[House Hearing, 113 Congress]
[From the U.S. Government Publishing Office]
EXAMINING DRUG COMPOUNDING
=======================================================================
HEARING
BEFORE THE
SUBCOMMITTEE ON HEALTH
OF THE
COMMITTEE ON ENERGY AND COMMERCE
HOUSE OF REPRESENTATIVES
ONE HUNDRED THIRTEENTH CONGRESS
FIRST SESSION
__________
MAY 23, 2013
__________
Serial No. 113-48
[GRAPHIC NOT AVAILABLE IN TIFF FORMAT]
Printed for the use of the Committee on Energy and Commerce
energycommerce.house.gov
__________
U.S. GOVERNMENT PRINTING OFFICE
85-438 WASHINGTON : 2014
________________________________________________________________________
For sale by the Superintendent of Documents, U.S. Government Printing Office,
http://bookstore.gpo.gov. For more information, contact the GPO Customer Contact Center, U.S. Government Printing Office. Phone 202-512-1800, or
866-512-1800 (toll-free). E-mail, [email protected].
COMMITTEE ON ENERGY AND COMMERCE
FRED UPTON, Michigan
Chairman
RALPH M. HALL, Texas HENRY A. WAXMAN, California
JOE BARTON, Texas Ranking Member
Chairman Emeritus JOHN D. DINGELL, Michigan
ED WHITFIELD, Kentucky Chairman Emeritus
JOHN SHIMKUS, Illinois EDWARD J. MARKEY, Massachusetts
JOSEPH R. PITTS, Pennsylvania FRANK PALLONE, Jr., New Jersey
GREG WALDEN, Oregon BOBBY L. RUSH, Illinois
LEE TERRY, Nebraska ANNA G. ESHOO, California
MIKE ROGERS, Michigan ELIOT L. ENGEL, New York
TIM MURPHY, Pennsylvania GENE GREEN, Texas
MICHAEL C. BURGESS, Texas DIANA DeGETTE, Colorado
MARSHA BLACKBURN, Tennessee LOIS CAPPS, California
Vice Chairman MICHAEL F. DOYLE, Pennsylvania
PHIL GINGREY, Georgia JANICE D. SCHAKOWSKY, Illinois
STEVE SCALISE, Louisiana JIM MATHESON, Utah
ROBERT E. LATTA, Ohio G.K. BUTTERFIELD, North Carolina
CATHY McMORRIS RODGERS, Washington JOHN BARROW, Georgia
GREGG HARPER, Mississippi DORIS O. MATSUI, California
LEONARD LANCE, New Jersey DONNA M. CHRISTENSEN, Virgin
BILL CASSIDY, Louisiana Islands
BRETT GUTHRIE, Kentucky KATHY CASTOR, Florida
PETE OLSON, Texas JOHN P. SARBANES, Maryland
DAVID B. McKINLEY, West Virginia JERRY McNERNEY, California
CORY GARDNER, Colorado BRUCE L. BRALEY, Iowa
MIKE POMPEO, Kansas PETER WELCH, Vermont
ADAM KINZINGER, Illinois BEN RAY LUJAN, New Mexico
H. MORGAN GRIFFITH, Virginia PAUL TONKO, New York
GUS M. BILIRAKIS, Florida
BILL JOHNSON, Missouri
BILLY LONG, Missouri
RENEE L. ELLMERS, North Carolina
Subcommittee on Health
JOSEPH R. PITTS, Pennsylvania
Chairman
MICHAEL C. BURGESS, Texas FRANK PALLONE, Jr., New Jersey
Vice Chairman Ranking Member
ED WHITFIELD, Kentucky JOHN D. DINGELL, Michigan
JOHN SHIMKUS, Illinois ELIOT L. ENGEL, New York
MIKE ROGERS, Michigan LOIS CAPPS, California
TIM MURPHY, Pennsylvania JANICE D. SCHAKOWSKY, Illinois
MARSHA BLACKBURN, Tennessee JIM MATHESON, Utah
PHIL GINGREY, Georgia GENE GREEN, Texas
CATHY McMORRIS RODGERS, Washington G.K. BUTTERFIELD, North Carolina
LEONARD LANCE, New Jersey JOHN BARROW, Georgia
BILL CASSIDY, Louisiana DONNA M. CHRISTENSEN, Virgin
BRETT GUTHRIE, Kentucky Islands
H. MORGAN GRIFFITH, Virginia KATHY CASTOR, Florida
GUS M. BILIRAKIS, Florida JOHN P. SARBANES, Maryland
RENEE L. ELLMERS, North Carolina HENRY A. WAXMAN, California (ex
JOE BARTON, Texas officio)
FRED UPTON, Michigan (ex officio)
C O N T E N T S
----------
Page
Hon. Joseph R. Pitts, a Representative in Congress from the
Commonwealth of Pennsylvania, opening statement................ 1
Prepared statement........................................... 3
Hon. Joe Barton, a Representative in Congress from the State of
Texas, prepared statement...................................... 4
Hon. Frank Pallone, Jr., a Representative in Congress from the
State of New Jersey, opening statement......................... 4
Hon. Michael C. Burgess, a Representative in Congress from the
State of Texas, opening statement.............................. 6
Witnesses
Janet Woodcock, M.D., Director, Center for Drug Evaluation and
Research, Food and Drug Administration......................... 8
Prepared statement........................................... 11
Answers to submitted questions............................... 136
Scott Gottlieb, M.D., Resident Fellow, American Enterprise
Institute...................................................... 52
Prepared statement........................................... 55
Joseph H. Harmison, Owner, Harmison Pharmacies, on Behalf of
National Community Pharmacist Association...................... 70
Prepared statement........................................... 72
Elizabeth Scott (Scotti) Russell, Government Affairs Manager,
National Association of Boards of Pharmacy..................... 78
Prepared statement........................................... 80
Gabrielle Cosel, Manager, Drug Safety, The Pew Charitable Trust.. 84
Prepared statement........................................... 86
Gerry Migliaccio, Quality Systems Consultant, Migliaccio
Consulting..................................................... 93
Prepared statement........................................... 95
Submitted Material
Letter of October 9, 2012, from Mr. Dingell to United States Food
and Drug Administration........................................ 110
FDA response dated April 26, 2013............................ 113
Letter of October 16, 2012, from Mr. Dingell to U.S. FDA......... 125
FDA response dated April 26, 2013............................ 127
Statement of the National Association of Chain Drug Stores,
submitted by Mr. Pitts......................................... 129
Statement of Central Admixture Pharmacy Services, Inc., submitted
by Mr. Pitts................................................... 133
EXAMINING DRUG COMPOUNDING
----------
THURSDAY, MAY 23, 2013
House of Representatives,
Subcommittee on Health,
Committee on Energy and Commerce,
Washington, DC.
The subcommittee met, pursuant to call, at 9:58 a.m., in
room 2322, Rayburn, Hon. Joseph R. Pitts (chairman of the
subcommittee) presiding.
Present: Representatives Pitts, Burgess, Shimkus, Murphy,
Gingrey, Lance, Guthrie, Griffith, Bilirakis, Ellmers, Barton,
Pallone, Dingell, Engel, Capps, Matheson, Green, Butterfield,
Barrow, Christensen, Castor, and Waxman (ex officio).
Staff Present: Clay Alspach, Chief Counsel, Health; Mike
Bloomquist, General Counsel; Karen Christian, Chief Counsel,
Oversight; Paul Edattel, Professional Staff Member, Health;
Brad Grantz, Policy Coordinator, O&I; Sydne Harwick,
Legislative Clerk; Nick Magallanes, Policy Coordinator, CMT;
Carly McWilliams, Professional Staff Member, Health; Andrew
Powaleny, Deputy Press Secretary; Krista Rosenthall, Counsel to
Chairman Emeritus; Chris Sarley, Policy Coordinator,
Environment & Economy; Heidi Stirrup, Health Policy
Coordinator; John Stone, Counsel, Oversight; Brian Cohen,
Minority Staff Director, Oversight & Investigations, Senior
Policy Advisory; Alli Corr, Minority Policy Analyst; Eric
Flamm, Minority FDA Detailee; Ruth Katz, Minority Chief Public
Health Counsel; Elizabeth Letter, Minority Assistant Press
Secretary; Karen Nelson, Minority Deputy Committee Staff
Director for Health; Stephen Salsbury, Minority Special
Assistant; Rachel Sher, Minority Senior Counsel; and Ryan
Skukowski, Minority Staff Assistant.
OPENING STATEMENT OF HON. JOSEPH R. PITTS, A REPRESENTATIVE IN
CONGRESS FROM THE COMMONWEALTH OF PENNSYLVANIA
Mr. Pitts. The subcommittee will come to order. The Chair
will recognize himself for an opening statement.
The purpose of today's hearing is to hear from FDA and
healthcare experts regarding the history and importance of drug
compounding to patients and the current regulation of
compounding on the Federal and State levels. As we are all
aware, in the summer and fall of 2012 a Massachusetts company,
the New England Compounding Center, NECC, shipped over 17,000
vials of an injectable steroid solution from 3 contaminated
lots to healthcare facilities across the country.
After receiving injections of NECC's contaminated steroid,
over 50 people died from complications associated with fungal
meningitis; further, almost 700 others were stricken with
meningitis or other persistent fungal infections. The outbreak
ranks as one of the worst public health crises associated with
contaminated drugs in the history of the United States.
This committee began an investigation into the matter, and
on October 9th a bipartisan committee letter was sent to FDA
requesting details surrounding the outbreak and the prevention
of future outbreaks. On October 17, the committee sent a letter
to FDA asking for all documents related to the outbreak,
including internal memoranda and communications with NECC. The
Oversight and Investigations Subcommittee held a hearing on
November 14, 2012, where Dr. Margaret Hamburg testified
examining whether the meningitis outbreak could have been
prevented. Two days later, on November 16th, the committee sent
yet another letter to FDA stating that the agency had not
provided any of the internal communications or memoranda in
response to the October 17th letter.
It was not until March 21st, 2013, over 5 months after the
original request, and after being threatened with the
possibility of a subpoena, that FDA fully complied with the
committee's document request. It should be noted that the
Massachusetts Department of Public Health had fully complied
with the committee's document request, turning over thousands
of pages of documents related to its interactions with NECC
before the November hearing took place.
On April 16, 2013, the O&I Subcommittee held another
hearing entitled, ``A Continuing Investigation Into the Fungal
Meningitis Outbreak: Could It Have Been Prevented?'' and
released a 43-page report on its investigation into the NECC
tragedy. The report stated that FDA had been aware of potential
problems at NECC since 2002. During her testimony at the
November hearing, Dr. Hamburg repeatedly expressed uncertainty
about FDA's authority over compounding pharmacies, partially
due to conflicting opinions on the matter issued by two
different circuit courts of appeals in 2009.
This uncertainty, however, has not stopped FDA from
engaging in multiple enforcement activities against compounding
pharmacies engaged in practices similar to those of NECC since
the outbreak took place. This year alone, FDA has announced
recalls from compounding pharmacies in Augusta, Georgia, and
Lake Mary, Florida, and St. Petersburg, Florida. In addition,
the FDA in October of 2012 was prepared to issue new guidance
related to compounding enforcement under its authority under
Section 503.
Since the outbreak, however, the FDA has called for new
authority that creates a new category of compounding
manufacturers. From what I understand, there are concerns that
creating this new category could undermine drug safety by
lowering standards and also weaken intellectual property
protection.
I would like to thank Dr. Woodcock for appearing before us
today to explain her understanding of FDA's authority over
compounding pharmacies and what actions the agency is taking to
ensure that future outbreaks can be prevented. And I would also
like to thank all of our other witnesses for sharing their
expertise on compounding and its importance to patients.
Thank you. And I will yield the balance of my time to
Congressman Barton.
[The prepared statement of Mr. Pitts follows:]
Prepared statement of Hon. Joseph R. Pitts
The Subcommittee will come to order.
The Chair will recognize himself for an opening
statement.The purpose of today's hearing is to hear from FDA
and health care experts regarding the history and importance of
drug compounding to patients and the current regulation of
compounding on the federal and state levels.
As we are all aware, in the summer and fall of 2012, a
Massachusetts company, the New England Compounding Center
(NECC), shipped over 17,000 vials of an injectable steroid
solution from three contaminated lots to health care facilities
across the country.
After receiving injections of NECC's contaminated steroid,
over 50 people died from complications associated with fungal
meningitis. Further, almost 700 others were stricken with
meningitis or other persistent fungal infections.
The outbreak ranks as one of the worst public health crises
associated with contaminated drugs in the history of the United
States.
This Committee began an investigation into the matter, and
on October 9th, a bipartisan Committee letter was sent to FDA,
requesting details surrounding the outbreak and the prevention
of future outbreaks.
On October 17th, the Committee sent a letter to FDA asking
for all documents related to the outbreak, including internal
memoranda and communications with NECC.
The Oversight and Investigations (O&I) Subcommittee held a
hearing on November 14, 2012, where Dr. Margaret Hamburg
testified, examining whether the meningitis outbreak could have
been prevented.
Two days later, on November 16th, the Committee sent yet
another letter to FDA stating that the agency had not provided
any of the internal communications or memoranda in response to
the October 17th letter.
It was not until March 21, 2013--over five months after the
original request and after being threatened with the
possibility of a subpoena--that FDA fully complied with the
Committee's document request.
It should be noted that the Massachusetts Department of
Public Health (MDPH) had fully complied with the Committee's
document request--turning over thousands of pages of documents
related to its interactions with NECC--before the November
hearing took place.
On April 16, 2013, the O&I Subcommittee held another
hearing entitled ``A Continuing Investigation into the Fungal
Meningitis Outbreak: Could It Have Been Prevented?'' and
released a 43-page report on its investigation into the NECC
tragedy.
The report stated that FDA had been aware of potential
problems at NECC since 2002.
During her testimony at the November hearing, Dr. Hamburg
repeatedly expressed uncertainty about FDA's authority over
compounding pharmacies, partially due to conflicting opinions
on the matter issued by two different Circuit Courts of Appeals
in 2009.
This uncertainty, however, has not stopped FDA from
engaging in multiple enforcement activities against compounding
pharmacies engaged in practices similar to those of NECC's
since the outbreak took place.
This year alone, FDA has announced recalls from compounding
pharmacies in Augusta, GA, and Lake Mary and St. Petersburg,
FL.
In addition, the FDA in October 2012 was prepared to issue
new guidance related to compounding enforcement under its
authority under Section 503. Since the outbreak, however, the
FDA has called for new authority that creates a new category of
compounding manufacturers.
From what I understand, there are concerns that creating
this new category could undermine drug safety by lowering
standards and also weaken intellectual property protection.
I would like to thank Dr. Woodcock for appearing before us
today to explain her understanding of FDA's authority over
compounding pharmacies and what actions the agency is taking to
ensure that future outbreaks can be prevented.
I would also thank our other witnesses for sharing their
expertise on compounding and its importance to patients.
Thank you, and I yield the balance of my time to Rep. ----
--------------------------------.
Mr. Barton. Thank you, Mr. Chairman. I am glad to be here
today. We are glad to have Dr. Woodcock. She is a longtime
witness before the committee, and we have great respect for
her. We look forward to hearing what you have to say.
I think it is pretty obvious to neutral observers that the
facts do indicate that the FDA had authority that it refused or
chose not to use in the situation that we are investigating. I
am sure Dr. Woodcock will elaborate on that and may have a
counter point of view.
Mr. Chairman, on the second panel I have a good friend and
former constituent, Mr. Joe Harmison, who is in the audience.
He is the past president of the Texas Pharmacy Association, the
past president of the National Community Pharmacists
Association. He is that rare breed, he still owns and operates
his own pharmacy. The only thing I can find negative about him
is that he graduated from the University of Oklahoma School of
Pharmacy back in 1970. Other than that, he is a great guy and a
good friend, and I am sure he will be very helpful in his
testimony on the second panel.
I might also take personal privilege just to say that Mr.
Shimkus, to my right, threw out a runner at third base today in
our intersquad game, as we get ready to battle the Democrats
who have beat us the last 4 years in the congressional baseball
game. So Shimkus is getting in game for that. With that, I
yield back.
[The prepared statement of Mr. Barton follows:]
Prepared statement of Hon. Joe Barton
Thank you, Chairman Pitts for holding this hearing. I
applaud the Committee's oversight and investigative work on the
recent meningitis outbreak. The facts indicate that the Food
and Drug Administration did not use its full authority and act
quickly against the company compounding and distributing the
tainted medication. I look forward to hearing from our
witnesses today in the Health Subcommittee to determine what if
anything needs to be done legislatively to prevent further harm
to innocent Americans.
In particular, I would like to welcome a fellow Texan to
the hearing, Mr. Joe Harmison, testifying today on behalf of
the National Community Pharmacists Association. I have known
Mr. Harmison for twenty years or so and the Committee could not
have asked a more respected and experienced pharmacist to come
to DC to share the community pharmacy perspective regarding
issues relating to drug compounding. I hope he can explain the
vital role community pharmacies play in compounding drugs for
their patients and the difference between his operation and
those of his association versus what was happening at the
companies compounding the drugs that caused the recent
outbreak.
With that Mr. Chairman, I welcome the witnesses, look
forward to the hearing, and yield back.
Mr. Pitts. Chair thanks the gentleman.
Now recognize the ranking member of the subcommittee, Mr.
Pallone, 5 minutes for an opening statement.
OPENING STATEMENT OF HON. FRANK PALLONE JR, A REPRESENTATIVE IN
CONGRESS FROM THE STATE OF NEW JERSEY
Mr. Pallone. Thank you, Chairman Pitts. I am pleased that
the Health Subcommittee is finally having a hearing to examine
drug compounding. But, unfortunately, we are months behind.
While we are having our first hearing today to gather
information on this topic, our colleagues in the Senate have
already worked together to produce and mark up bipartisan
legislation in the Health Committee. And so I think this delay
is regrettable here.
Access to compounding drugs is crucial for patients who
have unique medical needs. We know that the New England
Compounding Center that distributed the contaminated compounded
product last year, resulting in the meningitis outbreak that
claimed over 50 lives and infected over 700 patients, was
clearly a bad actor. However, NECC will not be the last bad
actor. Similar tragedies will undoubtedly occur again unless we
address the significant gaps that exist in the current
regulation and oversight system of compounded products. If
patients are to have confidence in the safety and quality of
these drugs, we must ensure that compounders meet safety and
quality standards.
