[House Hearing, 116 Congress]
[From the U.S. Government Publishing Office]
SECURING THE U.S. DRUG SUPPLY CHAIN: OVERSIGHT OF FDA'S FOREIGN
INSPECTION PROGRAM
=======================================================================
HEARING
BEFORE THE
SUBCOMMITTEE ON OVERSIGHT AND INVESTIGATIONS
OF THE
COMMITTEE ON ENERGY AND COMMERCE
HOUSE OF REPRESENTATIVES
ONE HUNDRED SIXTEENTH CONGRESS
FIRST SESSION
__________
DECEMBER 10, 2019
__________
Serial No. 116-83
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
Printed for the use of the Committee on Energy and Commerce
govinfo.gov/committee/house-energy
energycommerce.house.gov
______
U.S. GOVERNMENT PUBLISHING OFFICE
44-495 PDF WASHINGTON : 2021
COMMITTEE ON ENERGY AND COMMERCE
FRANK PALLONE, Jr., New Jersey
Chairman
BOBBY L. RUSH, Illinois GREG WALDEN, Oregon
ANNA G. ESHOO, California Ranking Member
ELIOT L. ENGEL, New York FRED UPTON, Michigan
DIANA DeGETTE, Colorado JOHN SHIMKUS, Illinois
MIKE DOYLE, Pennsylvania MICHAEL C. BURGESS, Texas
JAN SCHAKOWSKY, Illinois STEVE SCALISE, Louisiana
G. K. BUTTERFIELD, North Carolina ROBERT E. LATTA, Ohio
DORIS O. MATSUI, California CATHY McMORRIS RODGERS, Washington
KATHY CASTOR, Florida BRETT GUTHRIE, Kentucky
JOHN P. SARBANES, Maryland PETE OLSON, Texas
JERRY McNERNEY, California DAVID B. McKINLEY, West Virginia
PETER WELCH, Vermont ADAM KINZINGER, Illinois
BEN RAY LUJAN, New Mexico H. MORGAN GRIFFITH, Virginia
PAUL TONKO, New York GUS M. BILIRAKIS, Florida
YVETTE D. CLARKE, New York, Vice BILL JOHNSON, Ohio
Chair BILLY LONG, Missouri
DAVID LOEBSACK, Iowa LARRY BUCSHON, Indiana
KURT SCHRADER, Oregon BILL FLORES, Texas
JOSEPH P. KENNEDY III, SUSAN W. BROOKS, Indiana
Massachusetts MARKWAYNE MULLIN, Oklahoma
TONY CARDENAS, California RICHARD HUDSON, North Carolina
RAUL RUIZ, California TIM WALBERG, Michigan
SCOTT H. PETERS, California EARL L. ``BUDDY'' CARTER, Georgia
DEBBIE DINGELL, Michigan JEFF DUNCAN, South Carolina
MARC A. VEASEY, Texas GREG GIANFORTE, Montana
ANN M. KUSTER, New Hampshire
ROBIN L. KELLY, Illinois
NANETTE DIAZ BARRAGAN, California
A. DONALD McEACHIN, Virginia
LISA BLUNT ROCHESTER, Delaware
DARREN SOTO, Florida
TOM O'HALLERAN, Arizona
------
Professional Staff
JEFFREY C. CARROLL, Staff Director
TIFFANY GUARASCIO, Deputy Staff Director
MIKE BLOOMQUIST, Minority Staff Director
Subcommittee on Oversight and Investigations
DIANA DeGETTE, Colorado
Chair
JAN SCHAKOWSKY, Illinois BRETT GUTHRIE, Kentucky
JOSEPH P. KENNEDY III, Ranking Member
Massachusetts, Vice Chair MICHAEL C. BURGESS, Texas
RAUL RUIZ, California DAVID B. McKINLEY, West Virginia
ANN M. KUSTER, New Hampshire H. MORGAN GRIFFITH, Virginia
KATHY CASTOR, Florida SUSAN W. BROOKS, Indiana
JOHN P. SARBANES, Maryland MARKWAYNE MULLIN, Oklahoma
PAUL TONKO, New York JEFF DUNCAN, South Carolina
YVETTE D. CLARKE, New York GREG WALDEN, Oregon (ex officio)
SCOTT H. PETERS, California
FRANK PALLONE, Jr., New Jersey (ex
officio)
C O N T E N T S
----------
Page
Hon. Diana DeGette, a Representative in Congress from the State
of Colorado, opening statement................................. 2
Prepared statement........................................... 3
Hon. Greg Walden, a Representative in Congress from the State of
Oregon, opening statement...................................... 4
Prepared statement........................................... 6
Hon. Frank Pallone, Jr., a Representative in Congress from the
State of New Jersey, opening statement......................... 7
Prepared statement........................................... 9
Hon. Brett Guthrie, a Representative in Congress from the
Commonwealth of Kentucky, opening statement.................... 10
Prepared statement........................................... 11
Witnesses
Mary Denigan-Macauley, Ph.D., Director, Health Care, Government
Accountability Office.......................................... 13
Prepared statement........................................... 15
Answers to submitted questions............................... 119
Janet Woodcock, M.D., Director, Center for Drug Evaluation and
Research, Food and Drug Administration......................... 47
Prepared statement........................................... 49
Answers to submitted questions............................... 125
Submitted Material
Article of January 31, 2019, ``Culture of 'Bending Rules' in
India Challenges U.S. Drug Agency,'' by Ari Alstedter and Anna
Edney, Bloomberg, submitted by Mr. Ruiz........................ 94
Article of May 10, 2019, ``Tainted drugs: Ex-FDA inspector warns
of dangers in U.S. meds made in China, India'' by Didi
Martinez, Brenda Breslauer, and Stephanie Gosk, NBC News,
submitted by Mr. Ruiz.......................................... 103
Article of October 29, 2019, ``In generic drug plants in China
and India, data falsification is still a problem,'' by
Katherine Eban and Sony Salzman, Stat, submitted by Mr. Ruiz... 112
SECURING THE U.S. DRUG SUPPLY CHAIN: OVERSIGHT OF FDA'S FOREIGN
INSPECTION PROGRAM
----------
TUESDAY, DECEMBER 10, 2019
House of Representatives,
Subcommittee on Oversight and Investigations,
Committee on Energy and Commerce,
Washington, DC.
The subcommittee met, pursuant to call, at 10:04 a.m., in
the John D. Dingell Room 2123, Rayburn House Office Building,
Hon. Diana DeGette (chair of the subcommittee) presiding.
Members present: Representatives DeGette, Schakowsky,
Kennedy, Ruiz, Kuster, Castor, Tonko, Clarke, Pallone (ex
officio), Guthrie (subcommittee ranking member), McKinley,
Griffith, Brooks, Mullin, and Walden (ex officio).
Staff present: Kevin Barstow, Chief Oversight Counsel;
Jeffrey C. Carroll, Staff Director; Manmeet Dhindsa, Counsel;
Austin Flack, Staff Assistant; Tiffany Guarascio, Deputy Staff
Director; Chris Knauer, Oversight Staff Director; Kevin
McAloon, Professional Staff Member; Kaitlyn Peel, Digital
Director; Tim Robinson, Chief Counsel; Nikki Roy, Policy
Coordinator; Emily Ryan, GAO Detailee; Andrew Souvall, Director
of Communications, Outreach, and Member Services; Benjamin
Tabor, Policy Analyst; C.J. Young, Press Secretary; Jen
Barblan, Minority Chief Counsel, Oversight and Investigations;
Diane Cutler, Minority Detailee, Oversight and Investigations;
Peter Kielty, Minority General Counsel; Ryan Long, Minority
Deputy Staff Director; Brannon Rains, Minority Legislative
Clerk; Kristin Seum, Minority Counsel, Health; and Alan
Slobodin, Minority Chief Investigative Counsel, Oversight and
Investigations.
Ms. DeGette. The Subcommittee on Oversight and
Investigations will now come to order.
Today, the subcommittee is holding a hearing entitled,
``Securing the U.S. Drug Supply Chain: Oversight of FDA's
Foreign Inspection Program.'' The purpose of the hearing is to
examine the Food and Drug Administration's ability to
effectively oversee the quality of drug products manufactured
in foreign countries.
The Chair now recognizes herself for purposes of an opening
statement.
OPENING STATEMENT OF HON. DIANA DeGETTE, A REPRESENTATIVE IN
CONGRESS FROM THE STATE OF COLORADO
Today's hearing focuses on an area of longstanding concern
to this committee that has taken on increased importance: The
safety and effectiveness of pharmaceutical products made in
foreign countries. Between 70 and 80 percent of active
pharmaceutical ingredients and 40 percent of finished drugs are
made outside the United States. In particular, China and India
produce a significant portion of the U.S. drug supply.
Because the FDA can't possibly test every new drug that
comes into the U.S., inspections of drug manufacturers abroad
are a critical way to ensure that manufacturers around the
world are following quality standards and producing drugs that
are safe and effective for the American public. However, the
history of the FDA's foreign drug inspection program is one of
challenges and incremental progress. As far back as 1998, the
GAO has been raising concerns with the FDA's foreign
inspections.
This committee has a long history of oversight in this
area. For example, in 2007, we held a hearing about weaknesses
in the FDA's foreign inspections program. At that time, the
agency was not conducting frequent inspections abroad and did
not have reliable data even to know how many firms it needed to
inspect.
FDA also struggled to hire inspectional staff, and its
inspectors did not have reliable translators to help them
conduct inspections in foreign-language countries. I remember
that hearing because I was there, and it was shocking.
The year after that hearing, the world was reminded why
securing the global pharmaceutical supply chain is critical,
when it was discovered that tainted ingredients were used to
produce heparin, which is a critical drug used in surgery and
during dialysis. As a result of that mishap, Americans died,
drug shortages occurred, and many lost confidence in FDA's
ability to regulate drugs manufactured abroad.
GAO's reports over the years have also noted
vulnerabilities in how FDA regulates foreign drug
manufacturing. For example, in 2010, GAO found that FDA may
never have inspected most foreign firms. FDA was also
struggling to staff up its foreign offices, which were intended
to make foreign inspections more efficient and effective.
Because of these and other issues, GAO placed FDA's foreign
inspections program on its high-risk list over 10 years ago.
Now, in response to these challenges, Congress increased
FDA's resources to conduct foreign inspections and granted the
agency new authorities over foreign firms. As a result, the
number of inspections FDA conducted increased overseas, and the
FDA implemented a risk-based approach to select firms for
inspection, regardless of whether they were domestic or
foreign.
Now, these were significant improvements, but here we are
back today because FDA's foreign inspection program still has
some unresolved challenges. In the GAO's written testimony
today, there are reports on the results of its recent travel
overseas to evaluate FDA's work. GAO still found some of the
same issues, unfortunately, that have been hindering FDA's
foreign inspection program for years.
The number of foreign inspections dropped in the last 2
years, after years of increases. Furthermore, when FDA conducts
inspections in foreign-language-speaking countries, it still
relies on the firm itself to provide a translator, raising
questions about impartiality. And despite the new resources,
FDA continues to struggle to hire enough inspectors, including
in the foreign offices, and frankly, there are some real
barriers to being able to do that.
These challenges take on real meaning when we see reports
of potentially unsafe products in the market. Over the last
year and a half, FDA has been announcing widespread recalls of
popular medications used by millions of Americans to treat
blood pressure and heartburn because of trace amounts of
carcinogens identified in multiple versions of these drugs.
Now, I understand each of these recalls involves its own
particular causes and factors, but taken together they raise
larger issues, and I'm really--Dr. Woodcock, I'm very happy
you're here today, because I look forward to hearing what the
agency's response is to these new GAO findings.
Before I close, I just want to emphasize a couple final
thoughts. First, the issues today affect both brand and generic
drugs. Many foreign firms provide the active pharmaceutical
ingredients used in both brand and generic versions of drugs,
so this can happen throughout the supply chain.
And finally, I want to emphasize, this hearing should not
be interpreted as an indictment of foreign drug manufacturing
generally. Americans should not feel that they cannot trust
medicines made abroad, nor should we swear off foreign-made
drugs. In fact, we're increasingly reliant on foreign
manufacturers, but we do need to make sure that all of these
issues which have been persistent for many, many years continue
to be addressed.
And with that, I want to thank both of our witnesses for
appearing today.
[The prepared statement of Ms. DeGette follows:]
Prepared Statement of Hon. Diana DeGette
Today's hearing focuses on an area of longstanding concern
to the committee that has taken on increased importance: the
safety and effectiveness of pharmaceutical products made in
foreign countries.
Between 70 and 80 percent of active pharmaceutical
ingredients (``API'') and 40 percent of finished drugs are made
outside the United States. In particular, China and India
produce a significant portion of the U.S. drug supply.
Because the Food and Drug Administration (FDA) cannot
possibly test every drug that comes into the U.S., FDA
inspections of drug manufacturers abroad are a critical way to
ensure that manufacturers around the world are following
quality standards and producing drugs that are safe and
effective for the American public.
However, the history of FDA's foreign drug inspection
program is one of challenges and incremental progress. As far
back as 1998, the Government Accountability Office (GAO) has
been raising concerns with FDA's foreign inspections.
This committee has a long history of oversight in this
area. For instance, in 2007, we held a hearing about weaknesses
in FDA's foreign inspections program. At that time, FDA was not
conducting frequent inspections abroad, and did not have
reliable data to even know how many firms it needed to inspect.
FDA also struggled to hire inspectional staff, and its
inspectors did not have reliable translators to help them
conduct inspections in foreign-language countries.
The year after that hearing, the world was reminded why
securing the global pharmaceutical supply chain is critical,
when it was discovered that tainted ingredients were used to
produce heparin--a critical drug used in surgery and during
dialysis.
As a result of that mishap, Americans died, drug shortages
occurred, and many lost confidence in FDA's ability to regulate
drugs manufactured abroad.
