[House Hearing, 115 Congress]
[From the U.S. Government Publishing Office]
EXAMINING IMPLEMENTATION OF THE COMPOUNDING QUALITY ACT
=======================================================================
HEARING
BEFORE THE
SUBCOMMITTEE ON HEALTH
OF THE
COMMITTEE ON ENERGY AND COMMERCE
HOUSE OF REPRESENTATIVES
ONE HUNDRED FIFTEENTH CONGRESS
SECOND SESSION
__________
JANUARY 30, 2018
__________
Serial No. 115-96
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
Printed for the use of the Committee on Energy and Commerce
energycommerce.house.gov
_________
U.S. GOVERNMENT PUBLISHING OFFICE
29-991 WASHINGTON : 2019
COMMITTEE ON ENERGY AND COMMERCE
GREG WALDEN, Oregon
Chairman
JOE BARTON, Texas FRANK PALLONE, Jr., New Jersey
Vice Chairman Ranking Member
FRED UPTON, Michigan BOBBY L. RUSH, Illinois
JOHN SHIMKUS, Illinois ANNA G. ESHOO, California
MICHAEL C. BURGESS, Texas ELIOT L. ENGEL, New York
MARSHA BLACKBURN, Tennessee GENE GREEN, Texas
STEVE SCALISE, Louisiana DIANA DeGETTE, Colorado
ROBERT E. LATTA, Ohio MICHAEL F. DOYLE, Pennsylvania
CATHY McMORRIS RODGERS, Washington JANICE D. SCHAKOWSKY, Illinois
GREGG HARPER, Mississippi G.K. BUTTERFIELD, North Carolina
LEONARD LANCE, New Jersey DORIS O. MATSUI, California
BRETT GUTHRIE, Kentucky KATHY CASTOR, Florida
PETE OLSON, Texas JOHN P. SARBANES, Maryland
DAVID B. McKINLEY, West Virginia JERRY McNERNEY, California
ADAM KINZINGER, Illinois PETER WELCH, Vermont
H. MORGAN GRIFFITH, Virginia BEN RAY LUJAN, New Mexico
GUS M. BILIRAKIS, Florida PAUL TONKO, New York
BILL JOHNSON, Ohio YVETTE D. CLARKE, New York
BILLY LONG, Missouri DAVID LOEBSACK, Iowa
LARRY BUCSHON, Indiana KURT SCHRADER, Oregon
BILL FLORES, Texas JOSEPH P. KENNEDY, III,
SUSAN W. BROOKS, Indiana Massachusetts
MARKWAYNE MULLIN, Oklahoma TONY CARDENAS, California
RICHARD HUDSON, North Carolina RAUL RUIZ, California
CHRIS COLLINS, New York SCOTT H. PETERS, California
KEVIN CRAMER, North Dakota DEBBIE DINGELL, Michigan
TIM WALBERG, Michigan
MIMI WALTERS, California
RYAN A. COSTELLO, Pennsylvania
EARL L. ``BUDDY'' CARTER, Georgia
JEFF DUNCAN, South Carolina
Subcommittee on Health
MICHAEL C. BURGESS, Texas
Chairman
BRETT GUTHRIE, Kentucky GENE GREEN, Texas
Vice Chairman Ranking Member
JOE BARTON, Texas ELIOT L. ENGEL, New York
FRED UPTON, Michigan JANICE D. SCHAKOWSKY, Illinois
JOHN SHIMKUS, Illinois G.K. BUTTERFIELD, North Carolina
MARSHA BLACKBURN, Tennessee DORIS O. MATSUI, California
ROBERT E. LATTA, Ohio KATHY CASTOR, Florida
CATHY McMORRIS RODGERS, Washington JOHN P. SARBANES, Maryland
LEONARD LANCE, New Jersey BEN RAY LUJAN, New Mexico
H. MORGAN GRIFFITH, Virginia KURT SCHRADER, Oregon
GUS M. BILIRAKIS, Florida JOSEPH P. KENNEDY, III,
BILLY LONG, Missouri Massachusetts
LARRY BUCSHON, Indiana TONY CARDENAS, California
SUSAN W. BROOKS, Indiana ANNA G. ESHOO, California
MARKWAYNE MULLIN, Oklahoma DIANA DeGETTE, Colorado
RICHARD HUDSON, North Carolina FRANK PALLONE, Jr., New Jersey (ex
CHRIS COLLINS, New York officio)
EARL L. ``BUDDY'' CARTER, Georgia
GREG WALDEN, Oregon (ex officio)
C O N T E N T S
----------
Page
Hon. Michael C. Burgess, a Representative in Congress from the
State of Texas, opening statement.............................. 1
Prepared statement........................................... 3
Hon. Gene Green, a Representative in Congress from the State of
Texas, opening statement....................................... 4
Prepared statement........................................... 6
Hon. Frank Pallone, Jr., a Representative in Congress from the
State of New Jersey, opening statement......................... 7
Prepared statement........................................... 8
Hon. Greg Walden, a Representative in Congress from the State of
Oregon, prepared statement..................................... 9
Hon. Fred Upton, a Representative in Congress from the State of
Michigan, opening statement.................................... 10
Prepared statement........................................... 11
Witnesses
Scott Gottlieb, Commissioner, United States Food and Drug
Administration................................................. 11
Prepared statement........................................... 14
Answers to submitted questions \1\........................... 236
George Williams, President-Elect, American Academy of
Ophthalmology.................................................. 61
Prepared statement........................................... 64
Answers to submitted questions............................... 249
Bruce Brod, Chairman, Congressional Policy Committee, American
Academy of Dermatologists...................................... 74
Prepared statement........................................... 76
Answers to submitted questions............................... 258
Shawn Hodges, Vice President, International Academy of
Compounding Pharmacists........................................ 84
Prepared statement........................................... 86
Jacob Olson, President and CEO, Skywalk Pharmacy, On Behalf of
The National Community Pharmacists Association................. 113
Prepared statement........................................... 115
Jenn Adams, Senior Vice President, Clinical Product Solutions,
Pharmedium Services............................................ 135
Prepared statement........................................... 138
Answers to submitted questions............................... 261
Molly Ventrelli, Vice President, Regulatory Affairs, Fresenius
Kabi........................................................... 144
Prepared statement........................................... 146
Answers to submitted questions............................... 268
Elizabeth Jungman, Director of Public Health, The Pew Charitable
Trusts......................................................... 151
Prepared statement........................................... 153
Answers to submitted questions............................... 273
Nancy Dargan, Former Patient of The New England Compounding
Center......................................................... 169
Prepared statement........................................... 171
Answers to submitted questions............................... 285
Submitted Material
Joint statement from the public health, manufacturing, and
outsourcing facility communities, submitted by Mr. Pallone..... 182
Statement of Hon. Michael D. Bishop, a Representative in Congress
from the State of Michigan, submitted by Mr. Upton............. 185
FDA slides, submitted by Mr. Green............................... 189
Statement of the American Society of Health-System Pharmacists,
submitted by Mr. Guthrie....................................... 196
Statement of the American College of Mohs Surgery, submitted by
Mr. Guthrie.................................................... 202
Statement of Avella, submitted by Mr. Guthrie.................... 206
Statement of the Outsourcing Facilities Association, submitted by
Mr. Guthrie.................................................... 208
Statement of the American Society of Cataract and Refractive
Surgery, submitted by Mr. Guthrie.............................. 211
Statement of the National Association of Chain Drug Stores,
submitted by Mr. Guthrie....................................... 222
Statement of the American Pharmacists Association, submitted by
Mr. Guthrie.................................................... 227
Statement of the American Academy of Allergy, Asthma & Immunology
and the American College of Allergy, Asthma and Immunology,
submitted by Mr. Guthrie....................................... 231
----------
\1\ The committee did not receive a response to Mr. Gottlieb's
submitted questions for the record by the time of printing.
EXAMINING IMPLEMENTATION OF THE COMPOUNDING QUALITY ACT
----------
TUESDAY, JANUARY 30, 2018
House of Representatives,
Subcommittee on Health,
Committee on Energy and Commerce,
Washington, DC.
The subcommittee met, pursuant to call, at 11:00 a.m., in
room 2123 Rayburn House Office Building, Hon. Michael Burgess
(chairman of the subcommittee) presiding.
Members present: Representatives Burgess, Guthrie, Barton,
Upton, Shimkus, Latta, McMorris Rodgers, Lance, Griffith,
Bilirakis, Long, Bucshon, Mullin, Hudson, Collins, Carter,
Green, Schakowsky, Matsui, Sarbanes, Schrader, Eshoo, DeGette,
and Pallone (ex officio).
Staff present: Adam Buckalew, Professional Staff Member,
Health; Karen Christian, General Counsel; Kelly Collins, Staff
Assistant; Zachary Dareshori, Staff Assistant; Paul Eddatel,
Chief Counsel, Health; Margaret Tucker Fogarty, Staff
Assistant; Adam Fromm, Director of Outreach and Coalitions; Ali
Fulling, Legislative Clerk, Oversight & Investigations, Digital
Commerce and Consumer Protection; Jay Gulshen, Legislative
Clerk, Health; Ed Kim, Policy Coordinator, Health; Bijan
Koohmaraie, Counsel, Digital Commerce and Consumer Protection;
Katie McKeogh, Press Assistant; Mark Ratner, Policy
Coordinator; Jennifer Sherman, Press Secretary; Danielle
Steele, Counsel, Health; Tiffany Guarascio, Minority Deputy
Staff Director and Chief Health Advisor; Samantha Satchell,
Minority Policy Analyst; Kimberlee Trzeciak, Minority Senior
Health Policy Advisor; and C.J. Young, Minority Press
Secretary.
OPENING STATEMENT OF HON. MICHAEL C. BURGESS, A REPRESENTATIVE
IN CONGRESS FROM THE STATE OF TEXAS
Mr. Burgess [presiding]. I would like to call the
subcommittee to order.
And I recognize myself for an opening statement.
Today's hearing marks the Health Subcommittee's first look
at the Compounding Quality Act, which passed under Title I of
the Drug Quality and Security Act nearly 5 years ago. Prior to
then, the last time Congress examined the drug compounding
issue was in 1997, when it passed the Food and Drug
Administration Modernization Act, touching upon the Food and
Drug Administration's authority to regulate compounded drugs
and establishing Section 503A in the Federal Food, Drug, and
Cosmetic Act.
A tragic outbreak of fungal meningitis in 2012, when the
New England Compounding Center shipped over 17,000 contaminated
vials of a compounded steroid medication throughout the
country, resulted in one of the worst and most fatal drug
safety incidents in the history of the United States, where
more than 750 people developed fungal infections in 20 states
and, subsequently, 60 people lost their lives. This outbreak
prompted Congress to act, with the Energy and Commerce
Committee taking the lead in the House, through a series of
investigations and a series of hearings on the issue.