While traditional compounders who mix medications to fill a
prescription for a specific person are regulated at the State
level, and drug manufacturers are regulated by the Federal
Government, there are a growing number of companies that do not
fall into either of these categories. Many companies are
compounding drugs without prescriptions and shipping large
quantities of the products across State lines; in essence,
acting more like manufacturers than the traditional
compounders. In the absence of clear lines of authority, these
companies experience very little State or Federal oversight.
So as we begin to examine drug compounding, I urge my
colleagues to use this as an opportunity to move forward to
determine what changes are needed rather than looking back and
casting blame. We must stop questioning whether the FDA needs
new authority. In fact, the past few months of examination by
our Oversight Committee and the Senate Health Committee it has
become abundantly clear that conflicting court opinions and
ambiguous language in the law show that the FDA does not have
adequate authority to oversee compounders. And that is why I
support efforts to help identify a new category of companies to
be subject to Federal regulation and oversight and provide FDA
the tools and resources it needs to properly regulate them.
So, Mr. Chairman, I hope today can be the start to this
committee coming together in a bipartisan manner to address
this issue and create greater clarity in the law so the
tragedies like the one involving NECC do not happen again. The
American people should know that the drugs that they receive
are safe and effective.
So I thank all our witnesses. I know we have a second
panel. I look forward to hearing about how Congress can best
address the gaps in regulation and oversight that were
unfortunately highlighted by the NECC meningitis outbreak and
how all stakeholders can work together to protect the public
health.
I don't know if anybody wants any of my 2 minutes on my
side. You would, Mr. Dingell? I yield to Mr. Dingell.
Mr. Dingell. I thank the gentleman for yielding. I thank
you for having this hearing. I welcome our first panel member
today. Good to see her back before the committee.
This committee has a great opportunity. We can quibble all
we want about whether we have the authority, whether it is
needed or not. Simple fact of the matter is people are dying,
people are being made sick. And many people in this compounding
industry, if that is what you want to say it is, have been
studying ways to get around food and drug regulation and to
continue, for all intents and purposes, becoming manufacturers.
The question is, do we want to persist on that while we
engage in a monstrous quibble, or do we want to get down and
cut the corners that come from courts and judges trying to
resolve a question that is probably well beyond their
competency.
Having said these things, I would urge us to move forward
on legislation, effective legislation. This committee has a
remarkable history in this Congress, which is noteworthy for
having done very little, to have in fact moved forward with a
number of important pieces of legislation in a bipartisan
fashion. I see no reason why we should not continue that kind
of effort with all the blessings to the public that that
obtains.
So I would urge us to move forward. Let's put these rascals
in the compounding industry into a place where they have law to
obey, where everyone understands what it is, and where we can
make our people safe. My State of Michigan suffered huge losses
to people in sickness and death stemming from wrongdoers who
were deliberately skating around the law. And unsafe
pharmaceuticals well beyond the reach of Food and Drug were in
fact poisoning and killing our people.
This is a wonderful opportunity. I commend you for making
it possible. I look forward to working with you. I commend my
colleague Mr. Pallone for his wise counsel and leadership. And
I look forward to working on this matter in an effective way
where we do go forward together to solve a major problem for
our people. Thank you.
Mr. Pitts. Chair thanks the gentleman.
Now recognize the vice chairman of the subcommittee, Dr.
Burgess, 5 minutes for an opening statement.
OPENING STATEMENT OF HON. MICHAEL C. BURGESS, A REPRESENTATIVE
IN CONGRESS FROM THE STATE OF TEXAS
Mr. Burgess. Thank the chairman for the recognition. And I
do support the efforts to examine the role that traditional
compounding pharmacists play in the healthcare system. I know
the value that they provide, having used them in my practice
for a number of years.
But we are also going to hear this morning how this
incident necessitates broad new authorities. Recently the Food
and Drug Administration has inspected over 50 compounding
facilities. You have to ask yourself, by what authority did
these 50 inspections occur? If the FDA has the authority today,
they had it 6 months ago. The fact is one of the following
statements must be true: The agency is acting without authority
and risking litigation or they have the authority and have
always had the authority and have simply failed to use it.
Documents obtained by the Oversight and Investigations
Subcommittee are deeply troubling, and I believe show FDA
negligence. New England Compounding Center was making upwards
of 30,000 vials of product without prescriptions and yet the
Food and Drug Administration questioned whether they had
authority under the Food, Drug, and Cosmetic Act over
manufacturing?
The Food and Drug Administration was aware that this
compounding facility was making poor products for years. They
never followed up on warning letters. Frustrated FDA staff
could not even warn the State of Massachusetts. Whistleblowers,
doctors providing dozens of adverse event reports and law firms
dealing with substandard conditions came forward and the FDA
did nothing. They didn't even pick up the phone.
This is an example of circling the wagons after the crisis,
and this member is having none of it. The bureaucracy held up
the guidance for years. Testimony that is as provided through
our Oversight and Investigations Subcommittee--the testimony
that has been provided to both the Oversight and Investigations
Subcommittee and this subcommittee today has been carefully
crafted to avoid asking who failed America and who allowed NECC
to introduce contaminated product in its supply line.
I cannot in good conscience entertain discussion of
legislation when not one person has been fired, reprimanded, or
held culpable at the Food and Drug Administration. In fact,
legislating transfers the blood of those dead and harmed from
the agency responsible to us, the subcommittee and to Congress.
Massachusetts fired people because they should have known,
and yet the Food and Drug Administration, who did know, now
wants new authority. To what end is new authority going to
provide protection to the public if the Food and Drug
Administration, by its own admission and track record, refuses
to pick up and use the tools they had at their disposal. The
Food and Drug Administration refused to go after those
operating so far outside the bounds of legality in traditional
compounding. Why in the world would we trust them to regulate a
legitimate compounder?
Until the agency admits where it failed the American
public, I for one am not going to be a party to letting them
get away with this dereliction of responsibility. To do
otherwise invites further incompetence from one of the most
important agencies under our jurisdiction and sets a dangerous
precedent for other agencies under our purview.
I would like to yield the balance of the time to the
gentleman from Virginia, Mr. Griffith.
Mr. Griffith. Thank you, Dr. Burgess.
Last fall's fungal meningitis outbreak was a true public
health crisis for our Nation. In Virginia's Ninth Congressional
District, which I represent, there were two deaths and 50
confirmed cases of fungal meningitis associated with the
sterile compounded injections from NECC. Approximately 1,400
patients in southwest Virginia were notified they could have
been exposed to fungal meningitis because they received tainted
steroid injections.
I clearly believe that FDA had the authority they needed to
prevent the fungal meningitis outbreak. NECC was a
manufacturer. The committee's thorough investigation has
demonstrated the agency failed in their oversight and did not
pursue regulatory action against NECC and Ameridose, who were
acting illegally as manufacturers, not as compounding
pharmacies, in violation of the Food, Drug, and Cosmetic Act.
With well over 130 community pharmacists provided
invaluable access to health care in rural and remote
communities in the mountains of southwest Virginia, I do not
support giving FDA broad new authority over the practice of
pharmacy, which is the jurisdiction of our States. The type of
compounding that goes on in our local pharmacies involves
making special medications subject to the needs of the
individuals based on a patient-specific prescription from their
physician.
The real problem is large-scale operations like NECC who
are acting illegally as drug manufacturers by making large
batches of drugs, some of which are just copies of FDA-approved
drugs, and then selling and shipping them all over the country.
In her testimony, Dr. Woodcock acknowledges that FDA was in
the final stages of publishing new guidance differentiating
pharmacy compounding from drug manufacturing. Three years
later, FDA finally had all of its ducks in a row and was ready
to go forward, but they did not do so in their draft guidance
document. I believe there are some areas that need
clarification. So we have been doing our due diligence to
understand this issue and develop legislation that will make it
clear how we define what a compounding pharmacy is, which is
and should be regulated by the States, and what a drug
manufacturer is, which should be regulated by the FDA.
Yield back.
Mr. Pitts. The chair thanks the gentleman.
That concludes our opening statements. We have two panels
today. Our first panel today we have Dr. Janet Woodcock,
Director of the Center for Drug Evaluation and Research, U.S.
Food and Drug Administration.
Thank you for coming, Dr. Woodcock. You will have 5 minutes
to summarize your testimony. Your entire written testimony will
be placed in the record. You are welcome and recognized for 5
minutes.
STATEMENT OF JANET WOODCOCK, M.D., DIRECTOR, CENTER FOR DRUG
EVALUATION AND RESEARCH, FOOD AND DRUG ADMINISTRATION
Dr. Woodcock. Thank you, Mr. Chairman, Vice Chairman,
Ranking Member, and members of the committee. Thank you for the
opportunity to testify.
This has really been an appalling tragedy of a kind not
seen really since the early 1900s, where American citizens were
harmed by grossly contaminated drug. But this is just the worst
of a long series of outbreaks over the past 2 decades that have
involved compounding pharmacies, and these have included
multiple deaths, blindness, hospitalizations, and other types
of harm. So this was just the worst of a continuing series of
outbreaks.
As the Commissioner testified, we should have been more
aggressive in applying our existing authorities to this
industry, despite the ambiguities in the statute and despite
challenges by industry. We are being more aggressive now, and
we are inspecting the pharmacies that we know about that
present the highest risk. And we are seeing really serious
systemic quality issues, particularly around sterility
practices.
In light of recent events, though, even with the tragedy
that has occurred, some of these firms challenge our authority
when we try to go in and inspect them, and they delay or deny
full access to our records. We have twice had to get
administrative warrants from the court and have U.S. marshals
accompany our inspectors. And we have had to threaten warrants
in other cases to get cooperation to inspect these compounding
pharmacies. And because we are inspecting and moving
aggressively doesn't mean we are going to prevail in court.
Make no mistake, if the approach to this isn't changed, and
I think legislation is probably the best approach, we will see
more of these tragedies. We are already, since the outbreak, we
have seen several episodes involving human harm from compounded
products.
Lack of clarity in our statutory authorities really isn't
the only concern. The industry has evolved tremendously since
the time of the corner pharmacist and traditional compounding
in response to a prescription. And this is still going on, and
FDA has always said we felt this was appropriate. But another
industry has grown up that is basically performing outsourcing
for hospitals and making large amounts of dosage forms, often
starting with FDA-approved products. And this industry was
really never contemplated in the kind of authorities that we
have.
So we feel that we need legislation to preserve the
benefits of traditional compounding, which is in response to a
prescription, and which we are not proposing that we should
have authority over, further authority over, while at the same
time giving us the right tools to regulate high-risk practices
and products. We feel we need legislation that requires
compliance with Federal quality standards; requires Federal
registration, because right now we don't know who they are, we
don't know where they are, and we don't know what they are
making; and requires reporting to FDA of adverse events so that
we can act before the problems get out of hand. Right now there
is no requirement to send us reports of death or other harm
that might occur with these products.
And for all pharmacy compounding we feel basic protections
should be in place, including the fact that FDA should have
access to the records so that we can go in and see whether they
are shipping large amounts of product, all right, and what they
are doing; and also, should there be an outbreak, we are not
delayed by having to go to a marshal and have access to the
shipping records.
A prohibition on compounding the most complex and highest-
risk products. Our drug manufacturers, as you know, have
problems manufacturing certain products because they are very
complex, and they put a tremendous amount of science and effort
into that. We don't think they should be compounded. That is a
small list, but we think that list should be maintained. And
clear labeling of compounded drugs to allow prescribers and
patients to make more informed choices.
We look forward to working with you to explore funding
mechanisms to support this oversight, should it be put in
place. Remember, I think it really is a matter of when this is
going to occur the next time, not if. That is the state that we
are observing of the industry when we are inspecting them. We
are all on notice, we owe it to the public and the victims of
this incident and the numerous outbreaks over the years to
provide better protection in the future. I look forward to
answering your questions.
Mr. Pitts. Thank you, Dr. Woodcock.
[The prepared statement of Dr. Woodcock follows:]
[GRAPHICS NOT AVAILABLE IN TIFF FORMAT]
Mr. Pitts. I will begin the questioning and recognize
myself for 5 minutes for that purpose.
Dr. Woodcock, since the outbreak, the FDA has executed
dozens of inspections and at least 11 companies were ordered to
stop producing some or all drugs. Have any of the companies you
inspected challenged the FDA authority? If so, how many?
Dr. Woodcock. Certainly, as I said, we have had several
challenge our authority to even go in the firm and look at
their records. Others have challenged and then yielded when we
got the lawyers talking to one another. Now, as far as whether
there will be court challenges, that is something I really
can't speak to. But that certainly has been the history in the
past.
Mr. Pitts. Can you provide a list to the committee of the
companies who you have inspected and who have challenged your
authority?
Dr. Woodcock. We will be happy to do so.
Mr. Pitts. According to the Senate HELP report, I quote,
``As a result of increased oversight from both State and
Federal regulators, at least 48 compounding companies have been
found to be producing and selling drugs that are contaminated
or were created in unsafe conditions or otherwise violate State
licensing requirements. Ten companies have issued nationwide
recalls of drugs compounded at their facilities. In at least
four cases, the recall was issued in response to documentation
of actual contamination. Further, 11 compounding pharmacies
have been ordered to cease and desist operations, including two
of those that had issued nationwide recalls.''
Now, as you said, some of these companies challenged the
FDA's authority. Can you explain how State and Federal
regulators executed this increased oversight?
Dr. Woodcock. Well, we identified firms that we knew about
basically from adverse event reports, from reports in the
paper, from advertisements they had on a Web page and so forth,
and we did a risk-based approach to inspecting what we felt
were the highest-risk firms, based on what we knew. We don't
know the whole universe of firms that are out there.
We also continue to do for-cause inspections. For example,
if we get a report from a health department about a cluster of
cases of an outbreak of one sort or another, we will
immediately go into that pharmacy and inspect them. In all of
those for-cause cases, we have gone in with the State
authority. So we have gone in together, all right. And in most
of the other inspections that we did that we planned, the 31
inspections, we have gone in with the State authorities as
well.
Mr. Pitts. What were the biggest challenges that you faced
during that period?
Dr. Woodcock. Well, the challenges mainly were getting
access in some cases to be allowed to inspect, all right,
particularly some of their records. But the real thing that we
have found is that the aseptic processing practices, which
means how you try to make a drug to ensure that it is sterile,
are not anywhere near the quality that is necessary to mass
produce sterile drugs. There is a tremendous deficit of quality
in their practices that almost assure that these drugs will at
some point be contaminated.
Mr. Pitts. What are some of the lessons the agency has
learned during the period of this outbreak?
Dr. Woodcock. Well, I think we have learned that there are
pervasive practices that are unsafe that are going on across
the portion of this industry that we have investigated.
Primarily, we are targeting those sterile manufacturers because
that is the highest risk when you are actually injecting drugs
into the body. So that is one thing we have learned, is the
pervasive nature of unsafe practices across the section of
industry that we have inspected.
Mr. Pitts. In your testimony you reference nine separate
incidents where compounded products caused deaths and serious
injuries. Explain briefly the actions the FDA took following
each of these incidents.
Dr. Woodcock. Well, over the years, our actions have been
primarily reactive. OK. So when we have learned of an outbreak,
as I said, we have gone in. Often we go in with the State. The
State, because they hold the pharmacy license, they are able to
shut down the firm right away. Like that is how those 11 firms
you referred to were shut down. OK.
We have to call for and we often do talk to the firm and
say we are going to go to the press if you don't do a recall,
because we don't have the authority--they don't hold a license
with us, so we can't just shut them down. We would have to then
go court if they still refused to shut down their operations.
Mr. Pitts. My time has expired. Chair recognize the ranking
member 5 minutes for questions.
Mr. Pallone. Thank you. Dr. Woodcock, your testimony
mentions the various court challenges that the compounding
industry has brought over the years regarding FDA's authority
over compounding pharmacies. But I would like to learn more
about that litigation and the impact it has had on FDA's
ability to oversee the industry.
Those cases center around Section 503A of the act, which
was enacted as part of the 1997 FDA Modernization Act. And that
law attempted to delineate when compounded drugs were new drugs
and therefore subject to FDA regulation. Section 503A also
restricted compounding pharmacies' right to advertise.
So I am going to put a map of the U.S. up on the monitors
here. It is up there. This map was not prepared by me or my
staff, it was actually prepared by the International
Association of Compounding Pharmacies, the main compounding
industry lobbying group. On this map, the red States and blue
States do not represent States that voted Democrat or
Republican. They represent the different rules under which
compounding pharmacies operate.
So let's look at the red States. Those represent the Ninth
Circuit Court, whose jurisdiction includes the Western States.
And as IACP notes on this chart, in 2001, the Ninth Circuit
Court ruled that the advertising component of Section 503A was
unconstitutional and that the rest of 503A was void because it
was inextricably tied to the advertising component, or that it
was not severable, as we say. Is that correct?
Dr. Woodcock. Yes.
Mr. Pallone. OK. Then in 2002, the Supreme Court agreed
with the Ninth Circuit that the advertising ban was not
constitutional, but the Court did not address the question of
whether that ban could be severed from the rest of Section
503A. The result of that decision then was that the advertising
ban was unconstitutional throughout the country, and the
entirety of Section 503A remained invalid in those red States
on the map. The Supreme Court decision also meant that whether
the remaining parts of Section 503A was effective in the rest
of the country was an open question. Is that your
understanding?
Dr. Woodcock. That is my understanding.
Mr. Pallone. So let's look now at the blue States on the
map, Texas, Louisiana, and Mississippi. Those States represent
the Fifth Circuit. 2008, the Fifth Circuit Court of Appeals
held that the unconstitutionality advertising restrictions did
not affect the standing of the rest of Section 503A. So that
means that in Texas, Louisiana, and Mississippi, Section 503A
is in effect. Am I correct on that?
Dr. Woodcock. That is my understanding.
Mr. Pallone. And am I correct that the gray States on the
map then represent the rest of the country, where we just don't
know how courts would rule on whether Section 503A, apart from
the advertising restriction, is or is not in effect?
Can you tell us what the impact of this 503A patchwork has
been on FDA's ability to oversee the compounding industry? Have
compounding pharmacies been able to take advantage of this
confusion over the law to block FDA's ability to aggressively
enforce the court authority it does have over compounders?
Dr. Woodcock. Yes, I think that definitely contributed to
the inability of FDA to have an effective regulatory program.
All right. We have different circuits with different meanings
of the statute that was passed by Congress in 1997. In some
areas, the statute is thrown out; in other areas, it is
partially operational; in other areas, we don't know if we went
to court what type of decision we would get.
Mr. Pallone. So this seems to me to be all that we as
Members of Congress need to see to understand the dire need for
clarifying the FDA's authorities here. What I don't understand
is I am hearing from the GOP here on the committee that they
don't seem to want to give the FDA additional authority even
though the Senate passed a bill on a bipartisan basis that
does. And yet I don't see any alternative.