GAO's reports over the years have also noted
vulnerabilities in how FDA regulates foreign drug
manufacturing. For example, in 2010, GAO found that FDA may
have never inspected most foreign firms. FDA was also
struggling to staff up its foreign offices, which were intended
to make foreign inspections more efficient and effective.
Because of these and other issues, GAO placed FDA's foreign
inspections program on its High Risk list over 10 years ago.
In response to these challenges, Congress increased FDA's
resources to conduct foreign inspections and granted FDA new
authorities over foreign firms. As a result, FDA increased the
number of inspections it conducted, and implemented a risk-
based approach to select firms for inspection, regardless of
whether they were foreign or domestic.
These were significant improvements. But despite that
progress, we are back here today because FDA's foreign drug
inspection program still has unresolved challenges. In its
written testimony today, GAO reports on the results of its
recent travel overseas to evaluate FDA's work. GAO found some
of the same issues that have been hindering FDA's foreign
inspection program for years.
GAO reports that the number of foreign inspections dropped
in the last two years, after years of increases. Furthermore,
when FDA conducts inspections in foreign language-speaking
countries, it still largely relies on the firm itself to
provide a translator, raising concerns about impartiality. And
despite getting new resources, FDA continues to struggle to
hire enough inspectors, including in its foreign offices.
These challenges take on real meaning when we see reports
of potentially unsafe products in the market. Over the past
year and a half, FDA has been announcing widespread recalls of
popular medications used by millions of Americans to treat
blood pressure and heartburn, because of trace amounts of
carcinogens identified in multiple versions of these drugs.
While I understand each of these recalls involves its own
particular causes and factors, taken together, they raise
larger issues and concerns that FDA has not fully addressed
longstanding vulnerabilities in its foreign inspections
program.
Before I close, I would like to emphasize a couple final
thoughts. First, the issues we will be discussing today affect
both brand and generic drugs. Many foreign firms provide the
active pharmaceutical ingredients used in both brand and
generic versions of drugs, so these issues can affect drugs
throughout the supply chain--which is all the more reason why
they must be addressed.
Finally, this hearing should not be interpreted as an
indictment of foreign drug manufacturing generally. Americans
should not feel that they cannot trust medicines made abroad,
nor should we swear off foreign-made drugs. In fact, we are
increasingly reliant on foreign manufacturers.
But if drugs are going to be made abroad, then Americans
must have confidence in the ability of FDA to effectively
regulate foreign suppliers. It is critical that FDA have the
resources and the capability to do this job and ensure that
every American can trust the safety and effectiveness of the
drugs they take.
Ms. DeGette. And I'm going to yield to the ranking member
of the full Energy and Commerce Committee, Mr. Walden, for
purposes of his opening statement, 5 minutes.
OPENING STATEMENT OF HON. GREG WALDEN, A REPRESENTATIVE IN
CONGRESS FROM THE STATE OF OREGON
Mr. Walden. Thank you very much, Madam Chair. And I want to
thank Ranking Member Guthrie for yielding to me. We've got
another hearing I have to get at that conflicts with this one,
so--and I want to thank our witnesses for being here. And,
Madam Chair, thank you for holding this really important
hearing, because our drugs and drug ingredients more and more
are coming from overseas, especially from China and India, and
manufacturers have ultimate responsibility for the safety and
effectiveness of these products.
But the FDA has an indispensable role to protect public
health, which I know you all take very seriously, by ensuring
that drug firms are complying with good manufacturing processes
and practices. Through this hearing, I hope FDA can further
strengthen its ability to fulfill its public health mission and
to protect the safety, effectiveness, and integrity of the U.S.
drug supply.
Today, we have the benefit of the Government Accountability
Office, their analysis, to assist us in our work. Over the
years, GAO has provided invaluable work to this committee on
FDA's foreign drug inspection program, and not long ago the GAO
reported that the FDA was not conducting enough drug
inspections overseas and lacked the resources and authorities
to adequately meet this inspection need. This committee
responded by enacting the Food and Drug Administration Safety
Innovation Act or--we'll just leave it at that--and the Generic
User Fee Act, or GDUFA--they have all these UFAs and ASIAs and
DASIAs and--well, anyway, FDA now has additional resources and
authorities and, to FDA's credit, has addressed the previous
disparity between the number of domestic and foreign
inspections conducted.
Earlier this year, as you know, the committee again asked
the GAO, on a bipartisan basis, to evaluate the current state
of the foreign drug inspection program. While progress has been
made in some areas, the GAO's preliminary observations indicate
the FDA continues to face persistent challenges in its ability
to conduct foreign drug inspections, and particularly in India
and China. This is concerning because the FDA is identifying
serious deficiencies during many foreign inspections.
Now, for years, the FDA leadership has spoken of
transforming the agency into a global health organization,
particularly in addressing imported drugs. But even with that
stated priority and the influx of user fees, FDA has told the
GAO and this committee that it can't hire enough inspectors to
fill vacancies among staff conducting foreign inspections. Now,
having sufficient numbers of inspectors is not a new problem.
The need to hire additional inspectors was part of the reason
that Congress gave the FDA the authority to collect user fees
for generic drugs.
Today, FDA not only has vacancies in its foreign offices
but also does not have enough inspectors in its dedicated
foreign drug cadre. The FDA recently received direct-hire
authority to address this problem, and I have questions today
about how this authority will be used to fill these vacancies,
as well as about FDA's hiring and retention efforts the past 6
years.
Other challenges to FDA's foreign drug inspection program
remain, and unlike domestic drug inspections, most foreign drug
firms actually receive advance notice of an FDA inspection. And
when the FDA inspectors are traveling from the United States,
which is often the case in most foreign drug inspections, the
FDA preannounces inspections and foreign drug firms generally
get 12 weeks in advance with a notice on when the FDA
inspectors are coming to their plants. The concerns raised by
recent investigative reports is this system gives plants ample
time to clean up evidence of unsanitary conditions, wrongdoing,
or data manipulation.
And I would just say as a side note, having been a licensee
of the FCC for 21 years in the radio business, I always would
have liked to have had a 12-week notice in advance when the FCC
was coming to inspect our station. We never got a fine, but we
would have made sure everything was completely in order. It
always was.
In 2014, to address these issues, the FDA instituted an
initiative in India, giving plants only short or no advance
notice of inspections, and as a result, the serious violations
uncovered by inspectors rose by almost 60 percent. So the
initiative was discontinued in 2015. FDA told the committee
they discontinued the initiative because it lacked protocols
and evaluation criteria.
However, the FDA still must believe there's value to short-
notice inspections, because you do conduct such inspections in
for-cause situations and conduct short-notice inspections
domestically.
Finally, in about 80 percent of the inspections, FDA sends
only one inspector, who is often reliant on the drug firm's
employees or agents to do the translation. What could go wrong
there? This solitary inspector, relying on the firm for
translation and perhaps even travel arrangements, is allocated
only a few days for the difficult task of inspecting a drug
plant that can be the size of a small city.
Meanwhile, the drug firm has about 3 months' advance notice
of the inspection. If the firm's unscrupulous, that's more than
enough time to subvert regulations by fabricating records and
concealing actual conditions. I think you get the point. So FDA
needs to respond to the overall challenges of foreign drug
inspections with more vigor. As they said in ``Jaws,'' ``You're
going to need a bigger boat.'' So we must maintain public
confidence and trust in our drug supply chain, and we look
forward to working with you to make that happen.
Madam Chair, thank you for having this hearing.
[The prepared statement of Mr. Walden follows:]
Prepared Statement of Hon. Greg Walden
Chair DeGette, thank you for this hearing. Our drugs and
drug ingredients more and more come from overseas, especially
from China and India. Manufacturers have ultimate
responsibility for the safety and effectiveness of these
products. But FDA has an indispensable role to protect public
health by ensuring that drug firms are complying with good
manufacturing practices. Through this hearing, I hope FDA can
further strengthen its ability to fulfill its public health
mission, and to protect the safety, effectiveness, and
integrity of the U.S. drug supply.
Today, we have the benefit of the Government Accountability
Office's (GAO) analysis to assist us. Over the years, GAO has
provided invaluable work to this Committee on FDA's foreign
drug inspection program. Not that long ago, GAO reported that
FDA was not conducting enough drug inspections overseas and
lacked resources and authorities to adequately meet this
inspection need. This committee responded by enacting the Food
and Drug Administration Safety and Innovation Act, or FDASIA,
and the Generic Drug User Fee Act, or GDUFA. FDA now has
additional resources and authorities and, to the FDA's credit,
has addressed the previous disparity between the number of
domestic and foreign inspections conducted.
Earlier this year, the committee again asked GAO on a
bipartisan basis to evaluate the current state of the foreign
drug inspection program. While progress has been made in some
areas, the GAO's preliminary observations indicate that FDA
continues to face persistent challenges in its ability to
conduct foreign drug inspections, particularly in India and
China. This is concerning because FDA is identifying serious
deficiencies during many foreign inspections.
For years, FDA leadership has spoken of transforming the
agency into a global health organization, particularly in
addressing imported drugs. But even with that stated priority
and the influx of user fees, FDA has told the GAO and this
committee that it can't hire enough inspectors to fill
vacancies among staff conducting foreign inspections. Having
sufficient numbers of inspectors is not a new problem--the need
to hire additional inspectors was part of the reason that
Congress gave FDA the authority to collect user fees for
generic drugs. Today, FDA not only has vacancies in its foreign
offices but also does not have enough inspectors in its
dedicated foreign drug cadre. FDA recently received direct-hire
authority to address this problem, and I have questions today
about how this authority will be used to fill these vacancies,
as well as about FDA's hiring and retention efforts the past 6
years.
Other challenges to FDA's foreign drug inspection program
remain. Unlike domestic drug inspections, most foreign drug
firms receive advance notice of an FDA inspection. When FDA
inspectors are traveling from the United States, which is the
case in most foreign drug inspections, the FDA pre-announces
inspections. Foreign drug firms generally get 12 weeks advance
notice on when FDA inspectors are coming to their plants. The
concerns raised by recent investigative reports is that this
system gives plants ample time to clean up evidence of
unsanitary conditions, wrongdoing, or data manipulation.
In 2014, to address these issues, the FDA instituted an
initiative in India giving plants only short or no advance
notice of inspections. As a result, the serious violations
uncovered by inspectors rose by almost 60 percent. The
initiative was discontinued in July 2015. FDA told the
committee they discontinued the initiative because it lacked
protocols and evaluation criteria. However, FDA still must
believe there is value to short notice inspections, because
they conduct such inspections in for-cause situations and
conduct short notice inspections domestically.
Finally, in about 80 percent of inspections, FDA sends only
one inspector, who is often reliant on the drug firm's
employees or agents for translation. This solitary inspector,
relying on the firm for translation and perhaps even travel
arrangements, is allocated only a few days for the difficult
task of inspecting a drug plant that can be the size of a small
city. Meanwhile, the drug firm has about 3 months advance
notice of the inspection. If the firm is unscrupulous, that is
more than enough time to subvert regulations by fabricating
records and concealing actual conditions.
Despite having the deck stacked against them, the committee
has seen and heard plenty of accounts about intrepid FDA
inspectors who have discovered serious misconduct at firms in
India and China, protecting our Nation's drug supply in the
process. We thank them for their service.
FDA needs to respond to the overall challenges of foreign
drug inspections with more vigor. As they said in ``Jaws,''
``You're going to need a bigger boat.'' We must maintain public
confidence and trust in our drug supply, and FDA needs to rise
further to meet the challenge. I welcome our witnesses and look
forward to the testimony.
Ms. DeGette. Thank you so much, Mr. Walden.
The Chair now recognizes the chairman of the full
committee, Mr. Pallone, for 5 minutes.
OPENING STATEMENT OF HON. FRANK PALLONE, Jr., A REPRESENTATIVE
IN CONGRESS FROM THE STATE OF NEW JERSEY
Mr. Pallone. Thank you, Chairwoman DeGette.
Today, the committee continues its longtime work of
conducting oversight of the FDA's foreign drug inspection
program. The program is a key piece of our efforts to ensure
that the prescription drugs Americans take every day are safe
and effective. Under the law, any firm, whether it's
basically--whether it's based domestically or overseas, that
seeks approval to market a drug in the U.S. must comply with
the FDA's current good manufacturing practice regulations.
Both foreign and domestic firms are held to the same
standards, which lay out the essential quality controls that
ensure drugs are safe for use, and those standards also apply
equally to both brand and generic manufacturers. While it's up
to the manufacturers to take the necessary steps to implement
the CGMP practices, FDA is tasked with inspecting facilities
around the world to verify they're in compliance.
In the past, the committee found that FDA was woefully
unprepared to take on the challenge of regulating and
inspecting foreign drug manufacturers. As part of our ongoing
oversight of this program, we found that foreign firms were not
being inspected with regular frequency, and FDA had no
permanent presence overseas, and its databases could not even
tell what firms were actively shipping products to the United
States.
And as a result of those disturbing issues, in 2012
Congress passed and the President signed the Food and Drug
Administration Safety Innovation Act of 2012, and that law
changed the way FDA selects firms to inspect, allowing it to
focus on more high-risk facilities, including those abroad. It
also increased FDA's authority over foreign manufacturers.
Then in 2013, the Drug Quality and Security Act provided
FDA with track-and-trace authority to give the agency more
tools to counter potentially dangerous drugs in the supply
chain. And again in 2017, Congress provided more resources to
FDA's foreign inspection program through the Generic Drug User
Fee Amendment.
Now, despite these new authorities and resources, FDA's
foreign drug inspection program continues to face challenges.
For instance, the number in foreign inspections has actually
declined the last 2 years. This is troubling because FDA had
been making progress in inspecting more facilities, up until 2
years ago, and FDA also continues to struggle with hiring staff
to conduct foreign inspections.
Again, this is all disturbing considering that Congress
provided the generic drug user fees in part to fund foreign
inspections. And I'm interested in hearing from the FDA on why
the number of foreign inspections has declined in recent years
and what's preventing them from reaching its capacity.