Today we will convene two panels of witnesses. And I do
want to welcome back Dr. Gottlieb, Commissioner of the Food and
Drug Administration. Thank you for coming back to our
subcommittee this morning.
The agency has been very active over the last several
months on drug compounding, most recently, releasing the 2018
Compounding Policy Priorities Plan. Your insights today, Dr.
Gottlieb, are certainly appreciated.
Later in our second panel, we will hear directly from
representatives of the pharmacies, physicians, patients, and
manufacturers who will share their perspective on the
implementation of Title I under the DQSA. We will also have a
patient of the New England Compounding Center to share her
personal story from the 2012 incidents and her experience since
that time. All of the testimony from today's hearing are
critical in our understanding of the compounding issue as the
Food and Drug Administration works to strike the proper balance
that would continue to advance patient safety while ensuring
patients access to compounded medication.
Being a physician who has worked with compounding
pharmacists during my time in practice, I know the important
role and the value that these individuals serve in the delivery
of patient care. Compounded drugs serve a unique need of
patients that cannot utilize an FDA-approved product due to,
for example, an allergy to one of the product's ingredients or
the primary route of the product's administration. Many of us
remember the swine flu epidemic of 5 years when compounding for
the anti-flu medications in an elixir form was absolutely
critical to protect children who had been recently infected.
Because of the process involved in creating a compounded
medication, we all acknowledge the fact that proper oversight
is necessary, whether by the Food and Drug Administration
itself or a state's regulatory body, such as its board of
pharmacy. Preventing poor compounding practices that can lead
to contamination or erroneous product strength, quality, and
purity is the goal we all aspire to, so that another New
England Compounding Center does not happen. Thinking back to
that fungal meningitis outbreak, I was not only heartbroken by
the patients' lives lost or harmed, but I was also troubled by
what seemed to be missed opportunities that could have
prevented the tragedy.
Title I of the DQSA accomplished two things. First, the law
further clarified the Food and Drug Administration's authority
to regulate traditional pharmacy compounding practices under
Section 503A, which had seen several court challenges. Second,
it added Section 503B to the Federal Food, Drug, and Cosmetics
Act, creating a new category of drug compounders known as
outsourcing facilities. These outsourcing facilities engage in
larger-scale, national distribution of sterile drugs in bulk
quantities and have, thus, heightened statutory requirements,
such as complying with good manufacturing processes and being
subject to certain registration, reporting, and inspection
requirements.
Over the last 4 years, the Food and Drug Administration has
issued numerous draft and final guidance documents, proposed
and final rules, and a draft memorandum of understanding to
implement the Title I provisions. There has been discussion and
debate over the manner that the agency has used to implement
Title I.
In my home State of Texas, there already exists in statute
the framework and manner in which a compounding pharmacy should
conduct its practice. Other stakeholders have also expressed
concern around office-use compounding and the prescription
requirement. I hope these and other issues in the drug
compounding space will be discussed today.
So, I am encouraged by the interest of all the stakeholders
involved in this important debate, many of whom are represented
today. I am certainly encouraged by the commitment of the Food
and Drug Administration with Dr. Gottlieb's commitment to work
with Congress in ensuring that patients have access to products
that are tailored to their clinical needs while equipping
agency officials with the requisite tools to protect public
health.
Again, I want to welcome our witnesses and thank you for
being here.
And I will recognize Mr. Green, 5 minutes, for an opening
statement.
[The prepared statement of Mr. Burgess follows:]
Prepared statement of Michael C. Burgess
The Subcommittee will come to order.
The Chair will recognize himself for an opening statement.
Today's hearing marks the Health Subcommittee's first look
at the Compounding Quality Act which passed under Title I of
the Drug Quality and Security Act (DQSA) nearly 5 years ago.
Before then, the last time Congress examined the drug
compounding issue was in 1997 when it passed the Food and Drug
Administration Modernization Act, touching upon the Food and
Drug Administration's (FDA) authority to regulate compounded
drugs and establishing section 503A in the Federal Food, Drug,
and Cosmetics Act (FFDCA). However, the tragic outbreak of
fungal meningitis in 2012, when the New England Compounding
Center shipped over 17,000 contaminated vials of a compounded
steroid medication throughout the country, resulted in one of
the worst and most fatal drug safety incidents in U.S. history,
where more than 750 people developed fungal infections in 20
states and over 60 people died subsequently. This outbreak
prompted Congress to act, with the Energy and Commerce
Committee taking the lead in the House through a series of
investigations and hearings on the issue.
Today we will convene two panels of witnesses. First, I
want to welcome Dr. Gottlieb, Commissioner of FDA, back to the
Subcommittee this morning. The agency has been very active over
the last several months on drug compounding, most recently
releasing the 2018 Compounding Policy Priorities Plan. Your
insights today are certainly appreciated.
Later, we will hear directly from representatives of
pharmacies, physicians, patients, and manufacturers who will
share their perspective of the implementation of Title I under
DQSA thus far. We will also have a patient of the New England
Compounding Center to share her personal story from the 2012
incident and her experience since that time. All of the
testimonies from today's hearing are critical in our
understanding of the compounding issue as FDA works to strike
the proper balance that would continue to advance patient
safety while ensuring patients' access to compounded medicines.
Being a physician who has worked with compounding
pharmacists during my practice, I know the important role and
value these individuals serve in the healthcare delivery
system. Compounded drugs serve a unique need of patients that
cannot utilize an FDA-approved product due to, for example, an
allergy to one of the product's ingredients or the primary
route of the product's administration. Because of the process
involved in creating a compounded medication, we all
acknowledge the fact that proper oversight is necessary,
whether by FDA or by a state's regulatory body, such as its
board of pharmacy. Preventing poor compounding practices that
can lead to contaminations or erroneous product strength,
quality, and purity, is the goal we adhere to so that another
New England Compounding Center does not happen again. Thinking
back to that fungal meningitis outbreak, I was not only
heartbroken by the patients' lives lost or harmed, but also
troubled by what seemed as missed opportunities that could have
prevented this tragedy.
Title I of DQSA accomplished two things. First, the law
further clarified FDA's authority to regulate traditional
pharmacy compounding practices under section 503A which saw
several court challenges. Second, it added section 503B to
FFDCA creating a new category of drug compounders know as
outsourcing facilities. These outsourcing facilities engage in
larger-scale, national distribution of sterile drugs in bulk
quantities and thus have heightened statutory requirements,
such as complying with current good manufacturing practices and
being subject to certain registration, reporting, and
inspection requirements.
Over the last 4 years, FDA has issued numerous draft and
final guidance documents, proposed and final rules, and a draft
memorandum of understanding (MOU) to implement the Title I
provisions. There has been much discussion and debate over the
manner the agency has implemented Title I of DQSA. In my home
State of Texas, there already exist in statute the framework
and manner in which a compounding pharmacy should conduct its
practice. Other stakeholders have also expressed concerns
around ``office-use'' compounding and the prescription
requirement. I hope these and other issues in the drug
compounding space will be discussed today. So, I am encouraged
by the interest of all of the stakeholders involved in this
important debate--many of whom are represented here today--and
the commitment of FDA to work with Congress in ensuring
patients have access to products that are tailored to their
clinical needs while also equipping agency officials with the
requisite tools to protect public health.
I again want to welcome our witnesses and thank you for
being here. I look forward to your testimony.
OPENING STATEMENT OF HON. GENE GREEN, A REPRESENTATIVE IN
CONGRESS FROM THE STATE OF TEXAS
Mr. Green. Thank you, Mr. Chairman, for having this
hearing.
In 2012, the interstate distribution of contaminated
compounded drug products led to an outbreak of fungal
meningitis in 20 states, which tragically resulted in 64 deaths
and left 750 people with infections that were often severe and
cause long-term damage. The New England Compounding Center, the
NECC, the entity responsible for the compounding and shipping
of the contaminated drugs, had been the subject of prior
complaints and had been investigated by both the FDA and the
Massachusetts State Board of Pharmacy. However, in part,
because of uncertainty over the validity of Section 503A of the
Food, Drug, and Cosmetics Act, it was not clear which copy, the
FDA or the state, was on the beat, and the NECC continued to
operate.
Unfortunately, while it was the most fatal incident to
date, the NECC outbreak was not a one-off event. It certainly
wasn't the first tragedy and hasn't proven to be the last. Just
last year, we learned that at least 43 patients were left with
diminished vision from a steroid antibiotic injection
compounded by a Texas pharmacy. FDA studies have found quality
problems with drugs compounded in other pharmacies, including
sub- and super-potent drugs and contamination. According to one
report, from 1990 to 2005, FDA became aware of almost 240
serious illnesses and deaths associated with improperly
compounding products, with the actual number likely to be
greater since pharmacies are not required to report adverse
events to the FDA. The Pew Charitable Trust published a report
in 2014 that identified more than 25 reported compounding
errors or potential errors linked to more than a thousand
adverse events between 2001 and 2013.
Following that NECC outbreak, Congress finally took action
with the Compounding Quality Act, CQA, and the Drug Quality and
Security Act, DQSA, was signed into law in 2013. In a sideline,
I want to thank my colleagues Congressman Griffith and
Congresswoman DeGette because we worked together on a
bipartisan basis to solve this problem. It solved to protect
patients and provide industry with clarity for drawing a
distinct line between the authority between state boards of
pharmacy and the FDA. CQA made two key changes in
reestablishing the FDA role regarding traditional compounding
under Section 503A, creating a new category of drug compounders
deemed outsourcing facilities under Section 503B.
The NECC outbreak and other adverse events underscored the
need to establish a strong legal framework to provide for safe
compounded medications that meet patients' needs while
clarifying and strengthening oversight of such drugs to protect
public health. There was an obvious need to address the growing
number of enterprises that had cropped up during the time of
legal uncertainty between the states and the FDA. Many of these
enterprises had come to act like drug manufacturers operating
outside FDA's standard oversight, often failing to meet current
good manufacturing practices and skirting oversight by
inappropriately operating under the guise of 503A pharmacy.
DQSA was not perfect, and like all compromises, not every
problem was solved to everyone's satisfaction, and not everyone
got exactly what they wanted. During bipartisan, bicameral
negotiations, we tried to address as many discrepancies as we
could and satisfy the needs of patients, providers,
pharmacists, and manufacturers. What is ultimately important is
that DQSA fixed the problems that led to the deadly fungal
meningitis outbreak and required the FDA to succeed where in
the past it had not.
Compounded medications fill an important role in our
healthcare system, offer patients an option when an approved
drug does not fit their needs. Patients' ability to timely
access safe compound drugs is vital, and pursuit of this goal
is something I believe we all share. I understand questions
remain about the office stock, bulk lists, the memorandum of
understanding, the interstate distribution, and copies of FDA-
approved products, and other issues. More needs to be done to
foster a robust 503B sector, support traditional pharmacists,
ensure patient access to needed medications, and inform
providers on how they can get the drugs they need when they
need them, so they can successfully treat their patients.
