the
account.
Customs has accomplished much of this by requiring each
submission of the data to be connected to a unique numerical
identifier. These identifiers can be related to one another
enabling cross-linking of companies that demonstrate
interrelationships.
Under the current regime the lack of integration of data
accounts means a human must notice slight differences in
company names to assess whether a foreign drug facility has
been ever inspected, and in this regard a unified registration
system could quite easily have prevented some of the deaths as
well.
Five, I believe the organization of the Agency contributes
to its inefficiencies. I recommend again establishing within
FDA an organization that reports to the Commissioner with the
mission of focusing on enhancing the safety of foreign made
products, all products.
I continue to believe fixing FDA's import and foreign
inspection problem requires it to be broken free from the
domestic operation, which produces much of the bureaucratic
inertia against change in this area.
This new organization would be responsible for all
important international-focused work-planning activities,
conducting facility inspections of foreign processors and
importers, overseeing and conducting border operations,
conducting foreign government and industry assessments and
training, and support trade negotiations in a manner to enhance
safety of imported products.
And to accomplish this, the new organization should be
directly funded rather than receiving its funding through the
product centers. A basic persistent infrastructure to manage
risk associated with all imported commodities must be
maintained regardless of the year-to-year changes that may
appropriately occur in program directions.
And six, and finally, perhaps an unpopular solution to some
involves the use of some third parties. In my opinion, FDA
should begin obtaining as much information as it can from as
many reliable sources as the Agency can find regarding the cGMP
compliance status and supply change security programs of
foreign drug facilities that are not inspected by FDA and are
not ever going to be inspected by the FDA.
Additional risk data could come in the form of third party
inspection and certification companies, accompanied by a robust
auditing process on both sides of the border. All such data
should be connected to the firm's unique identifier and
incorporated into the account data to permit its assessment in
light of other legacy and other agency data. This
recommendation would permit the Agency to focus its import
inspection and examination efforts on shipments representing
known and unknown risks.
And I thank the subcommittee Chair and the members for the
opportunity to discuss these important issues again.
[The prepared statement of Mr. England follows:]
Statement of Benjamin L. England, J.D.
1. INTRODUCTION
Mr. Chairman and Members of the Committee, I am Benjamin L.
England, founder and owner of an FDA consulting practice,
FDAImports.com, Inc., and a practicing attorney representing
foreign and domestic food, drug, medical device and cosmetic
companies in matters involving the U.S. Food and Drug
Administration (FDA). I am a 17-year veteran of the U.S. Food
and Drug Administration (FDA). From 1986 to 2003 I held the
positions of Regulatory Microbiologist in FDA's Baltimore
Microbiology Laboratory, Consumer Safety Officer and Compliance
Officer in FDA's Baltimore District Office, Special Agent with
FDA's Office of Criminal Investigations in the Miami Field
Office, Compliance Officer in FDA's Miami Resident Post, and
Regulatory Counsel to FDA's Associate Commissioner for
Regulatory Affairs (or ACRA) in Headquarters. I resigned my
most recent FDA position as Regulatory Counsel to the ACRA in
July 2003--a position I held in FDA for over 3 years as a Title
42 appointee. During my last 3 years at FDA, I was a key point
person for Customs and Border Protection, I chaired the FDA's
Counterfeit Drug Working Group, instituted the Joint Agency-
Industry Working Group to combat product counterfeiting and
tampering, which laid the ground work for the preparation of
FDA's initial Counterfeit Drug Task Force report, and co-
chaired FDA's Import Strategic Plan Steering Committee.
Along with my colleague, Mr. Carl Nielsen, who is also
before you today testifying on his own behalf, I established
the Agency's first series of Import Enforcement Training
Courses, and with a few dedicated FDA and Customs officials,
trained nearly every FDA import inspector, investigator, import
program manager, and compliance officer in the effective use of
Customs enforcement tools against products imported in the U.S.
in violation of FDA requirements.
At the outset, I am pleased the Committee has taken the
initiative to press for solutions for managing safety risks
associated with imported products--and to focus today
specifically upon FDA's foreign drug inspection program. I do
not feel it is necessary to reiterate all of the history in
this testimony, as it is a part of the record from previous
hearings. Some points, however, bear repeating. Further, since
my last appearance before you on November 1, 2007, more
evidence has appeared in the U.S. marketplace laying bare the
brokenness of the regulatory and information technology (IT)
systems FDA is hobbling along with and the real safety risks
that attend the Agency's present condition.
I highlighted in my previous testimony the counterfeit bulk
drug investigations of the 1990s, which were all but abandoned
by FDA. We discussed how reminiscent those cases were to press
accounts identified by the Chair related to counterfeit
articles, both finished and bulk, in any number for foreign
markets. Today we are confronted with serious adverse events
involving a widely used drug product that appears to have been
made using substituted active ingredients at a foreign facility
that was never inspected by FDA--because of some human error in
deciding whether an inspection had already been conducted or
should be conducted. I believe that we are truly on the brink
of a series of these events and that waiting for FDA to take
some action that actually mitigates risk or encouraging the
Agency to act unilaterally will be an exercise in futility. As
I said in the press and to your staff, Mr. Chairman, this
recent case appears to be the close cousin of the same conduct
discovered nearly two decades ago. At that time, it was through
intensive and smart facility inspections and by the efforts of
forward thinking forensic scientists and investigators the
activity was discovered. Moreover, the successfully prosecuted
counterfeit bulk drug case was made possible only through the
intellectual connections between certain domestic inspections
at U.S. facilities by a keen FDA investigator who had
previously conducted the foreign inspection of the bulk
supplier, coupled with follow up inspections at the foreign
supplier, which were themselves targeted with knowledge of
where evidence of illegal conduct was likely to be found.
It is no different today--except that we now have available
to us significantly improved technological solutions that may
prove useful to more precisely and efficiently identify,
target, and intercept safety risks prior to their realization
in the market place.
2. INTEGRATING THE SOLUTIONS ACROSS THE AGENCY
One of my greatest concerns as a former FDA official and a
current consumer is that Congress would jump to solutions that
are as ``stove-piped'' or ``siloed'' as the Agency. This is
particularly true with regard to FDA's information technology
systems. As the General Accountability Office (GAO) has
articulated several times over the last 15 years, the Agency's
legacy data systems are antiquated and not integrated. The FDA
has been striving for decades under a budget that is anemic
with regard to IT funding. Most Americans, I presume, would
find it quite astonishing that FDA personnel (humans) must make
decisions about whether a foreign facility should be (or has
previously been) inspected by reading the name and comparing it
to names in a number of data systems.
Even more astonishing would be the realization that FDA's
various registration systems--across all of its Centers and
regulated commodities--are not relationally integrated to
background agency data or to its operational systems. Humans
are still entering data bases and checking to see if a
registration, supplied during the importation process is ``in''
the system and whether the number ``belongs to'' the
manufacturer declared in an entry. FDA still receives its
manufacturer declarations via the Customs Manufacturer
Identification (MID) process and that MID must be translated in
FDA's systems to its own numbering system. Because of the
variations in the MID process, FDA ends up with duplicate or
triplicate numbers for the same facility--or far worse. Portal
overlays can help reduce the number of data base user names and
passwords an FDA official may have to remember--but they will
not integrate data. These realizations, among others, account
for at least some of the discrepancies in the Agency's data
with respect to how many foreign facilities have been or should
be inspected. This is an annoying result. But it is more than
annoying when the lack of integration of data accounts for a
regulatory regime which relies on a human to notice slight
differences in company names to assess whether a facility has
ever been inspected. In this regard, a unified registration
system could quite easily have prevented the recent heparin
scenario.
3. MORE THAN COUNTING COMPANIES
Although it is critical for FDA to be able to define its
universe, regulatory oversight requires far more than counting.
It is critical that FDA is able to obtain reliable and
affirmative evidence that foreign facilities manufacturing
drugs for the U.S market are operating within the scope of
FDA's current good manufacturing practices (cGMP) requirements.
This information can be derived from a number of sources--but
one primary and historical information source has been the
physical FDA inspection of the facility making the bulk active
pharmaceuticals and the finished dosage drugs. As discussed in
previous testimony, the drug manufacturing industry has
undergone significant changes over the last 15 years in how and
where its bulk actives and finished drugs are prepared, packed,
and labeled. Many more drugs are manufactured in foreign
jurisdictions now than ever before. FDA's inability to count
those facilities is indeed troubling. But the point of being
able to count them must be based upon FDA's ability to conduct
adequate oversight of how they manufacture the drugs we take. I
might add that without a number we can all point to, you are
also unable to assess how FDA is doing in evaluating the safety
and effectiveness of those drugs. Confidence in the system
understandably erodes.
The post-marketing surveillance inspections of drug and
medical device facilities are absolutely critical to assessing
the quality, purity, safety and effectiveness of the articles
they manufacture. I have never heard FDA or the domestic
industry as a whole say otherwise, although I am sure there are
different opinions as to the absolute frequency that should be
applied. Further, the sophistication of the inspector, the
sufficiency of agency inspection guidance, the amount of time
the facility is available to the inspector, and the depth and
scope of the inspection all play significant roles in the
reliability of the inspection results. The frequency of cGMP
surveillance inspections correlates directly to the level of
confidence FDA and the consumers enjoy respecting the critical
elements of the articles.