In 1997, for better or worse, Congress spelled FDA's
authorities over compounding pharmacies. I think that law is
out of date and should be updated. But putting that aside,
courts have invalidated that statute, our statute, in a major
swathe of the country. I think it is irresponsible for us to
stand by and expect FDA to cobble together a piecemeal approach
to regulating the practice of compounding pharmacy, a practice
that, as evidenced by the NECC, bears great risk for patients
all over the country.
I don't quite understand why my colleagues on the other
side, at least here in the House, not in the Senate, don't want
to step in and clarify the rules of the road. I think we have
to do that, otherwise we are going to continue to have these
problems with compounding pharmacies. And I hate to say
anything positive about the Senate, but they are moving in that
direction and we need to do the same.
Thank you.
Mr. Pitts. We are presently voting on the floor. We have
two votes. We will recess until the second vote is over and
then reconvene. We will have another series of vote around
noon. So if you can stay, Dr. Woodcock, we will recess at this
time for floor votes and be back as soon as the members finish
their second vote.
[Recess.]
Mr. Pitts. Time of our recess having expired, we will
reconvene and continue our Q&A session. Chair recognize the
vice chair of the subcommittee, Dr. Burgess, 5 minutes for
questions.
Mr. Burgess. I thank the chairman.
And thank you, Dr. Woodcock, again for being here.
So between 2002 and 2012, according to our investigation on
Oversight and Investigations Subcommittee, the New England
Compounding Center was the subject of at least 52 adverse event
reports. Numerous offenses documented throughout the
investigation that was undertaken by both FDA and State
regulators.
So, you know, the big question is, why not do something?
Why not take action? And to tell you the truth, it was a little
hard to read through some of the emails that we finally got.
Your folks were literally pulling their hair out about we can't
just send another warning letter, we have already sent one to
which it took us 2 years to respond and we will have to do
something. And it was like they got right up to the point of
having to do something and then no one wanted to do it. Is that
an unfair assessment.
Dr. Woodcock. Well, I am unable to comment specifically on
NECC because of the ongoing criminal investigation. However,
generally, I would say we should have been more aggressive
overall in this industry. There was a pattern for many firms
that we were looking at of adverse events. And, as I said,
there were a series of outbreaks. Every year, practically, we
would have an outbreak due to contaminated compounded product,
and we should have been more aggressive in going after this
industry.
Mr. Burgess. Well, again, I just don't understand some of
your folks. They just had to be losing their minds over this
stuff. Samia Nasr, a name kept coming up in the emails that
were provided to us. Does she still work at the agency?
Dr. Woodcock. Yes.
Mr. Burgess. I know you can't comment on employment. But, I
mean, I think she did the right thing to bring all these things
to people's attention, but it must have driven her crazy that
the people just above her wouldn't do something.
Dr. Woodcock. As I said, overall, we should have been more
aggressive as this industry continued to be responsible for
outbreaks. We investigated outbreaks, we investigated reports,
and we did respond reactively to problems. But we did not
proactively do everything we could.
Mr. Burgess. And as a consequence you had 50 deaths and 500
people who are living with long-term disability as a
consequence of the Exserohilum in the betamethasone.
Dr. Woodcock. Well, we have more people who have died than
that. We have people blinded. We have people with disabilities
as a result of these outbreaks over the last 12 years. And I
would say, frankly, if you want my opinion, that we could have
done more----
Mr. Burgess. I do.
Dr. Woodcock [continuing]. The States should have done
more, and Congress could have intervened when these statutes
were struck down.
Mr. Burgess. You know, and the ranking member had a nice
map up there. He made a nice little comment about red and blue
States. But, honestly, the 503A limitation doesn't affect
Massachusetts at all. I mean, we are talking about Texas and
California, Fifth Circuit, Ninth Circuit, but Massachusetts is
outside that. So what prevented you in Massachusetts?
Dr. Woodcock. As I said, I can't specifically discuss this
particular case because of the ongoing investigation.
Mr. Burgess. OK.
Let me ask you this: How difficult is it to get an
injunction from a judge? You go a judge and say, we have got a
problem here. How difficult is it to get an injunction?
Dr. Woodcock. We, as I understand it, I am not one of the
agency lawyers, I am a physician, as you know, but we make a
recommendation to the Justice Department, who then proceeds to
do the legal activities. And just because we initiate legal
action doesn't necessarily mean we will prevail in court.
Mr. Burgess. How many times have you not prevailed?
Dr. Woodcock. I don't know. We can get back to you.
Mr. Burgess. Would you get us that information?
Dr. Woodcock. Absolutely.
Mr. Burgess. Out of all of the challenges that you have
submitted to companies, how many have actually stood up to you
and said, we don't want to do it?
Dr. Woodcock. I think there are--we do bring our cases that
have the best facts, all right, as we sort through the cases we
put forth those that have the best facts that we would be most
likely to win.
Mr. Burgess. Well, again, it is just so frustrating to
think that the guidance that supposedly was going to come out,
that was going to solve this problem, just really seemed to be
enmeshed in the bureaucracy for 3 years. Is that a fair time
length?
Dr. Woodcock. I think that is fair. However, that was
trying to make the best of a bad situation. We do not have the
tools that fit this industry, right?
Mr. Burgess. You know what? I disagree. Because do you not
have power under the Food, Drug, and Cosmetic Act to regulate
manufacturers?
Dr. Woodcock. Yes.
Mr. Burgess. You define manufacturers. Someone is making
30,000 vials of stuff a month, is that a manufacturer?
Dr. Woodcock. Well, say, if I am Janet the pharmacist, all
right, and I have a pharmacy that is licensed in a State,
right, and I am compounding drugs, right, and then I decide,
well, I want to broaden my activities, and my State allows the
anticipatory compounding and my State allows office stock,
right, so I can compound those in advance of or without a
prescription and send them. And there is no----
Mr. Burgess. 30,000 vials a month?
Dr. Woodcock. There is no--what is the number? That is the
thing we have been struggling with for 12 years. Is it 10
vials? Is it 1,000 vials?
Mr. Burgess. Well, let me ask you this question.
Dr. Woodcock. There is no volume limit in the statute.
Excuse me for interrupting you.
Mr. Burgess. Well, Massachusetts Board of Pharmacy fired
people. Is the Food and Drug Administration going to let anyone
go?
Dr. Woodcock. No.
Mr. Burgess. No?
Dr. Woodcock. No.
Mr. Burgess. I yield back, Mr. Chairman.
Mr. Pitts. Chair thanks the gentleman.
Now recognize the gentlelady from Florida, Ms. Castor, 5
minutes for questions.
Ms. Castor. Thank you very much.
I wanted to get just to that point. Where do we draw the
line? Because I think as legislation is developed, and your
testimony is that you do not want and it is not appropriate to
capture the community pharmacists who are compounding----
Dr. Woodcock. That is correct.
Ms. Castor [continuing]. And that is not the source of
problems. So where do you recommend the dividing line should
be? What is the criteria in law? Has the Senate addressed this
in their bill? Where do they carve out so that the community
pharmacists that are compounding are protected and others that
have exceeded that and are really the large-scale
manufacturers, how do we develop that criteria?
Dr. Woodcock. Well, the Senate is attempting to set forth a
framework, and we feel they are going in the right direction.
But those clear lines between who is a drug manufacturer, who
is a traditional compounder, and who is the new category of
compounding manufacturing, we still feel are not clear enough.
So that we could have people masquerading--and some of the
other witnesses I think are going to talk about this, by my
reading of their testimony, OK--that we could have people
masquerading as traditional compounders or as compounding
manufacturers who really were competing with the generic drug
industry or the innovator drug industry and actually should
have sent us applications and paid a user fee and gone through
the established process that we have had in the United States
since 1962. And so that is really the issue, is how do you draw
those boundaries.
Ms. Castor. And what are your recommendations then?
Dr. Woodcock. Well, what we had proposed is that we pick
off the highest risk category, which is those sterile products
that are shipped interstate. All right. So they are shipped
around the country. That is probably the highest risk, because
the longer you store the sterile product the more likely, if
they are contaminated, that there will growths that can grow
up. And obviously sterile products are a high risk. And
interstate is one sort of marker for volume.
And this industry that has grown up, the outsourcing
industry is valuable to hospitals. We have heard from the
hospitals. They feel they can't do without these folk. And they
generally take FDA-approved products and they mix them or they
put into convenience dosage forms. If you have gone to a clinic
in an office building and you have had a procedure, you may
have received products from one of these firms that put you to
sleep or whatever. And they package them, say, in syringes and
so forth and send them to these various clinics and also to
hospitals.
We feel that type of industry, they produce in pretty high
volume that is the highest risk. And they should have full
aseptic processing controls, just like the regular drug
industry does. So we agree with carving them out and having
certain requirements for them, but not submitting a new drug
application, having to pay a user fee, and going through that
entire process.
Ms. Castor. So highest risk, crossing State lines.
Dr. Woodcock. State lines.
Ms. Castor. Sterile products.
Dr. Woodcock. Right.
Ms. Castor. You recommend. And then to clarify your last
part regarding--what if it is a compounding that is going to
hospitals within a State.
Dr. Woodcock. Well, what we propose is that would be
regulated by the States. The States could decide whether they
have capacity to do that. I think you may hear from some of the
other witnesses that in fact that type of compounding,
especially at volume, because it is the mass production that
really increases the risk, both the risk of contamination and
the consequences of contamination once it occurs, because it
goes to so many people, right, and the risk is there for
intrastate, but the States we feel could decide whether they
would regulate those type of activities or not permit them,
right.
And then the traditional compounding is really where a
doctor--and I have done this too, all right--a doctor writes a
prescription to a pharmacy and asks them to, for an individual
patient who has a specific need, to make a dosage form that
isn't available commercially because they have a very specific
medical need for that. We feel that should be preserved, but a
box should be put around it and there shouldn't be competition
with established generic products. Because there is always more
risk than for a regular product for any of these compounded
products.
Ms. Castor. Thank you very much.
Mr. Pitts. Chair thanks the gentlelady.
Now recognize the chair emeritus of the full committee, Mr.
Barton, for 5 minutes for questions.
Mr. Barton. Thank you, Chairman Pitts.
I have very troubled, Dr. Woodcock, by your opening
statement. I do give you credit for integrity and honesty and
forthrightness. But you ended up saying that it is not if this
is going to happen again, it is when it is going to happen.
That is pretty strong. You are talking about people dying.
And I have attended, not in their entirety, but I have
attended every hearing that we have done on this issue with
NECC. And it is not that Republicans are not willing to
regulate, it is not that we are not concerned. It is that we do
think there is a true State-Federal partnership, and we do
think that State regulatory authority is as good as Federal if
it is within the State. And we don't see a reason to preempt
the States unless the States either can't do it or won't do it.
And what struck me in the answers to Dr. Burgess' questions
was at some point in the process anybody at the FDA could have
picked up the phone and called the State regulatory authority
and apparently never did.
Now, I don't understand that. If you really believe that
what you said is true, that it is not if it is going to happen
again, it is when it is going to happen again, if you have a
list of compounders that you think are problematic or in danger
of actually endangering human life, if you really think the FDA
doesn't have the authority to shut those people down or make
them clean up their act, you have an obligation, or somebody
that is designated by you, to call the State regulatory
authority to inform them of the problem and to take whatever
steps are necessary to make sure that the State does.
Now, why haven't you done that? Or why haven't people at
your agency done that? That is what I don't understand.
Dr. Woodcock. We have done that more recently. And we have,
as I said, we have worked hand in glove with the State
authorities. We have done joint inspections with them. They
have taken the steps to close down many of these pharmacies
after the inspection. And we are sending them our findings, we
send them letters. We post our 483s, which are our findings of
the inspection, so they that are available to the public. And
we work very closely with the State authorities.
However, there are 23,000 compounding pharmacies in the
United States, according to the industry. They don't have to
tell us who they are and they don't have to report to us if
they have problems. So we are----
Mr. Barton. Well, but they can't operate if they don't tell
you or don't tell the State. You are not telling me there are
23,000 compounding pharmacists that are operating out in the
ether and that are not subject or not licensed by somebody.
Dr. Woodcock. They are licensed by States. They are
licensed pharmacies. And I read a report by some of the members
who looked at what amount of control and tracking the States
have over the different pharmacies, and many States do not have
a lot of understanding of what activities those pharmacies are
engaged in, particularly whether they are shipping to other
States and so forth. Different patterns in different States,
but not all States really have close control over what those
pharmacies are doing as far as compounding.
Mr. Barton. Well, the witness that is in my district, Mr.
Harmison, I have been in his pharmacy. I mean, he is the true
small independent businessman. He has got a compounding room, I
think one or two rooms, and has two or three pharmacists,
including himself.
Now, I have also been in other compounding pharmacist
situations in Texas where they have 10 or 15. And it is much
more of a mass production-type situation. So there is a
difference. But the FDA, in conjunction with the States, should
be able to determine who has jurisdiction and what needs to be
done.
I don't think Mr. Pitts or Mr. Upton or any of the
Republicans are unwilling to sit down and help clarify, to use
your term, what needs to be done. If there truly is a gap and
it truly is best to regulate at the Federal level, I would say
that the Republicans are open to it. But if it is simply a
question of communication between the Federal Government and
the State regulatory authority, I would encourage you to
facilitate that communication, because I don't want ``if'' to
become ``when.''
Dr. Woodcock. Right. Well, we had a 50-State meeting. We
have been in close contact with the Association of National
Boards of Pharmacy. So we are talking to them twice a week. We
are talking to all the State boards in the States where we go
in and have these inspections. And, as I said, we do the
inspections with them.
We have heard from many States that they would prefer
Federal regulation of these larger-scale facilities. But the
real question here is and has always been the question is where
to draw the line. All right. So you have the traditional
pharmacist, they are compounding in response to a prescription.
I, as a physician, I have written prescriptions for compounded
products that were very valuable to my patients. That is one.
All right. And you mentioned, OK, then there is somebody, if
they have five rooms----
Mr. Barton. My time has expired, and the chairman has been
very gracious. We can work on helping define and helping to
clarify. I think there is a bipartisan trust on this committee
and this subcommittee that can do that, if you and the
stakeholders will begin to communicate with each other. I think
this is a solvable problem. But it is not necessarily the
answer it is going to be more Federal regulation. It may be,
but it is not automatic that it will be.
With that, Mr. Chairman, thanks your time, and I yield
back.
Mr. Pitts. Chair thanks the gentleman.
And now recognize the ranking member emeritus of the full
committee, Mr. Dingell, 5 minutes for questions.
Mr. Dingell. You are most courteous. Thank you, Mr.
Chairman. I ask unanimous consent to insert 2 letters which I
wrote to FDA in the record----
Mr. Pitts. Without objection, so ordered.
Mr. Dingell [continuing]. As well as responses from FDA.
And I thank you, Mr. Chairman.
[The information appears at the conclusion of the hearing.]
Mr. Dingell. Now, these questions will be mostly yes or no.
Does FDA have the authority to require all compounding
pharmacies to register with the agency?
Dr. Woodcock. No.
Mr. Dingell. Yes or no?
Dr. Woodcock. No.
Mr. Dingell. Please submit for the record the new authority
that you need.
Next question: Does FDA have the authority to require all
compounding pharmacies to report adverse events?
Dr. Woodcock. No.
Mr. Dingell. What authority is needed? Submit for the
record, please.
Does FDA have the authority to require all compounding
pharmacies to follow good manufacturing practices? Yes or no?
Dr. Woodcock. No.
Mr. Dingell. What authority is needed? Submit it for the
record.
Question four: Does FDA believe nontraditional compounders
should be subject to appropriate good manufacturing practices
the way manufacturers are? Yes or no?
Dr. Woodcock. Yes, as appropriate.
Mr. Dingell. What is the authority which is needed? Submit
for the record.
Does FDA believe risk-based inspection schedules are
appropriate for nontraditional compounders? Yes or no?
Dr. Woodcock. Yes.
Mr. Dingell. What authorities do you need to achieve that
end? Submit for the record.
Does FDA have full authority to see all records when
inspecting a compounding pharmacy? Yes or no?
Dr. Woodcock. I think that is being contested, as you know.
Mr. Dingell. Yes, you have that problem between the
different circuits.
Dr. Woodcock. Yes.
Mr. Dingell. Plus submit to us what authority is needed.
Does FDA need additional authorities in these areas to
ensure that outbreaks of the kind we have seen does not happen
again? Yes or no?
Dr. Woodcock. Yes.
Mr. Dingell. Yesterday, my colleagues in the Senate
advanced bipartisan legislation giving FDA more authority over
compounding pharmacies. It is my hope we in the House will do
the same thing. I have long believed that we must provide
agencies like FDA with clear authorities and necessary
responses to properly help and to carry forward their mission.
U.S. FDA has a fee system for the approval of pharmaceuticals
and medical devices, amongst others. Please inform us whether
you need that kind of authority, for purposes of the record.
Now, if we gave FDA the authority in this area, and I
believe we should, I believe we also should have a strong user
fee program. Would you submit for the record some information
justifying such thing if you believe that is appropriate,
Doctor.
Dr. Woodcock. Yes.
Mr. Dingell. Now, would the user fee contained in the
Senate bill provide the FDA with the necessary resources to
carry out these new authorities? Yes or no?
Dr. Woodcock. Partially, 50 percent.
Mr. Dingell. OK. Now, I have got just a little bit of time
left. I am reminded of the situation we have here. We have got
people being killed because we have unclear authorities. We
have a responsibility to see to it that we clarify that as a
part of our oversight responsibilities.
There is a great joke that they tell about a fellow who got
a letter from an undertaker saying that his mother, or his
mother-in-law, had just had a stroke and passed on. And he
asked for instructions. He said should we cremate, should we
bury, or should we embalm. And the guy thought for only a
second and he sent back a telegram saying, do all three, take
no chances.
Now, I think here we have got a problem where people are
being killed by a dichotomy in the industry. And, Doctor, I
want you to tell me, you have roughly three classes of
compounders. Right? You have got essentially the manufacturing
compounders who ship all over the country, huge volumes. Right?
Dr. Woodcock. Correct.
Mr. Dingell. You don't have very clear authority over them,
do you?
Dr. Woodcock. No.
Mr. Dingell. And the States don't have the resources to do
it, do they?
Dr. Woodcock. That has been documented.
Mr. Dingell. OK. Now, having said that, you also have the
ordinary pharmacies. We are not particularly after them. And
they are supposed to be regulated by the States. They are
licensed by the States. And they are identified by State
regulations to the States. Right?