As the FDA and stakeholders continue to work on the
implementation of DQSA, and the agency, patients, providers,
and industry continue to learn and adjust, I hope we can work
together to refine the rules of the road, so patient access
isn't unduly diminished and patient safety is upheld.
Thank you, Mr. Chairman. I yield back my time.
[The prepared statement of Mr. Green follows:]
Prepared statement of Hon. Gene Green
Thank you Mr. Chairman.
In 2012, the interstate distribution of contaminated
compounded drug products led to an outbreak of fungal
meningitis in 20 states, which tragically resulted in 64 deaths
and left more than 750 people with infections that were often
severe and caused long term damage.
The New England Compounding Center (NECC), the entity
responsible for compounding and shipping the contaminated
drugs, had been the subject of prior complaints and had been
investigated by both FDA and the Massachusetts state board of
pharmacy.
However, in part because of uncertainty over the validity
of Section 503A of the Federal Food Drug and Cosmetic Act, it
was not clear which ``cop''--the FDA or the state--was on the
beat and the NECC continued to operate.
Unfortunately, while it was the most fatal incident to
date, the NECC outbreak was not a one-off event.
It certainly wasn't the first tragedy and hasn't proven to
be the last.
Just late last year, we learned that at least 43 patients
were left with diminished vision from a steroid antibiotic
injection compounded by a Texas pharmacy.
FDA studies have found quality problems with drugs
compounded by other pharmacies, including sub- and super-potent
drugs and contamination.
According to one report, from 1990 to 2005, FDA became
aware of almost 240 serious illnesses and deaths associated
with improperly compounded products, with the actual number
likely being greater since pharmacies are not required to
report adverse events to the FDA.
Pew Charitable Trusts published a report in 2014 that
identified more than 25 reported compounding errors or
potential errors linked to more than 1,000 adverse events
between 2001 and 2013.
Following the NECC outbreak, Congress finally took action
and the Compounding Quality Act (CQA) of the Drug Quality and
Security Act (DQSA) was signed into law in 2013.
It sought to protect patients and provide industry with
clarity by drawing a distinct line of authority between state
boards of pharmacy and the FDA.
CQA made two key changes: re-establishing FDA's role
regarding traditional compounding under section 503A and
creating a new category of drug compounders deemed
``outsourcing facilities'' under section 503B.
The NECC outbreak and other adverse events underscored the
need to establish a strong legal framework to provide for safe
compounded medications that meet patients' needs while
clarifying and strengthening oversight of such drugs to protect
public health.
There was an obvious need to address the growing number of
enterprises that had cropped up during the time of legal
uncertainty between the states and FDA.
Many of these enterprises had come to act like drug
manufacturers operating outside FDA's standard oversight, often
failing to meet current good manufacturing practices and
skirting oversight by inappropriately operating under the guise
of a 503A pharmacy.
DQSA was not perfect, and like all compromises, not every
problem was solved to everyone's satisfaction and not everyone
got exactly what they wanted.
During bipartisan, bicameral negotiations, we tried to
address as many discrepancies as we could and satisfy the needs
of patients, providers, pharmacists and manufacturers.
What was ultimately important is that DQSA fix the problems
that led to the deadly fungal meningitis outbreak and require
the FDA to succeed where in the past, it had not.
Compounded medications fill an important role in our health
care system and offer patients an option when an approved
product does not fit their needs.
Patients' ability to timely access safe compounded drugs is
vital, and pursuit of this goal is something I believe we all
share.
I understand questions remain about office stock, bulks
lists, the Memorandum of Understanding and interstate
distribution, copies of FDA-approved products, and other
issues.
More needs to be done to foster a robust 503B sector,
support traditional pharmacists, ensure patient access to
needed medications, and inform providers on how they can get
the drugs they need when they need them so they can
successfully treat their patients.
As the FDA and stakeholders continue to work to implement
DQSA, and the Agency, patients, providers and industry continue
to learn and adjust, I hope we can work together to refine the
rules of the road so patient access isn't unduly diminished and
patient safety is upheld.
Thank you and I yield back.
Mr. Burgess. The Chair thanks the gentleman. The gentleman
yields back.
Pending the arrival of the full committee chairman, Mr.
Walden, let me recognize the gentleman from New Jersey, 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, Mr. Chairman.
I would like to submit to the record a joint statement from
the Association for Accessible Medicine's Biotechnology
Innovation Organization, the National Association of County and
City Health Officials, Pew Charitable Trusts, Pharmaceutical
Research and Manufacturers of America, PharMEDium, and Trust
for America's Health. If I could ask unanimous consent to have
a copy of it----
Mr. Burgess. Without objection, so ordered.
Mr. Pallone. Thank you.
[The information appears at the conclusion of the hearing.]
Mr. Pallone. Mr. Chairman, thanks for holding today's
hearing on the Compounding Quality Act, which passed with broad
support from stakeholders and bipartisan, bicameral support in
Congress in 2013. Passage of the Compounding Quality act was
about patient safety. Congress came together in response to the
horrible tragedy of actions by the New England Compounding
Center, or NECC, that led to 64 people losing their lives. And
despite a history of complaints and investigations by both the
FDA and the Massachusetts State Board of Pharmacy, NECC was
allowed to continue compounding products given to patients on a
scale and in a manner that should never have been allowed. The
new law was meant to clarify drug compounding laws. It was also
supposed to make clear the lines and requirements for
traditional pharmacies that want to compound and those
pharmacies that compound on a larger scale.
I think we all agree and support maintaining patient access
to compounded drug products. Undoubtedly, there are patients
with unique medical needs for which a traditional prescription
drug product is not appropriate, whether for pediatric
patients, seniors, or those with allergies. However, we must
all remember that compounded drug products are not without
risk. Compounded drug products are not reviewed by FDA prior to
coming to the market for safety and effectiveness. Traditional
compounding pharmacies are also not required to report on the
compounded drug products they produce or report adverse events.
While this law was intended to prevent another tragedy like
the one at NECC, adverse events associated with compounded drug
products are still occurring. Since passage of the law, there
have been more than 140 recalls associated with compounded
drugs. We have also seen reports of serious health events. For
example, just last summer, 43 patients suffered vision
impairment after receiving compounded eye injections of a drug
containing a combination of a steroid and an anti-infective
agent. Also, last year three infants received a compounded
morphine preparation that was 25 times the strength that was
indicated on the label, resulting in at least one
hospitalization. These are just two examples of why clearly
identified standards and requirements must be maintained if we
are going to protect patient health.
Recently, FDA released the agency's 2018 Compounding Policy
Priorities Plan identifying next steps the agency will be
pursuing in regards to implementing the Compounding Quality
Act, including revisions to current guidance. As FDA moves
forward, I would caution the agency to ensure that any
revisions that it makes do not enable an environment that could
allow for another NECC to occur. We must maintain appropriate
patient safeguards and clear lines between what activities are
permissible for traditional pharmacies and what activities are
permissible for outsourcing facilities. Patient safety and the
protection of public health must be at the forefront of any
guidance revisions that the FDA considers, and the American
people deserve confidence that the drug products they receive
are safe and held to strong quality standards.
So, I want to thank Commissioner Gottlieb and all of our
witnesses for being here today. I want to go beyond just
today's hearing, Commissioner, and mention that you have been
really great at trying to reach out to Members of Congress,
much more so than most of the agency leaders. So, thank you for
that. And I look forward to a robust discussion about the
implementation of the Compounding Act.
I yield back, Mr. Chairman.
[The prepared statement of Mr. Pallone follows:]
Prepared statement of Hon. Frank Pallone, Jr.
Thank you, Mr. Chairman, for holding today's hearing on the
Compounding Quality Act, which passed with broad support from
stakeholders and bipartisan, bicameral support in Congress in
2013.
Passage of the Compounding Quality Act was about patient
safety. Congress came together in response to the horrible
tragedy of actions by the New England Compounding Center (NECC)
that led to 64 people losing their lives. Despite a history of
complaints and investigations by both the FDA and the
Massachusetts State Board of Pharmacy, NECC was allowed to
continue compounding products given to patients on a scale and
in a manner that should have never been allowed. The new law
was meant to clarify drug compounding laws. It was also
supposed to make clear the lines and requirements for
traditional pharmacies that want to compound and those
pharmacies that compound on a larger scale.
I think we all agree and support maintaining patient access
to compounded drug products. Undoubtedly there are patients
with unique medical needs for which a traditional prescription
drug product is not appropriate, whether for pediatric
patients, seniors, or those with allergies. However, we must
all remember that compounded drug products are not without
risk. Compounded drug products are not reviewed by FDA prior to
coming to the market for safety and effectiveness. Traditional
compounding pharmacies are also not required to report on the
compounded drug products they produce or report adverse events.
And while this law was intended to prevent another tragedy
like the one at NECC, adverse events associated with compounded
drug products are still occurring. Since passage of the law,
there have been more than 140 recalls associated with
compounded drugs. We've also seen reports of serious health
events. For example, just last summer, 43 patients suffered
vision impairment after receiving compounded eye injections of
a drug containing a combination of a steroid and an anti-
infective agent. Also last year, three infants received a
compounded morphine preparation that was 25 times the strength
that was indicated on the label resulting in at least one
hospitalization. These are just two examples of why clearly
identified standards and requirements must be maintained if we
are going to protect patient health.
Recently FDA released the agency's 2018 Compounding Policy
Priorities Plan identifying next steps the agency will be
pursuing in regards to implementing the Compounding Quality
Act, including revisions to current guidance.
As FDA moves forward, I would caution the agency to ensure
that any revisions that it makes does not enable an environment
that could allow for another NECC to occur. We must maintain
appropriate patient safeguards and clear lines between what
activities are permissible for traditional pharmacies and what
activities are permissible for outsourcing facilities. Patient
safety and the protection of public health must be at the
forefront of any guidance revisions FDA considers. The American
people deserve confidence that the drug products they receive
are safe and held to strong quality standards.
I want to thank Commissioner Gottlieb and all of our
witnesses for being here today. I look forward to a robust
discussion about the implementation of the Compounding Quality
Act.
Thank you.
Mr. Burgess. The Chair thanks the gentleman. The gentleman
yields back.
The Chair now recognizes the gentleman from Michigan, Mr.
Upton, 5 minutes for an opening statement.
Mr. Upton. Well, thank you, Mr. Chairman, and I would ask
unanimous consent to put Chairman Walden's full statement into
the record.
Mr. Burgess. Without objection, so ordered.
[The prepared statement of Mr. Walden follows:]
Prepared statement of Hon. Greg Walden
It has been nearly 5 years since enactment of the
Compounding Quality Act as a part of the Drug Quality and
Security Act. The signing of that law was set in motion by an
unprecedented public health tragedy caused by the egregious
actions of a compounding pharmacy in Massachusetts. The New
England Compounding Center distributed contaminated drugs
across America to be injected into the spines and joints of
unsuspecting patients. Over 750 individuals were infected with
fungal meningitis, more than 60 lost their lives, and those who
were spared continue to suffer the devastating impact to this
day. In fact, one of the witnesses we will hear from, Nancy
Dargan, has bravely shared the heart wrenching details of her
near-death experience and the consequences she and her loved
ones continue to bear. While this devastating event was
historic in its magnitude, it was not the first time patients
had been harmed by improperly compounded products and it wasn't
the last.