The cGMP (or Quality System) requirements are intended to
address the adequacy and appropriateness of the manufacturing
process, the design of that process, the equipment used in the
process, the control and adequacy of raw materials subjected to
processing, the source of those ingredients, the qualifications
of the facility's critical personnel, the packaging, labeling,
and failure evaluation processes, and post-distribution
monitoring, including company recall procedures. FDA's current
inspection frequency for foreign prescription finished drug and
active ingredient manufacturers is reportedly on a 13-year
inspection cycle. FDA is required to inspect corresponding
domestic drug facilities on a 2-year cycle. When you compare
this foreign facility inspection cycle (for Rx Active
Pharmaceutical Ingredient manufacturers alone) to the increase
in the numbers of imported drug shipments over the last 10
years, one can see its impact historically and can predict that
impact prospectively.
For instance, according to FDA data, from 1991 to 2000 the
number of FDA-regulated import shipments increased by 272% and
in 2001 alone there were more than 7 million imported
commercial lines of entry. \1\ In 2002, approximately 7.8
million lines of FDA-regulated commercial shipments were
imported. From 1997 to 2002, the number of imports of every
kind of FDA-regulated product at least doubled. In 2007, FDA
had jurisdiction over more than 17 million imported commercial
lines of entry under its jurisdiction will be imported. This
represents two doublings in the sheer number of entry
transactions every five years since 1997. FDA's inspection
resources directed at assessing the safety of imported products
and evaluating the manufacturing systems of foreign facilities
has remained static throughout that time period. \2\
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\1\ A commercial line of entry is the equivalent of a line on a
commercial invoice covering the sale of a product from a foreign
exporter to a U.S. importer, owner, or consignee. A line may consist of
a single laser DVD reader from Taiwan, regulated by FDA as an
electronic product, or it may consist of 10 x 40 foot refrigerated
containers of cantaloupes from Mexico. With regard to drugs, a line may
be a shipment of 10 cases of retail ready over-the-counter (OTC)
tablets of acetaminophen or a container of several metric tons of
relatively pure bulk active pharmaceutical ingredients. A single
invoice may have one or dozens of lines. FDA counts its import
transactions by commercial line of entry. Each FDA-regulated line is
subject to FDA jurisdiction based upon the legal definitions of the
various products in the FDCA.
\2\ More regretfully, even though roughly half of all FDA-regulated
products consumed in the U.S. are either manufactured in whole or in
part in a foreign country, as I recall by the summer of 2003
approximately only 7 out of every 100 dollars spent by FDA regulating
products under the Agency's jurisdiction was focused on FDA's import or
foreign programs.
---------------------------------------------------------------------------
Based upon my experience at FDA, which is further informed
by statements from FDA in the press and in testimony before
various congressional committees, roughly 60% of the total
number of commercial lines of entry consists of food imports;
25% consists of imported medical devices; and 10% consists of
imported drugs and biologics. Using these proportions, FDA is
responsible for ensuring the quality, safety and efficacy of
nearly 2 million imported drug shipments per year.
As I testified in November 1, 2007, FDA's list of
``uninspected'' foreign API manufacturers exporting to the U.S.
ranged from 242 to 4,600, depending upon the criteria used to
populate the list. \3\ The reasons for such disparity include
the FDA's multiple, ``siloed'', antiquated and non-integrated
IT systems; the lack of a meaningful gatekeeper for the
Agency's drug establishment registration process; and the
Agency's insistence to mitigate the usefulness of FDA's
historical import entry (OASIS \4\) transactional data.
---------------------------------------------------------------------------
\3\ See Statement of Jane E. Henney, M.D., FDA Commissioner, Before
the Subcomm. on Oversight & Investigations, Comm. on Commerce, U.S.
House of Representatives, http://www.fda.gov/ola/2000/
counterfeitdrugs.html (Oct. 3, 2000).
\4\ ``OASIS'' is an acronym that stands for FDA's ``Operational and
Administrative System for Import Support.'' See FDA's discussion of
OASIS at http://www.fda.gov/ora/import/oasis/home--page.html.
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Today, it is apparent that all of these factors persist at
FDA and the Agency is still struggling to identify the scope of
the universe of foreign drug firms under its jurisdiction--
whether we speak in terms of all foreign firms exporting drugs
for human or animal consumption or merely foreign firms that
FDA believes ``should be'' inspected. Lacking the ability to
identify the larger, total universe of foreign drug firms
exporting drugs to the U.S., the attempt to reduce that total
to a more manageable ``high risk'' universe for targeting
inspections has little foundation in reality. Consequently,
FDA's current range of foreign drug firms exporting drugs to
the U.S. that should be inspected by FDA is from 3,000 to
6,700. \5\
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\5\ These numbers are derived from two separate FDA data systems
and thus the disparity. The lower number is reportedly from FDA's Drug
Registration and Listing System (DRLS). The higher number is a downward
departure from data stored in ORADDS, the OASIS data warehouse.
Therefore, the lower number is taken from the process whereby foreign
manufacturers report data to FDA in order to meet two of the most basic
minimum requirements to export drugs to the U.S.: drug registration and
drug listing; and the higher number is taken from the process whereby
Customs brokers report to Customs and to FDA through OASIS the identity
of foreign manufacturers actually exporting drugs to the U.S. This
discrepancy alone is troubling. It is unclear over what time frame the
two numbers were derived and whether they correlate. Further, it
undercuts FDA's traditional argument that OASIS data is unreliable
simply because it represents self reporting through the importation
process. DRLS also represents self reporting to FDA, and in the import
declaration environment, there is another agency, Customs and Border
Protection, that strictly governs and enforces proper data reporting.
---------------------------------------------------------------------------
So at present, FDA is tasked with evaluating the safety and
effectiveness of nearly 2 million imported shipments of drugs
from as many as 6,700 foreign facilities, any number of which
have not been visited by an FDA inspector for as long as a
decade (or have not been visited at all, as in the case of the
Chinese supplier of heparin potentially linked to 81 deaths in
the U.S.). FDA is doing this with an IT system that contains
multiple duplicate or triplicate facilities with different or
non-unified numerical identification systems, literally dozens
of data bases that are disconnected, and a couple hundred
people on a part time basis. This certainly seems to be a
resource problem--but it is far more than that.
4. WHY NOT JUST SAMPLE MORE?
As stated in my previous testimony, when FDA is virtually
absent in the foreign market assessing compliance with cGMPs,
the Agency is left with attempting to assess risks associated
with foreign sourced drugs and drug ingredients using its
import operations. The FDA's current import program, however,
focuses primarily on FDA approved application, facility
registration, and drug listing database submissions, label
reviews, and finished product testing. These approaches are
incapable of assessing the cGMP compliance and therefore the
quality and safety of imported drugs. Although testing can tell
FDA something about the quality and even the safety of an
imported product, finished product testing at the border (or
anywhere along the supply chain) is not a statistically valid
method for predicting the safety of later or earlier untested
shipments--even other shipments from the same processor.
Where product (and patient) safety is so dependent upon an
ongoing and rigorous manufacturing quality system, finished
product testing is not even a valid way to determine product
safety within the same shipment. Compliance with FDA's drug
cGMP program is the only (current) framework within which the
Agency can justify relying upon the results obtained from
finished product test. Finished product testing is confirmatory
only. Without an assessment and understanding about the
conditions of manufacture within the facility, the finished
product test results are anecdotal at best. Such an approach
cannot predict, measure, assess, or assure drug safety.
Any question about this premise is laid to rest with a
simple observation from a recent drug safety crisis. FDA now is
maintaining that because it took some time for any number of
laboratories to identify the contaminant in the heparin, which
has caused such tragic loss of life recently, the FDA concludes
that there are ``limitations as to what inspections can tell
you.'' This is an appalling and irresponsible position. To the
contrary, the absence of a meaningful and recurrent FDA
inspection presence has far more to do with the events of
recent months than almost any other factor. The evidence as to
product safety (and security) is found only in the facilities
and companies that make and move products into the U.S. market.
Lacking a robust foreign drug inspection program, which takes
into consideration all elements of prescription and non-
prescription foreign drug manufacturing in its scheduling and
preparation, promotes a ``catch me if you can'' foreign drug
compliance culture.
I would only add that if FDA's IT systems were capable of
linkage using a unique numerical identification system with
some level of verification of registration data, then I dare
say the system could be designed to flag any submission to the
Agency, linked with the unique numerical identifier, with an on
screen warning that the facility submitting the data has not be
inspected by the Agency. This alone would have enabled FDA to
assess whether the manufacturer of the heparin should be
approved as a source for the finished dosage manufacturer.
Instead, FDA personnel had to resort to recognizing slight
variations in the names of two firms.
5. ACCOUNT-BASED OVERSIGHT PROVIDES ADDITIONAL BENEFITS
Other government agencies having regulatory oversight over
hundreds of thousands of companies, transactions, and
compliance procedures have begun to move to account-based
regulatory processes to integrate the many steps the agencies
must take to assess risks. For instance, Customs, with more
than three times the number of import transactions, the
responsibility for enforcing virtually every federal law in the
importation arena, and the added weight of ensuring the
security of imported products and our port infrastructure, has
moved to account-based processing. As FDA notes in its various
import safety proposals and (purported) risk-based food safety
plans, Customs' development of its Automated Commercial
Environment (ACE) and the International Trade Data Systems
(ITDS) will assist the government in improving its
interoperability. However, FDA's background data systems
(managing, for instance approval submissions, registrations,
listings, 510(k)s, Food Canning Establishment registrations,
bioterrorism registrations, drug master file submissions, to
name a few) will not be integrated with the final
implementation of ACE or ITDS. Although Customs will require a
unique numerical identifier from any company providing data
into its systems (and for any company identified in such
submitted data), FDA will still have to translate that unique
identifier into its own registration system--and back into its
duplicative, disconnected systems. So it is true that FDA will
be able to obtain its import data from one place--as will the
other border agencies--however, FDA's own systems will remain
disconnected, non-integrated and stove-piped.