Dr. Woodcock. Yes. We believe the traditional practice of
pharmacy compounding should be preserved and regulated by the
States.
Mr. Dingell. OK. Now, then we have the additional situation
where you have the hospitals. And they have either in-house or
they have people who contract with them to compound them to
meet the specific needs of patients in the hospitals. Right?
Dr. Woodcock. Correct.
Mr. Dingell. What authorities do you need there?
Dr. Woodcock. Well, we believe that the hospitals could
operate under the regular rules of pharmacy. These are hospital
pharmacies that are licensed by the State and also regulated by
other authorities. We believe that outsourced contractors
should be regulated under the compounding manufacturing.
Mr. Dingell. So here now you have a muddled situation where
the courts are getting in and assisting us to confuse an
already obfuscated situation, and we need to do something to
clarify it. And since the great events in Michigan, where a
bunch of my constituents and others were killed, we have seen
that the compounders have continued their same merry practices
of disregarding the law and proceeding to send noxious
compounds around that are compounded in unsafe atmospheres and
climates. Is that right?
Dr. Woodcock. We have seen since the outbreak----
Mr. Dingell. Yes or no?
Dr. Woodcock. Yes. Yes.
Mr. Dingell. Mr. Chairman, I have used 44 seconds too many.
Thank you.
Mr. Pitts. Chair thanks the gentleman.
Now recognize the gentleman from Virginia, Mr. Griffith, 5
minutes for questions. Mr. Griffith, you are recognized for 5
minutes.
Mr. Griffith. Thank you, Mr. Chairman.
Thank you, Dr. Woodcock.
I am looking at your draft, not for implementation report
on pharmacy compounding that was done in August of this year,
and I want to clarify this court issue. Disagree with me and
tell me yes or no, I will ask you at the end of each part of
this. But it appears that in April of 2002, based on this
report, and I believe it to be correct, that the U.S. Supreme
Court affirmed the Ninth Court's decision related to
advertising and solicitation, but did not take up the
severability as to whether or not the rest of the act would be
in place after that date. Is that correct?
Dr. Woodcock. My understanding, yes.
Mr. Griffith. And is it also correct that the Fifth Circuit
found it was severable, and that decision came out in 2008?
Dr. Woodcock. Correct.
Mr. Griffith. The FDA took no action--am I correct the FDA
took no action to clarify the law between 2002 and 2008 when
the Fifth Circuit came out with their opinion, isn't that
correct? Yes or no.
Dr. Woodcock. Yes.
Mr. Griffith. And it would also be correct that from 2008
until the incident with the fungal meningitis, the FDA never
came to Congress and said we need clarification, isn't that
true? Yes or no.
Dr. Woodcock. Yes.
Mr. Griffith. And isn't it true that you were working on
these draft guidelines because you believe there was a way to
figure out around the court decision issue and regulate to the
best of your ability with the Ninth Circuit being a little more
difficult but that is why you worked on these guidelines for
over 3 years; isn't that correct?
Dr. Woodcock. As I said, we were trying to make the best of
a bad situation.
Mr. Griffith. Wouldn't the right thing to have done to have
come for clarification on the severability and just reenact the
old law and take the advertising section out, the only part
that any court said actually violated the Constitution and the
whole issue was severability; wouldn't that have been the
better thing to do from 2002 until 2012?
Dr. Woodcock. Yes, I think in retrospect that would have
been better. I think there was a fear getting a worse----
Mr. Griffith. Was there a fear of coming to Congress and
asking for help when you needed it?
Dr. Woodcock. Well, you know, the late Senator Kennedy did
develop a bill and asked around about it with some other
Senators and there was so much opposition that they never
introduced that. And I think that was----
Mr. Griffith. Did the bill do anything other than clarify
that the bill could be severed and that the only parts that
weren't in place or should be in place were the advertising
restrictions?
Dr. Woodcock. I am not familiar with what exactly it is.
Mr. Griffith. Because I don't know what was in that bill
and I suspect there was something other than clarifying the law
was in there.
Dr. Woodcock. Oh, yes.
Mr. Griffith. And I would have to say in the draft guidance
that you all were about to propose the FDA defined a new
framework for compounded drugs that would be administered in a
health care setting and basically what you proposed was was
that you could compound for more than one patient in the
hospital setting or in a medical practice setting as long as
there was a prescription that followed if you knew you were
going to use it in like in an ophthalmological setting or in a
hospital setting as long as you could tie that later to a
direct patient, isn't that correct?
Dr. Woodcock. That is my understanding.
Mr. Griffith. And so under that reading of that, other than
clarifying that the advertising section is no longer the law,
you really didn't need any new authority to do that, did you?
Dr. Woodcock. To make that interpretation?
Mr. Griffith. Yes or no? To make the interpretation.
Dr. Woodcock. I don't understand your question.
Mr. Griffith. It is in your guidance request so I assume
that is correct. Is that correct?
Dr. Woodcock. That is correct.
Mr. Griffith. And I appreciate that. And I am looking up to
see how much time I have left.
We also have this business about talking to the States.
There is nothing that prohibited you in the law from talking to
the States when you got complaints from say Colorado or Ohio,
which actually happened in the NECC case, nothing prevented you
from calling Massachusetts, did it?
Dr. Woodcock. No.
Mr. Griffith. And, in fact, in the guidelines you are
setting up a new way to make that work so it is efficient,
isn't that correct?
Dr. Woodcock. The guidelines----
Mr. Griffith. The guidelines of sharing information between
the States and making sure that everybody is keeping an eye on
these folks.
Dr. Woodcock. The guidance, hmm, yes.
Mr. Griffith. So you didn't need any new authority to do
that, did you?
Dr. Woodcock. We don't need authority to talk to the
States. We do that all the time in many different areas of
regulation.
Mr. Griffith. But you failed to do that in the NECC matter,
and I guess my concern is, is that while I too have learned to
respect your veracity and think you are a great witness, much
better than that other lady that came in here, we couldn't get
anything straight out of her, so I do appreciate it--but I
would have to say that one of my concerns is that the FDA had
all these tools available to it, if it had chosen to do so and
I understand people make mistakes, things happen, I understand
that, I am not being critical, but instead of asking for new
authority shouldn't we just clarify the fact that the
advertising restrictions aren't the law, and that if there are
areas that need to be clarified, not giving new authority but
just clarifying some things, that we could follow your guidance
proposal from August of last year and come up with a pretty
good proposal, isn't that true? Yes or no.
Dr. Woodcock. No. I don't think so.
Mr. Griffith. So that was a bad proposal that you all were
putting guidelines out on?
Dr. Woodcock. The guidance----
Mr. Griffith. Yes or no. Were those guidance proposals bad?
Dr. Woodcock. They were based on the 503, which is not
really that workable for the current industry that we have. I
am sorry I can't give you just a ``no'' answer. I don't think
we have a good----
Mr. Griffith. All right. I am out of time so if you could
submit your recommendations I would greatly appreciate it.
Mr. Chairman, I yield back.
Mr. Pitts. The chair thanks the gentleman, and now
recognize the gentleman from Texas, Mr. Green, 5 minutes for
questions.
Mr. Green. Thank you, Mr. Chairman.
Dr. Woodcock, thank you for being here today, and I am
concerned that the majority side has looked at this issue and
said the FDA has the necessary authority to properly regulate.
As Commissioner Hamburg explained at the last meeting, the
current level of scrutiny being applied by the FDA is a result
of the outbreak. The court case may be strengthened, but a
favorable ruling on the authority over compounding
manufacturers and non-traditional manufacturers is far from
certain.
As a result, I think we must pass limited legislation that
allows the FDA to regulate compounding manufacturers across
State lines. The draft currently being debated in the Senate is
a good first step, but I think there are some changes we could
made to strengthen the bill.
In her testimony before the committee, and I won't judge on
Commissioner Hamburg's testimony, asserted the agency needs
greater authority over large compounding pharmacies that are
essentially manufacturers. The Senate legislation would create
a new category of compounding manufacturers that would be under
FDA regulatory authority.
Commissioner Hamburg also told us that the FDA agrees that
the regulation of a traditional pharmacy compounding should be
left to the State legislators and State boards of pharmacy. We
have laws in my home State of Texas that allow when medically
necessary and in very limited circumstances a compounding of
medications before the receipt of a patient specific
prescription for administration in the office of the
prescribing physician. Those are called office use compounding.
It is my understanding a majority of States have these similar
laws.
Dr. Woodcock, what do you recommend that Congress craft or
how do you recommend that Congress craft language to give the
FDA the necessary authority to regulate large, interstate
compounding manufacturers while still preserving the ability of
States to regulate the traditional compounders?
Dr. Woodcock. It is a complicated question. We want to make
sure that the traditional compounders can flourish because they
provide a valuable service but not that they don't go to 20
rooms or 50 rooms, right, and start making large scale. So
there have to be boundaries there.
Traditional manufacturers, obviously, have to submit
applications to FDA, pay user fees and then undergo review and
frequent inspections for GNPs. The hospitals have told us, the
hospitals in your district and all around the country have told
us that they rely on this industry now for the compounding
manufacturing industry, if you wish to call it that, for
certain services that used to be done in the hospitals but are
now outsourced. However, these operations are proceeding under
the rubric compounding right now but they are doing something
quite different and in a larger scale. And so if Congress would
see fit, what we are saying is not we want more regulation, we
want regulation that would fit this new activity, right, and
would be appropriate for that and allow them to flourish.
Mr. Green. I only have a couple minutes. For example, if a
hospital in Houston wants to contract with a company in
Massachusetts, that still should be under FDA authority.
Dr. Woodcock. For sterile products is what we are
proposing, so if they want to get injectables from a New Jersey
firm, they want to buy injectables and use it in their hospital
or in their clinic, we think that should be under FDA authority
if those are sterile products.
Mr. Green. OK. Do you agree that legislation should clarify
the current law in the area and protect the ability of States
and boards to decide what is the appropriate scope of practice
for traditional pharmacies?
Dr. Woodcock. Absolutely.
Mr. Green. Including the areas of anticipatory and office
use compounding?
Dr. Woodcock. Well, we have to make sure that it draws the
line and doesn't allow them to produce, say, and how do you do
that, is 17,000 vials, is that anticipatory compounding? You
have to have some clarity on that.
Mr. Green. It seems like it would be. What is the FDA's
position on office use compounding pursuant to State law where
it occurs? Under the current Federal law, FDCA, and under the
legislation being considered in the Senate?
Dr. Woodcock. Well, right now, under current Federal law it
is blurry, all right, as far as how much you could make? You
all are saying to me that you think you can tell what a
manufacturer is but there is no bright line in the statute that
says when you cross that line and become a manufacturer.
Mr. Green. And that is our job to define that.
Dr. Woodcock. That would be very useful.
Mr. Green. The other thing I am concerned about is
traditional compounder in an area that is close to State
boundaries. Again in Massachusetts with New England there is
maybe a different problem whereas in Texas it is not that big a
problem except along our border with other States.
How do we keep those traditional compounders from being
classified if they work across State lines, geographically
fairly close, from being classified as a compounding
manufacturer?
Dr. Woodcock. Well, we think there are some Federal
standards that ought to be in place, OK, that distinguish even
a traditional compounder so that there are certain things that
they are held to do and then they remain traditional
compounders.
Mr. Green. Thank you, Mr. Chairman. I appreciate it and
look forward to working on the legislation.
Mr. Pitts. The chair thanks the gentleman. I now recognizes
the gentleman from Pennsylvania, Dr. Murphy, 5 minutes for
questions.
Mr. Murphy. Thank you for being here, Dr. Woodcock, I have
the highest respect for you and I appreciate your candid
conversations.
I want to cut to the chase here because I don't want this
to be a political discussion and I think it is being mislabeled
as that.
I held hearings in my Subcommittee on Oversight and
Investigation and it was my impression we weren't getting clear
answers about missteps within the FDA. And I just want to make
sure that I know that the FDA is saying we have learned from
our problems and here is how we change.
So let me run through a series of questions with you and
help get that on the record.
First of all, the FDA has repeatedly cited the fact that
the Fifth and Ninth Circuit Courts of Appeals have issued
conflicting decisions on whether section 503A of the Food, Drug
and Cosmetic Act remains valid, and in a written statement on
November 14th of last year oversight committee hearing
Commissioner Hamburg cited the Circuit Court's split as having
``amplified the perceived gaps and ambiguity associated with
FDA's authority over compounding pharmacies.''
Now the Fifth Circuit Court decision was July 2008, is that
correct?
Dr. Woodcock. Right.
Mr. Murphy. In May 2009, just prior to Commissioner Hamburg
being confirmed, a briefing was provided to Acting Commissioner
Joshua Sharfstein proposing several paths forward in light of
the Fifth Circuit's decision upholding 503A.
Do you recall participating in that briefing? Yes or no.
Dr. Woodcock. No.
Mr. Murphy. The FDA produced to the committee an email
chain from the Office of the Chief Counsel from July 2009. A
copy of this document I think is now in front of you. The top
email is from Michael Landa, FDA's Acting Chief Counsel at the
time, and notes the plan is to enforce section 503A nationwide
except in the Ninth Circuit and that, quote, Josh is on board,
unquote.
Mr. Landa then notes that Dr. Sharfstein, quote, would
touch base with Peggy but did not think she would have any
objection, unquote. Do you know whether or not Commissioner
Hamburg was consulted in the decision to proceed with
enforcement of section 503A?
Dr. Woodcock. I do not know affirmatively, no.
Mr. Murphy. Do you suspect that she did or----
Dr. Woodcock. I would suspect that she was.
Mr. Murphy. Thank you. And if you turn to the second page
of that email chain, the leader of the compounding team in
FDA's drug center, your center, notes that Dr. Sharfstein and
Deb Otter asked to chart the timeframe for each step we plan to
do to implement the new plan.
Dr. Woodcock, this plan had yet to be implemented when the
outbreak began in September, 2012, am I correct?
Dr. Woodcock. That is correct.
Mr. Murphy. And yes or no, prior to announcing the new plan
FDA felt as though it needed to draft a new guidance document
detailing the approach it would be taking as well as various
regulations that 503 required? Yes or no.
Dr. Woodcock. That is my understanding.
Mr. Murphy. Thank you. And yes or no, during this time
period inspections and enforcement actions came to a
standstill.
Dr. Woodcock. My understanding is that it is not true, that
we did certainly went for cause inspections.
Mr. Murphy. Certainly with NECC.
Dr. Woodcock. I can't comment specifically on NECC. I am
sorry.
Mr. Murphy. Is that----
Dr. Woodcock. Due to the ongoing criminal investigation.
Mr. Murphy. I understand. By August 2012 your center signed
off on another draft guidance document that was going through
final clearance, yes or no.
Dr. Woodcock. Yes, my understanding.
Mr. Murphy. Thank and a briefing has been had, in fact been
scheduled to discuss the new guidance documents with
Commissioner Hamburg back in September 2012, is that correct.
Dr. Woodcock. That is correct.
Mr. Murphy. And yes or no, Commissioner Hamburg testified
before O&I that she was really not that aware of issues related
to drug compounding until after the meningitis outbreak;
therefore, would any additional changes to this draft document
guidance have been made based on Commissioner Hamburg's input.
Dr. Woodcock. I don't know. That would be speculation.
Mr. Murphy. OK. The point is the agency had a solution here
that would have allowed it to conduct inspections was my
understanding. But so the FDA failed to even acknowledge the
existence of this guidance document until it produced it to
this committee in March of 2013, well after the FDA promoted an
entirely new regulatory paradigm.
Here is where I want you to help clarify this for all of
us. My question is what does FDA now know about the compounding
industry that it did not incorporate in this guidance document
and is provided as a learning experience to make some changes?
You may respond.
Dr. Woodcock. What we have seen as we have done inspections
of this industry, we have focused on the highest risk areas and
we have seen violations of aseptic processing, that basically
mean that there is no insurance of sterility of the products
coming out of these compounding pharmacies.
And this means that this outbreak that we have seen will
happen again. Since the outbreak, we have had an instance of
fungal bodies being observed in an IV bag ready to be given to
a cancer patient, all right, that came from a compounding
pharmacy. We have also had other instances of patients having
eye infections and other instances of non-sterility of
products. So we have had harm as well as the nonsterile
practices that lead to the harm.
Mr. Murphy. With regard to the way that FDA approaches
these things and I understand you are looking for more
authority to handle some things but what we really need to know
is within the realm of the authority you already had--and I am
not asking you to hang anybody out right now, that is not the
purpose of this hearing--but are there internal lessons that
the FDA has learned they could have handled some things
differently that could have possibly led to different results
other than dealing with the lawyers' issues here.
Dr. Woodcock. Well, I think we should have been more
aggressive. There was great concern about our, the limitations
of our authority and that we would lose and then have even less
ability to influence this industry. But in retrospect I think
it would have been more important to simply go forward and see
how it turned out in the courts, aggressively exert our current
authority, which is primarily new drug authority.
Mr. Murphy. Thank you. That is why I like hearing from a
physician instead of a lawyer. I will need to submit these e-
mails for the record if that is all right, Mr. Chairman.
Mr. Pitts. Without objection, so ordered.
Mr. Murphy. Subject to redactions by staff.
Mr. Pitts. The chair thanks the gentleman and now
recognizes the gentlelady from California, Mrs. Capps, for 5
minutes for questions.
Mrs. Capps. I believe--am I before Mr. Engel?
Mr. Pitts. Yes.
Mrs. Capps. Oh.
Mr. Pitts. We are going in order of appearance.
Mrs. Capps. OK, all right. I thank you. I just want to
thank you for your testimony today, Dr. Woodcock, and I want to
thank Mr. Pallone for holding this necessary hearing. This is
an important issue and I believe needs to be revisited.
Under current statute, a great deal of uncertainty and
variation exists between regulations. And this uncertainty
creates gaps that can lead to compromised patient safety, as we
have seen most recently with the meningitis outbreak. We cannot
wait for another public health crisis to act, and what we have
right now isn't working.
Dr. Woodcock. Right.
Mrs. Capps. I believe you would agree. Families don't have
the peace of mind they are receiving effective drugs that they
can trust and compounding pharmacies across the States are not
on a level playing field. Many States are inadequately
inspecting facilities. After a similar incident in my State of
California almost a decade ago, regulations were enhanced and
sterile compounding pharmacies now require an inspection or
accreditation through a national agency. You know, this isn't
good enough because many hospitals and clinics in California
buy drugs from out of state, compounding pharmacies in other
States, including the Massachusetts pharmacy. So hospitals and
States don't exist in isolation. Hospitals have a great need to
be able to buy large quantities of compounded drugs.