Following the New England Compounding Center tragedy, this
Committee worked to get to the bottom of what went wrong-
clearly the system for oversight of compounding had failed to
protect public health. The Subcommittee on Oversight and
Investigations conducted a thorough examination, and published
a report that served as the basis for the policies of the
Compounding Quality Act.
While products approved by the FDA as being safe and
effective should be relied on in the majority of circumstances,
there is an appropriate role for compounded medical products in
our health care system. Certain patients have unique medical
needs and cannot be treated with available FDA-approved
products. Furthermore, as we'll hear from our physician
witnesses today, certain medical specialties require the
availability of compounded medicines in their offices to
provide timely and efficient treatment. In drafting the
Compounding Quality Act, this Committee sought to strike the
right balance.
Where medications are compounded in advance of a patient
specific prescription to be stored for future use, it is vital
that they be prepared under heightened standards for safety and
that FDA play a larger role. While it is important to maintain
patient access to medications that can be tailored to meet
their unique needs, it is just as important that sufficient
safeguards are in place to ensure these medications are safe,
work as intended, and prepared under sanitary conditions.
Pharmaceutical compounding has traditionally been regulated at
a state level, but when compounding begins to look more like
manufacturing we have learned that patients are at the greatest
risk. Over time, even before the 2012 meningitis outbreak,
Congress has sought to increase the FDA's oversight where
compounding goes beyond patient-specific activity. A
prescription written for a patient is what clearly delineates
between traditional compounding for an individual's needs, and
manufacturing.
While outsourcing facilities are intended to meet
healthcare providers' needs for office-stock compounded
products, it is also critical that implementation of the law
does not undermine our nation's drug approval framework. The
regulatory system for both innovative therapies and generic
drug products, reflects an intricate balance, keeping us on the
cutting edge of medicine while making more affordable
medications available to millions of Americans. It now falls on
FDA to uphold the integrity of that system, by making sure that
outsourcing facilities do not evade the requirements of the
Hatch-Waxman Amendments, and do not undermine the protections
in place that drive pharmaceutical research and development.
For FDA to achieve the goals of Congress, FDA must ensure
that outsourcing facilities do not compound products that are
essentially copies of approved drugs. That includes compounding
that consists solely of preparing an approved product for
administration as indicated in that product's labeling, or that
involves no more than trivial modifications to approved
therapies. FDA must also guarantee that bulk drug substances
are not used in compounding by outsourcing facilities, until
there has been a final determination that there exists a clear
clinical need to do so.
I'd like to thank all of our witnesses for being here
today, particularly Commissioner Gottlieb, to share your
expertise on this important topic. The Energy and Commerce
Committee is committed to making sure that patients have access
to safe and effective medicines that meet their needs, and this
Compounding Quality Act is an important aspect of that goal.
Mr. Upton. And also, a letter from our colleague, Mr.
Bishop, enter the letter into the record.
Mr. Burgess. Without objection, so ordered.
[The information appears at the conclusion of the hearing.]
OPENING STATEMENT OF HON. FRED UPTON, A REPRESENTATIVE IN
CONGRESS FROM THE STATE OF MICHIGAN
Mr. Upton. So, Mr. Chairman, the 2012 outbreak of the
fungal meningitis resulting from contaminated steroid
injections manufactured by the New England Compounding Center,
NECC, was certainly a failure of epic proportions. Of the 753
people that were sickened by the outbreak, 264 called Michigan
their home. Yes, we were the largest state hit. Nineteen of the
64 deaths caused by the tragedy were from Michigan, and three
of them were constituents of mine.
I was chairman of the full Energy and Commerce Committee at
the time that this happened, and we immediately launched a
bipartisan investigation to find out what went wrong. I am not
going to go through the full history of what happened then, but
I will say that those at the NECC who were responsible were, in
fact, brought to justice. And this committee crafted
legislation to empower the FDA to ensure that the heinous acts
of negligence like this one would never happen again. We wanted
to fix the problem.
That legislation, the Drug Quality and Security Act, DQSA,
is currently being implemented by the FDA, and it takes a
number of measures to ensure safety, not the least of which are
much-needed restrictions on the use of bulk compounded material
as opposed to FDA-approved products when there is not a
clinical need to do so.
I am pleased to see the new Commissioner here to update us
on how DQSA implementation is going and what we in Congress can
do to help move the process along. We appreciate cooperation,
and again, the cooperation of Members on both sides of the
aisle.
And I will yield back the balance of my time.
[The prepared statement of Mr. Upton follows:]
Prepared statement of Hon. Fred Upton
The 2012 outbreak of Fungal Meningitis resulting from
contaminated steroid injections manufactured by the New England
Compounding Center (NECC) was a failure of epic proportions. Of
the 753 people sickened by the outbreak, 264 call Michigan
home. My home state was the hardest-hit. Nineteen out of the 64
deaths caused by this tragedy were from Michigan and three of
them were constituents of mine.
I was serving as Chairman of the full Energy and Commerce
Committee at the time this all happened and immediately
launched an investigation to find out what went wrong. I won't
go through the full history of what happened then, but I will
say that those at NECC who were responsible were brought to
justice and this committee crafted legislation to empower the
FDA to ensure that heinous acts of negligence like this one
never happen again.
That legislation, the Drug Quality and Security Act (DQSA),
is currently being implemented by the FDA. It takes a number of
measures to ensure safety, not the least of which are much-
needed restrictions on the use of bulk-compounded material as
opposed to FDA-approved products when there is not a clinical
need to do so.
I am pleased to see Commissioner Gottleib here to update us
on how DQSA implementation is going and what we in Congress can
do to help move the process along.
Mr. Burgess. The Chair thanks the gentleman. The gentleman
yields back.
And we do want to thank all of our witnesses for taking
time to be here today and taking time to testify before the
subcommittee. Each witness will have the opportunity to give an
opening statement, followed by questions from members. We will
have two panels today.
The first panel, we will hear from Dr. Scott Gottlieb, the
Commissioner of the United States Food and Drug Administration.
Dr. Gottlieb, once again, we appreciate your being here
today, and you are recognized for 5 minutes for your opening
statement, please.
STATEMENT OF SCOTT GOTTLIEB, COMMISSIONER, UNITED STATES FOOD
AND DRUG ADMINISTRATION
Dr. Gottlieb. Thank you, Chairman Burgess, Ranking Member
Green, members of the subcommittee. I appreciate the invitation
to testify at today's hearing on implementation of Title I of
the Drug Quality and Security Act.
We are all here together today because, more than 5 years
ago, we grappled with the devastating consequences of the 2012
outbreak of fungal meningitis caused by the manufacturer that
was compounding under the guise of a state-licensed pharmacy
that shipped contaminated compounded drugs throughout the
country. It led to more than 750 illnesses and 60 deaths in 20
states.
Because of this tragedy, Congress acted to ensure that
something like this would never happen again. No one wants to
see another such outbreak occur, and I am personally committed
to ensuring that FDA does its part to help prevent future
deaths from poor quality compounded drugs.
The 2012 outbreak as well as other issues we have seen
through our compounding oversight underscore the need to
improve compounding practices and more robust oversight of
compounders, supported by close federal and state
collaboration. It also highlighted the need for a clear legal
framework that would provide for compounding to meet patients'
needs while also equipping the FDA with authorities to address
unlawful practices that threaten the public health.
Unfortunately, since enactment of DQSA, there have been
other tragedies and cases of serious and unnecessary patient
harm which reinforce why our work is so critical. The FDA's
compounding program is a priority for the FDA, given its
profound public health implications, and we are committed to
implementing the DQSA framework.
We have issued 24 draft guidances and final guidances, a
final rule, and three proposed rules, and a draft MOU with the
states. We have held eight meetings with the Pharmacy
Compounding Advisory Committee to discuss 48 bulk drug
substances nominated for use in compounding, as well as six
categories of drug products nominated for the list of drugs
that present demonstrable difficulties for compounding.
On the oversight and enforcement front, since enactment of
the DQSA, the FDA has conducted nearly 500 inspections and we
have issued more than 180 warning letters advising compounders
of significant violations of federal law. We have overseen more
than 150 recalls involving compounded drugs, and we have worked
with DOJ on multiple civil and criminal enforcement actions and
set up a joint task force with them.
But I know there is still a lot left to be done, and I know
that there are some who say we haven't implemented certain
aspects of DQSA with the speed you had hoped. We have had our
own challenges addressing certain aspects of this complex
framework, including our constant challenge to make sure we are
striking the right balance between safety and access, and
addressing the oftentimes very divergent views on these issues.
I want you to know I am personally committed and involved in
these efforts and committed to getting these things right, to
making sure that we strike a careful balance and take measure
of your concerns.
In implementing the DQSA over the years, FDA has aimed to
develop policies that support the growth of the outsourcing
facility sector. Compounding pharmacies and outsourcing
facilities can help meet the legitimate patient needs when an
FDA-approved drug is not available to meet such medical needs.
We know that we must balance the critical role that compounding
plays in helping patients and providers advance public health
while ensuring that compounders do so in a manner that protects
patients from poor quality compounded drugs and does not
undermine the drug approval process.
And so, our actions to date, as well as the comprehensive
2018 Compounding Policy Priorities that we unveiled a few weeks
ago, focus squarely on protecting patients from harm and
establishing regulatory clarity, so our outsourcing facilities
can meet important protections in Section 503B and our quality
standards.
One of my key goals is to make it more feasible and lower
cost for a large swath of pharmacies to transition to becoming
outsourcing facilities, which are subject to greater FDA
oversight. We are also working to help ensure patient access to
compounded drugs when they need them. For instance, we are
taking steps to help providers identify outsourcing facilities
that make, or would be willing to make, compounded drugs for
office stock to treat patients who have medical need for them.
Let me be clear on one thing. I am committed to getting the
things we have committed to done. All of the commitments made
under the plan I released 2 weeks ago will be completed in
2018.
I would like to just close by briefly mentioning another
critical public health matter. Today we took new action to
address the epidemic of opioid addiction. We took steps to
limit the dispensing of Loperamide, an OTC drug, that is
increasingly being abused for its opioid-like qualities when it
is taken at very high doses and dangerous doses. I hope you
will take the time to look at the statement we issued, as we
continue to work together to address this critical public
health crisis. There is no magic bullet to solving this crisis.
It is only going to be through continued and vigilant steps,
like the one we took today, that I can hope we can start to
reverse some devastating trends.
I look forward to answering your questions today and
continuing to share more with you during the year ahead, as we
build on our past efforts as part of our public health mission.