If FDA moved to an account-based system to regulate
products in the supply chain, wherever they may be found, and
if FDA only accepted data when a Customs-comparable unique
numerical identifier is provided with the submission, the
Agency would be able to begin the process of internal data
integration and meaningful data connectivity with Customs and
other border agencies. Inspectional data, import data, adverse
event data, and submission data could all be connected via the
unique numerical identifier. The data systems could then be
connected to FDA's operational data systems (FACTS and OASIS)
to permit integration with importation data transmitted by
Customs and to help target domestic and foreign facility
inspections and border evaluations, inspections, and sampling.
The account-based system would develop over time eliminating
the now ever-present duplications in firm data and would enable
FDA to actually identify the scope and size of the ``hay
stack'' as it exists in the real world. \6\
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\6\ In my view, the unique numerical identifier should be site
specific and should be capable of verification by government and
private systems and processes. Because of the amount of consolidation
that can occur in any economic market, whether developed or developing,
the identifier must be able account for mergers, acquisitions, business
closings etc. Consider, for instance, the ownership changes that can
occur over the current FDA foreign inspection cycle of 13 years. Entire
countries can disappear or newly emerge in the same geographical
location over that amount of time.
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With an account based regulatory system, the assessment of
user fees (or review fees) can be predicted with greater
specificity, FDA can identify the size and scope of its
regulated industry, modifications, mergers, and facility
closings can be identified and tracked, post-market events can
be connected to product source, objectionable conditions
observed at manufacturing facilities can be tracked through
supply chains more readily, supply chains are more transparent
and interagency coordination improves dramatically. These are
just a few of the benefits.
6. CONCLUSION
A. Missed Opportunities for Change
In conclusion, I reiterate my previous testimony regarding
steps going forward. The efforts of over 100 dedicated FDA
personnel from all of FDA's product Centers, the Office of
Regulatory Affairs (ORA), the field offices, the laboratories,
the various information technology offices, and the office of
international programs should be presented to Congress and
industry in an open forum to enable the Agency to learn risk in
the real world. FDA's foreign drug inspection program is only
one means for FDA to assess and mitigate risks related to
imported drugs. Foreign sourced drugs, whether finished or
ingredients, active or inactive, must also pass through the
bottleneck of FDA's and Customs' import assessment. Although it
is true that FDA's import program is woefully inadequate today,
only addressing imported drug risks in terms of increased
foreign inspections leaves open risks that may arise in between
foreign inspections (even if conducted every 2-3 years) or in
the product supply chain (e.g., product counterfeiting,
commingling, or tampering). Further, as FDA will never cross
enough foreign thresholds to enable the Agency to apply
inspection data on all imported drug shipments--more than just
additional resources for foreign inspections is needed.
Shortly after September 11, 2001, FDA's Leadership Council
established an Import Strategic Plan Steering Committee. By
spring 2003 the Import Strategic Plan was virtually complete.
FDA developed the ISP from the contributions of more than one
hundred Agency experts in all product Centers, field and
headquarters components, laboratories, international programs
staff, the General Counsel's Office and the Office of Policy,
Planning and Legislation.
The ISP's principles were simple but far reaching: Push the
current FDA import evaluation process from the extremely
limited border transaction to a life-cycle process, which:
Intentionally gleans information from all points along an
article's supply chain;
Assesses that information based upon FDA requirements and
risk of harm;
Delivers the assessment to border inspectors, compliance
officers, and electronic screening systems for reliable
targeting decisions; and
Results in the facilitation of safe products and
enforcement against products that are unsafe.
The significance of the ISP and its proposed action items
rests in what it represents: an internal agency demand for a
dramatic shift in thinking about the identification, assessment
and mitigation of risks in the international supply chain. Many
of the ISP proposals are indeed costly. However, many could
have been implemented nearly immediately and would have begun
the process of increasing FDA's import efficiency and
effectiveness using existing resources. It is this shift in
thinking that FDA's middle and upper management seems to
continue to resist. I believe that all involved in the ISP
process recognized the import problems--even in 2003-are
complex and cannot be solved with FDA's traditional regulatory
approaches and philosophy.
B. Some Proposed Changes Going Forward
First, any action by this Subcommittee should include a
significant resource investment targeted directly for
reengineering FDA's stove-piped IT systems. IT improvements
recommended in the ISP are a contingency for executing any
serious risk-targeting strategies for foreign inspections and
import interdiction of unsafe drugs. This investment, however,
cannot be targeted solely at drugs and devices, for the same
operational systems must manage the other 90% of imported
shipments and the inspection of other products. The IT fix must
either be across all Centers and ORA or it must occur at the
Department level to leave open the option of breaking food
regulation out of FDA and combining it with other food
regulators into a Food Safety Administration as a sister to the
remaining Drug & Device Agency.
Second, I recommend the establishment within FDA of an
organization reporting to the Commissioner with the mission of
focusing on enhancing the safety of imported products--all
products. I continue to believe fixing FDA's import and foreign
inspection problem requires it be broken free from the domestic
programs, which produce much of the bureaucratic inertia
against change in this area. A new organization would enable
proper staffing, allocation of human resources at ports of
entry, management and implementation of ISP-based strategies.
It should be responsible for all import and international
focused work-planning activities; conducting facility
inspections of foreign processors and importers; overseeing and
conducting border operations; conducting foreign government and
industry assessments and training; and support trade
negotiations in a manner to enhance safety of imported
products. To accomplish this, the new organization should be
directly funded, rather than receiving its funding through the
product Centers. A basic persistent infrastructure to manage
risks associated with all imported commodities must be
maintained regardless of year-to-year changes that may
appropriately occur in program directions.
Third, section 302(b) of the Bioterrorism Act, which
enables FDA to implement risk-based strategies for managing
food imports, should be expanded to cover all other FDA-
regulated products including drugs. This would clarify FDA's
authority to facilitate the importation of drugs that are in
compliance with FDA requirements and pave the way for
distinguishing between and among shipments based upon
verifiable risk data.
Fourth, FDA should be required to inspect foreign drug
facilities (at least those that fall into categories FDA admits
should be inspected on a regular basis) at the same frequency
as domestic facilities.
Fifth, FDA should work with Customs to adopt a uniform
numerical identification system to begin the process of
regulating its industries using an account-based system. This
would enable FDA to integrate its numerous and disparate
background data systems and to interrelate the data it receives
from Customs and other government agencies.
Sixth, FDA should publish and begin implementing the ISP in
accordance with the plan's guiding principles, goals, and
themes.
Seventh, FDA should begin developing programs for obtaining
as much information as can be obtained from as many reliable
sources as the Agency can find regarding the cGMP compliance
status and supply chain security programs of foreign drug
facilities that are not inspected by FDA. This population of
drug manufacturers will always exist, and simply saying it
represents too many companies for oversight or too much data to
digest is no answer at all. Additional risk data could come in
the form of third party inspection and certification companies,
accompanied by a robust auditing process on both sides of the
border, by foreign inspectorates, or by other U.S. Government
Agency inspections and information. All such data should be
connected to the firm's unique identifier and incorporated into
the account data to permit its assessment in light of other
legacy and other agency data. I continue to hold to the view
that obtaining and assessing all available risk data better
enables FDA to (a) target its foreign and domestic inspections;
(b) interdict and examine high-risk imported drug shipments
(related to product safety); (c) follow up in the domestic
market those shipments that proceeded through the border with
inadequate inspections; and (d) facilitate imported drug
shipments that are likely to have been manufactured in
accordance with FDA's cGMP requirements. This would permit the
Agency to focus its most earnest import inspection and
examination efforts on shipments representing known and unknown
risks.
Eighth, FDA requires additional resources to conduct more
foreign inspections and import examinations and to develop and
publish meaningful Agency guidance relating to identifying and
managing risks in the full life cycle of imported products.
Ninth, FDA should rely on Customs and Border Protection and
the Department of Homeland Security (DHS) to manage security
risks associated with FDA regulated imports. DHS' security
programs should be expanded to incorporate product security
risks (such as product counterfeiting and tampering) rather
than focusing solely upon the security of in-transit cargo or
inbound containers.
* * *
I thank the Subcommittee Chair and Members for the
opportunity to discuss these important issues and I look
forward to answering any questions.
----------
Mr. Stupak. Thank you, and thank you to everyone for your
testimony today.
Mr. Hubbard, Mr. Nielsen, Mr. England, I believe you were
here when the Commissioner testified. What would each of you--
if you would just give me quick--what would you each do if you
were the Commissioner? How would you come to address this
issue? Give me the top 3 things you would do, starting with
you, Mr. Hubbard.
Mr. Hubbard. First you have got to know who is making our
drugs and sending them to us. So you need registration. And I
think you've mentioned that.
Mr. Stupak. OK. A foreign vendor registration we were
talking about.
Mr. Hubbard. Everyone that is in the supply chain, all the
way back to the pig--the pig farmer and his heparin. So at
least we know who they are and where they are. That is, I
think, number one. Second, you need to get over there and look
at all the facilities and see what you find. Because we don't
know now because we don't go there. And, thirdly, as I think
these gentlemen have mentioned, you have got to have some sort
of IT system to track it.