Now, today's hearing focuses on FDA's efforts,
manufacturers have the responsibility to guarantee their
products are safe and effective. We have to do what we can to
ensure that manufacturers continue to produce high-quality drug
products, including through innovative methods such as
continuous manufacturing. Those methods not only help control
quality but also enable firms to compete in the global market.
And this one final point I'd just like to keep in mind is
that the issues we'll be discussing today affect all kinds of
drugs throughout the supply chain. Much of the press coverage
has framed these issues as a generic drug issue, but the fact
is that the majority of active pharmaceutical ingredients for
both generics and brands come from foreign countries.
Generic drugs have saved Americans billions of dollars and
are critical to lowering healthcare costs across the board. FDA
must ensure that any company, whether brand or generic, that
wishes to market drug products in the U.S. adheres to the same
quality standards. That not only provides a level playing field
but confidence in American consumers that the drugs they're
taking will be safe and effective.
So, again, I look forward to hearing from our witnesses
about what's being done to ensure that confidence and what more
is needed to secure the Nation's drug supply. And unless
anybody wants my minute, I'm going to yield back. Thank you,
Madam Chair.
[The prepared statement of Mr. Pallone follows:]
Prepared Statement of Hon. Frank Pallone, Jr.
Today, the committee continues its longtime work of
conducting oversight of the Food and Drug Administration's
foreign drug inspection program. This program is a key piece of
our efforts to ensure that the prescription drugs Americans'
take every day are safe and effective.
Under the law, any firm--whether it is based domestically
or overseas--that seeks approval to market a drug in the United
States must comply with FDA's Current Good Manufacturing
Practice (CGMP) regulations.
Both foreign and domestic firms are held to the same
standards, which lay out the essential quality controls that
ensure drugs are safe for use. Those standards also apply
equally to both brand and generic manufacturers. While it is up
to the manufacturers to take the necessary steps to implement
CGMP practices, FDA is tasked with inspecting facilities around
the world to verify their compliance.
In the past, the committee found that FDA was woefully
unprepared to take on the challenge of regulating and
inspecting foreign drug manufacturers. As part of our ongoing
oversight of this program, we found that foreign firms were not
being inspected with regular frequency, FDA had no permanent
presence overseas, and its databases could not even tell it
what firms were actively shipping products to the United
States.
As a result of these disturbing issues, in 2012, Congress
passed and the President signed the Food and Drug
Administration Safety and Innovation Act of 2012. The law
changed the way FDA selects firms to inspect, allowing it to
focus on more high-risk facilities, including those abroad. It
also increased FDA's authorities over foreign manufacturers.
Then, in 2013, the Drug Quality and Security Act provided
FDA with ``track-and-trace'' authority to give the agency more
tools to counter potentially dangerous drugs in the supply
chain. And, again in 2017, Congress provided more resources to
FDA's foreign inspection program through the Generic Drug User
Fee Amendments.
Despite these new authorities and resources, FDA's foreign
drug inspection program continues to face challenges. For
instance, the number of foreign inspections has declined the
last 2 years. This is troubling because FDA had been making
progress in inspecting more facilities up until 2 years ago.
FDA also continues to struggle with hiring staff to conduct
foreign inspections.
Again, this is all deeply disturbing considering that
Congress provided the generic drug user fees, in part, to fund
foreign inspections. I am interested in hearing from FDA on why
the number of foreign inspections has declined in recent years
and what is preventing it from reaching its capacity.
While today's hearing focuses on FDA's efforts,
manufacturers have the first responsibility to guarantee their
products are safe and effective. We must do what we can to
ensure manufacturers continue to produce high-quality drug
products, including through innovative methods such as
continuous manufacturing. Those methods not only help control
quality, but also enable firms to compete in the global market.
One final point to keep in mind is that the issues we will
be discussing today affect all kinds of drugs throughout the
supply chain. Much of the press coverage has framed these
issues as a ``generic drug issue''--but the fact is that the
majority of active pharmaceutical ingredients (API) for both
generics and brands come from foreign countries.
Generic drugs have saved Americans billions of dollars, and
are critical to lowering healthcare costs across the board. FDA
must ensure that any company, whether brand or generic, that
wishes to market drug products in the United States adheres to
the same quality standards. That provides not only a level
playing field, but confidence in American consumers that the
drugs they are taking will be safe and effective.
I look forward to hearing from our witnesses about what is
being done to ensure that confidence, and what more is needed
to secure the Nation's drug supply.
I yield back.
Ms. DeGette. The gentleman yields back.
The Chair now recognizes Mr. Guthrie for 5 minutes.
OPENING STATEMENT OF HON. BRETT GUTHRIE, A REPRESENTATIVE IN
CONGRESS FROM THE COMMONWEALTH OF KENTUCKY
Mr. Guthrie. Thank you, Chair DeGette, for holding this
very important hearing.
The adequacy of FDA's oversight of the U.S. drug supply has
been a longstanding issue for this committee. This committee
has long been at the forefront of increasing access to reducing
the price of drugs in the United States, particular in our
effort to expand access to generic drugs.
Over the last three decades, the pharmaceutical industry
has been globalized, and drug manufacturing has shifted
significantly from the United States to overseas. Today, about
80 percent of ingredients for America's drug supply are
manufactured overseas, and roughly 40 percent of drugs in the
finished form are imported.
FDA has the responsibility to monitor the safety and
effectiveness of drugs through inspections of drug
manufacturing. Over the years, the Government Accountability
Office has reported that the FDA has been slow to make
recommended changes to the foreign drug inspection program in
response to a globalized environment.
In 2012, this committee bolstered FDA's foreign drug
inspections with additional authorities in the Food and Drug
Administration Safety Innovation Act and funding through the
Generic Drug User Fee Act. With this support, the FDA has
increased the number of foreign drug inspections from 333 in
2007 to 935 in 2018. Through a recent agreement with the
European Union on greater cooperation on drug inspections, the
FDA has even more resources to focus drug inspections in high-
risk facilities.
While important improvements have been made, FDA has
persistent challenges. Past GAO reports and investigative
reporting have raised concerns about the ability of FDA to
oversee a globalized supply chain when 80 percent of the
inspections involve only one inspector. Translation is often
provided by the firm to be inspected, and most of the
inspections are preannounced with firms getting 2 to 3 months'
advance notice.
In contrast, domestic facilities are usually inspected
without notice. These conditions are concerning because there
have been notable cases of systematic falsification and
deception by firms determined to subvert FDA regulations.
Putting FDA at this kind of disadvantage against such
misconduct is not acceptable, particularly when we're talking
about drugs consumed by millions of Americans daily.
The FDA has known for decades about the need to globalize
its foreign inspection program and operationalize it
effectively. A strategy is needed to change the unbalanced
dynamic where domestic facilities are usually inspected without
notice, yet foreign facilities are given up to 3 months to
prepare.
Despite the additional resources provided by user fees
since 2013, it appears the FDA has a deficit of inspectors for
several years. For staff based in the United States, FDA
management should consider every tool available for creative
hiring incentives and consult with other Federal agencies who
effectively staff similarly situated personnel.
FDA getting direct-hire authority is a good start, but more
must be done to increase hiring and, just as important, retain
and promote inspectors who take on these responsibilities. With
additional staff, FDA should increase the number of inspections
conducted by teams rather than a single inspector and with
translators independent of the firm being inspected.
Surveillance inspections are data-dependent, yet the
potential for negligent or corrupt business practices overseas
is well known. A trust-based inspection system must be closely
evaluated to assess the true usefulness of data, information
accepted at face value from the foreign-based facilities.
With the majority of drug ingredients in drugs being
imported into the U.S., we are vulnerable to drug shortages,
compromises in quality, and reliance on foreign sources. The
question for FDA should not be how do we find solutions;
instead, the question should be how quickly can we put
solutions into action to continue to make sure America's drug
supply is safe.
On another note, while I know it's not the direct focus of
today's hearing, I want to emphasize that lowering drug prices
is one of the top things I hear back home and one of my top
priorities as a member of this committee. I am disappointed
that this week we are going to go through--pursue partisan
legislation on the floor instead of bipartisan policies that
have broad support.
I look forward to working with my colleagues to advance
bipartisan reform that will actually lower drug prices while
preserving innovative research. The FDA must maintain the
public's confidence in America's drug supply by ensuring it has
a smart, effective foreign drug inspection program strategy
that is not just planned or discussed but is both operational
and successful. I welcome the witnesses, and I look forward to
the testimony.
I yield back.
[The prepared statement of Mr. Guthrie follows:]
Prepared Statement of Hon. Brett Guthrie
Thank you, Chair DeGette, for holding this very important
hearing. The adequacy of FDA's oversight of the U.S. drug
supply has been a longstanding issue for this Committee.
This committee has long been at the forefront of increasing
access to and reducing the price of drugs in the United States,
particularly in our efforts to expand access to generic drugs.
Over the last three decades, the pharmaceutical industry
has become globalized and drug manufacturing has shifted
significantly from the United States to overseas. Today, about
80 percent of ingredients for America's drug supply are
manufactured overseas, and roughly 40 percent of drugs in the
finished form are imported.
FDA has the responsibility to monitor the safety and
effectiveness of drugs through inspections of drug
manufacturing. Over the years, the Government Accountability
Office (GAO) has reported that the FDA has been slow to make
recommended changes to the foreign drug inspection program in
response to a globalized environment.
In 2012, this committee bolstered FDA's foreign drug
inspections with additional authorities in the Food and Drug
Administration Safety and Innovation Act and funding through
the Generic Drug User Fee Act. With this support, the FDA has
increased the number of foreign drug inspections from 333 in
2007 to 935 in 2018. Through a recent agreement with the
European Union on greater cooperation on drug inspections, the
FDA has even more resources to focus drug inspections in high-
risk facilities.
While important improvements have been made, FDA has
persistent challenges. Past GAO reports and investigative
reporting have raised concerns about the ability of FDA to
oversee a globalized supply chain when 80 percent of
inspections involve only one inspector, translation is often
provided by the firm to be inspected, and most of the
inspections are preannounced, with firms getting 2 to 3 months
advance notice. In contrast, domestic facilities are usually
inspected without notice. These conditions are concerning
because there have been notable cases of systemic falsification
and deception by firms determined to subvert FDA regulations.
Putting FDA at this kind of a disadvantage against such
misconduct is not acceptable, particularly when we are talking
about drugs consumed by millions of Americans daily.
The FDA has known for decades about the need to globalize
its foreign inspection program and operationalize it
effectively. A strategy is needed to change the unbalanced
dynamic where domestic facilities are usually inspected without
notice, yet foreign facilities are given up to 3 months to
prepare.
Despite the additional resources provided by user fees
since 2013, it appears that FDA has had a deficit of inspectors
for several years. For staff based in the United States, FDA
management should consider every tool available for creative
hiring and incentives and consult with other Federal agencies
who effectively staff similarly situated personnel. FDA getting
direct hire authority is a good start, but more must be done to
increase hiring and--just as important--retain and promote
inspectors who take on these responsibilities.
With additional staff, FDA should increase the number of
inspections conducted by teams rather than a single inspector,
and with translators independent of the firm being inspected.
Surveillance inspections are data-dependent, yet the potential
for negligent or corrupt business practices overseas is well-
known. A trust-based inspection system must be closely
evaluated to assess the true usefulness of data and information
accepted at face value from foreign-based facilities.
With the majority of drug ingredients and drugs being
imported into the U.S., we are vulnerable to drug shortages,
compromises in quality, and reliance on foreign sources. The
question for FDA should not be ``How do we find solutions?''
Instead, the question should be ``How quickly can we put
solutions into action to continue to make sure America's drug
supply is safe?''
On another note, while I know that this is not the direct
focus of today's hearing, I want to emphasize that lowering
drug prices is one of the top things I hear back home and one
of my top priorities as a member of this committee. I am
disappointed that my colleagues on the other side of the aisle
have chosen to pursue partisan legislation on the floor this
week instead of bipartisan policies that have broad support. I
look forward to working with my colleagues to advance
bipartisan reform that will actually lower drug prices.
The FDA must maintain the public's confidence in America's
drug supply by ensuring it has a smart, effective foreign drug
inspection program strategy that is not just planned or
discussed but is both operational and successful. I welcome the
witnesses and look forward to the testimony.
Ms. DeGette. The gentleman yields back.
I ask unanimous consent that the Members' written opening
statements be made part of the record.
Without objection, so ordered.
I would now like to introduce our witnesses for today's
hearing, Dr. Mary Denigan, who's the Director of Healthcare,
Government Accountability Office. Welcome. And Dr. Janet
Woodcock. We usually just have a reserved seat for you at all
times, Dr. Woodcock. Thank you for being back with us today.
She's the Director of the Center for Drug Evaluation and
Research at the U.S. Food and Drug Administration.
Both of you are aware that the committee is holding an
investigative hearing, and when doing so, we have the practice
of taking testimony under oath. Do you have any objections to
testifying under oath?
Let the record reflect the witnesses responded no.
The Chair then advises you that, under the rules of the
House and the rules of the committee, you're entitled to be
accompanied by counsel. Does either of you wish to be
accompanied by counsel?
Let the record reflect the witnesses have responded no.
If you would, then, please rise and raise your right hand
so you may be sworn in.
[Witnesses sworn.]
Ms. DeGette. Let the record reflect the witnesses have
responded affirmatively, and you're now under oath and subject
to the penalties set forth in title 18, section 1001 of the
U.S. Code.
The Chair now will recognize our witnesses for a 5-minute
summary of their written statements. In front of each of you is
a microphone and timer and a series of lights. The timer will
count down your time, and the red light will turn on when the 5
minutes has come to an end.
Now I'd like to recognize you, Dr. Denigan, for 5 minutes.
STATEMENTS OF MARY DENIGAN-MACAULEY, Ph.D., DIRECTOR, HEALTH
CARE, GOVERNMENT ACCOUNTABILITY OFFICE; AND JANET WOODCOCK,
M.D., DIRECTOR, CENTER FOR DRUG EVALUATION AND RESEARCH, FOOD
AND DRUG ADMINISTRATION
STATEMENT OF MARY DENIGAN-MACAULEY, Ph.D.