[The prepared statement of Dr. Gottlieb follows:]
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
Mr. Burgess. The Chair thanks the gentleman for his
testimony, and we will move into the question portion of the
hearing. I will begin with questioning and recognize myself for
5 minutes.
Commissioner, in the information you provided us, you had a
list of adverse events associated with drugs prepared by
compounding facilities in the past 5 years. Presumably, that is
the lifetime of the DQSA. The one at the top of the list has
been mentioned by a couple of people on the dais this morning,
in Texas, some steroid antibiotic eye injections that caused
problems with vision loss. Is there something more that could
have been done in DQSA to prevent this or was the problem found
more rapidly because of the tools that you were given in the
DQSA? Help us sort of understand. Here is something that
happened in my backyard. Is it something that we should have
worked harder to prevent or was, in fact, the outbreak less
than it would have been because you had tools to use?
Dr. Gottlieb. Well, thank you for the question,
Congressman.
I think, as we start to exercise these new authorities, we
are learning a lot. The scope of the kind of enforcement
activities we take have also changed. In the early days of
implementation and historically, a lot of the focus has been on
issues of sterility with things like eye drops or things that
are used intravenously or intramuscular injections.
I think what we are seeing more and more, and where we are
starting to focus more of our inspectional activities, is on
formulations that are compounded in ways where they might be
super-potent. The challenge is that, when the pharmacies make
potency errors, it is usually a logarithmic, log error, so
thereby a factor of 10 or 20. So, you can get potencies that
can cause significant harm.
I think this underscores the need to make sure that, when
drugs are being compounded on a wide basis and distributed on a
wide basis, it is done in facilities where we can apply GMP
standards to them. And this is, in part, why I think Congress
contemplated the whole creation of the 503B structure, where
drugs that would be used on a wider scale would be compounded
under that kind of supervision.
Mr. Burgess. Let me ask you a question. Obviously, it was
before your tenure when we had the hearings after the New
England Compounding Center problems. But it was clear to some
of us during the course of those investigations and the work
that the committee did--and Chairman Upton was correct to
reference it; this committee, the full committee, took the
leadership on this issue. But there were places where the FDA
clearly fell short of its responsibility to protect public
health, despite what appeared retrospectively to be clear
warnings that the New England Compounding Center was engaged in
dangerous activities. So, are you confident that the FDA now
has the clear authority it needs to ensure that we don't see a
repeat of those things that happened in 2012?
Dr. Gottlieb. I testified at those hearings as a private
citizen in 2013 here in Washington. I was working at a think
tank at the time and weighed in at the time. I think I felt
what Congress contemplated was a framework that gave the FDA
the proper tools to provide oversight over this industry. But I
think we need to keep in mind that we are now implementing a
framework on an industry that is vast, that grew up, that was
allowed to grow up largely outside regulatory purview for a
long period of time, and retrofitting a regulatory framework
back onto an already existing industry is always a difficult
task.
Do I believe the authorities and the tools that we are able
to exercise are robust? I do. I think that it is going to take
time to get them fully implemented and get the kinds of tools
and practices we want applied over that industry. And it is
superimposed on an environment where, admittedly--and people
have good arguments on both sides of this debate--there has
been some discussion around how FDA is using those authorities
and whether they are using them in an appropriate fashion. I
believe we are and I believe we need to continue to move
forward.
Mr. Burgess. Yes, I expect we may hear about that this
morning in our second panel. I guess that is the concern. Or
what I would like to ask is the efforts that you and the agency
have taken to engage the physician community, patient
community, other stakeholders, where they may have perhaps the
feeling that things have tightened up too much.
Dr. Gottlieb. Well, this isn't going to work unless we are
working closely with the providers and the state authorities.
This law, Congress contemplated a framework that very much was
envisioned where FDA would have close collaboration with
medical societies and state authorities, and there was a lot of
shared jurisdiction between the Federal and the state framework
around both the 503A and the 503B facilities. States dually
inspect a lot of the 503B facilities.
So, I think it is going to be very important for us to
continue to work closely with the state communities and the
provider groups. I believe we have. I think that there is more
alignment there than perhaps is widely perceived, as obviously
some 503A pharmacies that want to engage in certain practices
where there is a line that we need to draw to make sure that we
are providing the proper oversight, and I think we are going to
hear about that tension today. I think that is a large place
where we still have some area of disagreement.
Mr. Burgess. Very well. I want to be respectful of
everyone's time because we do have a long hearing today. I am
going to recognize Mr. Green for 5 minutes for questions.
Mr. Green. Thank you, Mr. Chairman.
Thank you, Dr. Gottlieb, for being here this morning, but
also the good work you are doing at the FDA.
I appreciate the continued emphasis the FDA has put on the
issue of compounding drugs and hope to keep working with the
agency on implementation in our shared goal of striking the
right balance, so we can promote patient access without
compromising patient safety. I am encouraged to see the FDA is
actively working to implement the patient safety measures that
are included in the DQSA.
In particular, I am pleased to see that FDA is taking steps
to encourage registration of 503B outsourcing facilities. In
your 2018 Compounding Policy Priorities Plan you suggested the
FDA will be taking a more risk-based approach to the
development and implementation of current good manufacturing
practices, or CGMPs. I understand FDA is working on revising
the 2014 draft guidance to apply CGMP requirements in a way
that is tailored to the nature of the specific operations
conducted by an outsourcing facility and move away from one-
size-fits-all. I appreciate the agency's goal of improving
patient safety by making the regulatory framework more flexible
by recognizing volume as a factor in its risk-based evaluation.
Can you elaborate more about the agency's thinking around
what has been referred to as ``503B-light''?
Dr. Gottlieb. Thanks for the question, Congressman.
What I am envisioning is a framework where--the GMP
standards are not a fixed standard. It is a risk-based
standard. We want to try to devise that framework in a way
where we could titrate the level of the regulatory touch to
what the facility is doing, the size of the facility, how many
drugs they are developing, how they are shipping them, whether
the drugs are oral drugs or they are parenteral drugs that are
going to be injected, which would be sterile drugs and have
higher risk.
The idea is that, by trying to adjust the level of the
regulatory oversight to the level of risk, we could potentially
allow more 503A facilities to make the conversion into being
503B facilities. That is why we are taking the time to revise
that guidance.
There are things where we have some flexibility, like
retention of samples, lot release, the stability studies that
we require, where if it is a pharmacy doing something on a
small scale, not shipping widely, compounding drugs that are
relatively low-risk, we might be able to dial back some of that
level of regulatory oversight versus someone who is engaging in
larger-scale manufacturing. But, again, with the goal of seeing
more 503A pharmacies become 503B pharmacies where they are able
to engage in the kinds of things that some pharmacies want to
do.
We want to bring down the cost of doing that. We have done
some economic analysis around what it would cost. I think it is
still a little bit too expensive to see some of the small 503A
pharmacies opting into that. So, we are trying to take another
crack at that.
Mr. Green. OK. Thank you.
And I do have concerns about the possibility of creating a
two-tiered system. In the pursuit of flexibility, I am
concerned of the impact this may have on 503B facilities that
compound biologics, which are especially vulnerable to
degradation.
How would you respond to these concerns? Can you tell me
how you plan to ensure that CGMPs that apply to 503Bs will hold
these facilities to the highest standards of sterility and
stability?
Maybe I didn't understand that language.
[Laughter.]
Dr. Gottlieb. I understand your concerns. I share them. The
first thing I am going to do is come up with a better name for
it than ``503B-light,'' before that takes hold.
But I will tell you that we are very mindful of that. So,
for example, you reference biological products. They are
particularly vulnerable to contamination and to bacterial
growth. That would be something that would be higher-risk,
where we would apply more oversight.
We are talking about trying to create a standard that is
flexible, as is all our GMP oversight. It is a risk-based
framework. If a pharmacy is engaging in small-scale
manufacturing of relatively low-risk products, they wouldn't be
subject to all of the same requirements that someone who is
engaging in large-scale manufacturing of higher-risk sterile
products would be. As they move through the continuum of risk,
our level of oversight would increase. It needs to be a
flexible standard. It is a flexible standard in every other
realm of our regulation. It ought to be here. But you are
absolutely right that there is a continuum of risk, and we need
to be very mindful that we are matching our regulatory touch
appropriately to that level of risk.
Mr. Green. Could you submit your economic analysis for the
record, for the committee?
Dr. Gottlieb. I can provide it just off the cuff right
here. When we looked at it--and again, this was very
preliminary work and it is in draft form--but when we looked at
it, we estimated that it would cost a large manufacturer about
a million dollars to become a 503B facility, a large pharmacy,
and a medium-sized pharmacy, about $600,000. We think that
there are things we can do to further titrate the level of
regulatory touch, that there are more buckets. Because, again,
a 503A pharmacy that wants to engage in relatively low-risk
compounding but still ship, but they are developing low-risk
products on a small scale in small batches, there are ways, I
think, to adjust the level of regulation to more appropriately
match the level of risk that they are creating.
Mr. Green. Well, I understand you want to use resources
where the problem is.
Dr. Gottlieb. Exactly.
Mr. Green. And I appreciate that.
Dr. Gottlieb. We want to be efficient.
Mr. Green. Thank you, Mr. Chairman. I know I am out of my
time.
Mr. Burgess. The Chair thanks the gentleman. The gentleman
yields back.
The Chair recognizes the gentleman from Texas, the vice
chairman of the committee, full committee, Mr. Barton, 5
minutes.
Mr. Barton. Thank you, Mr. Chairman.
And, Commissioner, thank you for being here. I want to echo
what Mr. Pallone said. You have been accessible, and we
appreciate your personal availability to the members of the
subcommittee.
I have been on this committee for 32 years. We have got an
ongoing sense of friction or tension between the FDA and the
compounding pharmacist. It is kind of a love-hate relationship.
A lot of my compounding pharmacists in Texas are fairly
active in the national compounding associations. They have a
feeling that the big, old bad federal FDA picks on them. How
would you respond to that? Do you think your FDA picks on
compounding pharmacists? Or do you think that they are being a
little bit too sensitive?
Dr. Gottlieb. Well, I am not going to comment on their
feelings and their motives. I am certainly sensitive to the
concerns; I would say that, Congressman. This is an important
reason why we want to make sure we are working closely with the
states. Because I think if we are working cooperatively with
the states, and the states are able to assert their
responsibilities and obligations under DQSA, but in concert
with us, I think that the more that we can rely on local
regulation, the more that local pharmacies are going to feel
that they have a closer continuity to the nexus of the
oversight, if you will.
Mr. Barton. OK. Well, that leads to my next question. It is
almost like you and I coordinated. I was going to ask this, you
were going to answer that, then I would follow up.
What is the current relationship in terms of a working
relationship or a cooperative relationship between the FDA and
the state regulatory authorities that oversee compounding
pharmacists? Do you think it has improved? When we had the
problem back in 2010-2011 that led to the bill that you have
talked about, Massachusetts and the Federal FDA didn't seem to
get along at all. They didn't talk to each other, didn't share
information. Today would you say that that relationship has
improved, is good? How would you characterize it?