And there are many more things you need to do, but I would
put those 3 things as sort of the sequential first things to do
to begin to get a grip on this problem.
Mr. Stupak. Mr. Nielsen.
Dr. Nielsen. I do believe--I do believe IT has to be the
first item, and there has to be funding. It is for the center.
It is for the ORA. Coupled with that, I would say number two is
functional organizational structure to deal with the issues at
hand; and I do concur with what Ben said, that there does need
to be a separate entity.
I also recommended that, in my written statement, that the
foreign inspection oversight, the border operations, and
oversight of the importers are all extremely related as far as
risk; and I do believe a formation of an organization with the
responsibility and funded and empowered will provide solutions
that will work. And certainly funding is still a big issue, but
the funding needs to be attached to very specific events with
articulated outcomes or expected outcomes.
Mr. Stupak. Mr. England.
Mr. England. I think there are two levels. One is, what do
you do in the instant event; and I think that the FDA is doing
probably the best they can in trying to figure out where this
product came from.
Mr. Stupak [continuing]. Heparin you mean?
Mr. England. Yes, right. The specific heparin situation. I
disagree entirely with the theory that the inspection couldn't
have had a significant impact in preventing this. I mean, I
think if we keep in mind that the inspection that we have now
seen the 483 for occurred after the adverse events, and we
still saw the conditions we saw. If FDA had been there prior to
the adverse events during a pre-approval inspection, I'm
inclined to believe that they would have seen a facility in
even worse condition, in which case they would not have been in
a position to be a source for this product.
Mr. Stupak. Hang on. OK.
Mr. England. So I think--I think that the foreign
inspection component is absolutely critical, and it has been
for years. I also think that because of the mandate that FDA
has to inspect the domestic industry every 2 years, you end
up--I think FDA ends up trying to reach that mandate to the
exclusion of the foreign market where it doesn't have the
mandate and that it tries to do the best it can.
Most of the foreign inspections, in reaction to the idea
that, well, even some foreign inspections were conducted and
yet there was still contaminated product that came from perhaps
those facilities, those inspections were probably 2-day pre-
approval inspections. The inspection we just saw at this
facility regarding heparin was probably a 5-day, I believe,
inspection, far more deep. In the United States, that would
have been a 10- to 12- to 16-day inspection.
Maybe that is not necessary to find the appearance of a
violation and prevent that product to come in, but I would
agree that a 2-day inspection may not be able to produce this
or to be able to find these kinds of problems. So I think
inspections.
But if you don't have the IT, it really doesn't matter what
you do. You can't put together a risk-based program. I mean,
even Customs work, the integration with international trade
data systems, the FDA still has to have data to bounce that
data against. And without integration on the FDA side, you can
go one place to get the data, but you can't really do much with
it anyway.
Mr. Stupak. We are going to have a hearing next week,
actually, next Tuesday, on heparin.
I don't mean to belabor the heparin point, but, Mr.
England, you brought up--and I think Mr. Melancon brought up,
too--it is our understanding that this plant was never
inspected, but Baxter did inspect it. Where is the corporate
responsibility here or why would Baxter inspect it and we still
have all these problems that were highlighted in the document
that you indicated with the FDA inspection?
I mean, if we had had--if the FDA did inspections, would
that also pressure Baxter then in this case to make sure that
what they are doing as inspections are robust and complete and
safe for the American people?
Mr. England. First, I don't want to get into a liability
question, because I just don't. I have not seen any of the
documents on those inspections. I have no idea what the scope
of the Baxter review was.
Mr. Stupak. It is called response----
Mr. England. I mean, the importer of a product has
responsibility to ensure that the product they are importing is
in compliance with U.S. law. In the case of an API, that means
that they should have some--they should be able to make some
assertions as far as the product having been manufactured in
compliance with GMPs. That is from the Federal perspective.
Mr. Stupak. If the government system broke down here
because it was never in fact inspected and if the private
company that is making the profit here broke down, the American
people are truly just at risk then. I mean, there is nothing we
can do other than a re-overhaul of the FDA.
Mr. England. I believe--I believe that that is not an
overstatement.
Mr. Stupak. Mr. Nielsen, you're trying to jump in there.
Dr. Nielsen. And coupled with that, as far as
responsibility is, I do think there has to be a reevaluation of
the good manufacturing and practice regulations. It is not a
new topic for the Agency, for a rewrite of the drug GMPs.
Mr. Stupak. Any idea last time that was rewritten, Mr.
Hubbard?
Mr. Hubbard. 2003. They are relatively new, but they're
very general. They don't really deal with some of the problems
that arise here.
Mr. Stupak. OK. Dr. Crosse, we're focusing quite a bit on
IT here with these questions I was asking. But yet on page 12
of your testimony you talk about the Foreign Vendor
Registration Verification Program, and I was pressing the
Commissioner to try to give us some kind of idea on when it is
going to happen. And, in your testimony, FDA currently plans to
award this contract of May '08, but yet you cite for an example
the Agency has not yet established the criteria it would use to
determine which establishments would be visited for
verification purposes to determine how many establishments it
would verify annually. Does it look like one of these things
where the FDA is going to award a contract but yet not have the
criteria before we even have the contract?
Dr. Crosse. It is not clear to us. This is something that
is very new, and it was difficult for us to get very much
information about it. Our understanding yesterday, after we
submitted this statement, is now that it has been pushed off to
June but that they do still intend to move forward in trying to
establish some program.
It is not clear to us what exactly is going to be done
under this contract, whether they are going to perform onsite
inspections of a certain proportion of facilities, how they are
going to select those facilities, what is going to be involved
in the verification, what information they're going to get
beyond just is there a building there and do they manufacture
drugs. It is really unclear at this point, and we were not able
to get very many specifics from FDA about it.
Mr. Stupak. And I think Mr. Nielsen or Mr. England
mentioned the Shared Establishment Data Service. That all would
have to be dovetailed into this, also, would it not? FDA needs
to know about it, but Customs needs to know what is coming in
and--what's coming in. Could you probably get the information
quicker by going to Customs? Because at least they know what is
coming into this country.
Dr. Crosse. It is not clear how this backtracks to a
particular facility that is manufacturing a drug. The
information that is coming in from Customs is again--sometimes
they have difficulty linking back in that way. And as I said in
my statement, there is not yet agreement that this SEDs system,
the unique identifier that would be used with Customs, is going
to move forward, because it requires the agreement of a large
number of Federal agencies, and they all have to fund the
changes to their systems to make this work.
Mr. Stupak. My time is running out, and I think we'll
probably go a second round, because I enjoy this panel, and you
have good suggestions.
But, Dr. Cassell, if I may, on page 56 of the Science Board
report there is a recommendation--and I pressed the FDA last
time and never got a commitment. So let me ask it this way.
There is a recommendation that the FDA develop a comprehensive
plan that includes how and when the Agency would respond to the
recommendation.
Has anyone from the FDA, after you submitted a report, got
back with the Science Board and said, here is what we're trying
to do. Help us implement. Here are our recommendations to
implement--I mean, you gave them a blueprint on how to fix
things. Have they worked with you to try to get it implemented
or say here is our priorities? What happened after you
submitted your report?
Dr. Cassell. To my knowledge, they have not gotten back to
the Science Board. I'm only one member of the Science Board.
They could have talked to others to share with us specifically
how they would propose to implement their recommendations.
I'm aware, however, they have begun the review of ORA and
NCTR that we have recommended, and I am aware that a chief
scientist has been appointed, although that was not in
relationship to our recommendation but, rather, it seems the
PADUFA legislation that also recommended the chief scientific
officer.
Outside of those three things, I'm not aware of other
activities that are ongoing.
Mr. Stupak. And as the chair of the Science Board, your
Science Board members are available to help the FDA implement
these recommendations, are they not?
Dr. Cassell. Well, I'm not a chair of the Science Board,
but, rather, I was chair of the subcommittee that conducted the
review. But just, still, a member of the Science Board. But the
Science Board clearly is eager to help in any way.
Mr. Stupak. Mr. Shimkus for questions.
Mr. Shimkus. Thank you, Mr. Chairman.
I, too, want to commend the chairman for the hearing and
this panel in particular.
This has been held up maybe before. This is the hearing
record from the 105th Congress, which is my first Congress,
Volume III, 11 years ago. Far be it from us 11 years from now
when someone goes through and holds this up that we haven't
done this.
I liken this to--one of my other responsibilities was
telecommunications and interoperability for first-line
responders. We have had Katrina. We've had September 11th.
We're still--yes, we are still struggling, and we're trying to
move. But, you know, people's lives are at risk, and so I--you
all have been a great panel.
If everybody was living by the golden rule or the second
table of the law and loving their neighbor and not wanting to
steal, we wouldn't have this problem. But we live in a sinful
world, so--but the folks that are producing illicit drugs to
enter our consumer market, we ought to identify them. They
ought to be punished to the full extent. Why can't we just say,
you don't comply with our inspection regime, you don't sell in
our country?
Mr. Hubbard. Well, that is one of the things that I think
is mentioned in Chairman Dingell's bill. The concept is, for
both food and drugs, is if someone can't show that they are
meeting our standards, they ought not to be sending us food,
and the FDA ought to have the ability to say, did this company
demonstrate that it met the standards? And if the answer is no,
it doesn't come in. And then you've shifted the burden from FDA
to find the problem back to the producer to show he is doing a
good show.