Dr. Denigan-Macauley. Chair DeGette, Ranking Member
Guthrie, and members of the subcommittee, thank you for the
opportunity to discuss preliminary findings from our ongoing
work, examining FDA's foreign drug inspection program. It is
imperative that Americans have access to safe and effective
drugs, whether produced here or abroad. Today, the majority of
brand-name, generic, and over-the-counter drugs are
manufactured overseas, primarily in India and China. However,
we have had longstanding concerns about FDA's ability to
oversee the increasingly global supply chain.
In 1998, we reported the FDA had significant problems
managing its foreign inspection data and conducted infrequent
inspections of foreign establishments compared to their
domestic counterparts. Since then, we have returned to the
topic multiple times and found that many of these problems
persist.
In 2008, for example, we determined that, because of
inaccurate data, FDA did not know how many foreign drug
establishments were subject to inspection. In addition, we
found that FDA continued to inspect relatively few foreign
establishments and that, when it did, investigators faced
unique challenges that influenced how the inspections were
conducted.
For example, unlike in the United States, where an
establishment has no notice that an investigator is coming, FDA
routinely gave foreign manufacturers significant notice.
Further, FDA investigators had to rely on English-speaking
employees of the very establishment that they were inspecting
to translate, including key documents that demonstrated
compliance with good manufacturing practices.
In 2010, we found that, while FDA was conducting more
inspections overseas, many establishments had still never been
inspected. We also identified shortcomings in the operations of
the foreign offices that FDA opened in order to provide the
agency with important in-country information and inspection
capability. In 2010 and again in 2016, we found that the
offices faced persistently high vacancy rates, raising
questions about their effectiveness.
As a result of these challenges, we added FDA's oversight
of medical products, including drugs, to our high-risk series,
citing FDA's inability to ensure the quality of drugs
manufactured overseas as an area of particular concern.
This brings me to our current work. While the number of
foreign drug inspections increased from 2012 to 2016,
inspections have since dropped due to continued inaccuracies in
data and investigator shortages. FDA is also still having
trouble filling positions in foreign offices as well as
positions for domestically based investigators who conduct the
majority of these inspections overseas.
We also found that FDA still provides up to 3 months'
advance notice for most foreign inspections, which gives
establishments the opportunities to fix problems before the
investigator arrives.
Further, investigators face persistent challenges when they
travel overseas. As we learned on our site visits to India and
China and in conversations with investigators based there and
in the United States, lone investigators often had to inspect
manufacturing campuses covering acres of land in rural areas.
The majority have little flexibility to extend their time at a
facility because travel schedules require back-to-back
inspections.
In addition, FDA continues to send investigators into
establishments without translators. This is particularly
problematic in China, Japan, and South Korea. Investigators are
left to rely on translators provided by the drug manufacturer
that is being inspected, and there can be uncertainties about
the accuracy of the information they receive. One investigator
we spoke to said he had to resort to a translation app on their
phone to conduct their work.
In closing, foreign manufacturers continue to be a critical
source of drugs for millions of Americans, and FDA uses
inspections as a key tool to ensure the quality of those drugs.
FDA has made significant changes to adapt to the globalization
of the drug supply chain and has greatly increased the number
of inspections conducted overseas. However, the agency
continues to face many of the same challenges that we
identified in the past, raising questions about FDA's ability
to conduct inspections overseas that are equivalent as required
by law to those done here in the United States.
Thank you, Chair DeGette, Ranking Member Guthrie, and
members of the subcommittee, for holding this important hearing
and continuing your oversight. This concludes my remarks. I am
happy to respond to any questions you may have.
[The prepared statement of Dr. Denigan-Macauley follows:]
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
Ms. DeGette. Thank you, Doctor.
Dr. Woodcock, you're now recognized for 5 minutes.
STATEMENT OF JANET WOODCOCK, M.D.
Dr. Woodcock. Thank you.
Well, around the turn of the century, pharmaceutical
manufacturing began to move out of the U.S., as people have
already stated, but FDA was slow to react to this change. The
agency had a longstanding inspectional organization called the
Office of Regulatory Affairs, or ORA, that was organized around
domestic sites that were called districts, and these districts
inspected facilities, whether they had foods, drugs, devices,
or whatever, within the boundaries of each district. And then
they would volunteer inspectors to go outside of the U.S. from
those districts.
FDA also had very poor and inaccurate data systems. So,
unless a foreign site was part of an application in which it
was overtly brought to FDA's attention, then it might not get
inspected. And also in the data systems, there was a huge
number of incorrect and duplicate sites. So the GAO said we had
all these thousands we hadn't inspected. Many of them didn't
really exist or they were duplicates of another site, but we
didn't have data systems that could identify that.
As detailed in my testimony, by 2005, FDA was taking steps
to rectify the situation. Center for Drugs began requesting
more and more ex-U.S. GMP surveillance inspections, other than
just the preapproval inspections that had been going on, using
a risk-based model for site selection. Despite this, the ORA,
the field organization, was hampered by the requirement for
every 2-year domestic GMP inspections with no statutory
requirement for ex-U.S. establishments.
Much of this changed, as people said, in 2012 when Congress
passed FDASIA and the generic drug user fee program. FDASIA
removed the 2-year domestic requirement and replaced it with a
risk-based global approach to inspections. GDUFA provided ORA
with additional resources to inspect the generic industry in
both domestic and foreign.
At this time, FDA also took major changes in how we
regulate pharmaceutical quality. I personally led a major,
major reorganization of the Center for Drugs' quality function.
And I assumed the role of Acting Director of an office--a newly
formed Office of Pharmaceutical Quality. We cleaned up the
inventory, creating the current site catalog that has lists of
the existing firms that import drugs into the United States as
well as the U.S. firms that make drugs for the U.S.
We established the Office of Surveillance inside the Office
of Pharmaceutical Quality. The whole point of surveillance
office is to surveil the inventory, and we can get into that
later, but their job is to make sure we're looking at
everything and what--and do trend analysis. And we established
clear responsibilities between the Office of Compliance and
other offices in CDER.
Subsequently, the Office of Regulatory Affairs undertook a
major reorganization, the first in an extremely long time, and
they established inspectorates along product lines, so now we
have a drug inspectorate, right, rather than having districts
that do everything. They developed new SOPs called the Concept
of Operations that established a uniform process for doing
inspections both foreign and abroad for drugs.
As a result of all these changes, by 2016, foreign
surveillance inspections had exceeded domestic, and this trend
continues, as shown in the testimony. There had been a large
uptick and warning letters as previously uninspected sites that
were identified by the GAO and by our catalog were evaluated.
FDA's really currently up to date on our sites. We know there
are always new sites coming in. We assign them inspections, and
we are on top of all these sites as in the--documented in the
testimony. We expect performance of sites in India and China to
improve as they're subjected to continued U.S. oversight.
Despite this, there is much more to do, including hiring
inspectors and foreign office personnel--this is under way--
transforming the site selection model into a true quantitative
predictive model, but that will require data, us getting data,
rather than PDF, which is what we get now, stimulating advanced
manufacturing, and standardization and internationalization of
quality standards. And finally, as we put in our shortage
report, we're suggesting recognizing quality maturity as an
important factor in manufacturers' production.
Happy to answer questions. Thank you.
[The prepared statement of Dr. Woodcock follows:]
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
Ms. DeGette. Thank you so much, Dr. Woodcock.
It's now time for Members to ask questions, and the Chair
will recognize herself for 5 minutes.
And one of the reasons why we do hearings like this on a
continual basis is so that we can monitor these difficult
issues over time. And this committee, as I said in my opening
statement, has been working on foreign drug inspections for
several decades now.
It seems to me, Dr. Denigan, after hearing your testimony,
some of the--number one, we've made a lot of progress over the
years, and Dr. Woodcock talked about some of that progress that
we've made, but we still have some sort of stubborn issues that
continue. And, listening to your testimony, it seems like some
of them are, number one, we're giving advance warning to these
facilities before we go; number two, we have problem getting
independent translators to come, so we don't know about the
reliability of what our inspectors are being told; number
three, unique challenges of staffing with overseas inspections;
and number four, the quality of data.
Are those some of the issues that you had identified?
Dr. Denigan-Macauley. Yes, that's correct.
Ms. DeGette. And, Dr. Woodcock, what's your view of issues
like that that just continue to be difficult to address?
Dr. Woodcock. There are tradeoffs on many of these.
Obviously, we'd like to be fully staffed, but the entire FDA
has suffered some administrative problems with hiring, and many
of the centers are down in personnel. The field has recently
received direct-hire authority. They hope to bring on 20 people
that they're onboarding, and then we'd hope to hire----
Ms. DeGette. Twenty people to do foreign inspections?
Dr. Woodcock. Well, they will--first, they'll have to get
trained to be inspectors, right?
Ms. DeGette. OK.
Dr. Woodcock. And then some of them will reach the ability
to become foreign inspectors. They hope to bring on 50 in all,
because they do have a number of vacancies.
The foreign offices, again, none of these are within my
chain of command, but they have explained to me they are really
working on hiring. They have vacancies as well.
Ms. DeGette. And to what do you attribute these vacancies?
Is it just the vacancies we've seen throughout the agency since
2016?
Dr. Woodcock. There are--the administrative problems are
one problem with vacancies. Another problem with vacancies, of
course, is the roaring economy and the fact that people can
make more money elsewhere.
The Center for Drugs, for example, we have to hire 400
people to net less than a hundred, because we're losing--you
know, we're so attractive--our staff is so attractive
elsewhere, so--but we do have administrative problems with
hiring.
The foreign offices, it's more complicated. People don't
necessarily want to move their family overseas to some area in
India for many years. And----
Ms. DeGette. Dr. Denigan, I see you nodding at that. Would
you like to comment on that?
Dr. Denigan-Macauley. Yes, it is correct. I mean, once they
even--through the direct-hire authority, while it's good, it
still is going to take 2 to 3 years for that inspector to be
able to get the experience to then be able to go overseas, as
Dr. Woodcock had mentioned. And plus, if it takes 2 to 3 years,
even if they are ready to go, we found that it can take up to 2
years just to get over to the post. And if you're talking about
uprooting families, getting security clearances, medical
clearances, finding schools, housing, things like that, you can
give up in the process. So it is very challenging.
Ms. DeGette. And, Dr. Woodcock, what can we do to try to
alleviate some of those challenges and expedite it? Is there
something Congress can do to help?
Dr. Woodcock. All right. Well, I think there are many
things Congress can help us with. In the hiring area, I
believe--you know, many of the things that were discussed, for
example, a single investigator. Well, if we sent a team, then
we do half as many inspections. So we're going to need more
investigators if we want to have fuller coverage. All right?
Translation, we are working on that. We do have the
funding, and we are working on getting contracts for
independent translators per country that, you know, are not
related to the firm or any other part of the country.
Unannounced inspections is, again, a tradeoff, because they
are very inefficient, because we send people over there and
then they aren't operating, and they're in the middle of China
and they don't have anything to inspect, for example. So
that's--if we had--we agree that they would be useful, but we
feel that there's a tradeoff there between actually covering
the inventory and then how deeply we can cover the inventory,
and that should be obvious. So hiring, very important.
The authorities you gave us under Cures is really helping
the Center for Drugs in hiring people quickly that are
qualified scientific experts. And so those type of authorities
are very helpful.
Ms. DeGette. Thank you. Thank you so much. Lot more
questions, but good news, we have a lot more Members here.
Mr. Guthrie, I recognize you for 5 minutes.
Mr. Guthrie. Thank you very much. And I appreciate it. And
we're kind of going down the same path, I think, with our
questions.
First for Dr. Denigan, just to establish the difference in
on-site--or preannounced and unannounced inspections. So do
announced or unannounced inspections better enhance the
integrity and effectiveness of an inspection, and how does the
FDA use both announced and unannounced?
Dr. Denigan-Macauley. So, generally, the FDA uses
unannounced inspections with their foreign offices. They've
said that for logistical reasons they need to give up to 12
weeks' notice for those coming from the United States because
of the challenges of just doing the logistics. So that's a real
value of the foreign offices because they're there, they have
the in-country intel, and they can get there for the
unannounced inspections.
Mr. Guthrie. Great. Thank you very much.
And it does, Dr. Woodcock, kind of make sense logistically
it's easier to do unannounced inspections, easier to send an
inspector to Long Island than to interior of China, and I
understand the issues with that. Having said that, how do you
weigh the risk of maybe we need to do an unannounced inspection
even if you--I know you have to call ahead. How do you weigh
the risk of besides? All right, there's one, we're just going
to do an unannounced inspection even though we risk of getting
there and they're not operating or those types of things?
Dr. Woodcock. Yes. We do, for example, for cause. Say, if
we have a whistleblower or a complaint, we will go in
unannounced, even in a foreign country. So we do unannounced
inspections both by foreign offices and domestic. But I will
say, I mean, it is just a hypothesis anecdotal that the
unannounced inspections are so much better, that it's worth all
the costs, all the time. Ninety percent of the data integrity
problems that have been found recently have been found by our
domestic inspectors going and doing announced inspections. And
why is that? Because they're very good. Because our regulations
under part 11 require them to have computer systems with audit
trails. And either they don't have those, or if they have
messed around with them, our people can find it. So they have
found a lot of the problem--a lot of the problems have been
found by announced inspections.
Mr. Guthrie. OK. Before I came here, I was in
manufacturing. I was a quality engineer. So do you use
independent auditors? Is that permissible with you? Because I
know when Ford or GM will do auditor, they'll hire--or the
company being audited to sell to them will hire someone to come
in that everybody agrees is an independent auditor.
Dr. Woodcock. Yes. If companies get into trouble, all
right, and they are having trouble meeting the minimum
standards, which are GMPs, we would frequently suggest to them
that they use independent consultants who audit them. Sometimes
they will give us reports on the progress of the firm.