Dr. Gottlieb. Well, I will tell you the relationship is a
lot better today and gets better with time. I think it is
continuing to expand in terms of the scope of the collaboration
and just through the contact we are having with state
authorities. Those relationships are important to sound
regulation being built. We invite states to join us on
inspections. We hold monthly meetings with the National
Association of Boards of Pharmacy. We provide training to state
compliance officers. There are frequent telecons with state
officials.
You don't have to take my word for it. You could look at
the GAO report in 2016 that looked at this very question of
what the perception was of the states of FDA's communication
with the states, and 60 percent said very or somewhat
satisfied. They were very or somewhat satisfied with the
communication. Now a ``D'' usually doesn't sound good, but in
this context I think it was. It was supportive of my contention
that the relationships are much improved from where they were
when I was at FDA the last time, prior to NECC. Twenty-three
percent reported they were dissatisfied. We want to work on
that. I think, hopefully, if I come back here a year from now
and we are talking about this, we are going to be able to talk
about an even more cooperative environment.
Mr. Barton. With respect to the opioid crisis, are there
some special task forces, special programs, extra effort being
utilized right now between the FDA and the state regulatory
authorities? And kind of as a secondary question, would you
consider the opioid crisis more of a federal issue or a state
issue, or is it about 50/50?
Dr. Gottlieb. Well, I think it is an everything issue. I
have said before that I think that this is beyond the scope,
certainly, of any one agency, but even the Federal Government,
to try to tackle it. We are going to need to work closely with
local officials to try to address this crisis. And we have been
doing that. We have had a lot of conversations with local
officials, state AGs, on different things that we could be
doing in collaboration with the states around various aspects
of this crisis.
I would say that the one thing that I am still very
concerned about is the level of federal oversight in the IMFs,
in the international mail facilities. I have spoken with some
of the Members about this, and trying to get more resources
into those facilities, particularly FDA resources. We play an
important role in those facilities doing track and trace and
analysis on some of the synthetic fentanyl coming in and doing
investigations to trace them back to their source. And that is
a big concern of mine.
Mr. Barton. The last question, the Pharmacy Compounding
Advisory Committee currently has no one on it who is a
compounding pharmacist. Don't you think there should be at
least one voting member who is an actual compounding pharmacist
on that committee?
Dr. Gottlieb. We are going to be issuing a solicitation
probably within days--the FR notice is with my office--to
solicit a new member or members on that committee. So, there
will be an opportunity to expand the composition of that
committee. As you know, there are 12 members on that committee.
One is appointed by the NABP, one by USP. It leaves 10 members.
Of those, seven are licensed pharmacists. I think five are
physicians in total. So, there is good clinical representation.
To the extent that someone with a business perspective of being
a pharmacist can add to the composition of that committee in a
thoughtful way, that is something we would certainly think
about.
There is one compounding pharmacist on the committee. He is
the industry rep.
Mr. Barton. But he doesn't get to vote.
Dr. Gottlieb. He doesn't get to vote, you are right. We
will certainly take this into consideration. I have heard the
concerns of Members on this. We will certainly take it into
consideration as we think about the new solicitation.
Mr. Barton. I would encourage that.
And I yield back.
Mr. Burgess. The gentleman yields back. The Chair thanks
the gentleman.
The Chair recognizes the gentlelady from California, Ms.
Eshoo, for 5 minutes, please.
Ms. Eshoo. Thank you, Mr. Chairman, for holding this
hearing.
And, Commissioner Gottlieb, it is good to see you, and
thank you for your testimony and your work on this issue.
We spoke, I think it was last summer, about--at that point,
there was a recent incident of patients being harmed by
compounded products. Specifically, there were 50 patients, some
of whom went blind after receiving a compounded antibiotic
during cataract surgery last July.
I was talking to a doctor friend this last week. I said,
``What's the most common surgery in the country?'' And he said
cataracts. So, that really broadens this out when you think of
50 patients, some of whom went blind during their cataract
surgery. It wasn't too regular for them.
Obviously, we need to do everything we can to protect
patient safety, so that these incidents stop happening,
including, I think, following up on the warning letters.
There are two areas that I have always thought that are
absolutely fundamental to what we do, both when I was in county
government and here in the House of Representatives. That is
public health and public safety. The two are combined in this
issue.
So, what I want to ask you is, of the dozens of warning
letters posted by FDA, how often have you pursued enforcement
action? And what else can the agency do with its enforcement
resources to ensure that compounded drugs are safe?
Dr. Gottlieb. I appreciate the question. It gets at
something that we are trying to work, which is to improve our
collaboration with DOJ to try to make sure that we can bring
enforcement action when we see something particularly
egregious, so we issue a warning letter and a firm is non-
compliant. That was the genesis of the task force that we
formed with DOJ. It is early days; I think it is yielding
dividends in terms of our ability to work cooperatively. But
this is something that we are looking at, pushing on, trying to
do more of.
Ms. Eshoo. Have there been any enforcement actions?
Dr. Gottlieb. There has absolutely been enforcement
actions, and there is activity that we have in progress.
Obviously, we are always working on various activities. But I
am hopeful that we will be able to continue to work effectively
with DOJ in this regard.
Ms. Eshoo. In the two sections of the Compounding Quality
Act--let me say something, because I listened to the
conversation earlier about the FDA, what Congress did, what
happened, and then, what Congress did. I think it is important
for all of us to recall that the FDA had not been given
authority by the Congress in this very area when the tragedy
that took place out of Massachusetts, that spread out over the
country, took place. So, I know there are a lot of questions to
be raised, but the FDA did not have the authority. In my book,
I think that the Congress didn't maybe on a proactive basis
examine the issue and give the agency the authority.
At any rate, in the two sections of the Compounding Quality
Act, it defines that drugs may only be compounded from bulk
drug substances when FDA-approved drugs are in shortage. Now,
recently, the agency announced enforcement discretion related
to an interim list of substances that include more than a
hundred approved drugs.
So, what specific steps are you going to take to ensure
that there is a legitimate clinical need for the bulk drug
substances currently being used by compounders and how are you
going to enforce this?
Dr. Gottlieb. I think you are referring to the 503B bulk
drugs list, right?
Ms. Eshoo. Right. Right.
Dr. Gottlieb. So, as you know, we received about a thousand
nominations for different drugs to be on that list. We have
selected 200 that we allowed onto that list under what we call
Category I drugs. Now what we need to do is go through and
reexamine all 200 to make sure they belong on that list. And we
believe some of them are going to fall off and perhaps many
will fall off. Some might be added, but probably many are going
to fall off.
We are going to issue in March a guidance document that I
outlined in the 2018 plan we put out that is going to define
the parameters in which we are going to do those assessments.
And then, we need to go through and assess each drug
individually, which, as you know, is a resource-intensive
process. Each evaluation is between 20 and 80 pages long.
Probably the first complement of drugs that we will render
a decision on will be this fall. It is probably going to be a
small number. It may be five drugs. But we need to go through
that entire list.
But it is important to put in perspective where that 200
came from. Those were drugs that were currently being
compounded off of bulk substance at the time that this law was
implemented. So, what we effectively did was freeze the market.
What we said was we don't want to create more compounding, but
we also don't want to start pulling things out of the
marketplace and create access issues, especially with respect
to the outsources, because we want to see this industry grow
up, for one. And on the second hand, we have now new regulatory
tools to assert good manufacturing practices. So, we can
provide more oversight. So, the idea was to freeze the market
while we, then, did those assessments, which is what we are
doing now.
Ms. Eshoo. Thank you very much, Commissioner. I couldn't
mean that more. You are in such an important role in the life
of our country. So, thank you very much.
Thank you, Mr. Chairman.
Mr. Burgess. The Chair now would like to recognize the
gentleman from Kentucky, the vice chairman of the Health
Subcommittee, Mr. Guthrie.
Mr. Guthrie. Thank you, and thank you, Mr. Chairman.
Thank you, Commissioner, for being here today.
I kind of want to follow up on what was just said. Five
years ago there was a judge in Kentucky, a very prominent
citizen, Eddie Lovelace of Albany, Kentucky, who went in for a
routine procedure and was contaminated with medicine from the
New England Compounding Center and died just shortly after what
was going to be a routine procedure. Obviously, his family and
the whole community is devastated, and Dr. Lovelace is just one
person who was affected by this awful outbreak. And this was
tragic and it is the reason I believe we must ensure compounded
drugs are safe while striking a good balance of access to
compounded drugs.
It is the theme of what you have said this morning, but I
thought I would just give you a more open-ended look at it.
Because in your testimony you mention the balance that is
needed. And so, I just want to give you the floor to, how are
you ensuring that Americans have access to lawfully-marketed
compounded drugs while ensuring safety? You have addressed that
just earlier, but I just give you the time.
Dr. Gottlieb. I think the way to ensure that, to be very
direct, is to make sure this law gets implemented. I think that
this was a good vision by Congress and it is a good framework
that provides FDA with the tools that it needs to provide
proper oversight. We need to now make sure it gets implemented.
I think where we are going to be able to continue to
improve the posture of the industry, and the ability of this
industry to provide the critical products that patients need
and access to drugs, is going to be to try to see the 503B
outsourcing sector become more viable. I think many of us, when
this law was first implemented, envisioned that that sector
would grow much more quickly than it has. And I think if there
are things that we can do through regulation, and I think that
they are, to help that industry continue to expand, that is
going to be important because, ultimately, that is going to
provide more access to the kinds of sterile drugs that some
people need on a wider scale and need to be distributed to
institutions. The 503A facilities provide a critical function
on a local level, giving patients differentiated products
through the practice of pharmacy, so that they can get products
that are individualized, tailored to their clinical needs.
Mr. Guthrie. Do you think 503A should report adverse
outcomes to the FDA?
Dr. Gottlieb. As you know, the bulk of the adverse events
that are reported by 503 facilities are typically either not
reported or reported to the states. The states do share that
information with us. They are not directly reported to FDA.
Would it help FDA target its inspections better if they had
access to that information more readily? I would have to say it
would. It would make it more efficient. A lot of our
inspections of 503A facilities are for-cause inspections, are
on the basis of information. But I think that this is also an
area where, through our cooperation with the states, we are
going to get access to that information where we need it.
Because if we are working closely with the states, they are
going to help guide us where we should be inspecting. Because,
for example, a 503A facility might be engaging in activities
that tip it over into being a 503B and subject to the federal
scheme.
Mr. Guthrie. Thank you. Thank you for those answers.
And if I could change the subject just for about a minute
or so left, I had an oncologist that contacted my office. Her
daughter is an intern in the office. I know her pretty well.
And she was stating concern on the shortage of saline, so to
change it a little bit. She said it has been exasperated by the
flu epidemic this year. We see these shortages in just basic
medicines. And so, can you please provide the most recent FDA
developments of the saline shortage?