Mr. Migliaccio suggests in his written testimony that there
should be no special regulatory program for these large scale
drug compounders. Instead he implies that they should be
treated like conventional drug manufacturers and should have to
go through the new drug application process to manufacture and
distribute any drugs.
My question now, Dr. Woodcock, could you explain to us why
you believe requiring new drug applications for all drugs would
not be warranted and what the consequences would be
particularly for hospitals if FDA were to take such an
approach?
Dr. Woodcock. Well, that approach would be our current
authorities. It is not that we don't have current authorities.
Our current authorities require submission of applications,
payment of a user fee, thanks to the user fee bill you all
passed for generics recently, and we have had the new drug one
for a while, and review of all the information, a large package
submitted to the agency, and then we inspect those facilities
frequently, including a preapproval inspection to make sure
everything is OK before the product gets out on the market. So
that is our current authorities.
Now many of these outsourcers, what they are actually doing
is taking FDA approved products and putting them into
convenience forms or putting them into, combining them, say for
hyper alimentation or something like that, and then shipping
them around the country based on patient need.
The industry has basically told us that they can't make all
these different very patient specific forms and convenience
forms. And there are questions of efficacy that are related
because these are already FDA approved products. The key is,
and this used to be done by the hospital pharmacy, by the
clinic they would do this. I did this when I was an intern, all
right, when the interns were able, had to be kind of worker
bees. So we made up the chemotherapy, we put things into bags
and the nursing staff would do this as well or the hospital
pharmacy.
Now, with the very large scale of medicine they want to buy
these, and many of the clinics are in office buildings, they
don't have a pharmacy or clean room there. So they need to
order these products, right.
Mrs. Capps. I want to get to another question.
Dr. Woodcock. I am sorry. It is so complicated. Let me
finish then. So there isn't good regulatory fit right now. It
isn't where we say we have to have all these broad new
authorities, no, there is no fit for this industry that has
grown up.
Mrs. Capps. All right. I want to make sure that I am able
to enter a statement from the American Society of Health System
Pharmacists which addresses this issue as well. Their statement
details the many ways in which hospitals have come to rely on
compounded medications from outside compounding pharmacies
which you are alluding to.
And I want to ask that this statement that I am holding up
be entered into the record.
Dr. Woodcock, if there is a time for you to address this,
would a two-tiered regulation system that clarifies a uniform
set of rules for compounding manufacturers while preserving the
State's role in traditional pharmacy compounding be a practical
thing?
I will just let you comment on that.
Dr. Woodcock. Yes. We have proposed something like that as
something that would be practical but it would require a new
regulatory scheme for this new industry that has evolved to
make sure they are making the product safely. It is no good to
have convenience products if they are contaminated or they are
super potent or there are other things wrong with them.
However, of course that is up to Congress whether they want
this industry to persist because our current regulatory
authorities require submission of application.
Mrs. Capps. I see. OK, thank you. I yield back.
Mr. Pitts. And did you want to submit that for the record?
Mrs. Capps. Yes, I would like to.
Mr. Pitts. Without objection so ordered.
The chair recognizes the gentlelady from North Carolina,
Mrs. Ellmers, 5 minutes for questions.
Mrs. Ellmers. Thank you, Mr. Chairman, and thank you, Dr.
Woodcock, for being here today. I just want to clarify a few
terms because we are putting terms out and I want to make sure
I am understanding them. When we are talking about traditional
compounders, who are we talking about?
Dr. Woodcock. We are talking about pharmacies, licensed
pharmacies who react to a prescription for a specific
individual patient and make a specialized dosage.
Mrs. Ellmers. And right now that is under the authority of
the State, not under FDA, correct?
Dr. Woodcock. Correct.
Mrs. Ellmers. And when we are talking about the compounding
manufacturers, how is that different from the term drug
manufacturers.
Dr. Woodcock. Compounding manufacturers is a new term that
is contained in the Senate bill, OK----
Mrs. Ellmers. Right, so this is Senate language.
Dr. Woodcock [continuing]. To reflect this large scale
industry. They are not usually reacting to a prescription. They
are making things that hospitals need and order frequently so
they make them at large scale like a drug manufacturer. But
often they are not--a drug manufacturer starts from scratch.
They start from what we call the active pharmaceutical
ingredient, which often someone will buy from India or China,
bring it in, test it and then make the product.
Mrs. Ellmers. So sometimes it may be in a different form
but is it not the same product, and you are saying that because
products might be coming from somewhere else that that is the
essential difference?
Dr. Woodcock. No, there are two different activities that
are lumped under this compounding manufacturing. One is what we
call the outsourcers, OK, they get generally outsource from a
hospital or clinic, something the clinic or hospital pharmacy
used to do, all right, and that is putting things in syringes,
little IV bags, diluting chemotherapy, getting everything all
right so they can just hang it on the patient rather than
having to do that----
Mrs. Ellmers. Rather than having to actually do it in
house. Now----
Dr. Woodcock. That is one. And then the other is people who
are doing larger scale compounding.
Mrs. Ellmers. Larger scale. And that would currently fall
under the jurisdiction of the FDA.
Dr. Woodcock. That is what kind of is under dispute.
Mrs. Ellmers. And that is what we are trying to get to is
when do we make that distinction between compounding pharmacy
and compounding manufacturer.
Dr. Woodcock. And also a manufacturer who is already a
pharmaceutical company has to submit an application to FDA and
be under that regime.
Mrs. Ellmers. Now, currently, so basically the compounders
have the same regulations and requirements as the drug
manufacturers? Yes or no?
Dr. Woodcock. No.
Mrs. Ellmers. And I am not just talking about numbers but I
am just talking about regulations again, is this State versus
Federal, is that the main difference that we are talking about?
Dr. Woodcock. The States regulate pharmacies. They license
pharmacies and these activities right now occur all in licensed
pharmacies.
Mrs. Ellmers. OK. What are the changes to compounding you
propose making in order to prevent the meningitis outbreak last
year to ensure compounded products are safe? If you can just
quickly give us an idea of what you would like to see.
Dr. Woodcock. Well, limit the traditional compounding to
more or less reaction to a prescription, OK, and compounding
something for a specific patient, that is traditional
compounding. And don't allow compounding of really complicated
dosage forms that even the traditional manufacturers have
trouble making. Then we are saying establish a new group, the
compounding manufacturers is what the Senate called them. They
don't get prescriptions, but they have to register and list
with FDA. Tell us who they are, what they are making and where
they are located, right, and then they have to submit adverse
events to us. And they would be subject to proper GMP
requirements to make sure they make safe products, OK, but they
wouldn't have to submit applications to us.
Mrs. Ellmers. But you did mention application process a
moment ago. Can you repeat that?
Dr. Woodcock. Sure. Some of the members are talking we have
current authorities, yes, we do have authorities. Our
authorities are you are a new drug manufacturer or a generic
drug manufacturer, you must submit an application to us. You
must a pay user fee or you should not be producing drugs in the
United States.
Mrs. Ellmers. So once that application process is
fulfilled, that, it is just so that you know that that
particular facility exists and what their plan of action is?
Dr. Woodcock. I am sorry, it is really hard to do this.
That is our current authorities. That is how we regulate
generic drugs and new drugs in the United States, all right,
through that process. That is not what compounding is.
Mrs. Ellmers. OK. Now let me ask this question. The number
and how much a parmacy is making seems to be the issue of where
it falls, what jurisdiction. In your own words, where do you,
where would you see that line of action? What do you see, how
much product can a compounder make without being designated a
manufacturer?
Dr. Woodcock. That is what we have been struggling with
since the 503 was passed, OK, there is no line in there in the
statute. And so what is an inordinate quantity? We don't know.
Is it 10 units? Is it 1,000 units? Is it 17,000 units? So we
have endeavored to use other criteria to say, OK, when you
would be subject to Federal jurisdiction.
Mrs. Ellmers. Well, my time is expired but obviously that
is the main question here. So thank you.
Dr. Woodcock. We would be happy to work with you.
Mr. Pitts. The chair thanks the gentlelady and now
recognizes the gentleman from New York, Mr. Engel, 5 minutes
for questions.
Mr. Engel. Thank you, Mr. Chairman.
Dr. Woodcock, thank you for the good work that you do. We
appreciate it very much.
Dr. Woodcock. Thank you.
Mr. Engel. I want to first ask a New York question. New
York, it is my understanding that New York has no licensing
requirements specific to compounding pharmacies and according
to the National Conference of State Legislatures there is no
requirement that New York pharmacies comply with the U.S.
Pharmacopeia chapter 795 or 797 compounding standards and
according to the Pharmacy Compounding Accreditation Board,
which accreditation is entirely voluntary, they say there are
only 10 pharmacies in all of New York accredited for pharmacy
compounding.
So that being said, I am pleased that no New York
pharmacies were included as part of the FDA's most recent risk-
based priority inspections of 31 sterile compounding
pharmacies. So what I want to ask New York specific is, does
the FDA know which pharmacies in New York are compounding
medications?
Dr. Woodcock. We have no way of nothing in any State, OK,
we have been told by the industry that there are 23,000
pharmacies that may engage in some form of compounding across
the country, but we don't know who they are, where they are or
what they are making, because they don't have to tell us.
Mr. Engel. So I assume then that the answer would be ``no''
to this, does the FDA currently have the authority to collect
and test samples or examine the records of a compounding
pharmacy in New York? And can you elaborate on why this
information is critical for public health and safety?
Dr. Woodcock. Well, we do believe we have the authority to
go in and get samples and look at records but it has been
contested.
Mr. Engel. OK. Thank you. I am intrigued by the part of
your written testimony which lays out a proposed risk-based
framework for a new legislative approach to compounding to
ensure patient safety and health.
First, you proposed dividing the world of compounding into
non-traditional compounders which would be subject to FDA's
jurisdiction and traditional compounders who would remain under
State oversight.
Is there a concern that non-traditional compounders may
create a category of pseudo drug manufacturers? And if so, how
do you protect against that?
Dr. Woodcock. Well, there is a concern that traditional
manufacturers could actually be drug manufacturers in disguise
and that non-traditional manufacturers could be. And for
traditional we really feel that prescription requirement and
the statement of medical need for the patient is important, for
non-traditional we have proposed a series of things, including
that they would register and list with us so we would not who
they are and also not make copies of commercially available
drugs.
Mr. Engel. You mentioned the need for sort of do not
compound list as part of this framework. Can you explain why
this is necessary and why you cannot do this using your current
authority?
Dr. Woodcock. Yes. Well, we feel that products say we have
withdrawn from the market for reasons of safety should not be
allowed to be then compounded and U.S. citizens would then be
exposed to them again. And we are seeing this now as you know
in dietary supplements, we have to go after them because they
sneak in drugs that have been pulled off the market, all right.
So that is one category.
Another category might be very difficult to manufacture
dosage forms where the pharmaceutical industry that has a lot
of science available to them and a lot of engineers and
scientists still have trouble making them reliably, some of the
patches, some of the inhalers and so forth.
Mr. Engel. You sort of touched on this, but can you
elaborate further on what steps the FDA is taking now utilizing
the authority that you believe the that FDA has to conduct
improved oversight over compounding pharmacies?
Dr. Woodcock. Well, it is more oversight on whether it has
improved because we are having to go to the ones we read about
or we know about or we have had prior actions and we are doing
a risk-based approach and going to those pharmacies as well as
going to pharmacies where you have had reports of problems
recently, all right, and for cause type of inspections.
And as I said, we are going in with the States, the State
board of pharmacy, their investigators, we often do an
inspection together and we are taking very aggressive action.
But we do not, for example, have recall authority, we cannot,
we don't have the authority, we don't have recall authority for
any drugs, right, and we do not have the authority to shut
these pharmacies down, they are licensed by the State, but we
have shared full information with the States, and they have
shut 11 pharmacies down as a result of the findings in these
inspections.
So that is improved oversight, but we will see about if we
go to court like what kind of response we get from the courts
as far as our authority.
Mr. Engel. Well, again thank you for the good work that you
do. And I especially appreciate your testimony here this
morning. It is concise, it is to the point. When we ask a
question you respond very pointedly and it is very much
appreciated. Thank you.
Dr. Woodcock. Thank you.
Mr. Pitts. The chair thanks the gentleman. The chair now
recognizes the gentleman from New Jersey, Mr. Lance, 5 minutes
for questions.
Mr. Lance. Thank you, Mr. Chairman. And good morning to
you, Doctor. You stated to Dr. Murphy that if you had it to do
over, you might move more aggressively regarding the situation
that, unfortunately, occurred, is that accurate?
Dr. Woodcock. Well, I think we would have moved
aggressively as we are now against all pharmacies. There was no
way to predict at any time which of these pharmacies will cause
this problem. And as I said, it will happen again because the
conditions under which these sterile products are manufactured
are not acceptable and the products are contaminated.
I have learned, what I have learned from this is the
resilience of the human body to microbial invasion because we
have cultured many samples from these pharmacies and we have
grown organisms. And we haven't had outbreaks and that is
because both the human body can repel them and because some of
them aren't human pathogens.
Mr. Lance. Thank you. This is a very complicated subject
and certainly I think answers require more than ``yes'' or
``no.''
Dr. Woodcock. I am sorry.
Mr. Lance. And you don't have to be sorry at all, I think
that this is extremely complicated.
One of the difficulties as I read the background
information is the split in the circuits.
Are you advised by attorneys at the Department of Justice
on these matters or do you have attorneys at your own agency
regarding the significant split between the Fifth and the Ninth
Circuit and the Supreme Court decision?
Dr. Woodcock. We have our staff attorneys that belong to
the Office of General Counsel at HHS and they are the FDA
branch of that, and then they work with the Justice Department
as well.
Mr. Lance. Perhaps you are not the appropriate person to
ask, but it seems to me, speaking as an attorney, that there
needs to be much greater clarification so that there can be one
standard across the Nation and not a split between the
circuits, with the Supreme Court decision that did not answer
the question fully.
Would that be your understanding?
Dr. Woodcock. That is my understanding. I am not a lawyer,
but I appreciate clarity when I try to perform regulations.
Mr. Lance. And I would hope moving forward in our
responsibilities to protect the health of the Nation in
conjunction with your responsibilities that we could work
together to clarify the situation.
I have 2-1/2 minutes, and I defer to Dr. Burgess.
Mr. Burgess. I thank the gentleman for that. Well, Dr.
Woodcock, what is it about the Exserohilum fungus that rendered
it such a bad actor? You said sometimes the human body actually
can resist these things, sometimes they don't even register.
But Exserohilum was a bad one.
Dr. Woodcock. Let me talk in general so I am not talking
about NECC, but clearly it is the amount of bioburden of the
contamination and that is why shipping these--bioburden means
how many organisms are in there, OK, for the nonclinicians in
the room--and so shipping something around unrefrigerated,
which is happening a lot, OK, if you happen to get something in
there, it gets a long chance to grow, all right. If you put it
in a part of the body that is sort of protected from the immune
system a little bit or is particularly vulnerable, if you
inject with a steroid, we have had multiple outbreaks where
there is an injection with a steroid and of course steroids
suppress the immune system so then that weakens that part of
the body and even systematically weakens the body's ability to
respond to infectious attack because of the actual medicine
that has been given. But we have had sepsis from IV products.
Nine people died in 2011.
Mr. Burgess. Let me just stop you there because we could
obviously could go on. But that is significant because you have
a steroid which inhibits fighting infection, you have a space
in the epidural space that is relatively protected from white
blood cells and things that normally fight infection, it is
preservative-free because it is going into the epidural space
if you had preservatives that would be bad for nerves so.
Dr. Woodcock. High risk.
Dr. Burgess. So it is the confluence of bad events. So you
know this stuff is high risk.
On the issue of manufacturing, I just have to tell you
looking at the notes compiled by the other subcommittee,
Oversight and Investigations, going back to May 10, 2012, when
the Colorado Board of Pharmacy issued to NECC a cease and
desist order and the same day FDA's Denver office informed New
England the cease and desist order, New England compliance
officer responsible for NECC spoke to an optometrist with the
U.S. Department of Veterans Affairs inquiring about whether or
not they could use NECC to repackage Avastin. This
communication is significant because once again it confirms
that FDA understood that NECC was acting like a manufacturer
not a traditional compounding pharmacy. An email response ``I
did not think they could use firms if profiles were
unacceptable. NECC Framingham is profiled as a manufacturer
because we determined that they are a manufacturer and not a
compounding pharmacy,'' an email from the compliance officer
for the New England district to FDA May 11, 2011.
Dr. Woodcock. Well, I am not going to argue with you about
this particular case because I can't talk about the case. But
clearly the decision about whether a firm is making, is making
product legally under 503A would be for the courts ultimately,
all right, that is just how it was set up.
Mr. Burgess. But under the Food, Drug and Cosmetic Act, if
I may, you have the regulatory authority over manufacturers and
your own compliance officers identified NECC is a manufacturer,
acts like a manufacturer, walks like a manufacturer, they are a
manufacturer.
Mr. Chairman, I will yield back.
Mr. Pitts. The chair thanks the gentleman and I now
recognize the gentleman, Mr. Butterfield, for 5 minutes for
questions.
Mr. Butterfield. Thank you, Mr. Chairman. And thank you,
Dr. Woodcock, for your testimony today.
I will be brief. The hour is certainly getting late. But in
studying this issue, Mr. Chairman, it seems that the FDA lacks
clear direction and clear authority over what can be done once
a compounding pharmacy is found to have failed to meet the
standards.
And so, Dr. Woodcock, after the meningitis outbreak at the
New England Compounding Center about a year ago, FDA increased
its inspection of compounding pharmacies. I think that is true.
The findings by Federal investigators have been alarming. And
hopefully there will be more aggressive investigations.
I want to take you to the subject of sequestration. FDA is
understaffed, underfunded and stretched very thin, at least
that is what we have been told. How are the cuts from
sequestration hindering the FDA and your inspectors from
conducting the thorough oversight that is critical to patient
health?
Dr. Woodcock. Well, don't forget, the Energy and Commerce
Committee overall have been very concerned that we haven't been
to manufacturers overseas, traditional drug manufacturers, and
that has been partly due to our resource limitations. Now we do
have the user fee, the Generic Drug User Fee Act, and that will
allow us to increase our inspectors who go overseas but my
point is even the traditional industry we have difficulty
covering that adequately. Now there are over 20,000 compounding
pharmacies, and we don't know who is who. And so----
Mr. Butterfield. Can some of your lack of resources be
attributable to sequestration?