Meanwhile, the firm won't be able to import into the United
States because we do have a very strong regulatory tool for
foreign manufacturing, which we can do an import alert, and
then they can't send anything to the United States while
they're remediating their problems. So we do--and when we do
consent decrees, it may include reports by external auditors.
Mr. Guthrie. OK. Well, thanks. Just kind of specific
questions to make sure we get it get on the record. Does the
FDA have evaluation criteria for effectiveness of its foreign
drug inspection program? If so, what are the criteria? And has
FDA conducted any sort of review of the effectiveness of the
overall program, and if so, what are the findings?
Dr. Woodcock. Well, I think that's a very good question. I
believe that we really need to do more of this. Of course, it's
hard to assess the counterfactual, what would have happened if
we weren't there, right? And so we do need to, as I said in my
oral testimony, we really need to work on standardization of
the inspection program, standardization internationally, and
then we can put in some evaluations about the consequences or
the results.
Mr. Guthrie. Great, thanks. I want to ask a final question.
I know we talked this week about nitrosamine and NDMA found in
trace elements that, if anybody hears that you're more at risk
of not take--you need to take your blood pressure--you're more
at risk of high blood pressure than any risk from nitrosamine.
So I want to establish that before we go forward. But have
you--what have you done--what's the reaction of FDA? Are you
testing for NDMA during its foreign drug inspections now?
Dr. Woodcock. Right. No, that's not really possible. That's
a different part of the FDA. I think some folks have a
misunderstanding what an inspection can actually do. It can
look at what the firm does, all right? It can't really--we
don't go and do----
Mr. Guthrie. You're not testing--you're inspecting, not
testing?
Dr. Woodcock. That's correct. So what--we have some of the
best drug laboratories in the world, and they have been doing--
they establish the test first, the benchmark tests that are
being used, and we posted them so everyone could use them. And
then we are getting samples. We've tested over 1,500, I think,
samples of different drugs for nitrosamines, and we're
continuing this testing and getting the manufacturers to do the
testing as well.
Mr. Guthrie. I'm out of time. I want to emphasize really
quick, but if somebody's taking medicine and they think it's in
this category, they need to take their medicine?
Dr. Woodcock. They need to, and what's on the market now--
--
Mr. Guthrie. I want you to say that.
Dr. Woodcock [continuing]. Of the ARBs of the blood
pressure medicines is OK. We've recalled the ones that aren't
OK.
Mr. Guthrie. OK, thank you.
Ms. DeGette. I just--I know the witnesses know this, but I
just want to let you know that Members are going to be coming
back and forth between this hearing and a, unfortunately,
coscheduled hearing with the Health Subcommittee.
With that, I'm going to thank Mr. Tonko for staying here
and recognize him for 5 minutes.
Mr. Tonko. Thank you, Madam Chair, on both counts.
As we heard from GAO today, one of the big challenges that
FDA inspectors face in certain foreign countries is the
language barrier. We have heard throughout the years that FDA
inspectors are not usually provided with an independent
translator. In fact, GAO's testimony notes that FDA generally
relies on the firm itself to provide a translator. According to
GAO, FDA investigators stated that this practice, and I quote,
``can raise questions about the accuracy of information FDA
investigators collect,'' close quote.
So, Dr. Denigan, what type of concerns does the use of
nonindependent translators raise?
Dr. Denigan-Macauley. Yes. The use of a nonindependent
translator definitely raises concerns about the accuracy of the
information that they're receiving, particularly in those
countries such as South Korea, China, Japan, where their native
tongue would not necessarily be that language. The
investigators that we spoke with said that at times people can
provide translation that they don't have the knowledge to be
doing the translation. It's simply the only person in the
company that can speak English and, therefore, is doing it. So
it could be inaccurate that way. It can be misinformation on
purpose. So there are a variety of concerns that we would have
with not having an independent translator.
Mr. Tonko. Well, this isn't a new issue. So does GAO and
the subcommittee, as we go forward, need to look more closely
at it, since we raised the same concerns over some 10 years
ago?
Dr. Denigan, why has this been such a longstanding problem
if it was identified 10 years ago?
Dr. Denigan-Macauley. I don't know that I have the answer
to that. I know that FDA has made significant changes, but they
have not made progress in this area of providing translators.
The China office, however, has taken initiatives to use their
foreign nationals that work for FDA to help with the
translations, and at times they have said the company is not
interpreting correctly. This is what is really being said.
Mr. Tonko. And, Dr. Woodcock, FDA told committee staff that
using translators from the firm puts inspectors at a
disadvantage. Are you comfortable with inspectors in a foreign
country relying on a translator who works for the company FDA
is inspecting?
Dr. Woodcock. No. I think it would be better for us to have
our own translators, and we are in the process of seeking out
contracts so that we can do that.
Mr. Tonko. And as you do that, like, what is involved in
the exploring of having more independent translators doing
these foreign inspections?
Dr. Woodcock. Well, we have to go through the contracting
process, which is elaborate, but we can get that done, and
there are certainly large number of groups--because there's a
great deal of commerce with China and India--there are a large
number of independent translating groups that exist that one of
which could be contracted in each country to provide this type
of service to the FDA inspectors.
Mr. Tonko. And, Dr. Denigan, based on your audit and
discussions with FDA inspectors, what are the concerns
associated with sending a single inspector to conduct a foreign
inspection?
Dr. Denigan-Macauley. There are a variety of different
concerns. One can be safety. For example, on one audit over in
China, the auditor was actually whisked away to a room and was
held because they didn't believe that they were the auditor.
And, until the Chinese counterpart was able to have
conversations, she feared for her own safety. And actually, I
think in that example--sorry, that was a bad example--there
were two there, but even with two, that was of a concern.
The other thing is, these campuses are huge, they're quite
large, and it's very difficult to be able to do a complete
inspection. And, if you're coming from the United States, then
you don't have the flexibility, necessarily. You have to get a
certain amount of inspections done in 3 weeks. And so, if you
take more time at one spot to be able to do a thorough
inspection, then you're taking away from another inspection.
Mr. Tonko. And, Dr. Denigan, it's reported that 80 percent
of its foreign drug inspections--the FDA's report, that 80
percent of its foreign drug inspections are performed by
solitary inspectors. Do you believe that that number is making
a huge impact on the ability to sufficiently inspect these
facilities?
Dr. Denigan-Macauley. I do know that domestic inspections
also have solitary inspectors, but they don't have the
challenges domestic stateside that they have overseas. And when
we go and we visit these plants, I mean, they are in very
remote locations and in cultures that are different than our
own, and it does raise concerns.
Mr. Tonko. I thank you very much.
And with that, Madam Chair, I yield back.
Ms. DeGette. Thank you very much.
I now am pleased to recognize the gentleman from West
Virginia for 5 minutes.
Mr. McKinley. Thank you.
I think, Dr. Denigan, you said in your report and in some
of the documents that, now that the FDA has opened offices, the
GAO has reported that the open offices in China, India, Europe,
Latin America, and elsewhere to increase the number of
inspections that are taking place, this since 2009. So from an
engineering perspective, I want to see from the metrics. Now,
so have these increased number of inspectors being on site,
have they led to--are we seeing fewer recalls, better
productivity? What are we seeing from the result of having the
increased inspection?
Dr. Denigan-Macauley. So that's one of the reasons that GAO
has made recommendations over the years, that FDA needs to tie
the outcomes of what the foreign offices are doing to results,
so that they can better measure their impact. One would think
that, with unannounced inspections, that you could tie, for
example, looking at the number of warning letters or the number
of serious problems that they find.
Mr. McKinley. So are you testifying that it has been--it's
been cost effective to do this?
Dr. Denigan-Macauley. No, I'm not saying that. I'm saying
that FDA has not looked at how effective the offices have been.
Mr. McKinley. OK, thank you.
Now, let me go back, again, Dr. Woodcock, here a little bit
on--I come from the construction industry. We also have some
coal mining in West Virginia. Neither one of those industries,
neither one of them get an advance notice when there's an OSHA
or MSHA coming into their sites. I can't--I'm still struggling
with your idea or your concept of giving advance notice to
someone to come in. Can you try that one more time to get it
past me? Because I'm not buying this idea of ``We're going to
let you know,'' because we know China's gaming the system. Give
me a little help.
Dr. Woodcock. Certainly. We--as I said, we began as a
domestic agency, and domestic inspections are not preannounced.
However, when we began inspecting overseas, different countries
have visa requirements. The travel is--you know, the location
of the site was difficult to ascertain. Now, that's improved
over time with various things, and particularly it was
difficult to know whether the site would be manufacturing at
the time we inspect them. That's very important.
Mr. McKinley. OK. I'm not buying the thing about the visas,
because I would assume that so much of it is taking place in
China. We have someone or a group of people over there, that
they're going to continue to travel the circuit and do their
inspection with that.
Dr. Woodcock. No. The number of inspectors we have in China
and India are not sufficient to perform the number of
inspections that are needed. So most of the inspections need to
be done by domestically based inspectors who are sent to other
countries. And those are the ones----
Mr. McKinley. Can you come to the office? I'd like to
follow up on this, because I don't think we have enough time to
get into that. But I'm not convinced at all that a
preannounced--alerting someone that we're going to come in and
look at you is going to get the results we want.
Now, I also--but I want to follow up also with you on the
thing that 90 percent of American prescriptions, from what I
understand, are generic, but they only amount to about 56
percent of the recall. So I'm curious, either one of two
things, either they're doing a good job replicating them or
they need more scrutiny. Which is it?
Dr. Woodcock. I'm not familiar with the figures you're
using on the recalls. Could you explain a little bit more?
Mr. McKinley. Yes. I don't have the source of that, but we
have 56 percent of all of the recalls have been generic. If
that's not correct, if you don't--and I can't back that up just
at this moment--what is that? What would you say is the
percent? Is it comparable?
Dr. Woodcock. Well, we'd be glad to work with you on this,
because I think it's a little more complicated than that. In
the first years after a new innovator product is launched,
there may be safety recalls and different things that are
unrelated to the quality of the product. So first you have to
talk about what kind of recalls are you talking about, and then
where did you get these statistics, because I'm not really
clear on this.
Mr. McKinley. Well, the reason I'm saying that--I only have
a few seconds left--is there are some Members of Congress who
have been suggesting that generic drugs are not safe. I'm
trying to make a determination whether or not they are safe or
not based on the fact that if 90 percent of us are generic and
only 56 percent are recalled, does that mean they're safe, or
what's happening? Are generic drugs safe for people to take?
Dr. Woodcock. Yes. We stand behind the generic drugs. I
will point out that we do have good safety detection systems,
right, and the biggest risk right now we see to the public is
from compounding where we have multiple outbreaks that we
continue to have of humans beings harmed by compounded drugs.
Mr. McKinley. Thank you.
Dr. Woodcock. So we have a system that can detect problems
when they occur, and we do not have problems with 90 percent of
the drug supply. The generic drug supply is reliable.
Mr. McKinley. My time's expired. So before I get yanked,
I'll yield back.
Ms. DeGette. I thank the gentleman.
Now I'd like to recognize the gentleman from California,
Mr. Ruiz, for 5 minutes.
Mr. Ruiz. Thank you very much.
This issue is becoming more and more important because of
the inability of middle-class families to afford their
medications, and they're getting medications from other places,
as well as legislative ideas to import medications to help
lower the cost for people. And as a doctor, I'm concerned
because we know what a placebo pill can do to a diabetic's
blood sugars. And when patients think that they're--they need
to take a certain drug, they're actually taking a different
drug. And then, if it's contaminated, then it may make their
illness even worse.
So the FDA faces the enormous challenge of inspecting the
thousands of firms around the world producing drugs for the
United States. Compounding the challenge is the fact that, over
the years, some firms have reportedly engaged in fraudulent
behavior to cut corners and deliberately conceal failures from
the FDA inspectors.
In the past year, for example, press reports have offered
disturbing accounts of such fraud. In January, Bloomberg News
reported incidents of, quote, ``computer files found deleted
and employees caught on a company's own security cameras
shredding documents the night before an inspection,'' unquote.
In May, NBC spoke to a former FDA inspector and reported
that, quote, ``FDA inspectors struggl[ed] to keep up with
foreign drug manufacturers that may bury or hide problems in
their production,'' unquote. In an article in October in Stat
News, it was reported that violations of data integrity are
persistent and ongoing in overseas drug manufacturing plants.
Madam Chair, I would like to request that these reports be
entered into the record.
Ms. DeGette. Without objection, so ordered.
[The information appears at the conclusion of the hearing.]
Mr. Ruiz. Thank you.
Dr. Denigan, when you traveled abroad for your audit work
and talked to inspectors in China and India, did you hear
stories such as these?
Dr. Denigan-Macauley. Unfortunately, we did. There were
instances where inspectors gave 30 minutes' notice they were on
their way, and when they got there, they saw documents, bags of
documents being disposed of. And they said, ``Don't do it,''
took photos, ran in to show their credentials. In the time that
they got back, in the few minutes it took to show their
credentials, they blatantly disregarded them and disposed of
them.
Mr. Ruiz. Dr. Woodcock, you were quoted in the previously
mentioned Bloomberg News story that there were high profile
cases of, quote, ``overt and deliberate fraud,'' unquote, by
certain drug companies. Dr. Woodcock, how should we put these
reports in perspective? How pervasive do you think this problem
is? And what tools does FDA have to sufficiently root out any
cheating or data manipulation, if it is occurring?
Dr. Woodcock. First of all, I should point out that we see
this in the United States or in the North America or the
Americas as well as ex-U.S. We have seen cases of--serious
cases of data integrity problems.
The second thing I should point out, which gets to----
Mr. Ruiz. So how--so how pervasive is this?
Dr. Woodcock. Well, that's what I'd like to show here.
Slide 12. If I could show--pull up the slides. No?
Mr. Ruiz. Just tell me if you can, because my--the time is
ticking.