Dr. Gottlieb. There are two different components to this,
or, actually, three different components to this. There were
these small bags that were in shortage prior to the hurricane
that struck Puerto Rico, the 100-milliliter bags that are
typically used to dilute drugs and, then, administer drugs to
patients. That shortage was exacerbated by the hurricane
because one of the primary manufacturers of those bags is
located in Puerto Rico and was knocked out of production. That
facility is now back in full production. In fact, all the
facilities that we have concerns about in Puerto Rico are now
back on grid power and most of them are at full production.
And we have brought in additional supply from additional
facilities out of ex-U.S. manufacturing sites, to make up for
that shortfall. So, there should be much more supply coming
into the market.
There is also a shortage of the larger-volume bags. While
we haven't declared a shortage, there are spot shortages of the
1-liter bags that are used for volume repletion, and those are
also being strained by the flu, the flu outbreak. We have taken
additional steps to bring in additional supply of the 1-liter
bags as well.
There is also some tight supply of the empty 1-liter bags
because a lot of compounding pharmacies and hospitals, when
they can't get access to filled bags, they buy empty bags and
fill them themselves in a compounding-type facility.
We have taken additional steps. We are going to have more
to say about this on Thursday. I was going to put it out today,
but we were delayed in getting our information out. We are
going to be putting out a statement on Thursday talking about
the steps we are taking to get more of those empty bags onto
the market. Some of those were manufactured in Puerto Rico.
I will just close by saying that the time it takes for a
bag to go from the manufacturing line to your hand in the
hospital as a clinician is about 6 weeks. I don't know this
isn't a more efficient supply chain, but that is what I have
been quoted. It takes weeks for it to make its way to the
provider setting. And so, the additional supply that we have
brought on--and it is substantial--is going to take some time
to flow through the market.
Mr. Guthrie. Thank you for your attention to that. You all
have been really good to work with.
Thank you.
Mr. Burgess. The Chair thanks the gentleman. The gentleman
yields back.
The Chair recognizes the gentlelady from Illinois, 5
minutes for questions, please.
Ms. Schakowsky. Thank you, Dr. Gottlieb. But I want to
apologize that I missed much of your testimony. We have a
number of hearings going on that I had to be at.
I also wanted to thank you for meeting with some of us
about Essure, the contraceptive device that I know has harmed
many women, from meeting with some of those women. So, I hope
we can continue that conversation because I am very concerned
about it.
Most people presume that the prescription that the doctor
writes for them, and they fill it, is safe and effective. This
is true because the FDA is considered the absolutely gold
standard in drug review.
We have all talked about now the 64 people who tragically
died because of this drug at the New England Compounding
Center. So, obviously, that was an impetus for passing the
Compounding Quality Act to improve safety.
And so, I wanted to just say that drugs that enter the
bloodstream, the eye, the spine, are supposed to be sterile,
but the FDA has received adverse events reports that these
compounded products were contaminated, reminiscent of the
problems at the NECC.
There have also been reports of sub-/super-potent drug
products in 2016. Three babies received compounded morphine
that was 20 times stronger than the label indicated. One of
those infants had to be rushed by helicopter to a nearby
children's hospital.
So, here's my first question: Commissioner Gottlieb, the
FDA has been active in implementing the Drug Quality and
Security Act. There have been over two dozen guidance documents
issued, four rules, numerous public engagements focused on
proper implementation of this law. While these are meaningful
steps, what more can we do to reduce the number of adverse
events associated with compounded drug products?
Dr. Gottlieb. I will just start out by echoing your
concerns, Congresswoman. All drugs have risks. We know that.
But I don't think anyone should be put at risk because a drug
was improperly manufactured. At the very least, we should
guarantee that a drug that purports to be manufactured in a
certain way and purports to be sterile is actually a sterile
product. That is the bedrock and the essence of what we are
trying to achieve with respect to the authorities under this
law.
I think that there are things that we can do going forward,
including continued implementation. We have heard the concerns
of Congress that certain aspects of how we have implemented
this have been slower than Congress expected. I think we didn't
fully appreciate the complexity of this law. But I think, as we
continue to implement this framework, we are going to be able
to exert even better and more efficient oversight. And that is
going to increase the level of safety and assuredness that the
public can have.
I think there is more that we can do on the enforcement
side as well, getting back to the other question. That is going
to be an area that we continue to look at, both in terms of
what we are doing, how we target our inspections based on what
we are learning, looking at issues like potency now because we
see those coming up more, as well as what additional resources
we can put against it.
This is a program--and I don't want to get too deep into
the resource question; I will save it for an appropriations
hearing, but----
Ms. Schakowsky. Feel free. Feel free.
[Laughter.]
Dr. Gottlieb. But this is a program where we do operate by
in some cases begging, borrowing, and stealing from other
aspects of the agency, other parts of the agency. For example,
the team that I have, the policy team in the Drug Center that
is working on the guidance development that you referenced and
a lot of this policy development, is four people. They borrow
resources from the review divisions, but, remember, those
reviewers that they are tapping have PDUFA goals and BsUFA
goals and GDUFA goals. They have user fee goals against their
time that they have to prioritize their time in certain ways.
So, I think that there is certainly an opportunity to think
about how we can grow this program in ways that could better
address some of those safety issues.
Ms. Schakowsky. What more do you think the FDA could and
should do to ensure safety at 503A compounding pharmacies?
Dr. Gottlieb. I think getting in place the MOU is going to
be an important step. The MOU will provide for adverse event
reporting back to FDA through the states. And so, I think that
as we get that framework in place, I think that there is going
to be a lot more we could do to better target our inspectional
resources in areas of risk, in areas where the 503A facilities
might be crossing into being a 503B facility that would be
subject to GMP standards.
So, I am hopeful. We are making good progress on that. We
are going to have it out this year. I am hopeful that, as we
get that agreement in place with the states, that is going to
increase our level of oversight.
Ms. Schakowsky. Well, we will be looking at that. Thank you
very much.
I yield back.
Mr. Burgess. The gentlelady yields back. The Chair thanks
the gentlelady.
The Chair recognizes the gentleman from Michigan, 5 minutes
for questions, please.
Mr. Upton. Thank you, Mr. Chairman.
And, Dr. Gottlieb, it is good to see you here again. We
appreciate your go-to attitude in trying to get things right.
We understand that and we are with you every step. We
appreciate your work on opioids, something that impacts every
one of our districts.
And I have to say, as we worked on the Cures legislation
out of this committee, the $500 million extra that we added to
the FDA budget was almost a no-brainer. So, we appreciate the
work of your crew, and we want to make sure that you have the
resources to make sure that things, in fact, are safe and that
you are not missing any steps.
I have got a couple of specific questions for you.
Hopefully, I can get through all three.
It is critical that, until the clinical need list is
issued, the FDA not permit bulk drug substances to be used in
compounding, absent a final determination of clinical need,
once all statutory criteria have been satisfied. Can you
confirm that, once the FDA has identified its criteria for
clinical need, that bulk drug substances, including those that
the FDA has currently placed in Category I, would not be
permitted to be used in compounding, absent such a
determination?
Dr. Gottlieb. Well, we have put out the essential copies of
this, which you know, the essential copies guidance. We are
going to have the criteria for the development of the bulk
drugs list for the 503B facilities, which is what I believe you
are referring to, because we are further along on the bulk
drugs lists for the 503B facilities, we will have that criteria
out in March. And by the end of the year, we will have
specified some bulk drugs that should either come on or off
that list. There could be some that fall out pretty quickly
from that list, based on safety considerations or a clear lack
of clinical need. And so, we are going to do those assessments.
Then, we are going to also have to contemplate how we
change our inspectional priorities to prioritize inspecting or
taking action on the basis of 503B facilities compounding drugs
that might not be on that list. Right now, under our risk-based
framework, we need to change some protocols in terms of how we
go about looking for some of those other questions, to your
point.
Mr. Upton. Is the President's budget going to include more
money for inspections?
Dr. Gottlieb. Well, I don't want to get ahead of the
President. So, I am not fully aware of what is going to end up
in the budget. It is probably a question best put to OMB at
this point.
Mr. Upton. It was never Congress' intent that small tweaks
to approve drugs, like minor changes in concentration or
inactive ingredients, would satisfy the criteria for clinical
need and open the door to compounding from bulk substances
under the DQSA. Would you agree that a clinical need can only
be found where there exists a genuine patient need unable to be
addressed by approved drug products requiring a significant
change from the approved drug?
Dr. Gottlieb. Well, again, Congressman, I don't want to get
ahead of my career officials who right now are drafting
guidance to define that very question. But the type of
definition that you put forward would certainly seem to comport
with a reasonable interpretation of what a final standard would
be.
Keep in mind, also, that we articulated in the essential
copies guidance, and we are going to re-articulate in the
guidance that we put out in March, that if there is an FDA-
approved product available that you can compound from, you have
to compound from that product. So, if a 503B facility is
compounding from bulk, but they can otherwise be compounding
from an FDA-approved product, for example, diluting it down if
they are providing a more dilute formulation to satisfy a
certain clinical need, they have to start with that FDA-
approved product. That is a principle that we have put forward.
I think that is going to address some of the issues that have
been raised with respect to what is on and not on the 503B
bulks list at this time.
Mr. Upton. And when do you think that order will be made?
Dr. Gottlieb. That is a principle that I believe we put
forward. I believe that is articulated in the copies guidance
that we just put out, but it is going to be re-articulated in
the March guidance that we put out. The question will then
become, well, when are you going to take enforcement action
solely on the basis of that issue? Because it is one thing for
us to put out a guidance. If people don't follow our guidance,
we have to take enforcement action. And that is where I
mentioned that we are going to relook at protocols and how we
prioritize our enforcement activity, on the basis of those
kinds of considerations as well.
But, as you know, we have a risk-based framework. We
prioritize our limited inspectional resources and enforcement
resources in places where we believe there is direct patient
risk. And we are still in a realm where we are dealing with a
lot of direct patient risk before we just look at, for example,
economic harm, although that certainly is within the criteria
that we look at and will be within our protocols.
Mr. Upton. Thank you. I yield back.
Mr. Burgess. The Chair thanks the gentleman. The gentleman
yields back.
The Chair recognizes the gentlelady from Colorado, Ms.
DeGette, 5 minutes for questions, please.
Ms. DeGette. Thank you, Mr. Chairman.
As Mr. Green mentioned, he and Congressman Griffith and I
worked really hard after that terrible tragedy of the New
England Compounding Center to come up with our Compounding
Quality Act, which was subsequently folded into the Drug
Quality and Security Act. We are really proud of that
bipartisan work. But, as we are seeing today, it takes constant
tweaking and review to make sure that these pieces of
legislation are working.
Commissioner Gottlieb, one of the things that I am hearing
from a lot of stakeholders about is what to do about office
use. A lot of providers are saying that people are having
difficulty accessing types of medication because of the
requirement that we have for prescription. Now what they say is
that these medicines are not lucrative enough to use 503B
outsourcing facilities, but that the patients need them. And
so, there are shortages.