Dr. Woodcock. Oh, yes, absolutely. Well, sequestration took
another bite out of what was already a stressed agency,
particularly as far as inspectional coverage and now, to give
you perspective the whole drug industry has about 5,600
establishments, all right, and so we try to inspect those on a
regular basis. To say now that there are 20,000, 26,000, 28,000
compounding pharmacies the question how do we get there, and
then sequestration has reduced our funding, our user fee
funding as well as our base appropriation funding.
Mr. Butterfield. And is that really having a negative
impact on your work?
Dr. Woodcock. Absolutely.
Mr. Butterfield. Now does your agency fully understand that
sequestration is not a 1 year process, it is a 10-year process
so unless it is repealed or modified it is going to continue
for some years to come.
Dr. Woodcock. We have grave concerns about our continued
ability to operate our programs under the various financial
stresses that we have and these new activities that we need to
take on.
Mr. Butterfield. What is an FDA Form 483?
Dr. Woodcock. That is a form with the investigators'
observations that is left with the firm at the end of the
inspection.
Mr. Butterfield. Are these posted on the Web site?
Dr. Woodcock. Yes. They are public.
Mr. Butterfield. OK. And from what we can gather, some 48
form 483s that have been conducted are posted on the Web site?
Dr. Woodcock. Yes. We are posting them publicly to make
sure that people understand what our findings are.
Mr. Butterfield. What are some of the worst conditions that
have been observed by some of your inspectors?
Dr. Woodcock. Well, primarily, it relates to not keeping,
not having practices that would assure the product would be
sterile. Don't forget, these are going to be injected in
people's bodies, into their eyes, around their spinal cord into
their veins and the practices would allow fungal spores, mold,
contamination from the body of a person so that would be
bacteria, to actually get into the products and then multiply.
Mr. Butterfield. Finally, are there any tools other than
money, of course, that Congress can provide to the FDA so the
American people can feel more assured that the compounded drug
they are taking is prepared in a safe and secure way?
Dr. Woodcock. We need clear lines of authority. We need to
know what the States regulate, what the Feds regulate and what
our authorities are. If we regulate part of the industry, I
would like to know who they are, where they are located and
what they are making so that then we can then prioritize where
to go because we are not going to get to thousands and
thousands of sites in the next several months.
Mr. Butterfield. Thank you. You have been very kind. I
yield back.
Mr. Pitts. The chair thanks the gentleman. I now recognize
the gentleman from Utah, Mr. Matheson, 5 minutes for
questioning.
Mr. Matheson. Thank you, Mr. Chairman. Dr. Woodcock, it is
always good to have you before the committee. I have always
appreciated my conversations with you and I appreciate your
trying to highlight an issue where I think it is all important
we take a hard look at this and figure out a better way to go
forward. If I want to oversimplify this hearing, that is kind
of where we are.
I fear my questions may be a bit repetitive for what you
may have already covered that is the reality of being the last
people asking questions.
But I was interested as I understand it when you were
discussing, when the FDA discussed some informant actions back
in 2006, after--can you tell me at that point what actions--can
you elaborate what actions were discussed by the agency 7 years
ago? Are you familiar with that discussion that took place?
That is before your time. Maybe you can't answer that.
Dr. Woodcock. No. No. I wasn't. I wasn't head of Center for
Drugs at that time either.
Mr. Matheson. You present several policy options in your
testimony, and it is going to provide FDA some different
authorities for certain compounders. Can you describe how those
options, how they might have played out, allowed the 2012
outbreak to play out differently than it did if you had those
options at that time?
Dr. Woodcock. If we have clear Federal authority and a
clear idea of what is traditional compounding and what is not
traditional compounding because don't forget this industry
maintained they are working within the scope of State pharmacy
practice. That is what they have maintained all along, all
right, and so we need a clear understanding of what is the
scope of traditional pharmacy compounding practice which FDA
has already supported as appropriate in providing
individualized therapy for people, and what is beyond that and
requires Federal oversight, and to make sure that is
delineated. And I think you will hear from the other witnesses,
that is delineated from people masquerading as one of these
buckets who are actually drug manufacturers. So we need clarity
in whatever.
And if Congress decides not to allow compounding
manufacturing at all, all right, then we have heard from the
hospitals and the clinics that that would be a tremendous
burden on them because they would have to take back all this
that they had outsourced.
Mr. Matheson. Mr. Chairman, that is all I am going to ask
now. I will yield back.
Mr. Pitts. The chair thanks the gentleman. I now recognize
the ranking member of the full committee, Mr. Waxman, 5 minutes
for questions.
Mr. Waxman. Thank you very much, Mr. Chairman.
Dr. Woodcock, your testimony states that the current legal
framework does not provide FDA with the tools it needs to
appropriately regulate the compounding industry in its current
state. You explained that you are referring both to section
503A and other parts of the Federal Food, Drug, and Cosmetic
Act.
I would like to start with section 503A. Obviously as you
explained to Mr. Pallone, there are major questions about
whether it would even remain in effect if challenged in most of
the country apart from the Fifth Circuit. With regard to the
circuit split, Representatives Barton and Griffith have asked
why you could not fix this with guidance.
Can you explain what a guidance could or could not do to
address the circuit split?
Dr. Woodcock. Certainly. A guidance says on every page that
it is not binding either on FDA or the industry. That is what
it says on every page. It is more or less an explanation of our
thinking. It doesn't add new requirements or cannot solve
differences in court opinions.
Mr. Waxman. But putting that aside you say that section
503A actually contains provisions that have impeded FDA's
ability to effectively regulate pharmacy compounding.
Can you elaborate on what those provisions are and how they
have impacted FDA's oversight of compounding pharmacies?
Dr. Woodcock. Yes, well, I think there are provisions in
there that are vague, and so we need clarity about what is the
line. So, for example, it says you shouldn't compound without a
prescription in inordinate amounts. What is ``inordinate?''
That is in the eye of the beholder. The industry has maintained
that all of their activities, regardless of their scale, are
within the scope of traditional pharmacy compounding.
Mr. Waxman. The Oversight and Investigations Subcommittee
of Energy and Commerce conducted a detailed investigation
involving thousands of pages of FDA documents.
One thing we found in that investigation is that for years,
going back to the Bush administration, key FDA decision makers
have in numerous internal meetings and memoranda indicated that
section 503A is inadequate and that new legislation is
necessary.
Are you familiar with any of these documents or any of
these internal discussions?
Dr. Woodcock. Well, I was present in the early 2000s when
the court cases came down, all right. We had been preparing to
try and implement 503A and making the preparations for that
when the Circuit Court and then the Supreme Court ruled. So I
am familiar with that set of discussions.
Mr. Waxman. Well, is it fair to say that the agency leaders
going back to the Bush administration understood that they
needed new legislation because of fundamental weaknesses in
section 503A?
Dr. Woodcock. Yes, it was very difficult to implement in
any reasonable manner.
Mr. Waxman. Mr. Chairman, the notion that FDA is asking for
legislation simply to cover for past mistakes or in some sort
of power grab is not correct. For years through two different
administrations, agency leaders have known that there were
problems with the underlying law.
Let's turn to the other provisions in the act apart from
section 503A.
Dr. Woodcock, your testimony indicated that you are
encountering difficulty when you attempt to inspect compounding
pharmacies now using your current authorities. You mentioned
that you actually had to seek a warrant in two cases after the
pharmacies delayed or refused your access to records.
Can you describe in more detail exactly what has happened
during those inspections and describe which current statutory
provisions are contributing to the difficulties you have faced
when attempting to conduct inspections?
Dr. Woodcock. Well, I probably can't speak to statutory
provisions. I am sorry. But what has happened is we have gone
in there and, as I said, the industry has long maintained that
we do not have authority over these licensed pharmacies that
are in States, right, and so we go in and we ask to either
inspect or to inspect records. And they say under some of the
court cases that have occurred we don't have to turn over
records to you.
Mr. Waxman. So some might argue that there is no problem
here since you were eventually able to conduct the inspections
and obtain the records you were seeking. But can you----
Dr. Woodcock. Certainly.
Mr. Waxman [continuing]. Speak to that assertion?
Dr. Woodcock. The real problem is what is clarity? What is
a compounding pharmacy? What is a traditional compounding
pharmacy? What about the status of these large scale and how do
you define a large scale operation? You might say, well, I know
it when I see it. OK, but how do you----
Mr. Waxman. Well, I was amazed to hear during your
responses to earlier questions that in order for FDA to begin
conducting the more recent inspections, you had to actually
look in the newspapers and at the television ads and Web sites
to even know where the compounding pharmacies were.
Obviously, we don't ask you to search the Internet or watch
TV to figure out where drug manufacturers are.
What is the difference here and do you need new authority
to remedy the situation?
And before you answer that, not only are we uncertain as to
the continued validity of FDA's authorizing statutes with
respect to compounding pharmacies, but that statute itself is
plagued by problems. And so I think we need to clarify the
situation.
But why should you have to go on TV and the Internet to be
able to do inspections?
Dr. Woodcock. Because they don't have to tell us who they
are, where they are operating, and what they are making. They
don't have to submit anything to us. They are operating under
State law. And they don't have to send us adverse events if
they occur, even deaths, and we would read about them in the
paper, hear about them from the CDC or State health department,
or a consumer or doctor will call us.
And that is how we learn about this. And we don't know of
all this universe of 28,000 firms. We don't know what they are
doing. And so you might say, well, you should know about this.
But when it happens, most of our actions have been reactive to
things that we have heard about.
Mr. Waxman. Thank you very much. Thank you for your
indulgence, Mr. Chairman.
Mr. Pitts. The chair thanks the gentleman.
We are voting now on the floor so we will again recess
until the floor votes are concluded, and then we will come back
and reconvene with the second panel.
I think all of the members have asked their questions.
There may be some follow-up questions and we will ask you to
please respond when we send you those.
Dr. Woodcock. Certainly.
Mr. Pitts. So at this point we will recess until conclusion
of floor votes.
[Recess.]
Mr. Pitts. The time of our recess having expired, we will
reconvene our hearing. At this time, I would like to request
unanimous consent to enter a statement from the National
Association of Chain Drug Stores into the record. Without
objection, so ordered.
[The information appears at the conclusion of the hearing.]
Mr. Pitts. At this point, I will introduce our second
panel. Today on our second panel we have Dr. Scott Gottlieb,
resident fellow, American Enterprise Institute. Mr. Joseph
Harmison, owner, Harmison Pharmacies, on behalf of the National
Community Pharmacist Association. Ms. Elizabeth Scott Russell,
Government Affairs Manager of the National Association of
Boards of Pharmacy. Ms. Gabrielle Cosel, Manager, Drug Safety
Project, Pew Health Group at the Pew Charitable Trust. And Mr.
Gerry Migliaccio, Quality Systems Consultant, Migliaccio
Consulting.
Thank you all for coming. You each will have 5 minutes to
summarize your testimony. Your entire written statement will be
entered into the record.
So, Dr. Gottlieb, we will begin with you. You are
recognized for 5 minutes for an opening statement.
STATEMENTS OF SCOTT GOTTLIEB, M.D., RESIDENT FELLOW, AMERICAN
ENTERPRISE INSTITUTE; JOSEPH H. HARMISON, OWNER, HARMISON
PHARMACIES, ON BEHALF OF NATIONAL COMMUNITY PHARMACIST
ASSOCIATION; GERRY MIGLIACCIO, QUALITY SYSTEMS CONSULTANT,
MIGLIACCIO CONSULTING; ELIZABETH SCOTT (SCOTTI) RUSSELL,
GOVERNMENT AFFAIRS MANAGER, NATIONAL ASSOCIATION OF BOARDS OF
PHARMACY; GABRIELLE COSEL, MANAGER, DRUG SAFETY, THE PEW
CHARITABLE TRUSTS
STATEMENT OF SCOTT GOTTLIEB
Dr. Gottlieb. Thanks a lot, Mr. Chairman Pitts, Mr. Ranking
Member Pallone, and members of the committee. Thanks for the
opportunity to testify today. I have a longer statement for the
record. I would like to summarize a few key points for you this
morning.
The tragic deaths of 55 Americans and the sickening of more
than 740 resulting from contaminated steroid injections that
were shipped by a disreputable firm have rightly focused public
attention on a largely unfamiliar but prominent part of the
drug supply chain, the practice of pharmacy compounding.
Before this Congress are proposals to tighten Federal
regulatory oversight of these compounding pharmacies and the
practice of pharmacy more generally. Observers are calling on
Congress to give the FDA more oversight of these firms. New
laws merit consideration. We should articulate clear and bright
lines between a legitimate practice of pharmacy compounding and
those firms operating illegally as large-scale manufacturers
under the guise of a pharmacy license. Some key considerations
should, in my opinion, guide this work.
First, there exists a practice of pharmacy. It was never
intended that all compounding would create a new drug and be
subject to FDA regulation but for the enforcement discretion or
for the willingness of Congress to provide explicit exemption
to certain pharmacists and certain activities that pharmacists
undertake.
Second, FDA has authority to target compounders that cross
the line between the practice of pharmacy and engage in drug
manufacturing under the guise of a pharmacy license. What FDA
largely lacks is ease of administering this authority. FDA is
generally not able to force firms to submit advance information
to the agency before the firm is suspected of any wrongdoing,
and so that the agency is more efficiently able to identify
firms engaged in wrongdoing and target its oversight.
Third, FDA generally lacks tools and resources to regulate
a new class of firms that the agency has dubbed nontraditional
compounders. I would argue that the firms in question here are
not compounders, and calling them such confuses different
issues. Rather, they are engaging in the bulk, large-scale
repacking and manufacturing of sterile preparations of FDA-
approved drugs, typically in advance of and often not in
response to prescriptions for individual patients.
To the degree that these large-scale operations prepare
sterile volumes of drugs in a bulk form and ship these units
widely, they present some novel risks and they have the
potential for what I would call distributed risks. The public
health could benefit from applying additional oversight to
these firms, especially requirements that they adhere to good
manufacturing practices.
Fourth, as we address issues of supply, we must also
address the policy decisions that have increased demand for
products from some disreputable firms, from large-scale
compounders who are breaking existing law and violating
existing regulations. For example, the recent crackdown on
manufacturing of generic drugs have shifted a lot of the demand
for generic preparations to compounders. Likewise, decisions by
FDA to suspend enforcement against compounders in certain
select situations where the agency and policymakers had
concerns about the high cost of FDA-approved drugs relative to
the low costs of compounded versions has also given greater
license to certain compounders to bend, if not break existing
law.
Consistent enforcement is going to be especially important
if we create a new class of compounders that FDA has dubbed the
nontraditional compounding. If FDA doesn't exercise its
enforcement evenly and consistently, which means not allowing
firms to compound identical versions of FDA-approved products,
then the agency will give more incentive for drug makers to
remask themselves as nontraditional compounders to skirt FDA's
new drug requirements.
Finally, the market for compounding drugs is evolving very
quickly. It is consolidating as other entities like
distributors could well start buying out the large compounders.
As this process unfolds, it will leave behind a much different
compounding industry. This should serve as a cautionary tale to
all of us. We should be mindful that the rules that we might
write today would no longer be applicable to the market that we
see tomorrow.
Thank you for the opportunity to testify this morning. I
look forward to your questions.
Mr. Pitts. Thank you, Dr. Gottlieb.
[The prepared statement of Dr. Gottlieb follows:]
[GRAPHICS NOT AVAILABLE IN TIFF FORMAT]
Mr. Pitts. Mr. Harmison, you are recognized for 5 minutes
for opening statement.
STATEMENT OF JOSEPH H. HARMISON
Mr. Harmison. Thank you, Mr. Chairman. I wish I could speak
as quickly----
Mr. Pitts. Poke the button on that. If you will push the
button, speak into the mike, please. Thank you.
Mr. Harmison. OK. Excuse me.
Chairman Pitts, Ranking Member Pallone, Vice Chairman
Burgess, thank you for the opportunity to be here today. As
stated, I am Joe Harmison. I am a practicing pharmacist,
pharmacy owner, and past president of the Texas Pharmacy
Association and the National Community Pharmacists Association.
NCPA appreciates the opportunity to share the community
pharmacist's perspective regarding issues relating to drug
compounding. NCPA represents the views of community
pharmacists, including 23,000 independently owned community
pharmacies. According to an NCPA member survey, 86 percent of
our members do some kind of compounding. This can range from
flavoring pediatric liquids to changing dosage forms to pay for
patients that can't take oral solids to topicals to injections.
In my practice, we mainly emphasize pain medications. And we
are U.S. Pharmacopeial 797 standard compliant.
Our hearts go out to the families who have suffered from
the tragic events surrounding New England Compounding Center,
and NCPA is committed to working with Congress on the issues of
practice that exceed State-regulated compounding. NCPA commends
the committee for taking a closer look at those actions and
inactions that led to the tragic NECC event. We believe the
committee is taking the proper steps to address this tragedy by
focusing its investigations on what steps should have been
taken and oversight that ensures that the proper regulatory
bodies are exercising their full authority.
Compounding is the backbone of pharmacy. It goes back to
the time of the alchemist. For centuries, pharmacy only did
compounding, until World War II, then commercially prepared
medicines became more prevalent, which is still the thing
today. But it did start dawning on people a couple of decades
ago that there are people that need something that just isn't
commercially available. So compounding came back into being an
important part of the pharmacy practice.
Another thing, compounding serves to bridge a gap which we
are experiencing more and more when commercial products are not
available. Patients must be assured that they are not forced to
go without medicines or their treatment because medications are
unavailable and compounding for that medication is prohibited
or tied up in a bureaucracy. It is important to reiterate that
pharmacist compounding is an integral part of pharmacy
profession and meets patients' needs in hospitals, long-term
care, home infusion, hospice, every community setting I can
think of.
NCPA has always and will continue to advocate that pharmacy
compounding is best regulated by the State boards of pharmacy
while manufacturing oversight is the purview of the FDA.
Pharmacy compounding medication is an important part of the
medical care and allows dispensing custom-made medications and
should continue to be related by State boards of pharmacy, as
all other medical profession licenses are.
State boards of pharmacies currently oversee all aspects of
pharmacy and in most cases their records are public. So it is
not hard to obtain who is doing what. If the FDA has concerns
about appropriate licensed pharmacy, then the FDA currently has
the authority to ask the State board of pharmacy to work with
them to address the issues. If it is found that they have an
entity that is acting under the guise of a pharmacy and is
exceeding its State-regulated authority, then the States board
of pharmacy should suspend the license of that pharmacy until
it complies with the State regulations or meets the FDA
regulations to be a manufacturer.