Mr. Shimkus. Yes, I'm not a big--I'm not well received by
the trial lawyers, but I'm thinking if they had some good ones
in China, we may not have this problem sometimes because they
would be going after these firms that are illicitly putting
other elements in these drugs and taking advantage.
There are a couple parts of the testimony that we found
compelling and--talk about. One of the questions this deals
with, if we don't have institutional reform in the FDA and we
just give them more money, what would be the result, do you
think, Mr. Nielsen?
Dr. Nielsen. Probably a little more of the same. Until
there is a real change in direction in how resources are
allocated, how priorities are selected--for example, I don't
think it is just an issue of getting more resources, but there
has to be a hard look as to how existing resources are also
used. Even if the entire domestic industry is being inspected
at the total expense of lack of oversight of the foreign supply
just does not make sense.
Mr. Shimkus. Mr. England, do you want to chime in?
Mr. England. Yes. I think that to a certain extent--I can
give you just a couple of examples. I wish I brought slides
with me.
Because if you look at the organizational structure of the
FDA--you know, when the act was established in 1906, nobody
imported anything in here. So the imports regime was set up
under a curtain context which doesn't exist anymore.
And similarly, as time went on to the 1900s, there was some
functionality in FDA for managing import issues. But most of
what was coming in was bulk ingredients that was for further
manufacturing. In those circumstances, FDA would ensure that
there was inspection and quarantining that was happening on the
domestic side and that they were properly qualifying--properly
qualifying the vendors. So they'd use the domestic inspection.
Now we have a whole lot less of that. Now, in the drug
industry, it is actually still very much like that, which is an
example, for instance, with heparin, which is why you still
have to do inspections of those bulk facilities.
But--so now you've got--you've got a situation where FDA
has a division of import operations and policy that Carl was
the director over, and he is responsible for managing OASIS,
the IT system. He has absolutely no authority over anybody in
the field. He cannot tell them to do anything. So he can have
all the great ideas in the world to fix a situation, but he
lacks the power to make FDA move.
And those are the kinds of organizational structures that
exist. It is an appendage. It is an appendage.
Mr. Shimkus. Let me follow up, because you all sat in to
hear the Commissioner and his testimony, and my opening
statements talked about how well-intentioned individuals go
into the bureaucracy trying to slay the dragon and really walk
away not being able to do so. I think there are more examples
of that occurring than really transforming. Because some of the
terminology--we talked about stovepipe and silos. I mean--and
in my opening statement, a comment was if you were to just
rebuild, I mean, stop and restart the process, how would we go
about getting to that area of where we need to be?
So the question is, based upon listening to the
Commissioner, did you get a feeling that there was an
understanding of the transformational nature, that the FDA has
to change, or did you get a feeling--I think the frustration is
that it is not a 100 percent commitment.
Mr. England?
Mr. England. Yes. I don't want to characterize the
commitment level. I think, though, however, that part of it is
that we are at a stage I think now where the Agency is saying
what a number of us have been saying for literally a decade as
far as this risk and these kinds of things that are out there.
And they are starting to say it. But I also think that FDA has
lost a fair number of people who actually would have known how
to do it. So they are in some ways a little bit perplexed as to
what the steps ought to be.
Also--I also feel that they feel pressure from Congress and
from this committee and other committees perhaps that they
should be doing certain things because it was mandated, even if
maybe those aren't the best things to be doing. So I think they
are a little bit between a rock and a hard place.
But I also would add that it does take more--we are way
beyond strategy, way beyond planning, that the Agency should be
assessing, OK, what can we not do right now in order to do
these things that are priority and start this shift.
Mr. Shimkus. Part of stovepipe--and this may be just a
couple of panelists. It is not directed to anybody. Whoever
wants to chime in. Address the frequency debate both--
obviously, we can't talk about frequency if we're not
inspecting overseas. If we were, what would be the frequency
there versus the frequency here?
You're talking about--Mr. England just mentioned mandated
things that we have to do and may be--and my previous with the
Commissioner talking about, you know, if a manufacturing
facility has a 10-year record of being inspected every year
with zero defects, shouldn't we consider frequency evaluation
in that venue?
Anyone want to chime in real quick? Mr. Hubbard.
Mr. Hubbard. Well, I think as a start you do need the same
frequency. But I think Commissioner von Eschenbach was correct
in that, over time, you do want to move towards a risk-based
system. If you've got a facility, as you say, that has been
doing very well and makes a relatively low-risk drug, then
maybe that gets a pass every 2 years; and someone who is not
doing a good job or makes a high-risk drug gets inspected every
year.
But they can't even begin that shift without resources, in
my view. They would have to strip inspectors out of domestic
inspections to fund anything foreign at this point, And then we
could see the deterioration of our domestic drugs. So it is
kind of----
Mr. Shimkus. I want to tie into the flexibility of domestic
inspectors. I understand that. We get that there needs to be
more resources but also the flexibility of being able to move
an inspection regime and the frequency debate with
international concerns.
Mr. Hubbard. Well, that raises a whole other issue. Because
they are having difficulty finding enough people willing to go
to these countries. I think the Agency would like to create a
foreign inspectorate of people that are hired for that purpose,
posted in these countries and in sufficient numbers to do the
coverage. And I think that is a good idea personally.
Mr. Shimkus. Go ahead, Mr. Nielsen.
Dr. Nielsen. I would also say that that is another scenario
where the integrated IT function is critical. You can gather
all of this information, but you just as well not have it if
you can't get access to it.
Mr. Shimkus. That's right. And I wanted to move--Mr.
England, I just want clarification, and I think it ties in with
IT. You propose what is called the accounting system approach.
Can you just again for the--elaborate just for someone who is
simple-minded, how is that a change?
Mr. England. Yes. An account-based system, an account-based
approach, as opposed to a transactional approach. Right now, if
you look at the way FDA manages its import program, for
instance, everything is on a line-by-line basis. Now, sometimes
they will make some decisions based upon history of a
processor. For instance, I would presume, based upon the
warning letter, that this manufacturer of heparin is now on an
import alert. Now, whether that works or not is a completely
different question, because I think the import alerts don't
work anyway in far too many cases. But, ordinarily, the Agency
is doing transaction by transaction; and the inspector or the
evaluator is trying to figure out whether to let this one in
rather than--for instance, on a registration basis, someone
registers, they--if there is a user fee, there is a user fee.
Mr. Shimkus. Do you think the FDA can do that now? Does it
need legislative authority? Can they--can that be part of the
change in dynamics?
Mr. England. I think they could do it now. I would be
surprised if they didn't have the authority to move to that
system. They probably don't have the resources to do the IT
piece of it, but I don't see an authority problem with it.
Mr. Shimkus. Thank you, Mr. Chairman. My time has expired.
I appreciate your----
Mr. Stupak. Mr. Melancon for questions.
Mr. Melancon. Thank you, Mr. Chairman.
Mr. Hubbard, has there been--and I have only been here in
the Congress for 3 years now. Has there been a period in time
somewhere where, appropriation-wise, the Department was given
some monies because of the concern with inspectors, that money
was taken and then used other places? I have heard rumors of
that, and I don't know if----
Mr. Hubbard. Well, the best example is, after 9/11, HSS
Secretary Thompson was very concerned about foreign products in
general from a bioterrorism point of view, and with a lot of
pushback from the White House, he demanded the hiring of new
inspectors for the ports. And FDA very rapidly hired 650 new
inspectors in 2003, hired them in a matter of weeks and trained
them and had them going very quickly. The subsequent budget
cuts, though, took away all those inspectors; and now they are
actually back with fewer than they had before 9/11. So all
those 650 folks are gone.
Mr. Melancon. And they were just--instead of maybe trying
to keep them on and then retraining them for foreign----
Mr. Hubbard. There was no money to pay them. So they--it
really wasn't that people were fired. It was an attrition. As
inspectors retired or left, they couldn't--so they just
disappeared over about 4 or 5 years.
Mr. Melancon. Now, that was--I wasn't sure what the
scenario was. I just heard that there were fewer people than
there were at certain periods as of 9/11.
You mentioned in your testimony that China had been
associated with a number of problems related to counterfeiting
and tainted exports. Should the FDA consider treating the
country's products, particularly in areas we have seen problems
such as drug exports, different than other countries who have
not advanced--who have more advanced regulatory systems, i.e.,
should we be focusing on China specifically?
Mr. Hubbard. I certainly think that less-developed
countries need inspection, at least an initial inspection.
One concept that we looked at a few years ago was to say
that if a country or given product from a country was
repeatedly problematic then that would trigger a greater degree
of regulation so that that country would then have to come to
the FDA and say we fixed whatever problem you found; future
shipments to the United States will meet your standards and
demonstrate that. And that would mean that countries that don't
have a problem, that don't send bad products wouldn't have to
do anything different. But countries with a problem, they would
have to step up.
Personally, I think that concept is one that could be
valid. But I think it is partly met by Chairman Dingell's bill
through the certification concept.
Mr. Melancon. So the tainted food, the toothpaste, the
fish, what have we done? Have we just slapped their wrist and
moved on?
Mr. Hubbard. The way the law works now is FDA has to catch
each shipment, find the problem and say you can't come in.
Since they only inspect 6/10ths of 1 percent, very little gets
caught. So you need to shift it the other way and say they
need--the ones that are caught, they need to do something more.