Dr. Woodcock. About--in the United States, about 93 percent
of firms who are inspected pass the inspection, right. In
India, 83 percent. So there's a 10 percent difference. That
means 83 percent of the firms we inspect fail to be adequate
and pass the inspections. They have the lowest percentage.
China's percent passed is very close to the United States'.
Mr. Ruiz. Do you--I have about a minute left. Do you feel
that unannounced or short-notice inspections could help you
better discover manufacturing issues or even data quality
issues when they are occurring?
Dr. Woodcock. Certainly. Those are desirable. You just have
to think about the tradeoffs in doing that. But no one is
opposed to those, and we do them routinely for for-cause
inspections.
Mr. Ruiz. Recently, the FDA told the committee that firms
were inspected every 2\1/2\ years, more or less, but given that
the reports we have seen about this issue with some firms,
including what you yourself have called, quote, ``overt and
deliberate fraud,'' are you comfortable inspecting foreign
firms as the current model and resources allow?
Dr. Woodcock. Well, as I said, 90 percent of this fraud has
been detected under the current system in the way----
Mr. Ruiz. So your--so your acceptable level of error is 10
percent. You're trying to tell me that it is OK to have 10
percent error in inspecting the quality and the safety of our
medications?
Dr. Woodcock. We don't know what the error rate is because
it's impossible to show a counterfactual, as I said earlier. We
know that we detect fraud fairly routinely when we go in, even
on an announced inspection, because we can look at the computer
records and----
Mr. Ruiz. So do you think that it's working?
Dr. Woodcock. I believe, as I said earlier, that we could
use more inspectors. We could do more unannounced inspections.
That would be desirable. We could have more team inspections.
Mr. Ruiz. My time is up. Thank you.
Dr. Woodcock. Those things would be good.
Mr. Ruiz. Thank you.
Ms. DeGette. The Chair now recognizes the gentleman from
Virginia for 5 minutes.
Mr. Griffith. Thank you very much.
Always good to have you all here. Thank you so much,
particularly Dr. Woodcock, who always does a great job. But
I've got some tough questions today.
So, Dr. Woodcock, according to an article in Wired in July
of 2017, a drug firm in northeastern China, in essence, took an
FDA inspector and her translator hostage during an inspection.
Dr. Denigan mentioned this earlier. The FDA employees were
finally freed after about an hour when Chinese regulators
interceded. And the FDA Deputy Director concluded in an
internal email that the firm resorted to appalling intimidation
tactics because the inspection was not going well. However, FDA
declined to classify the incident as an inspection refusal,
which would be grounds for an automatic import ban, because the
firm manager wasn't making a specified refusal when he
imprisoned the FDA employees.
Why isn't imprisonment of FDA employees classified as a
refusal of inspection by the firm? And let me just say so folks
back home understand. It was the conference room that Dr.
Denigan mentioned earlier. Imprisoned is a legal term of art as
I'm using it here. It does not mean they were placed in a dank
cell and only allowed to have food and water, bread and water
brought in. But it is technically an imprisonment when you
refuse to let somebody leave the conference room.
So, you know, how come that wouldn't be grounds for an
automatic import ban? It seems like to me it ought to be.
Dr. Woodcock. Well, that's a legal question that lawyers
would have to sort out, whether it met the context.
Mr. Griffith. And I've never had great respect for the
lawyers at FDA after NECC, and they refused to get a search
warrant after Ohio and Colorado both told them there were
problems, and nobody in the FDA legal office thought that was
sufficient to get the probable cause to get a search warrant,
which might have saved 53 lives.
That being said, you know, it seems to me it would
constitute circumstances, you know, of delaying, denying, or
limiting inspection or refusing to permit entry or inspection
for purposes of section 501(j)(2), little 2, under the Food and
Drug and Cosmetic Act.
And, Dr. Denigan, you mentioned some things earlier that
were similar to that--not quite as bad as taking somebody a
prisoner--but why aren't we being more forceful with these
foreign companies and just saying, ``If you don't cooperate,
you're out, you won't be selling in the United States''?
Dr. Denigan-Macauley. Well, actually, as part of our
ongoing work, I think the inspectors have raised concerns, and
they've put them down as serious deficiencies, and there has
been times where those concerns have been downgraded. And we
plan to look at that in our ongoing work.
Mr. Griffith. And I appreciate that. You know, I was
brainstorming on this last night because, to me, this is
extremely important, you know. We're working on bringing down
prices of drugs, but making sure the drugs actually do what
they're supposed to and are not adulterated, don't have harmful
products in them is extremely important.
And you talked about the large campuses and how it's hard
for people to cover the large campus. So, as we were
brainstorming, and I want to hear from both of you as to why
this wouldn't be something we ought to be talking about.
You know, we could get young people right out of undergrad
to come in there. They don't need 3 years of training. You may
need somebody like that to do the big stuff, but you don't have
to be a gourmet chef to go into a French restaurant and
determine that the bathroom is not clean.
It would seem to me that, for pennies on the dollar, lots
of young people would love the opportunity to travel abroad and
go in and help somebody who's got all that 3 years of training,
but help somebody figure out, ``OK, building A is dirty. I
don't know what's going on. You might want to go look at it.''
It seems to me we could magnify our inspections and our ability
to inspect if we did something like that, and I'm happy to work
with you on it.
Dr. Denigan, what do you think of that? And, Dr. Woodcock,
I'd like your opinion too. I always respect both of you.
Dr. Denigan-Macauley. Sure. Well, we certainly heard
stories of bathrooms that they were using that were covered in
feces. They had to go outside to be able to use the facility,
raising questions about good manufacturing practices.
Mr. Griffith. And you don't need 3 years of training to be
able to see that, do you?
Dr. Denigan-Macauley. No.
Mr. Griffith. Dr. Woodcock, what do you think? Is this
something we ought to be talking about?
Dr. Woodcock. Well, it raises the question, Should ORA, the
field organization, change its model somewhat? That's what
you're proposing.
Mr. Griffith. That is what I'm proposing.
Dr. Woodcock. And have more of a sliding scale of
capacities, translators----
Mr. Griffith. Right.
Dr. Woodcock [continuing]. And so forth. And I think that's
worth talking about as far as how--how we cover the entire
range of problems.
Mr. Griffith. Because, as we're importing all of these
substances, whether they be substances that are used for
compounding pharmacies or whether they are actual drugs that go
straight to the consumer, it just seems to me, yes, you want to
have your top dog, but you also can use folks who can just go
in and take a look at the bathroom. And it doesn't take a
genius to figure out or somebody with 3 years of specialized
training to figure out the bathroom is dirty and there's feces
everywhere. Thank you very much.
And my time is up, and I yield back.
Ms. DeGette. I thank the gentleman.
The Chair now recognizes the gentlelady from New Hampshire
for 5 minutes.
Ms. Kuster. Thank you, Chairwoman DeGette, for your
continued leadership on ensuring the safety and inspection of
our drug supply chain. And I want to thank our witnesses for
being with us today.
Recently, I heard from a constituent from Nashua, New
Hampshire, who was very concerned about his blood pressure
medication, which has had several recalls. Despite his
concerns, he also acknowledged the balance that must be struck
in ensuring the safety of our drugs but also the supply of
drugs. And it's certainly true and something some of my
colleagues have mentioned here today.
Outside of the high cost of prescription drugs, one of the
other most frequent concerns I hear about is drug shortages.
This committee helped to lead the way in working with FDA and
stakeholders to ensure that the agency has the additional
authorities and flexibilities that you need to inform and
respond to drug shortages as they occur. But, at the same time,
we must ensure that every American has access to safe
medication through your quality inspection.
So let me turn to my questions. Dr. Denigan, is it true
that staffing in these offices has been a continuous issue
since the offices have opened overseas? And if so, why is that?
And what is the impact on the foreign inspection program, and
if you will, what do you need from us?
Dr. Denigan-Macauley. Yes. Staffing continues to be a
problem, and there were visa problems over in China that have
since been resolved so that they've been able to get more staff
over there. But, overall in the foreign offices, staffing has
been a challenge, and they have critical vacancies of these
expert investigators.
Ms. Kuster. Now, I know Mr. McKinley asked a series of
questions. This appears to be a very bipartisan hearing in
terms of our concerns about the effectiveness of the foreign
offices and how you intend to address those staffing concerns.
If you are not satisfied that the FDA has fully evaluated how
its foreign offices should be utilized and improved, what is it
that you need from us? Is this a resources issue? What--how can
we be helpful? I assume that's the point of this whole hearing.
Dr. Denigan-Macauley. Well, I think what's concerning is
that the data of understanding the number of establishments is
challenging to get, and you have firms over there that are
registering with FDA that don't necessarily have to. Unlike
medical devices, there's no charge to register because it looks
good, right. You're registered for FDA overseas, and so that
creates noise in the database. And if you don't know the
universe of those that you need to be inspecting, I think it's
very hard to be able to come up with a strategic workforce plan
to know the number of folks that you need to be able to carry
out the inspections.
Ms. Kuster. So couldn't we do something about that? If
we're giving them permission to send this medication into our
country for sale, somebody's making a profit. Can't we link
that more clearly to where has this been made and be much more
specific about this? I mean, they have an incentive to want to
bring this medication in.
Dr. Denigan-Macauley. Right. I think that that's what FDA
wants to do is to be more strategic about their workforce
planning and more risk-based, which GAO appreciates, but they
should put their limited resources at the places with the
highest risk.
Ms. Kuster. Dr. Woodcock, do you want to respond? I mean,
do you need legislative authority to make this a much more
direct link? Why don't we just say, ``If you want to send
medication into our country, you need to tell us precisely
where it's being made, and we're going to come out and look at
it.''
Dr. Woodcock. All right. They usually have to do that now,
all right, for application products. So if you send in an
application for a generic drug or an innovator drug, you have
to tell us where it's going to be made. And we do preapproval
inspections before we even let that product on the market.
Ms. Kuster. So, presumably, you know where they're being
manufactured?
Dr. Woodcock. Well, not only do we know where, we go there,
unless we've been there recently. However, for--there's some
loopholes for compounding and for over-the-counter monograph
drugs that don't have applications. That's a very large
segment, and that's many of the never being--been inspected
that were----
Ms. Kuster. Do you need us to close those loopholes?
Dr. Woodcock. It would be--I think we would be interested
to work with you on the issue that they can ship to the United
States without ever being inspected right now, because all they
have to do is register.
Ms. Kuster. Right.
Dr. Woodcock. And there are other data points, as I alluded
to in my verbal testimony, that would be very useful for us to
receive as data. For example, we don't know the volume. We
know--you said maybe 20 percent of APIs made in the United
States, but it may only be an infinitesimal fraction of the
actual volume, because we only know the facilities, not how
much they're making. And they tell us----
Ms. Kuster. Well, I hope you--my time is up, but I hope you
will work with our committee to tighten this up, because these
loopholes sound dangerous to the American people. Thank you.
Dr. Woodcock. We would be delighted. Thank you.
Ms. DeGette. The gentlelady from Indiana is recognized for
5 minutes.
Mrs. Brooks. Thank you, Madam Chairwoman. And thank you
both for being here and for focusing on this critically
important subject.
I want to stay focused a little bit on the staffing issues.
And I'm curious, Dr. Woodcock, has the FDA ever used outside
consultants to study this in-depth problem rather than GAO--you
know, and I appreciate GAO's recommendations and ideas, but
this is very complex. Have you used outside consultants, and
what have been the results?
Dr. Woodcock. We used outside consultants to look at the
administrative hiring problems we had, and we even had a public
meeting on that that went over all the different problems. The
direct hire should help some of that.
As far as an outside consultant to think about the
workforce in ORA and how it's deployed, and actually, the
people in the foreign offices actually report to a different
component, a third component of FDA that's not the Center for
Drugs and not ORA. And so I don't know whether they've done a
study or not, but we can get back to you on that, and it is a
good idea.
Mrs. Brooks. Were there recommendations that were made that
have not been implemented, if you know, and if not, why not?
Were they not given, you know, sufficient credit in the
recommendations?
Dr. Woodcock. I believe in the recommendations that were
made on our administrative problems, there's been a stupendous
effort to try and turn this ship around and to get the hiring
process to something that can actually bring people on board in
a timely manner. And as I said earlier, Cures helps us for
positions that are Cures eligible.
So yes, we have acted on those recommendations, but the
hiring was so problematic, it's going to take us a long time to
recover from that.
Mrs. Brooks. It seems, even if you were able to hire enough
people, one of the things you said that I'm very concerned
about is the lack of--unless I didn't write this down
properly--standardized inspections, and this is an example.
Earlier this year, the committee sent FDA a bipartisan
letter asking about the FDA's India pilot program and why the
program wasn't extended. In response, FDA told the committee
that the drug inspection initiative was not extended, quote,
``based on lack of protocols and evaluation criteria. No formal
report or evaluation was completed.''
How is this possible? How is it possible that we've got
pilot programs with no evaluation, no protocols, no
standardized inspections? I mean, who would want to come work
for you if you're--if there's no roadmap and there's no
standardization of what their work product's supposed to be?
Dr. Woodcock. Well, there are two separate issues. There is
standardization that ORA has for what its inspectors do and how
they document it, and that is written down. And we are working
on what we call the new inspection protocol program, which is
changing to a more modern, more standardized inspection process
and protocol. We've already completed that for sterile
products, but we have to go through all the different kind of
products.
Mrs. Brooks. Do you need more people, Dr. Woodcock, to help
get this process? I mean, you've just mentioned sterile
products. I can't even imagine how many other products. Do you
need more people to be focusing on protocols and the
standardization of inspections?
Dr. Woodcock. If we had more people with doing analysis, as
you've pointed out, doing analysis and actually working on
these projects rather than, you know, doing the work--the day-
to-day work of trying to inspect all these firms, of course,
that would be very helpful.
And I will add, there's another component of this since we
did the Mutual Reliance Agreement with the EU and all those
countries, OK. They do their reports in all different
languages, naturally. And so all of us would benefit from a
very standardized report document that we could all read
without having to translate it into different languages.