All parties involved must make certain that the State
boards of pharmacy are adequately staffed, trained, and funded
to effectively regulate compounding. NCPA encourages the State
boards of pharmacy to acquire uniform compliance with USP 797
standards in order to provide more uniform product standards.
As such, every State will be assured that resident and
nonresident pharmacies alike are all in compliance with the USP
standards.
In most cases, compound medication must originate from a
prescription for a specific patient. There are times that we
may do things in advance, but we have to be able to prove that
we use historically a certain amount in a very short period of
time.
I see I am out of time. Compounding should not be defined
by nuance, such as types of product, whether it is sterile or
nonsterile, as risk of complexity of compounding is not solely
dependent on the product type. Neither is quantity of the
product made in a pharmacy of bearing because we can make many
different things and they are all safe. And interstate commerce
should not be--because we, was stated earlier, we are a border
State to 5 different States, and, being rural, there are places
that just have to go across State lines. But if it is the
issuance of a prescription for a specific patient for a
specific malady, this should be allowed and under the purview
of the States.
Thank you for the opportunity to be here. NCPA pledges to
work with Congress to put this to rest.
Mr. Pitts. Chair thanks the gentleman.
[The prepared statement of Mr. Harmison follows:]
[GRAPHICS NOT AVAILABLE IN TIFF FORMAT]
Mr. Pitts. Ms. Russell, you are recognized for 5 minutes
for opening statement.
STATEMENT OF ELIZABETH SCOTT (SCOTTI) RUSSELL
Ms. Russell. Thank you. Good afternoon, Chairman Pitts,
Ranking Member Pallone, and members of the subcommittee. The
National Association of Boards of Pharmacy appreciates the
opportunity to appear before you today and provide information
related to pharmacy compounding. I am Elizabeth Scott Russell,
government affairs manager for the association.
As part of a comprehensive action plan that assists States
following the meningitis outbreak, NABP partnered with the Iowa
Board of Pharmacy to begin conducting inspections of all of its
approximately 609 resident pharmacies, focusing first on those
delivering compounded drugs into Iowa. Our inspections
confirmed that the activities that occurred with NECC were also
occurring in other facilities in other States.
To date, NABP has inspected approximately 165 pharmacies
and is in discussions about similar inspection programs with
other States. We are building a system of proactive information
exchange for all pharmacies that will include verifications of
licensure, disciplinary checks, and assurances of a timely and
robust inspection that meets uniform standards at no cost to
boards to assist them in making licensure and registration
determinations for nonresident pharmacies.
NABP does believe that Federal legislation is needed to
provide the needed distinction between compounding and
manufacturing to address critical concerns and provide a safe
and equitable environment for both to occur in the best
interest of the patient. NABP supports the major concepts of
the legislation proposed by the Senate HELP Committee and
welcomes the proposed clarifications to the regulatory
uncertainties that currently exist, uncertainties that were a
primary factor leading to the recent meningitis tragedy.
In particular, NABP affirms that the regulation of the
practice of pharmacy remains the responsibility of the State
boards of pharmacy and agrees with the language in the proposed
Senate legislation that defines traditional pharmacy
compounding as part of the practice of pharmacy to be regulated
by State boards of pharmacy. NABP also supports the
establishment in legislation of a new category for the
preparation of nonpatient-specific sterile products that would
be registered and regulated by FDA and a clear distinction
between this new category and traditional pharmacy compounding.
Although we understand that some terminology must be
employed to describe this new category, we would prefer that
the term ``compounding'' not be included in the name because of
potential confusion with traditional pharmacy compounding.
NABP supports Federal legislation prohibiting entities that
fall into this new category also being licensed as a pharmacy
by the State, as this separation is essential to addressing the
ambiguous authority that currently exists between the States
and FDA; that is, who is responsible. Our experience affirms
the importance of a clear separation between manufacturing and
compounding and clarifying what activities fall under Federal
jurisdiction and what fall under State jurisdiction. Not having
a clear separation could also provide a veil for unscrupulous
entities to hide their activities.
NABP does not believe that the interstate distribution of
nonpatient-specific sterile products should be a required
criteria for meeting this definition, this new category, as is
in the Senate proposal. We understand the need to establish a
delineation point, but such differentiation between intrastate
and interstate distribution could create patient safety
concerns by allowing large-scale intrastate entities to avoid
Federal regulation. NABP could still support proposed
legislation that exempts intrastate distributions from the
definition for this new category provided the situation is
monitored for any additional future action that may be
necessary.
In conclusion, NABP believes there is a need for Federal
legislation that addresses the safe preparation of compounded
medications for patients, that distinguishes between
compounding and manufacturing, defines a new category of
manufacturers under FDA regulation, balances effective
regulation with reality, and carefully constructs the scope and
activities of this new category to meet patient needs while
maintaining necessary protections. We appreciate this
opportunity for input and are available to discuss our comments
and any legislative solution in greater detail. Thank you.
Mr. Pitts. Chair thanks the gentlelady.
[The prepared statement of Ms. Russell follows:]
[GRAPHICS NOT AVAILABLE IN TIFF FORMAT]
Mr. Pitts. Ms. Cosel, you are recognized for 5 minutes for
an opening statement.
STATEMENT OF GABRIELLE COSEL
Ms. Cosel. Thank you. Chairman Pitts, Ranking Member
Pallone, Vice Chairman Burgess, and members of the
subcommittee, thank you for the opportunity to testify on the
need for Federal legislation to improve the safety of
compounded medicines. My name is Gabrielle Cosel. I work on
pharmaceutical quality and safety at the Pew Charitable Trusts,
which is an independent research and public policy
organization.
Pharmacists have always compounded medicines. But many of
the activities we refer to as compounding today are far removed
from traditional pharmacy practice. In recent months, this
committee has stressed the responsibility of FDA to ensure the
safety of activities that depart from traditional compounding
and are more akin to manufacturing. Today I will focus on a
regulatory framework that clarifies the agency's role, ensures
that limited resources are used wisely, and sets clear
expectations for the industry.
First, though, it is important to look over the risks. The
fungal meningitis epidemic illustrates how patients can be
harmed by substandard compounded drugs. But it is far from an
isolated incident. My written testimony describes 19 additional
pharmacy compounding errors from the past decade that have
caused serious injuries and deaths in at least 29 different
States. The list includes meningitis, blood stream infections,
and at least 38 patients who suffered partial or complete
vision loss.
Recent history raises further concern. Two months ago, a
New Jersey compounder recalled all of its products because of
mold contamination. When a drug is produced in mass quantities,
the potential harms from a quality failure also multiply. There
are companies today that compound thousands of packages of
vials of medicines and ship them to buyers all over the
country. These activities have outgrown the State regulatory
structures established to oversee them. Federal law already
regulates some aspects of compounding, and today we urge you to
make changes to ensure clarity and effective oversight.
First, large-scale compounding should be subject to higher
quality standards, specifically applicable good manufacturing
practices. Second, the FDA is the appropriate agency to oversee
GMPs, and States should not exercise redundant oversight. And
finally, patients must be protected by ensuring that
compounders do not undermine gold standard FDA-approved drugs.
Compounding quality standards are currently set by the
States, and they are variable. Pew recently joined with the
American Hospital Association and the American Society for
Health System Pharmacists to host a summit on sterile
compounding, and experts at that meeting emphasized that
pharmacy compounding standards were never intended and are not
suitable for large-scale production. Compounding high volumes
or repeat batches of medicines involves standardized processes
and should be subject to applicable GMPs. The FDA is best
placed to enforce these standards, but resources should be
focused on activities that pose the highest public health risk.
Facilities that produce large volumes of sterile products that
may reach many patients or that carry out particularly high-
risk compounding, such as creating sterile products from a
nonsterile bulk ingredient, should be required to register with
the FDA.
FDA should issue regulation clarifying the criteria for
registration. As with pharmaceutical manufacturing, FDA should
inspect compounding facilities on an ongoing basis with a
frequency based on risk. And facilities should pay fees to
ensure FDA is adequately resourced to provide this oversight.
Under this framework, States may continue to require FDA-
registered compounding facilities to hold pharmacy licenses,
but State enforcement of quality standards should be preempted
for these facilities. To exercise effective oversight, the FDA
must have access to the records of facilities it regulates or
that it believes fall under its jurisdiction. This requires a
fix to current law. Even today, compounders continue to
challenge FDA's access to records. Key safety requirements
should also be set at the Federal level, such as a ``do not
compound list,'' and this should apply to all compounding
facilities.
It is important to state that large-scale compounding
cannot be addressed simply by requiring these facilities to
submit new drug applications. Some large compounders fill a
niche in our health system, such as for hospitals that don't
have sufficient capacity to mix drugs in-house. However, any
new regulatory scheme must not undermine the approvals process
and encourage compounding at the expense of traditional
manufacturing. While the goal is to ensure the quality of
compounded medicines, patients, doctors, and pharmacists should
prefer FDA-approved products whenever possible. Only the latter
go through pre-market review to establish safety, efficacy, and
bioequivalence, along with pre-approval of manufacturing
methods and facilities. Legislation should be clear that a
compounder may not make a copy or a variation of a marketed
drug except when that drug is in shortage or to address a
specific medical need of a specific patient.
In conclusion, I thank you for your leadership, and I urge
you to create a clear, workable framework to protect patients.
I welcome your questions.
Mr. Pitts. Chair thanks the gentlelady.
[The prepared statement of Ms. Cosel follows:]
[GRAPHICS NOT AVAILABLE TIFF FORMAT]
Mr. Pitts. Mr. Migliaccio, you are recognized for 5 minutes
for opening statement.
STATEMENT OF GERRY MIGLIACCIO
Mr. Migliaccio. Thank you, Chairman Pitts and Ranking
Member Pallone, for inviting me here to speak today. My name is
Gerry Migliaccio. I am a consultant in the area of
pharmaceutical quality systems. In 2012, I retired from Pfizer,
Incorporated, after a 33-year career in pharmaceutical
manufacturing and quality operations. For 11 of those years, I
served as the head of the Global Quality Organization at
Pfizer. So this experience has provided me with quite an
intimate knowledge of the quality requirements and regulatory
framework applicable to manufacturing medicines for the United
States public.
Patient safety is the highest priority for pharmaceutical
manufacturers. Companies comply with the gold standard of
quality manufacturing as defined by FDA's current Good
Manufacturing Practice regulations and the associated guidance
documents. These regulations apply to all prescription drugs
approved for sale in the United States, wherever they are made,
and extend to all components of a finished drug product,
including the active pharmaceutical ingredients.
FDA's regulations are based on the fundamental principle
that you cannot inspect or test quality into a finished
product. Quality must be designed into the manufacturing
process and designed into the product. The regulations also
drive manufacturers to establish a quality systems approach to
assure consistent quality.
In pharmaceutical manufacturing, quality systems and GMP
requirements begin at the investigational stage. FDA requires
that a new drug application describe the quality safeguards for
the proposed manufacturer of a new medicine in the Chemistry,
Manufacturing, Control section of the application. Part of the
evidence required by FDA to demonstrate safety and efficacy is
the requirement that a manufacturer provide, and I quote, ``a
full description of the methods used in and the facilities and
controls used for the manufacture, processing, and packing of a
new drug.''
The manufacture of medicines, whether by NDA holders or
large-scale compounders, involves similar activities and
similar potential for risk. Large-scale compounding can involve
mixing of active and inactive ingredients, as well as other
manufacturing steps. Therefore, in order to assure the safety
of the American public, the manufacture of medicines, whether
by manufacturers or by pharmacies, should be regulated in a
consistent risk-based manner. Large-scale commercial
manufacturing of prescription medicines, whether the producer
is designated as a pharmacy or as a manufacturer, should be
governed by the same high standards currently in effect for
pharmaceutical manufacturing and subject to the same inspection
and enforcement actions by FDA.
Moreover, large-scale compounders should be required to
prove that they can manufacture medicines consistently and
safely by submitting an application to FDA containing a
Chemistry, Manufacturing, and Control section, and submitting
to both pre-approval and routine GMP inspections.
Let me give you a personal perspective on the importance of
GMP regulations. During my career, I considered the regulatory
framework in the United States as the blueprint for assuring
safety and efficacy. Whether you are a small startup company or
a large multinational manufacturer, the regulations and
guidance documents provided a template for success. From
designing quality into a manufacturing process to the selection
of material suppliers to construction of facilities, the
selection of equipment, the training of employees, all the way
to the final approval to distribute the product, the
regulations and guidance documents provide for a consistent
risk-based approach to assure quality. The regulations have
also evolved to encourage innovation and continuous improvement
and to help support the justification of new technology to
further enhance quality assurance.
Therefore, it is just very logical to me that any large-
scale manufacturer of medicines, including compounders, should
comply with these same regulations. A manufacturer in full
compliance will have a high degree of assurance that the
medicines they produce will be of consistently high quality. A
large-scale company making thousands of doses of medicine with
the name ``Pharmacy'' on the door and another with the name
``Pharmaceutical Company'' on the door should be regulated in a
similar manner when they perform similar manufacturing steps
and present similar risks to patients.
Thank you for your attention.
Mr. Pitts. Chair thanks the gentleman.
[The prepared statement of Mr. Migliaccio follows:]
[GRAPHICS NOT AVAILABLE TIFF FORMAT]
Mr. Pitts. I will begin the questioning. And I recognize
myself for 5 minutes for that purpose.
Dr. Gottlieb, the FDA has proposed creating a new category
of, quote, ``nontraditional compounders,'' end quote. Do you
believe this has the potential to add confusion rather than
clarity to regulated industry?
Dr. Gottlieb. I do believe there is this category of
companies, large companies, that have grown up that basically
do the outsourced work of the hospitals. And it is not really
traditional compounding in the sense that we understand that
word. What they are really doing is sterile preparations of
drugs, breaking down FDA-approved products into different
formulations that make it easier to administer to patients, and
it is a completely different thing than what traditional
compounding is.
I do think it creates the potential that traditional
manufacturers might have a temptation to recast themselves into
this new category if we don't have very equal enforcement and
very aggressive enforcement of the existing law because there
will be an incentive to go into this pathway because it will be
sort of a regulatory light pathway.
The reason why Teva Pharmaceuticals doesn't, you know,
manufacture all the formulations of Propofol that doctors might
want is because if they went about doing that they would have
to file an ANDA for each one and pay a user fee for each one.
So if we create this category, it could be an incentive for
traditional manufacturers to try to move back into this new
category, and that wouldn't serve the public interest.
Mr. Pitts. To follow up, impact on intellectual property
rights. How would this new category potentially impact
intellectual property rights?
Dr. Gottlieb. Well, again, I think it could create an
avenue for people to try to game around the new drug
regulations to create products that would fit into this
category. And it is not an argument for not trying to think
about how we could apply GMP regulations to this emerging, this
new category of manufacturers. But it is an argument for trying
to make sure that we enforce existing law against compounders
who, for example, compound versions of FDA-approved products.
In recent years, the FDA has backed off enforcement that
was put into place to crack down on people who are engaging in
the compounding of drugs that exist in FDA-approved
formulations. And so that creates an incentive to try to
obviate existing intellectual property.
Mr. Pitts. Mr. Migliaccio, Director Woodcock mentioned on
the previous panel that the agency could not require
compounders to register with the FDA. However, the FDA has the
full authority to require manufacturers operating under the
guise of compounders to register with the FDA, like NECC. Isn't
that correct?
Mr. Migliaccio. Yes. Well, every manufacturing
establishment within a pharmaceutical company has to have an
establishment registration with the FDA.
Mr. Pitts. Hasn't the FDA recently used its manufacturing
inspection authority to inspect manufacturers acting under the
guise of compounding recently?
Mr. Migliaccio. I believe they have used their inspection
authority to attempt to inspect compounding manufacturers. And
I understand that they have been turned away in certain cases.
Mr. Pitts. Please explain the similar scope of risk between
NDA holders manufacturing drugs and large-scale compounders.
Mr. Migliaccio. Well, pharmaceutical manufacturers make
pharmaceutical products at very different scales. I mean, we
make small volume, we make large volume. Compounders are doing
the same thing. We are following similar manufacturing steps.
We are taking active ingredients and inactive ingredients,
combining them, trying to yield a product that has the potency
and purity required by the patient.
Compounding the problem with sterile products is the risk
around sterility. Sterility is not something that you can test
into a product. Yes, you do a sterility test, but it is not a
reliable measure of sterility. You have to have a very robust
system to assure sterility. And the GMPs require that we
actually prove that to the FDA before we can market the
product. We have to prove that we can assure sterility to a
very high degree before we can put a product on the market.
That is not the case, the risks are the same for compounding
pharmacies, but they don't have to provide that same evidence.
Mr. Pitts. Could legislation that applies different
standards adversely affect the quality of drugs made available
to patients?
Mr. Migliaccio. Oh, I believe that compounding pharmacies
making product at large volume are manufacturers and should be
regulated according to the manufacturing regulations, the GMPs,
which have proven to be very successful in protecting the
American public.
Mr. Pitts. Let me squeeze one more question in here, Mr.
Harmison. What safety precautions are you required to comply
with?
Mr. Harmison. I comply with USP 797 and State laws and
rules and regulations of the State of Texas.
Mr. Pitts. And can you briefly describe the importance of
traditional compounding that occurs in independent pharmacies
across the country?
Mr. Harmison. Mr. Chairman, that is a very broad subject.
If we are talking about somebody making a cream, there is one
thing. If I am making a sterile injection, that is quite
another thing. I am making a capsule for somebody. We still
strive, basically, we are not going to make anything we
wouldn't give to our children or grandchildren.
Mr. Pitts. Thank you.
My time has expired. Recognize the ranking member 5 minutes
for questions.
Mr. Pallone. I wanted to start with Ms. Russell. In your
testimony, you cite the need for FDA to be given new and better
authority over drug compounding. Obviously, your organization
is made up of State agencies that regulate the practice of
pharmacy, so you are in a unique position to have insight into
whether FDA needed new authority in this area.
So, Ms. Russell, your testimony describes the fact that
there were regulatory uncertainties that were a major factor
leading to the NECC meningitis tragedy. Can you elaborate on
what those--I always hate to say elaborate--but can you tell us
what those uncertainties were and how they contributed to the
meningitis outbreak?
Ms. Russell. Sure. I think that there are a number of
entities in the United States, across the United States, that
would tell boards of pharmacy that they were distributing
nonpatient-specific sterile products as an FDA manufacturer.
And they may have actually gone on FDA's Web site and
registered as a manufacturer and State boards of pharmacy
didn't think they had jurisdiction over those particular
activities. FDA didn't necessarily recognize them as an
approved manufacturer because they hadn't filed an NDA. So
there were uncertainties and ambiguities in who had
responsibility over these particular firms.