Because you know it is just going to keep on happening until
they fix the problem.
Mr. Melancon. In other words, if you start embargoing those
products that have problems, then either the people that are
importing or the people that exporting would start having a
concern?
Mr. Hubbard. That is exactly right. You need to put that
burden back on them so it costs them money to keep sending bad
food or bad drugs to us. Right now, it is just a cost of doing
business because FDA catches so little.
Mr. Melancon. Yes. Go ahead, Mr. England.
Mr. England. If I could, just briefly. And I agree with
those ideas in concept. The problem with it if we only go that
direction is that you're right back to a transactional mode
because you've got to figure out as those goods come to the
United States which ones are the ones that are subject to the
ban. You're still in that--which is still an IT issue, A.
And, B, it seems to me that if the FDA were to be able to
do more foreign inspections, they would be able to better
distinguish segments of industries and segments of--or kinds of
industries in contrast to others and actually incentivize, for
instance, in China, industries that are doing it right in order
to create examples even in China.
And I think that is a kind of a policy that encourages a
holding up of those that are meeting our standards rather than
just trying to catch--I think we're still trying to catch them
at the border, and I don't think it is going to be as
effective.
Mr. Hubbard. I agree with that. I don't think what I said--
I think you need both, you know.
Dr. Nielsen. And just a little clarity. The way the law is
written right now for the admissibility--Bill had said it is up
to the Agency to find the problem. It is not like USDA where
there is an existing permit requirement that affirms
compliance. And one of the possibilities with an account base
is to be able to link. In order to establish an account is to
have an affirmative process for that compliance.
Mr. Melancon. Is it your opinion in having similar problems
or countries within the union like we're having with imports
coming in that are tainted?
Mr. Hubbard. Well, certainly they have had a problem with
heparin. Germany has already had several deaths. And just today
I understand Spain has announced heparin adverse reactions. So
it can go anywhere. And, as the FDA said yesterday, there are
about a dozen countries that have gotten contaminated heparin.
Dr. Crosse. I would just add also that the EU doesn't do as
many inspections of the active pharmaceutical ingredients, the
API manufacturers like the facility in China. So they are less
likely to be doing those inspections.
I would also point out it is not a simple matter to just
say this country's products that are coming to the U.S. could
be problematic, because those products go other places and then
come to the U.S. For example, China ships many products to the
EU to be incorporated in finished products that are
manufactured there and then come to the U.S. So the chain can
go many directions.
Mr. Melancon. And, of course, I deal with shrimp because
I'm from south Louisiana. I understand that most of the shrimp
that are aquaculture-type shrimp or--that might be sent to the
EU, get discovered to be bad and where do they end up? They end
up here, I believe, if I'm not mistaken. So our own FDA isn't
protecting us on that foodstuff.
Mr. England, Mr. Hubbard and Mr. Nielsen, shouldn't we
require a hefty registration fee for those foreign
establishments to ensure that if a firm is going to register at
the FDA they are serious about exporting to the U.S. market?
Would that help clean up the foreign drug inspection database?
Dr. Nielsen. I think it can help, but I believe what is
more important is the link with the registration process, a
requirement to provide affirmative information that they can
make the product in conformance with FDA requirements. Even if
they didn't ship but they provided information that if they did
ship, it could be significant information. Even if they are
distributing somewhere else on the globe but they ultimately
intend to be here, there could be some utility. But the bottom
line is we need much more information than just who they are.
We need to know what the conditions are, can they make a safe
product.
Mr. Melancon. And that is kind of one--the point is, what
do we do to make them know up front that we are going to be
checking or that we want--we are going to be on top of it? I
mean, is there any specific recommendation?
Dr. Nielsen. I would modify the registration process. The
current registration process--and, as Bennett said, establish a
universal process for all of the commodities. But that process
was just totally inadequate. It is not just an IT issue. You
and I can register right now. OK? No problem.
Mr. Melancon. What does it cost me?
Dr. Nielsen. Nothing. You can go online and do it.
Mr. Melancon. Fill out the form?
Dr. Nielsen. That's right. But the bottom line--that is
just very cursory information. To make real risk-management
decisions, you need to know something about the operation. Are
they capable, even if it is the basics. And I think the
registration process should be more of a submission of more
information or develop some kind of process that will be
recognized by the Agency as verifying that this place does
exist, that it does have potable water, et cetera, whatever the
infrastructure is required for safety.
Mr. Melancon. Is there anywhere in this process bond that
are required of any of these folks that register or do
importing into this country? I.e., if I'm an insurance company
and I'm going to write a bond for you, I want to know damn well
that what you are shipping in that country I'm not going to
have to pay off on that. Do we require anything such as that?
Mr. England. Not for registration. There is a bond for
every importation. It is a basic importer's bond, and it is
usually for FDA purposes, FDA products, three times the invoice
value. So----
Mr. Melancon. So how--OK. It is three times the invoice
value of that one shipment.
Mr. England. Right.
Mr. Melancon. But if we don't have the authority to go
embargo every other pile that is coming in----
Mr. England. Well, I mean, at this point, they have the
authority to detain without physical examination any shipment.
And that's where you get to the--for instance, the countrywide
import alerts that we have for the wheat gluten and the soy
proteins and aquaculture coming out of China. Those are
countrywide import alerts. And the Agency does them now.
I think part of the question--I mean, the question about
whether the Agency has the authority to refuse has to do with
whether or not if someone delayed or denied an inspection in a
foreign facility, then FDA could automatically put them up into
an automatic detention and stop their products. But FDA has the
authority to do that now.
I think the reason it is not doing them is that--Carl hired
the guy who is running policy at DIOP now. They have 5 people,
I think. I mean, the people who are responsible for OASIS and
responsible for reviewing import alerts, there are 5 people
doing it, and we are talking about 17 million lines of entry
that these folks are responsible for.
That goes to resources. It goes to IT. It also goes to
theory and policy and where you put the resources. And I don't
think many people are really thinking about it inside the
Agency, because they're just trying to do what they have always
been doing and that is what--that's why I believe the series of
events are really just beginning, that we are going to see a
series of these from a number of different sources.
Mr. Melancon. Thank you. My time is up and this--Mr.
Chairman. Go ahead.
Mr. Stupak. Go ahead, Doctor. Do you want to answer this
question?
Dr. Cassell. Yes. I would just like to say that, to me, it
all goes back not only to the resources and priority setting
but people and the quality of individuals now, that we don't
have good people there.
We mentioned in our report the importance of constant
external peer review that would identify these problems, make
an argument for correcting them, stay on top of them before we
have an emergency. ORA, for example, we identified had never
had an external peer review. So this review that is ongoing
right now, it is the first time to our knowledge that has ever
occurred. I think a lot of these problems would not have
occurred had those processes been in place.
I just wanted to bring to the attention of everybody that I
think that the issue of personnel is critical--getting the
right people, recruiting them, retaining them, whether it be
the scientists or information technology specialists, which
they seem to have a hard time recruiting, are absolutely
critical to everything we are talking about today.
Mr. England. I would like to follow up, if I could, please.
I agree absolutely, entirely. When I say resources, I mean
humans as well, human resources. And I'm going to give you just
an example.
When the Office of Criminal Investigations came online in
1992, I went into OCI. I was one of the early agents that came
out of FDA and into OCI. And OCI was responsible from really
that point forward in conducting criminal investigations and
conducting investigations that where there is some suspicion of
fraud--CSOs, the Consumer Safety Office, or the inspectors,
they only started losing those skills.
I mean, many folks that used to do the investigations were
conducted by the regular inspectors. And now, once you had a
criminal enforcement arm, they began to--the inspectors began
to just have to check boxes off. And they--and I think that
there was a training--some training that was lost. I think
there was some intelligence that was lost. Not that they are
not intelligent, but as far as institutional knowledge about
how to think through these situations like the drug
investigations where just a keen investigator knew how to do
investigations and he was an inspector and he put 2 and 3
together, came up with the number 5, pulled in people, got
resources. And at one point we had 10, 12 grand juries running.
And so it can be done.
But I think that that part goes to the organizational
aspect of it. These inspectors can do it with the tools. If
they have the tools and they have the training and they have
the time to be in the facilities, they can do it.
Mr. Stupak. We would have a second round of questions, but
go back to OCI. On Ketek, the OCIs were doing their job, and
they were asked to do their investigation, and they were denied
the opportunity. And they got frustrated and basically are
leaving the Agency because they're not allowed to do their work
in some cases. It is more of a structural thing.
And we were talking of issues of mandates that the FDA--
we--this committee or our Energy and Commerce Committee, we
don't mean to micromanage the FDA on--mandate lots of programs.
But without quality of leadership at the top of the FDA, we
must resort to mandates as a trigger or a triage or emergency
patch to correct some of these most pressing issues.
And that's why I was pressing the Commissioner today on BPA
or on discussion draft of the legislation we have floating.
Because we want to move that quickly to try to give them the
resources they need to do their job and to help reconfigure the
FDA so we can get at this issue, which is getting to be a
growing problem.
Along those lines, on our legislation, Mr. Hubbard has
mentioned--and a couple of the others have mentioned it--if you
have some suggestions on things we should improve upon in that
draft, we are moving on that bill fairly quickly. So if you
have anything further, please get with us.
Dr. Cassell, you indicated new drugs, new biologics, the
genome, that active pharmaceutical ingredients, other things we
were going to be relying upon, given the multitude of
additional foreign firms--and you're going to see places like
Thailand, Vietnam and Malaysia are expected to start making
drugs and will likely export to the U.S. If we're grappling
with a problem right now and all these other countries come on
line and new medical discoveries come online, how are we ever
going to be able to keep ahead of the curve?