Mrs. Brooks. I was actually going to ask you about the EU
reliance. Can you please talk with us about what that means and
how long will it take us to realize the benefits from the
Mutual Reliance Agreements with the EU? And who else should
we--and what does it mean? Can you go into a little more detail
on that?
Dr. Woodcock. First of all, what it is, is we've agreed
with all the EU countries that their inspectors are qualified
to inspect the plants within their country boundaries, because
each country has different inspectors, right, and that we will
accept the results of those inspections, and they'll--they'll
send them. And then they don't have to come over to the U.S.
and inspect facilities that are here, because they accept the
results of our inspections. It doesn't extend to their
inspections in other countries, but it does free us up to go
send more people to India and China.
Now, that trend has been abrogated, as people pointed out,
by the loss of staff in ORA, the loss of people in the
inspectorate in the foreign offices, and so we haven't had the
capacity, and our number of foreign inspections has actually
gone down because of capacity problems, even with the MRA in
operation.
Mrs. Brooks. Well, I certainly hope our Mutual Reliance
Agreements can extend, and maybe we can look at other countries
as well. Thank you.
I yield back.
Ms. DeGette. Doctor, would it be possible to get a copy of
that independent report you're telling Congresswoman Brooks
about?
Dr. Woodcock. Absolutely. We can get that back to you.
Ms. DeGette. I think that'd be really helpful. Thank you.
The Chair now recognizes the gentlelady from Florida for 5
minutes.
Ms. Castor. Thank you, Chairwoman DeGette. Thank you both
for being here today.
I know we've focused a bit on the challenges in staffing,
and I'd like to focus a little bit more on the quality of FDA's
data. FDA's foreign drug inspection program relies upon having
quality data that allows FDA to know which firms to inspect and
to review those firms' inspection history. However, GAO has
long identified problems with the data FDA relies on for its
drug inspection program. In testimony today, GAO states, quote,
``data challenges we identified in our 2008 report continue to
make it difficult for FDA to accurately identify establishments
subject to inspection.''
Beyond staffing, Dr. Denigan, what are your main concerns
with the way FDA is collecting and using data related to its
foreign inspection program? How do these data collection
concerns impact the effectiveness of the foreign inspection
program?
Dr. Denigan-Macauley. Yes. So as I mentioned before, the
establishments--they have establishments in there that are
registering that don't need to, and that creates the extra
noise. And, while it's true that 40 percent of those
establishments didn't need an inspection, and therefore, FDA
was able to say that they went through their backlog, it still
creates an inefficiency. They have to take the time to clear
out to find out which one of those didn't.
And so the foreign offices can add value. For example, like
over in China where they're actually matching up to see does
that establishment really still exist. Because, as Dr. Woodcock
said, they do change. They go in and out, so it's a snapshot in
time. And further, their active pharmaceutical ingredient could
be produced in China, for example, and if they ship it to
Germany, then it's not subject to an inspection. I know that
FDA is very clear of that loophole.
Ms. Castor. OK. Let's talk about those two. And FDA told
committee staff that some firms on its foreign drug facility
list were, quote, ``washouts.'' Is that what you were referring
to?
Dr. Denigan-Macauley. Correct. Those are the washouts that
didn't need to be inspected but were on their list.
Ms. Castor. OK. Meaning that these firms were not actually
subject to inspection for various reasons, including because
they were no longer exporting to the United States.
Dr. Denigan, what is the difference--what is the
significance of these washouts previously included in FDA's
data? Do you have--you said you had concerns about it. I guess
this is a really good question for Dr. Woodcock.
Dr. Woodcock. Yes. Well, you know, we have various thoughts
about this. It's easy for people to register. You just can
register, and then you have a sort of branding. You can say,
``I'm registered in the United States,'' and you never have to
ship anything to the U.S. And so we have to go to the trouble,
as Dr. Denigan was saying, of figuring out where that firm is,
figuring out is it shipping anything into the U.S., what's its
status, and then crossing it off the list.
It's possible that some small barrier like a modest fee or
something might help with that. I don't know where--how we
could do that, but it is possible right now for a lot of firms
every year to register with the U.S. and actually not be
shipping drugs into the U.S. But it's also possible for them to
register and then ship without being inspected if they are one
of these loophole firms.
Ms. Castor. And then you also raise the problem with
facilities. You don't--FDA does not have a firm handle on the
volumes being shipped out. Why is that the case, and what are
you doing to address that?
Dr. Woodcock. Well, we're thinking of doing a regulation,
which would be a very long process. The companies have to tell
us in what's called right now the annual report. Remember, many
of these regulations are very old. But my understanding, at
least--I recognize I'm under oath, and I don't have total grasp
of the details--but they have to tell us that kind of stuff for
the past year. And then they--eventually, they submit that
annual report at some time in the next year. So it's a really
lagging indicator. And it isn't data, it's in a PDF of a
document that they send us.
And what would help, if you all wanted to know the volume
being shipped in the United States, we would need something
like quarterly data reporting as data in a database rather
than--you know, a fillable form rather than sending us a PDF a
year later about the volume that was shipped. If we had that
type of data, then we could really put together a more complete
picture of what's coming into the United States.
Ms. Castor. And you need legislative authority to move
towards a quarterly data report?
Dr. Woodcock. We think we could do that under regulation,
but it might take us 7 years.
Ms. Castor. Why 7 years?
Dr. Woodcock. Because it takes a very long time to do
regulations. I know I'm under oath.
Ms. Castor. Yes.
Dr. Woodcock. I can't say--you know, I can't predict. We
could say maybe never, right, or maybe we could do it a little
faster, I don't know, but it takes a long time to write,
propose, get comments on----
Ms. Castor. Gotcha. Yes. We, you know, understand.
Dr. Woodcock. I'm sorry.
Ms. Castor. Thank you very much. Thanks for making that
recommendation.
Ms. DeGette. The Chair now recognizes the gentleman from
Oklahoma for 5 minutes.
Mr. Mullin. Madam Chair, you forgot to say your good friend
from Oklahoma.
Ms. DeGette. My best friend.
Mr. Mullin. Best friend. There you go. Thank you. Thank
you.
Dr. Woodcock, thank you again for being here. I sure
appreciate your demeanor and your ability to answer the
questions the best you can.
I've got just a few questions I'm going to go through here.
How many drug inspections can the FDA conduct per year in India
and China? Currently.
Dr. Woodcock. Currently. We do have a slide on this. Does
anybody know what number that is?
Mr. Mullin. Everybody likes slides and PowerPoints, don't
we?
Dr. Woodcock. Yes. Sorry. It's slide No. 4. So if we can
get----
Mr. Mullin. We don't have to get it up. We can just--you
can just tell me.
Dr. Woodcock. OK. So in--well, this doesn't----
Mr. Mullin. While they're looking for it--let's let them
look for it. I'll go on to another question.
Dr. Woodcock. OK.
Mr. Mullin. How many would you like to be able to inspect
in China and India?
Dr. Woodcock. Well, if you don't mind me pushing back on
you a little bit.
Mr. Mullin. Sure.
Dr. Woodcock. What I would really like to have is a
predictive risk model that tells us based on a lot of data who
we should really go to next, who's the highest risk.
Mr. Mullin. Well, the last time you were here, we brought
up corruption in China and asked if that could bring up issues.
When you start thinking that 45 percent of all of the
ingredients in our drugs today made inside the United States
come from India and China, huge concern for all of us. And--and
so when you start talking about risk data, you can't get the
risk--you can't understand what it is you're looking for unless
you put your hands on it. I tell all my foremen and
superintendents that used to work for our companies when I ran
them that, you know, the best way to get the information is to
be in the field.
So, once again, how many would you like to be able to
inspect? If you could have your druthers and you could--
staffing wasn't an issue, what's our current level at now, and
where do you think we should be?
Dr. Woodcock. Well, it looks like we inspect about--in
China? Foreign, we inspect about under a thousand, 966. In
China, it looks like maybe about 400. I think it would be
higher. I think there would be more unannounced, as was said.
There would be more team inspections. I mean, those things all
would be desirable.
Mr. Mullin. So when you go inspect these other 40, what
percentage of violations do you find in these facilities?
Dr. Woodcock. Well, in the previous slide I showed, 83
percent of China--India passes, 90 percent of China passes, and
93 percent of the U.S. passes.
Mr. Mullin. Do you think that the 90 percent in China and
the 80--what did you say?
Dr. Woodcock. 3.
Mr. Mullin. 83 percent in India is actually accurate, or do
you think the--that's not an accurate number because they're
changing things before you walk in the door?
Dr. Woodcock. I believe there's always some--an inspection
is only a snapshot in time. They don't inspect every single
system----
Mr. Mullin. Sure.
Dr. Woodcock [continuing]. In the facility. We have lots of
cases where we had inspections that were OK, OK, and then all
of a sudden, everything was wrong.
Mr. Mullin. So do you believe it's easier for FDA to
inspect our drug manufacturers inside the United States or in
India or China?
Dr. Woodcock. It's obviously easier to inspect in the U.S.,
and there's a long history. Back in the nineties----
Mr. Mullin. Sure.
Dr. Woodcock [continuing]. There were many problems and
many consent decrees and things, but the intensity of the
oversight brought the level of performance up in the U.S.
Mr. Mullin. So what's the biggest barrier? Why do we have
45 percent of our drug ingredients made in China and India and
not here in the United States, if that's where the drugs are
coming to anyways?
Dr. Woodcock. The reasons that we discussed at the previous
hearing are cost of personnel, the lax environmental
regulations, which are very--it's a very important issue in
other countries compared to the U.S., and, you know, the cost
of doing business is lower.
Mr. Mullin. So we've basically regulated these
manufacturers out of the country?
Dr. Woodcock. Yes. Well, we feel that advance
manufacturing, which is what FDA has been trying to bring about
in this pharmaceutical sector for the last 20 years, would--you
could bring manufacturing back to the United States, because
it's not--it doesn't have a huge environmental impact. It has a
smaller footprint, and it's very cost effective, but there is a
cost of doing that.
And Sanofi has built a plant in Framingham that they
recently announced has successfully completed all its test runs
and is one of these plants of the future in the United States.
Mr. Mullin. We'd love to work with you moving forward on
that because we'd love to see the manufacturing come back, and
so anything our office can partner with the FDA on, consider us
a friend.
Dr. Woodcock. We would be happy, because we're very excited
about this.
Mr. Mullin. Thank you. I yield back.
Ms. DeGette. The gentlelady from New York is now recognized
for 5 minutes.
Ms. Clarke. Thank you, Madam Chairwoman, and I thank our
Ranking Member Guthrie, for convening this timely oversight
hearing on the Food and Drug Administration's inspection
program for foreign drugs. I'd like to thank you both as well,
our witnesses, for being here today to testify on behalf of the
FDA and the GAO.
The fact is that our drug supply is becoming increasingly
global. Many of the drugs that Americans rely on every day are
produced around the world. As such, FDA must adapt to this new
reality to ensure that our drug supply remains safe and that
the manufacturers are held accountable.
So let me start with you, Mrs.--Dr. Denigan. Why should we
be concerned that FDA's inspections of foreign manufacturers
might not be equivalent to its inspections of domestic
manufacturers?
Dr. Denigan-Macauley. Well, that equivalency is important.
They don't announce inspections here for a reason, and so you
want--for the same reason, you want to see--I know it's a
snapshot, but that's your best chance of being able to see what
the process actually looks like, not what it looks like after 3
months of working with a contractor, for example, to get into
compliance.
Ms. Clarke. One of the committee's longstanding concerns is
FDA's ability to get out and inspect the thousands of firms
around the world. After Congress gave FDA more authority and
resources, FDA was able to conduct more inspections. However,
after 2016, the number of inspections went back down.
Dr. Denigan, why did the number of FDA's foreign
inspections decrease in recent years, and what does this mean
for the FDA's ability to oversee the Nation's drug supply?
Dr. Denigan-Macauley. Well, I think, as Dr. Woodcock has
pointed out, the staffing shortages have been a tremendous
strain and have made it very challenging to conduct. In
addition, we do have concerns about the accuracy of the data to
understand the denominator of those that they need to inspect.
Ms. Clarke. Very well.
Dr. Woodcock, FDA has made improvements over the last
decade in its ability to inspect more foreign firms, and we are
appreciative of that work. But, as we just heard, there's more
work to be done on hiring inspectors and getting better data.
Dr. Woodcock, what is FDA doing about all the remaining
unresolved issues that GAO has identified in its recent work?
And we've been talking about these same issues for two decades
now.
Dr. Woodcock. Well, we have brought about a lot of change.
We're doing more foreign inspections now than we're doing
domestic inspections. We are working on hiring. The FDA has
just received direct hiring authority for the field inspectors,
and so they have 20 that they're onboarding. They expect to
hire a total of 50 by the end of this upcoming calendar year.
So that would be an addition in the pharmaceutical
inspectorate.
We've done what we can on data, and we're very interested
in working with the Congress on better data sources so that we
can have a better understanding of the firms that are shipping
drugs into the United States.
As far as cleaning up the registration database, there are
a variety of techniques we could use to do that. I mentioned
one, perhaps a modest fee for listing might discourage some of
these foreign entrepreneurs from listing with never having an
intent to ship into the United States, but there might be other
ways to do this, and we could talk about that.
And then, you know, better data that we could make a true
predictive model instead of our site selection model that we
have, but a true predictive model based on data would be a
tremendous advance.
We also are working on advance manufacturing, which could
actually bring manufacturing back into the United States, or if
it were outside the U.S., it would be much better controlled.
We would know even remotely with that kind of manufacturing if
things were going wrong.
Ms. Clarke. Well, Dr. Woodcock, that sounds promising. I'd
like to encourage us to really move in that direction, because
our reliance on foreign manufacturing, I believe, is only
likely to increase as we look at the sort of aging of
Americans, the boomer generation and the young folks coming up
who, you know, unfortunately, may need some pharmaceuticals to
make sure that their quality of life is preserved.