Mr. Pallone. So you also indicate that NABP is supportive
of the Senate legislation clarifying the distinction between
compounding manufacturers and traditional compounders. And you
further indicate that your recent inspections of compounding
pharmacies has underscored the importance of getting this
clarity through Federal legislation. So can you explain more
about what you have done in your inspection's undertaking? I am
curious about why, if any BP in the States have been able to
conduct such widespread inspections recently, that isn't
enough. In other words, what would be achieved by FDA through
new Federal legislation that can't be accomplished by the State
boards of pharmacy?
Ms. Russell. Maybe I wasn't clear. We do think traditional
pharmacy compounding should remain the purview of State boards
of pharmacy. But we do think that there are these entities that
are engaged in large-scale activities that more resemble
manufacturing and that FDA should have jurisdiction to inspect
and investigate those.
Our initial inspections that we have been involved in for
the State of Iowa, part of it has been trying to determine
which of these large-scale entities are engaged in these more
resembling manufacturing-type processes, and those are not
condoned by the Iowa Board of Pharmacy, nor most other States.
And we don't think that State boards of pharmacy have the
resources to be able to adequately inspect basically
manufacturing operators that are operating under the guise of
legitimate pharmacy practice.
Mr. Pallone. Thank you.
Let me ask Ms. Cosel. I would like to ask you a question
that we heard a little about during the first panel. That has
to do with hospital use of compounding medications. As we
heard, hospitals have increasingly come to rely on compounded
medicines that they obtain from large-scale pharmacies, and Dr.
Woodcock talked some about how FDA's authorities to oversees
these large-scale facilities are not appropriately tailored to
the task. So I wanted to ask you, do you agree that hospitals
do have a legitimate need for drugs from these large-scale
pharmacies? Can you explain more about why they have come to
rely on them? And what are your views on whether the FDA has
the right authorities to handle regulation of that type of
entity.
Ms. Cosel. Yes. And I think the question is very astute,
because it hits on just what is at hand today. There is a
question about bad actors and if they cross a certain line
whether they should be shut down. Yes. But there is also a
question of entities that do fill a niche in our healthcare
system, such as the outsources you reference, sir. And it has
become clear over the years that hospitals have increasingly
looked to outsourced operations to provide them sterile mixed
products, mixed variations of finished FDA drugs.
And the simple answer can't just be calling these entities
manufacturers and requiring them to submit a new drug approval.
We need to make absolutely clear that when you are compounding
on a large scale and filling this niche for the health system
you should be held to high quality standards, GMPs, as my
colleague Mr. Migliaccio testified on as well.
Mr. Pallone. Mr. Harmison, I have got a little time. Your
testimony can be summarized as follows: States always have and
always should regulate compounders with no role for the FDA.
But we know that numerous failure by Massachusetts regulators
led to the NECC tragedy. In light of this tragedy, is it still
your view--and I don't mean--you tell me if I am wrong--is it
still your view that States are capable of regulating large-
scale compounders?
Mr. Harmison. Yes, Mr. Pallone. I think if they have the
willpower to do it, they have the ability.
Mr. Pallone. So you don't think there is a role for FDA in
the regulation of large-scale compounders like NECC.
Mr. Harmison. I think the rule of the FDA is oversight. If
they think that there is a problem, they should go talk to the
State boards of pharmacy, say, come, go with me, let's inspect
this. If it is in violation of the State law, then the State
should take action on them. If they say, we don't have this,
somebody decide if they are a manufacturer. If they are a
manufacturer, certainly they are under the purview of the FDA.
Mr. Pallone. I don't know. It just seems to me that what
you are proposing sounds nice in theory, but I think much of
the testimony seems to indicate it doesn't work out
practically. But whatever, I don't want to put words in your
mouth. Thanks a lot.
Mr. Pitts. Chair thanks the gentleman.
Now recognize the vice chair of the committee, Dr. Burgess,
for 5 minutes for questions.
Mr. Burgess. Mr. Harmison, let's continue on that line for
a moment, because when another subcommittee of the Energy and
Commerce Committee, the Oversight and Investigations
Subcommittee first started this investigation, we were joined
by the brand new head of the Massachusetts Board of Pharmacy.
And the reason she was the brand new head was because the old
head had been recently dismissed because of the problems that
occurred.
We have heard from the FDA this morning that, no, we are
not going to replace anyone in our organization. And looks to
me like the Massachusetts Board of Pharmacy acted. Although
there may have been problems leading up to the crisis, their
response to the crisis and after seems much more reasonable
than what I have seen under the Federal regulatory agency. Is
that a fair assessment that I am making?
Mr. Harmison. As an employer, if I were in that position,
somebody wouldn't be in my employ anymore.
Mr. Burgess. Well, that is, you know, this was so baffling
about all of this. I mean, again, the poor individual who was
the head, the brand new head of the Massachusetts Board of
Pharmacy had to come here and answer some pretty tough
questions and some for which she no answer, and simply said
those people are no longer working for us. And you have to
wonder if whether or not there are civil or even criminal
activities are going to follow them for a while. I wouldn't be
surprised to learn that.
But, again, you have a large Federal regulatory agency, and
they are immobile. And not only are they immobile, after they
find out that there is a problem, but the months and years
leading up to this. Well, we are going to have to have
guidance, and, well, it is bound up in some stuff.
And I read you the email chain. From 18 months before this
crisis hit, they recognized that it was manufacturing, that
they were required to list these compounds, they were required
to submit to GMP. The people in the FDA understood that. And
for whatever reason it didn't translate to the street level to
get it done. In fact, I don't think the people that were
working in the agency, again, I just--the mental image, they
must be tearing their hair because they keep coming up to this
point waiting for someone to say ``go'' and no one ever said
``go.''
And that is the problem I see if we divested away from the
State agencies. Bad news at Massachusetts Board of Pharmacy.
You know, bad news at what happened. But at least they have
reacted in what I would consider a sensible way. I can't say
the same to the FDA. That is painful for me to say that.
Mr. Harmison. Well, if I can go back to an old Paul Newman
movie, it appears what we have is a failure to communicate
between regulatory agencies and enforcement agencies.
Mr. Burgess. Dr. Gottlieb, let me just ask you because you
have some experience working within the agency. Is that not
correct?
Dr. Gottlieb. Look, I think NECC was breaking existing law.
They were acting as a large-scale manufacturer under the guise
of a pharmacy license. They were compounding identical versions
of FDA-approved products, they were doing it in bulk, they
weren't doing it in response to prescriptions. They had had
previous GMP violations. So they were known bad actor.
I think the issue isn't necessarily what is FDA's
authority. FDA has extensive authority. I think that the
challenge is that they don't have ease of administrating
authority because they don't have the ability to compel the
submission of certain information. And it is not the posture by
which they typically regulate.
In the case of compounding, in many cases FDA is forced to
have to make an affirmative case before it could go in and
start to do its work. Typically, the FDA doesn't regulate that
way. Typically, the FDA regulates from a posture where they
compel submission of information to the agency and then they
are able to target their activities based on that information.
You know, under existing law they have extensive authority, in
my view, but it is authority that makes it administratively
more burdensome for them in this area than others.
Mr. Burgess. But, you know, the concept of an affirmative
case, and for heaven sakes, the system was blinking red for
years. For years. You had whistleblowers, you had people
bringing brochures in, you had people showing up saying, this
is what we heard at a conference. These guys were clearly
skating way beyond the edge, way beyond the fringe. And, OK,
well, it may not be the normal FDA posture to take an
affirmative case, when the evidence is laid in front of you, it
shouldn't take----
Dr. Gottlieb. Well, this one was obvious.
Mr. Burgess [continuing]. It shouldn't take years to come
to the conclusion of filing the action that eventually closed
the NECC. Is that correct?
Dr. Gottlieb. This was a known bad actor over a long period
of time--including, frankly, the time in which I was at FDA, we
sent out a warning letter to this firm in 2006.
Mr. Burgess. OK.
Thank you, Mr. Chairman. I will yield back.
Mr. Pitts. Chair thanks the gentleman.
And now recognize the ranking member emeritus, Mr. Dingell,
for 5 minutes for questions.
Mr. Dingell. Mr. Chairman, I thank you.
First question is for Ms. Russell of the National
Association of Boards of Pharmacy and also Ms. Cosel of the Pew
Charitable Trusts.
Ladies, do you believe that there is regulatory uncertainty
regarding the FDA's role in overseeing compounding pharmacies?
Yes or no?
Ms. Russell. Yes.
Ms. Cosel. Yes.
Mr. Dingell. Now, these next two questions are for Ms.
Russell. In your testimony, you mentioned that NABP partnered
with the Iowa Board of Pharmacy to inspect pharmacies which
deliver compounded drugs into Iowa. Is that correct?
Ms. Russell. Yes.
Mr. Dingell. Now, in your testimony also, you also mention
that your inspections found that what occurred at NECC was
happening elsewhere. Is that correct?
Ms. Russell. Yes.
Mr. Dingell. Could you briefly describe what you found at
some of the facilities where you found a repeat of this kind of
situation?
Ms. Russell. We found large-scale operations similar to
what NECC was doing where they were allegedly compounding or
producing bulk quantities of sterile injectable products, some
that were essentially copies of commercial products. We found
issues with compliance with standards for sterility compounding
and basically that they were shipping nonpatient-specific drugs
into the State of Iowa in violation of Iowa State law.
Mr. Dingell. What did the Iowa agency do about this?
Ms. Russell. Iowa is in the process of--they have got three
attorneys now working on the inspections that we provided. And
they have issued notices of regulatory hearing for 5 of the
first 6 pharmacies that we went in, which were some of the
larger-scale operations. Those hearings I believe will be held
in June this year, next month.
Mr. Dingell. They seem to be in great haste. Am I correct?
Ms. Russell. Pardon?
Mr. Dingell. They seem to be in great haste to get around
to processing this matter. Yes or no?
Ms. Russell. Yes.
Mr. Dingell. I don't see it that way.
Would you submit also for the record other details of the
events that you found, if you please?
Now, in your testimony you mentioned there has been 19
significant compounding errors since 2001. Is that correct?
Ms. Cosel. Yes, 20, including NECC.
Mr. Dingell. OK. Would you for the record submit the
details of those events, please, to us?
Ms. Cosel. Yes, sir.
Mr. Dingell. Now, how many people died as a result of these
incidents?
Ms. Cosel. Not including NECC, there were 22 deaths
associated with these incidents, and including NECC there were
77.
Mr. Dingell. Could you submit for the record the details on
these things, if you please?
Ms. Cosel. Yes, sir.
Mr. Dingell. Now, as far as you know, have there been
further problems with compounding pharmacies after the NECC
outbreak? Yes or no?
Ms. Cosel. Yes. We have seen a number of recalls related to
quality problems with compounded drugs this year.
Mr. Dingell. Could you submit again for the record what you
found in those matters?
Ms. Cosel. Certainly.
Mr. Dingell. Could you give us a brief perhaps picture of
what you found done in these instances and whether this was the
responsibility of the State agencies or the Feds?
Ms. Cosel. Well, I can give one example. There was a recall
by a Georgia compounder this year, I believe in March, of all
sterile products, because there were serious eye infections in
at least 5 patients associated with a contaminated eye
injection. In this case, this was a nationwide recall. So if we
are--if Congress is considering a new regulatory system that is
clear that large-scale compounding of high-risk sterile
products would be explicitly under FDA oversight, I think we
would have had a much better chance of ensuring the safety of
those processes.
Mr. Dingell. Particularly since they are shipping all
across the United States and this is touching many agencies,
many States, and people in many States and agencies. Is that
right?
Ms. Cosel. Yes.
Mr. Dingell. And, by the way, thank you for your patience.
It lets me get a lot more questions in.
Would you for the record please submit the information that
you have on these instances?
Ms. Cosel. Yes.
Mr. Dingell. Now, in your opinion, is the outbreak at NECC
an exception to the rule or do you believe that it is but one
example of a larger problem?
Ms. Cosel. It is certainly an extremely horrific example,
but it is just one of the larger issues we face. We acutely
need greater clarity on oversight structures for large-scale
compounding.
Mr. Dingell. And one of the things we have do is to clarify
it so that everybody knows who is supposed to and who can do
what. Is that right?
Ms. Cosel. Yes.
Mr. Dingell. Because we have the court cases that have
screwed up the interpretation by both State and Federal
agencies on this matter. Is that right?
Ms. Cosel. Legal uncertainty is one problem, as is changes
with the industry and the emergence of the large-scale sector.
Mr. Dingell. I have used more than my time. Thank you, Mr.
Chairman.
Mr. Pitts. Chair thanks the gentleman.
Now recognize the gentleman from Virginia, Mr. Griffith, 5
minutes for questions.
Mr. Griffith. Thank you, Mr. Chairman.
I have to tell you all, and I appreciate all of you being
here, that I think part of the problem is, is that we have a
clash of two worlds, the legal world and the medical world.
Because when I look at the authority granted to the FDA under
the code, with the exception of the advertising overreach,
which was stricken down, there is plenty of authority already
there to get to every problem that you all have raised today.
And that is my concern.
And I asked the doctor earlier, and she was very kind, you
know, this happened, the Supreme Court case came down that
dealt with the Ninth Circuit in 2002. Where was the request to
Congress to clarify? Because the only clarification is that the
rest of the authority granted, with the exception of the
advertising provision, should have been reenacted by Congress.
Now, can we tweak it a little bit and make it a little bit
better? I am sure we can. And I am certain that we will work on
that, because none of us want to see this problem happen again.
But I heard one of the witnesses, and I don't remember which
one now, say that they understood that there had been problems,
you know, getting the records and getting into things. And, in
fact, I think because the medical world--and I was a courtroom
attorney, and so maybe it is a little different, not attorneys,
but courtroom attorneys, they see things differently.
So I asked legal counsel who was here at a previous
hearing, for the FDA, do you have any trouble getting warrants?
And I expressed that my opinion always was as a defense
attorney, criminal defense attorney, that the government didn't
have too much trouble getting warrants. He said, that wasn't my
experience. And I asked him to get me information. Yesterday,
we received that information.
And, sure enough, FDA cannot point to a single example of
where they requested a warrant where they were denied that
warrant. So while the common belief is they have a hard time
getting this information, the data would indicate otherwise.
I also asked, how long does it take you to get the warrant?
And they said, in the most recent administrative warrant we
sought for a pharmacy, 10 days passed between when the refusal
was encountered and when the warrant was signed by the
magistrate judge.
I have got to believe that if, as somebody said earlier,
the blinking light, the red light warning, warning had been
going off for years, that if instead of being timid and being
afraid of the law, the medical folks had burst in, as often
police officers have to do--if they think somebody has a DUI,
they may not win the case in the end, but they get that person
off the road, at least temporarily, to see what is going on--
that is what should have happened in this situation.
Would you agree with that, Mr. Harmison, that that is
probably what should have happened, instead of coming in,
trying to rewrite the law.
Mr. Harmison. Yes, sir. If there is public safety at risk,
the State board of pharmacy absolutely has the power to come in
and say, wait a minute, you are shut down.
Mr. Griffith. Yes. And I think that the guidelines that
were worked on, never fully finalized, but that were worked on
in the draft guidelines of August of last year that we didn't
learn about until March of this year, make that clear as well.
Because it goes through and when it talks about distinguishing
between, as you all have called them different names, large-
scale producers or production of compounded drugs, large-scale
manufacturers, I think they are manufacturers. And I said in
one of the earlier hearings, you know, I can call myself the
Duke of Earl if I want to, but that doesn't mean I am getting
diplomatic immunity.
And that is where I think we run into this problem. But
when they did that draft, they said, when you are looking at
whether or not somebody is doing a compounded drug product that
qualifies for the exemptions, they came up with 10 guidelines.
And they are all significant and important, but I noted with
interest two of those. Number 8 says the licensed pharmacist or
licensed physician does not compound regularly or in inordinate
amounts any drug products. Number 10 says that you should have
a memorandum of understanding with the States so that you can
work out these areas that aren't clarified or in a State where
they have not entered into a memorandum of understanding the
pharmacists shouldn't be sending to another State more than 5
percent of the total prescription orders dispensed or
distributed by such pharmacy or physician.
These seem to me to be reasonable restrictions, and it
makes the definition that I think each one of the witnesses
here today is looking for, distinguishing between the
traditional pharmacy that is doing some things for their
patients and their customers and these large-scale
manufacturers who are, in fact, in my opinion, they are not
compounders in the traditional pharmacy sense, but they are, in
fact, manufacturers.
I look forward to trying to make sure that we clarify some
of that because I do think that part of the problem is, is not
having some street lawyers at the FDA who know that sometimes
you have got to go in and kick the courthouse door down and say
here is what we are doing. And when the judge sees the risk to
the public he will say, OK, I will sign the warrant, OK, we
will shut them down at least until we can find out whether or
not they are a risk to the public. I think the authority
already exists for that. I just think there has been some
timidity in the legal department at the FDA.
And when you talk about registration, when you look at the
rules in section 510 of the act, I think it is pretty clear
that unless you are a small town pharmacist you are supposed to
be registering anyway. Does anybody disagree with that?
Dr. Gottlieb, do you disagree with that?
Dr. Gottlieb. No, 510 has a requirement for registration.
And I think 503A actually lays out some criteria to try to
distinguish, you know, these illegitimate compounders from the
legitimate ones. So the language does exist and this could--
even 503A could be better interpreted in regulation. But I
think the compliance policy guide which you just quoted is a
very good start for that.
Mr. Griffith. I think they did a nice job in that guidance.
I am not going to say I would agree with every word of it, but
most of it is pretty good stuff and it indicates the FDA had
the authority to move forward even under the rules that they
now say they don't have the authority to do.
With that, I see my time is up and I yield back. But I do
appreciate all of you all staying through two vote series on a
long day. Thank you.
Mr. Pitts. The chair thanks the gentleman.
And with that, we again thank the witnesses for your
patience.
That concludes the questions of the members who are
present. There are other questions I am sure that other members
who are not here will also like to submit to you and we will
ask that you please respond promptly once you receive those
questions.
And I will remind members that they have 10 business days
to submit questions for the record, and Members should submit
those questions by the close of business on Thursday, June the
6th.
Very informative and important hearing. Thank you very much
for your attendance.
Without objection, the subcommittee is adjourned.
[Whereupon, at 1:50 p.m., the subcommittee was adjourned.]
[Material submitted for inclusion in the record follows:]
[GRAPHICS NOT AVAILABLE IN TIFF FORMAT]