Dr. Cassell. Oh, I agree. I think in some respects it is
almost mind-boggling when you think about the degree of the
complexity of the products increasing and especially in terms
of safety issues as it relates to biologics. They are not as
easily manufactured as you--we all know and appreciate as small
molecules. So I think, again, it goes back to assuring that we
have the latest scientific evidence for the decisions that
would be made, the best people making those decisions, the
technologies in place to improve upon our inspections.
We mentioned in our testimony, I think, in some of the
discussion on the 29th of January that the Department of
Defense, Department of Homeland Security has invested millions
of dollars in their information technology for doing datamining
in a lot of different topics, particularly as it relates to
biological weapons, and they have also developed very
sophisticated methodologies for detection in the field of both
chemicals and biologicals. These same methodologies could be
applied, I believe, to inspection in terms of quality control
as far as potential chemical and biological contamination of
our products.
I don't know to what extent the FDA has tried to leverage
those technologies and apply them or bring them on line, but I
think we have to begin to apply newer, better technology as
well as just be sure that the individuals that are performing
these functions are up to date in terms of what new science is
available to help resolve the problems.
Mr. Stupak. In the last panel, we talked a little bit about
this heparin and the altered drug, and I think Mr. Burgess
brought up the fact that it could have been for a criminal or a
deviant mind. But whether it is melamine or heparin, I don't
think we see that.
Is it really economic pressures putting pressure on to find
a cheaper substitute? As in melamine, you know, it was supposed
to be high protein, but it ended up--why would you alter a
drug? Does anyone care to speculate on that? I'm sure it is
just not criminal. I mean----
Mr. Hubbard. You have very good chemists over there. And
the best example is pharmaceutical grade glycerin is fairly
pricey, and antifreeze you can get down at the dollar store.
So, you know, it tastes the same; it looks the same. It is just
one will kill you, and one is perfectly safe. And, you know,
people just don't care about where it ends up going. And, of
course, a lot of children in Haiti and Panama and other
countries die because someone didn't care.
Mr. England. I think also, if I could quickly, that my
understanding was that there was a problem with some of the----
Mr. Stupak. The pig intestines. The pig stock, right.
Mr. England. So they were running into a capacity problem.
So it wouldn't surprise me that, under that pressure, that
there was some intent to find something to put it in there.
I'll point out, just quickly, the APIs that FDA approved--
and everything goes into a source inspection and finds an API
facility to be fined, the value of their product on the world
market doubles overnight. So, right now, you've got the
incentive, you've got cushion between guys who are--people who
are not approved and people who are. And it is a lot cheaper
sometimes to buy the product than it is to make it.
Mr. Stupak. So instead of using the pig intestines and
heparin and I use something else, do I have to get FDA approval
to make heparin in this manner and method or can I just say,
oh, no, this is OK because the end result is still heparin?
Mr. Hubbard. You're supposed to get approval. But, believe
me, you can get it for that.
Mr. Stupak. Is that common? I mean, we make substitutions
to a formula that we use?
Mr. Hubbard. You can't do that. You have to at least--it
depends on the severity of the change. If it is a very great
change, you have to get FDA approval. If it is a minor change,
you have to at least tell FDA so they can object.
Dr. Nielsen. I mean, one of the things to keep in mind,
even on the counterfeit APIs, like the carbamazepine, it has to
pass the test. Even if it is nominal, it has to pass the
identity test at least. And so it has--it is going to have to
look like that or else at least the safeguard at the end user
or the finished dose manufacturer will detect it.
Mr. Stupak. Mr. England, you mentioned the import alerts.
In fact, as this panel was seated, we've had three import
alerts just come out from the FDA on some foods and other
issues here. You're not a big fan of it. They don't work, you
said. Explain that a little bit further. And what should we do?
Mr. England. Right. I mean, what solutions perhaps there
might be as far as them not working, I think that is an IT
issue. There is evidence last year where products that were--
that should have been subject to a number of different seafood
a reporter rather quickly found 200-some-odd shipments that had
gotten through the system and had never been tested by the FDA
and had never been stopped, even though they were subject to
the criteria.
So when Carl was asked in the press as to whether or not
that surprised him, of course the answer is no. I mean, there
has been holes in that system forever. So putting up an import
alert is not an answer. It certainly is a piece, and it
certainly does put information out there.
I think another aspect of it is that I'm not so sure that
the FDA has the authority that it exercises sometimes in these
countrywide alerts. So if Congress wants FDA to have that, that
is something they may want to consider clarifying. But, in many
respects, the import alert is supposed to be just guidance to
the field, and it really ends up acting as a regulation.
And I think that is where the Agency begins to run into
some potential liability. They've been challenged a number of
times, and I don't think they have--I don't think FDA has won
yet when they've been challenged on an import alert as to
whether it was legitimate. To fix that--those sort of problems,
I think FDA----
In fact, Bill Hubbard, when he was in the Agency and along
with us, we went through a process of trying to establish what
we called a detention without physical examination rule that
basically described these are the kinds of evidence the FDA
might rely on to issue an import alert. Here is the kinds of
evidence we might seek in order to overcome it. And at least
you created a regulatory regime to manage it, and then your
guidance could be your alerts that are just applying the reg.
But there is a number of those kinds of situations, both
IT--and I think also the way that the authority is structured,
that the Agency is vulnerable, and it is not as effective.
Mr. Stupak. Let me just--and anyone can jump in on this
one. But, Mr. Hubbard, it is more directed at you.
I'm not a big fan of PADUFA, where you have a user fee that
gets your drugs approved with the new drug applications. But,
from a practical point of view, PADUFA has worked. I mean,
you've given them money. The drugs are approved by such and
such a time line. I'm not talking about the safety or efficacy
of it, but we've met those timelines, given the resources.
And I know Mr. Burgess kept bringing up the tobacco issue.
Again, they will be given the resources. If given the
resources, with a clearly defined mission, can the FDA--and the
Dingell bill, Dingell-Pallone-Stupak bill--we have a
registration fee that is probably going to be sizeable to fund
this program. Can the FDA do the job if given the resources in
a focused area as in PADUFA or tobacco regulation? Wherever
there might be--as long as resources are there and they--can
they attract the science people that we need to do the job in
this country?
Mr. Hubbard. I think absolutely. I think the programs in a
more funded FDA work well. You don't hear the criticisms about
them. And the programs that are not funded well are the ones
that everyone is screaming about.
The one problem with PADUFA is that it is sent to the OMB
and the appropriators. There is a lot of new money flowing into
FDA. So we can cut back on appropriations. And those cutbacks
have occurred in places like imports and food safety, not in
the drug-review programs. So it has had a negative consequence,
I'm afraid, in that sense.
Mr. Stupak. Sure. And in that sense, like the new money
coming into the FDA in the last budget, that is really from
MADUFA and PADUFA fees. There is really not that much new money
to take care of these shortfalls, and that's what we've got to
guard against.
But it seems like the $71 million we've been talking about
to do the proper inspections is probably a small amount; and we
can attract the science and the inspectors we need, provided we
have a dedicated funding source. Because I don't want to see an
example like this panel has pointed out where Homeland Security
had the 650 inspectors, got them right away right after 9/11,
got them trained and within 2 or 3 years they were all gone
because there was not a dedicated funding source. That seems--
--
Dr. Cassell, do you want to jump in on that?
Dr. Cassell. I think you're right to be concerned about
that. I, like Mr. Hubbard, though, believe given the resources
with emphasis upon the right people, not just warm bodies, I
think they can absolutely do the job.
The other thing that I would just encourage us all to think
about again, though, is to encourage putting in place this
external peer review, if you will, process. Because, to me,
that would also help ensure accountability. And in the long run
I know it is just one more committee for FDA to deal with. But
if you look at the NIH, if you look at CDC now, they have these
external review committees in place. The peer pressure does
play an important role in keeping things on track.
Mr. Stupak. My time is up.
Mr. Shimkus.
Mr. Shimkus. Thank you, Mr. Chairman.
Again, I appreciate the panel. I, too, am adverse--Federal
Government, we always overpromise; we underdeliver. If we set
up a trust fund, we all dip into it. So we--I think this
legislation would have a much better success if it was a
Dingell-Pallone-Stupak-Barton deal and Shimkus. Maybe we will
get there.
Because there are a lot of things that we agree upon and,
hopefully--I know the legislation is out for comment.
Hopefully, our folks--I'm going to check with Barton and Diaz
and see what they think of it.
I also thought about the current--well, it's an old series
of books and movies: Series of Unfortunate Events. And we don't
want this to continue to be a series of unfortunate events.
Everything does go back to leadership, though. I mean, I'm from
the military school of training, and someone at the top has to
drive transformational change. And that we are all skeptical--
--
And it goes back--it is not one--Commissioner von
Eschenbach has only been there 2\1/2\ years. Now that 2\1/2\
years really makes substantial changes, but there was guys
before him. There will be folks after him. There is other
administrations. And we have fallen to a dilemma that a lot of
us don't want to see. We want to see it fixed.
And I think you've got some great comments. You talked
about--Chairman Stupak talked about if other countries start
coming into the system. I wish legislatively we could stop--if
you're in a hole, the best way to get out of it is to stop
digging. We have got new entries into this. Maybe that is where
we start a regime. But then you have not being favorably
inclined to----
Mr. England, do you want to chime in on that?