So, Dr. Denigan, overall, do you believe the FDA is where
it needs to be to effectively regulate the drugs coming from
overseas, and if not, what more does the FDA still need to do?
Dr. Denigan-Macauley. Well, they certainly have made great
strides since 1998, and I know I'm going to run out of time.
But clearly, they need to work on getting folks on board,
keeping them on board, perhaps looking at other models. You
know, the Foreign Service, they're now a global agency, and
they weren't designed to be a global agency originally.
Ms. Clarke. Very well.
Thank you, Madam Chair. I yield back.
Ms. DeGette. Thank you very much.
The Chair now recognizes Mr. Walden for 5 minutes.
Mr. Walden. Thank you very much, Madam Chair, and again,
thanks for having this really important hearing. To our
witnesses, thank you both for being here.
Dr. Woodcock, FDA in January of 2014, the FDA began a pilot
program in India of no-notice and short-notice inspections of
drug manufacturing plants instead of customary preannounced
inspections. And over the course of 18 months, I'm told, the
unannounced inspections revealed some troubling conditions,
from a bird infestation at one plant to a plant that entirely
faked its environmental monitoring data, purporting to have
screened for microbile and contamination when it had not.
Under the India pilot program, the rate at which FDA
inspectors recommended the most serious findings of official
action indicated an increase by almost 60 percent. Yet in July
of 2015, the FDA discontinued the program and resumed
preannounced inspections.
So, considering the high rate at which inspectors found
serious violations, why did FDA discount--or discontinue, I'm
sorry--this program?
Dr. Woodcock. Well, this program was done by the India
office, is my understanding, OK, which reports through a
different structure. And apparently, it was simply--it wasn't
really a program, it was an initiative of the India office, and
they decided to conclude it after a certain amount of time. And
so----
Mr. Walden. Do you have any idea why, though?
Dr. Woodcock. No.
Mr. Walden. Because it would seem to identify a better path
forward if you're trying to uncover problems at these
facilities.
Dr. Woodcock. Well, there were resources involved. The
India office and other personnel had to do a lot of additional
work to arrange this travel and enable the inspectors to kind
of show up in a surprise. The foreign offices currently do
unannounced inspections when they have inspectors resident in
the foreign offices. They do unannounced inspections.
Mr. Walden. Do we have them in India and China?
Dr. Woodcock. Yes. We do have inspectors there.
Mr. Walden. But do they do unannounced inspections?
Dr. Woodcock. Yes, they can do unannounced inspections.
Mr. Walden. And do they?
Dr. Woodcock. Yes, uh-huh.
Mr. Walden. Yes.
Dr. Woodcock. It's the domestic people who travel over and
make these long trips where they're, for 3 weeks, they're going
to inspect three different silos. They want to make sure
they're operating and so forth that are the preannounced.
Mr. Walden. So, rather than discontinue due to--I've been
told it was also a lack of protocols and criteria that may have
led to this discontinuation. Do you think they should have
developed evaluation criteria or undertaken a formal review of
the program?
Dr. Woodcock. Well, again, I don't know enough about it.
Mr. Walden. OK.
Dr. Woodcock. It's not in my chain of, you know,
responsibilities. Certainly, we're being urged today to
evaluate--to develop and evaluate such a pilot.
Mr. Walden. Which is--and I'm sure you--you know that it
raises issues for us. I mean, we look at that and go, wow,
something--they were uncovering more when they did that type of
inspection.
Dr. Woodcock. Well, that isn't clear. And, with all due
respect to my GAO colleague, all these ideas are anecdotal. We
know that 90 percent of the fraud and so forth that we uncover
in our inspections is by--in foreign countries is by domestic-
based inspectors who go over there and do unannounced
inspections, and they still find this fraud and so forth. And a
tremendous amount has changed over this period, even from 2014,
but nobody is denying that unannounced inspections, team
inspections, more inspections in the foreign area wouldn't be a
good idea.
Mr. Walden. Dr. Denigan, do you want to comment on any of
this?
Dr. Denigan-Macauley. Sure. Based on the data that we have,
the whole value of the foreign offices is to provide--not the
whole value, but one of the major contributions of the foreign
office is to be able to get local intel. And, based on the
local intel that the India office found, they had lapses in
integrity of quality, production, laboratory data, significant
GMP deficiencies, and firms were found to have been creating
records. And so, with their initiative, they did 16 unannounced
inspections. And of those 16, 15 of the firms ended up with
serious problems. Now, mind you, they targeted firms that they
knew were high risk----
Mr. Walden. OK.
Dr. Denigan-Macauley [continuing]. But that's the value of
using your resources.
Mr. Walden. Yes. Dr. Woodcock?
Dr. Woodcock. So some of this is still going on, because
part of this program was to develop this intensive intel and
brief the inspector about all this before they go in. Now, the
Office of Surveillance that we formed in Office of
Pharmaceutical Quality with our reorganization, now provides
site dossiers for inspectors before they go into a site, and
that pulls together all sorts of information. It's probably not
as good as the local intel, but we try to get the foreign
offices to add that. But that's my point, you know, you're
comparing a little bit apples and oranges.
Mr. Walden. Right.
Dr. Woodcock. I mean, we do all the for-cause inspections
we do if we got intel, and we were going to go because of a
whistleblower, we would do unannounced.
Mr. Walden. All right. My time has expired. Thank you,
Madam Chair, and thanks to both of you.
Dr. Woodcock. Thank you so much.
Mr. Walden. We all want to get this right and make sure we
have a safe supply chain, so thank you.
Ms. DeGette. The Chair now recognizes the gentlelady from
Illinois for 5 minutes.
Ms. Schakowsky. Thank you so much, Madam Chairman.
There's so much going on today, and so I was in all kinds
of other places, and I missed your opening statements, and I
apologize for that. So I'm trying to figure out what to worry
about or not to worry about. And, for example, I received a--
where did it go?--a letter. Oh, OK. There it is.
I received a letter from a constituent, Chris Collins is
his name, in September. And he wrote to me about his belief
that, quote, ``offshoring of generic drugs has made the United
States exposed to potentially unsafe and ineffective medicines
and deprives us of a domestic supply of critical medicines in
case of a national emergency.'' And then he quotes from a book,
which may be totally a scam, I don't know, ``A Bottle of
Lies,'' that suggests in a quote that generic--quote, ``generic
drugs are poisoning us.''
So there are two issues here. One is offshore, that so much
of our supply is coming from overseas. What it says in our memo
is that FDA estimates that nearly 40 percent of finished drugs,
drug products, and 72 percent of active ingredients come from
overseas. So I'm trying to divide out----
He's also--he's complaining about generics and he's also
complaining about overseas. So first of all, is there a
difference in imports? We import brand name as well as
generics? Is that the case, Dr. Woodcock?
Dr. Woodcock. Yes. Those figures include both.
Ms. Schakowsky. And is it about even number of generics,
brand names, or----
Dr. Woodcock. That I could get you.
Ms. Schakowsky. OK.
Dr. Woodcock. We have all these figures cut many different
ways. But, certainly, a large number of brand names source
their API from India or China or elsewhere. And forever, a lot
of brand names have been made in Europe.
Ms. Schakowsky. So I'm trying to understand, Dr. Denigan.
So, from the GAO, what am I to be worried about? What is the
problem?
Dr. Denigan-Macauley. Well, it's true that the majority of
our drugs, whether it's generic, over-the-counter, or brand
name, are coming from overseas. And I think the concern is
ensuring that the current tools that FDA has at its disposal
are being used to their maximum. It would be great if we could
move towards advanced manufacturing and be able to enhance our
capacity here, but the fact of the matter is these are the
tools that they currently have, and they need to staff up these
offices, and they need to ensure that the inspections are as
equivalent as possible to here in the U.S.
Ms. Schakowsky. So it's something about minimum standards.
I'm looking for the language. It says the Current Good
Manufacturing Practices regulation, CGMP regulation, lay out
minimum requirements for the methods, facilities, et cetera. Is
that what we want? What is--minimum doesn't feel good to me.
Dr. Woodcock. Well, I just spoke to a large group of
manufacturers yesterday, many of them from brand name, and they
agree. All of them aim at this minimum. That's one of the
problems. That quote, I believe, or something like it, comes
from a report on shortages which points out that having true
reliability of a supply requires quality maturity. GMPs make
sure that, if you make a product, it'll be fit for purpose that
day. It doesn't say that 6 months later, you're going to be
able to keep making the product at the same level.
So we feel that we would like to have a positive program as
well where we recognize excellence wherever it occurs so we can
incentivize manufacturers and purchasers to recognize quality,
high quality.
Ms. Schakowsky. Is part of the problem, Dr. Denigan, we
have to staff up, there has to be more resources to do the
number of inspections that would make a difference?
Dr. Denigan-Macauley. Well, I'd be concerned at just
staffing up, because there's concerns on being able to not only
through the direct-hire authority to get them on board, but to
keep them on board. And there are problems that, indeed, they
go over on 2-year rotations in the overseas offices, and they
come home, and they don't have a good way of integrating them
back like they do with other offices that are more familiar
with how to do that.
Ms. Schakowsky. Thank you. I appreciate this.
I yield back.
Ms. DeGette. The Chair now recognizes the chairman of the
full committee, Mr. Pallone, for 5 minutes.
Mr. Pallone. Thank you, Chairwoman DeGette.
As has been mentioned today, this committee has been
examining FDA's foreign drug inspection program for nearly two
decades. And, without question, the FDA has made progress
thanks in part to new legislation. But I mentioned in my
opening statement, over the years, Congress has taken various
steps to improve FDA's ability to conduct foreign inspections.
But despite this, FDA's foreign drug inspection program
continues to be challenged by the same longstanding issues that
have persisted for years.
For example, as we heard from the GAO today, staffing
continues to be a constant challenge for FDA's foreign drug
inspection program. To assist, Congress reauthorized GDUFA,
which allowed FDA to collect generic drug user fees, which
could then be used to hire additional inspectors.
So, Dr. Woodcock, the 2016 GAO report found that only 8
percent of GDUFA inspectors were actually doing foreign
inspections. How has FDA used the GDUFA resource to increase
its foreign inspection capacity, if you will?
Dr. Woodcock. Well, the field has--the field organization,
ORA, has gotten what they call a cadre or group of people who
strictly do foreign inspections, and then they qualify the
other investigators to also be able to do foreign inspections.
So the goal is to probably increase the number of people who do
primarily foreign inspections. But we're challenged by the fact
the entire field force is way under capacity, and they need to
hire up.
Mr. Pallone. OK. We focused on FDA's role with these drug
products overseas, but we know that domestic importers also
play a role, and these companies have a responsibility to
conduct due diligence to know where they're getting their drug
products from and what kind of quality controls are used before
the drugs arrive here.
So, again, what role do U.S. companies play in ensuring
that the drug products they import are manufactured in
accordance with the quality standards?
Dr. Woodcock. Companies are required as part of good
manufacturing practices to validate their suppliers, to test
incoming APIs or excipients or other ingredients that they'll
put into their product if they're making them in the United
States to make sure they are fit for purpose. And that same is
true if, say, the finished dosage form is in Europe or in India
or wherever it is. There are requirements that you qualify your
raw ingredients and your suppliers to make sure that they are
the quality needed. So that's a requirement that has been in
place for a long time.
Mr. Pallone. But, in the FDA's Safety and Innovation Act,
Congress required that the commercial importers register with
the FDA, as you said, and that the agency should work with
Customs and Border Protection to issue regulations to establish
good importer practices for drugs. But can you provide the
committee with an update on this work? And what more do you
think domestic firms, especially those sourcing raw ingredients
from abroad, should be doing to ensure that the products are
safe?
Dr. Woodcock. Well, the Custom and Border Patrol, that is
within--under--the work with them is under ORA. I know
significant progress has been made, but I can't give you the
details. We can get back to you on that.
The API manufacturers and finished dosage form
manufacturers are supposed to qualify all the ingredients that
they may use and do tests that are applicable, safety tests or
quality tests, to make sure they're using the proper
ingredients, and that's their responsibility wherever they're
located.
The importers, it's more a matter of the data to make sure
we're getting the correct information about what's coming
across our border. Now, the agents are right at the border to
make sure that we are notified if an ingredient crosses the
border or a drug or whatever.
Mr. Pallone. All right. Let me just add one more thing. The
retail chains, they have a different role, as illustrated by
the case of Dollar Tree. In that case, FDA conducted
inspections of multiple foreign drug manufacturers and found
significant violations, such as not testing raw materials and
falsifying test results. So in addition to taking action
against those firms, FDA also issued a warning letter to Dollar
Tree, and they stated, quote, ``you're responsible for ensuring
that the drugs you distribute are manufactured in compliance
with all relevant CGMP requirements for drugs.''
So how are retail chains informed of unsafe products in its
supply chain? And what more can they do to ensure the safety of
the products that they offer for sale?
Dr. Woodcock. Right. Well, it depends on what role they
have. If they are a distributor, they have a certain role under
the GMPs. If they repack and relabel, then they have another
level. We can get back to you on the details of what
requirements are for every stage in that distribution chain,
but they do have requirements.
And you're pointing out one of the loopholes I talked about
earlier, that OTC drug manufacturers can register and then ship
without having an inspection. And so that's something that
allows this type of thing to go on.
Mr. Pallone. All right. Thank you. And I know through the
chairwoman, if you could get back to us in those cases where
you said you would, I'd appreciate it. Thank you.
Dr. Woodcock. We certainly will.
Ms. DeGette. The gentleman yields back.
I really want to thank both of our witnesses for
participating today. These are obviously important issues that
the committee remains interested in.
And I want to remind Members that, pursuant to the
committee rules, they have 10 days to submit additional
questions for the record to be answered by the witnesses, and I
ask that the witnesses would agree to respond promptly to any
such questions.
With that, the subcommittee is adjourned.
[Whereupon, at 11:52 a.m., the subcommittee was adjourned.]
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