Mr. England. Yes, just quickly, because this actually came
up early; and I don't know if I forgot to answer it or left it
for somebody else.
But the question is to whether or not--what is the point
about why are we going to China in order to try to do MRAs? Why
are we trying--probably 50 percent--Carl probably knows the
number better than I do--of what is imported either comes from
Canada or Mexico or comes through Canada and Mexico. And they
are right here. They are our NAFTA neighbors. We have access to
them. We have ways to put together risk-based programs, and we
can actually verify it.
I mean, my feeling is that if we were to focus where we
could apply risk-based principles and be able to have some
verification, trust but verify, and then you take the resources
and you put them where you really don't have any basis to trust
or verify, then I think you start creating incentives for
countries to want to be those countries and they want to be
like those countries. And you throw in the registration pieces
and expenses of that and where that money goes I think is
important.
I think, you know, your IT money and how that is applied is
a management decision. But when it comes to this, how you
address China versus other places, I think we have got--we
actually have the ability to show some leadership in markets
where we have access to show it, prove it and then begin to
create the incentives for other countries to come into it.
Mr. Shimkus. I want to go back to the account-based with a
question. Have you--or anyone might--I think everybody
understands the premise. Is there anything that the FDA is
doing right now that gives you hope that they are understanding
that or moving in that direction?
Mr. England. I would have to see what the current IT
proposals are. My recollection of the IT proposals as I left
and the ones I saw from November were--mostly was a portal
overlaying existing systems. Which means you still have your
silos. You just have them in one basket now.
Mr. Shimkus. What--let me jump--predict that we have all
been waiting--is that--would that--if that was taken hold of
and moved, would that be moving in that direction?
Mr. England. PREDICT would require integration to be most
effective. But PREDICT itself is not an integration system.
What it does do, though, is take data from multiple sources;
and it does think about that data using evolutionary
algorithms. But it also uses it with rules based looking at the
Agency's historical data. So it is hard to go from seafood into
other products without already having--being able to do some of
that risk analysis to think about how you're going to weight,
you know, these different characteristics. So it will not do
the integration, but I think it should be at the front end of
their inspection program as well. I mean, I think it just makes
the most sense.
Mr. Stupak. If I can jump in for just a minute. You know, I
sat through the '98 hearing when J.L. testified again about the
IT system, and it has been 10 years. Why is IT here such a
problem to get our hands around? It is not just FDA. It seems
like IT just seems to be a problem that the government can't
get its hands around, especially this one. We have got I think
seven different databases we are dealing with the FDA on food
and drug safety. Why has this been an insurmountable task that
we can't seem to get to?
Dr. Nielsen. From my observation, a good portion of the
existing legacy system is based on the need of a particular
product center. And ORA is not directly funded, and IT is not
directly funded. And that is why one of my proposals is--why I
believe a new entity, funded entity needs to be established, is
you have to start line item the IT. And ORA set it in the
position, doing a good portion of the post-market surveillance
work, what need for information from each of those silo legacy
systems. It has to be integrated.
The investigators and ORA either at the border or doing
facility inspections need information. They are going to go
from one industry to another. They may do a drug inspection, a
device inspection, a biologic inspection. So that is why the
integration. But it is not funded. It is just--it is not a
direct line. And ORA considerations, in my opinion, just have
not been at the fore.
Mr. Hubbard. If I may, Mr. Chairman, the IT is expensive.
The Science Board suggested it needed about $800 million. And I
think the folks at--above FDA have just not felt that it is
worthy. And, in fact, many years we would ask for money--around
the time of your '98 hearing, we were asking for money for
import IT. In fact, we would get cuts that said you don't
really--IT, that is not important. You can always use
efficiencies and do better. And it squeezed--it cut 10, 20
million. And so you have never had that commitment to fixing
the IT systems. So you have these 1970s and '80s systems
limping along, totally ineffective.
Mr. Stupak. Dr. Cassell.
Dr. Cassell. Yes. I would agree and just remind you in our
report we pointed out that FDA's IT budget is less than half of
that that CDC currently has, yet the information that needs to
be managed is far greater.
The other thing I have heard this week that is very
disturbing is that, while we were well on our way to developing
a new IT system for adverse event reporting, apparently the
backup system that we pointed out that didn't exist actually
doesn't exit. It was lost. They are 6 weeks behind in terms of
implementation, and the problem still hasn't been resolved. So
I think again this is one area that is urgent. It is critical
that it be fixed and fixed quickly.
Mr. Hubbard. Can you imagine the frustration at FDA last
year when the FBI decided its $800 million system didn't work
and threw it away and said we'll start over. Now, if they had
gotten that kind of money, I personally think FDA would have
spent that.
Mr. Stupak. Mr. England, go ahead.
Mr. England. Just real quick examples. One--because I think
some of this responsibility actually happens because Congress
sometimes tries to fix problems one piece at a time. Prior
notice, for example. FDA got mandated--you were mandated to do
due prior where they were given no money to put the IT system
together. So all the money they were going to use for OASIS
enhancements all went into prior notice, which, quite frankly,
I think didn't really accomplish very much.
Now, as we think about the idea of proposing a registration
system where people pay money for registration, some of that
money will go into what? An IT system. And it will be a
stovepipe system just like the rest of them. So as these
solutions come up, if they're not for across the entire agency,
it actually aggravates the problem. They start using that money
to create stovepipe solutions to manage the new mandate.
Mr. Shimkus. Yes, and that's one of the issues of the whole
institution; and, indeed, if you would rebuild it from the
ground up--and we've got to break down these barriers.
I'm going to throw out 3 phrases for the sake of time and
just have comments.
The appearance standard for kicking off an import alert and
then also the debate on extraterritorial jurisdiction on our
ability to hold overseas importers somehow more accountable
under the law. Any comments on that? Does that make sense? I
mean, I can go into the whole question, but you know the
phrases, right?
Mr. England. The appearance standard, I mean, right now the
Agency already has the authority under the appearance standard.
Nobody knows what it is. No judge has ever said so, nor will
the FDA ever want a judge to say so, because they would all of
a sudden have a standard that they would have to meet. But
there is no--the appearance standard--as long as it appears to
be in violation of the act, they can stop that product now.
And then the courts tend to defer to the Agency as to what
the appearance is. And is that right? Well, I represent other
people who don't like that, but you can see why judges do it.
As far as extraterritorial power, you're not really
reaching into those foreign governments with that standard. All
you're doing is--you're just saying, not in my backyard, not
here.
Mr. Shimkus. I know that the question is should that be
something that we legislatively consider?
Mr. Hubbard. The appearance standard is a relic of 1906. It
says the FDA has to define either that problem clearly or the
appearance of that problem and then stop the product. If you're
going to change the paradigm, you need to move the burden to
the producer to show they are making safe food or drugs, not on
FDA to find every single problem with every single shipment
when you have 20 million shipments.
Mr. Shimkus. Mr. Nielsen.
Dr. Nielsen. I think the task is to make certain it is
equal burden for the domestic and foreign industry or else it
is unfair competition.
Mr. England. I mean, just on the extraterritorial question,
I would think--it would seem to me where it would be difficult
is how you enforce it. I mean, if--and part of it--if you're
talking about some how penalizing----
Mr. Shimkus. I understand--I mean, we were talking about
heparin a lot, but if there is criminality----
Mr. England. The United States government already has power
to prosecute foreign nationals that commit those kinds of
crimes. They've done it before. They did it in the drug
investigations. Gerd--what is his name? Gerd Weithase was a
German national. He was involved in the manufacture--somehow
involved in the scheme----
Mr. Shimkus. You know, I'm getting help here, but I hear
that DOJ wants some explicit language to help us more fully
prosecute.
Mr. England. DOJ has often gone along with FDA and said we
agree. That would certainly help. It isn't clear that the Food
and Drug Cosmetic Act--and I think that clarification was not
going to hurt anything.
Mr. Shimkus. But if we are moving legislation, if we wanted
it clear, we could at least look at the language.
Mr. Hubbard. FDA would clearly like you to deal with the
extraterritoriality.
Mr. Shimkus. Thank you. I'm done, Mr. Chairman. Thank you.
Mr. Stupak. Mr. Melancon? No.
Well, thank you to this panel. It is always a very, very
good panel. We enjoy it. That's why I like the members to just
go on and ask the questions.
I mentioned the three recalls just while this panel was
empaneled. We had from China snow fungus, which is mushrooms;
from Vietnam, ginger; and from China, dried lily bulbs. Those
are three recalls--or alerts that just came in.
Mr. England. Not my clients----
Mr. Stupak. I thought I'd give you a heads-up.
Mr. Nielsen [continuing]. Yet.
Mr. Stupak. I am still trying to figure out what do we do
with dried lily bulbs.
Anyway, that concludes our questioning. I want to thank our
witnesses for coming today and your testimony and thank you
again. And, Dr. Cassell, be sure you tell your committee thank
you very much for their work and expertise.
I ask unanimous consent that the hearing record will remain
open for 30 days for additional questions for the record.
Without objection, the record will remain open.
I ask unanimous consent that the contents of our document
binder be entered in the record.
Without objection, documents will be entered into the
record.
That concludes our hearing. Without objection, this meeting
of the subcommittee is adjourned.
[Whereupon, at 3:00 p.m., the subcommittee was adjourned.]
[Material submitted for inclusion in the record follows:]
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