I want to be clear. I have got strong reservations about
undermining or loosening the DQSA's prescription requirement in
any way, given the consideration that any move in that
direction could have an impact on patient safety. But I do want
to make sure that patients with unique needs that cannot be met
by FDA-approved medications can get the treatment that they
need. It is really a balancing test.
And so, I wanted to ask you if you think there are ways
that we can resolve these potential access problems without
undermining the prescription requirement and exposing patients
to unnecessary risk.
Dr. Gottlieb. I appreciate the question, Congresswoman. To
your point, this is one of the tensions that we are grappling
with, because we care very much about these access issues that
you have highlighted and need to preserve the practice of
medicine. And we need to preserve the ability of physicians to
get access to these drugs to use in their offices.
We have seen an environment where we see more of the 503Bs
doing small batches. About one-third of registered 503Bs do
small batches. We are trying to take steps to better match
clinicians with 503Bs that either are currently manufacturing
drugs they might need, but also historically have manufactured
drugs that would be needed, and are willing to run small
batches. So, we are starting to post that information
prospectively on our website.
I think, as we also try to look at how we can create a more
flexible framework for how we apply GMP standards to the 503Bs
and see more smaller pharmacies that might want to make a
business in doing small batches become 503B facilities, where
they are still subject to GMP standards, I think that is going
to also help address this.
I made the comment earlier that the 503B sector has not
grown as quickly as we had envisioned and had hoped at the
time, including myself when I testified before this committee.
But I think that it is still early days, and I still think we
are going to see a robust industry take shape here.
Ms. DeGette. Do you think it would be helpful to work more
on giving timely and transparent information for providers
about which of these facilities are making these compounded
medications?
Dr. Gottlieb. I absolutely do. We are doing that. We do it
now prospectively. We are just starting to really do it,
because we are starting to get those reports electronically.
One of the things we are considering is, can we go back and do
it retrospectively, because we have the histories on what the
facilities used to produce. That could be helpful as well.
Ms. DeGette. It would help those facilities, too.
Dr. Gottlieb. It would help the facilities.
We are also going to be issuing either an FR notice to
create a docket to solicit from provider groups input, in a
more systematic way solicit input on where they are seeing
access issues around certain products, so that we could, then,
see what steps we could take to try to help provide more
efficiency to 503Bs that might want to make those products.
Because, right now, a lot of what we know is anecdotal.
Ms. DeGette. Right. Right.
Dr. Gottlieb. We want to develop that information on a more
systematic basis.
Ms. DeGette. In a systemic way.
Now one last thing about drug pricing. Some people say that
compounded alternatives to expensive medicines could actually
provide financial relief to patients. But I think there is a
real risk, in that marketing unapproved bulk compounded drugs
could be really risky to patients. I am concerned that some
press reports are already saying this is going on. I just
wondered, I don't think that, certainly, the policies that this
committee has endorsed are meant to be using compounded drugs
to lower prescription drug prices if it is at the expense of
patient safety. I am wondering if you can comment very briefly
on that.
Dr. Gottlieb. We believe that, if there is an FDA-approved
option available, that is always the best option for the
patient because it is going to provide the greatest assurance
of safety and efficacy for the patient and to the provider. And
I also believe, as you have seen me try to demonstrate through
the actions we have been taking, that there are a lot of
avenues we can go down to try to address the issues of cost and
competition in the marketplace. And we will continue to do
that.
Ms. DeGette. So, it is not one or the other really?
Dr. Gottlieb. It is not one or the other.
Ms. DeGette. I thank you.
Thank you, Mr. Chairman. I yield back.
Mr. Burgess. The Chair thanks the gentlelady. The
gentlelady yields back.
The Chair recognizes the gentleman from Illinois, Mr.
Shimkus, 5 minutes for questions.
Mr. Shimkus. Thank you, Mr. Chairman.
And Scott, it is great to have you here. I appreciate the
testimony.
This is a tough issue we have wrestled with for a long
time. I think my colleague, Congresswoman DeGette, just
actually kind of wove the story and the concerns that I have,
and when we talk to some of our folks in different
congressional districts.
So, the 503A and the 503B issue, for me, it always comes
down to the small-town, rural compounder and the way these
rules will be etched or the memorandum of understanding or the
batch size and the mileage distance, especially when you have
got a rural district--for me, it is 33 counties, five hours
north and south drive, a three-hour east-to-west drive. It is a
little different environment than a metropolitan area and a
different area of the return on investment based upon what you
are producing. You are not really going to manufacture for a
large group, but in a small batch. And then, you might have
across-state-line issues, especially in a rural area on the
Illinois-Indiana border. I see my colleague, Mr. Griffith,
nodding his head.
So, can you kind of weave for the small pharmacist
compounder, who I haven't had personally any problems as far as
I have represented that area--he is trying to address this
being able to provide what is being requested of him. Sometimes
it is even these issues with the--I am not a doctor--the eye
drop issue for the optometrist who doesn't have the shots in
the doctor's office, although it is something they need
immediately, in essence. And there is not a prescription
because the person hasn't come in yet to be able to get the
prescription. And then, you have a delay of providing the
medicine.
So, for that small compounder, what should he take home
from my vague question?
[Laughter.]
And what assurances can you give him that we are trying to
allow him to continue the work he has been doing?
And I know we have got our veterinarian here, too. These
guys also use their compounding ability in veterinarian
medicine. So, a veterinarian would ask the compounder in rural
America. So, he needs to be there for not just humans, but also
for the animal health that he also is able to provide for the
veterinarian.
Dr. Gottlieb. I can go a lot of different ways with this
question.
Mr. Shimkus. Well, I went a lot of ways with the questions.
[Laughter.]
Dr. Gottlieb. But I will go right to where I think you are
going, which is the question of the prescription requirement
and whether or not that small-town pharmacist who is providing
drugs over a large geographic area still needs to have a
prescription in hand in order to provide a drug back and the
difficulty of doing it over a large geographic expanse I think
is the essence of what you are asking.
The bottom line is that we believe that the line of
demarcation for what constitutes the practice of pharmacy
versus what constitutes drug manufacturing has to remain the
prescription. The practice pharmacy, if you go and look at the
bylaws of states and how they define a practice pharmacy, I did
that before coming to the hearing. I spent my weekend looking
at that. Embedded in the bylaws of state boards of pharmacies
is the idea of the prescription and the named patient. That is
the essence of what it means to be practicing pharmacy.
We also understand that Congress contemplated other
thresholds and struggled with it, and arrived back at the
prescription being the line of demarcation, both 20 years ago
when 503 was originally drafted, as well as when it was
recodified in DQSA. Because other kinds of schemes that were
contemplated, volume-based schemes, for example, didn't provide
the kind of delineation that you could apply a regulatory
structure to. We can't regulate against ``we'll know it when we
see it.'' We need a clear line that we can force against and we
can enforce against with our limited resources.
As far as veterinary medicine is concerned, as you know, we
recently pulled the guidance that sought to define what our
regulation was going to look like in that realm. And we pulled
that for a variety of reasons, but, largely, because we don't
think we got it right. I will say we will be reissuing that
this year. But I will say that the issues around compounding in
the veterinary space are different than issues around
compounding in the human space. The practice of pharmacy in the
veterinary space is a different kind of practice of medicine
than it is in the human space. And so, our framework will also
look different. It will be reflective of the practice of
veterinary medicine.
Mr. Shimkus. All right. Thank you.
Mr. Burgess. The Chair thanks the gentleman. The gentleman
yields back.
The Chair recognizes the gentleman from Oregon, Dr.
Schrader, 5 minutes for questions, please.
Mr. Schrader. Well, thank you.
And I thank my colleague for asking some good questions
about veterinary medicine. That is near and dear to our heart.
We use compounders a lot in our practice, I don't think
inappropriately, but, as you alluded to, the size of the
animal, the different metabolism of an animal, the lack of a
particular drug that has worked historically that is affordable
for my patients, that is a different beast to some degree. I
appreciate the thoughtfulness that USDA under your guidance and
FDA is actually approaching the whole veterinary guideline
issue. So, I want to thank you for that.
While I have had a lot of experience in using compounders
in smaller communities to make sure my patients get the best
medication possible, I am new to the regulatory framework with
all this. I don't profess to be knowledgeable. So, my questions
might be a little arcane and pretty obvious.
But the whole 503B opens up a potential, as I think you
have alluded to and some of the questions have alluded to,
problem for circumventing a lot of the regulatory framework
that our generic manufacturers, for instance, have to apply.
What are the major differences--well, first, I will say I fully
support the continued definition of pharmacy prescription. It
has to have a prescription to be able to do that. I think that
is for the safety of any patient, human or animal. That is
critical, and I urge you to continue to use that as a very
bright line.
But, having said that, then what do you see as the big
demarcation between your 503B regulatory framework versus your
generic regulatory framework? How do you see that as different,
and what constitutes the guidelines there?
Dr. Gottlieb. Right. By generic, I think you mean 503A,
traditional pharmacy compounding, 503B being the outsourcing
facility. And the difference is the prescription, whether or
not that the drug is being compounded on the basis of a named
patient in response to a lawful prescription from a provider.
That is the traditional practice of pharmacy. That is a 503A
compounder.
A 503B compounder is engaging in manufacturing. They are
manufacturing either in small batches or on a larger scale, not
in response to individual prescriptions that they have received
from a provider, but in anticipation of orders, and they are
doing advanced shipping. They might be doing what we all office
stock. They might be shipping to providers to allow those
products to be stocked inside the offices.
That is traditional manufacturing. There is no way around
it. Whether you do it with 10 units or you do it with 100
units, you are engaging in manufacturing, and those
circumstances, instead of applying the traditional regulatory
framework where they would be subject to regulations around the
sanitary conditions, which is what you would apply to 503A
pharmacy, in the context of the 503B setting you are applying
GMP standards, some form of GMP, not GMP-light, but some form
of GMP. I don't want to call it ``GMP-light''.
Mr. Schrader. So, similar to the generic manufacturing that
would go on?
Dr. Gottlieb. Subject to good manufacturing practices, I
mean, good manufacturing practices, as I said at the outset,
are not a fixed standard. They are risk-based. And so, they
look different depending on the manufacturer that you are
evaluating. But it would be some form of GMP standards that you
would be applying. You would be doing lot release, sterility
testing, batch testing. You would be retaining samples. You
would provide for the compounding in a sterile environment if
you are compounding a sterile product. So, you would be
applying the GMP standards, traditional GMP standards.
Mr. Schrader. Whatever level you are approaching that
manufacturer?
Dr. Gottlieb. There are basic principles of regulation with
respect to the good manufacturing practices. So, when we say
``level,'' I think that there are things you can do to make it
less expensive if you are doing it on a smaller scale. So, for
example, you require a lot of small batches. If you are only
going to be making a small batch, if you are only shipping a
small amount, you would require that facility to retain a lot
of samples. There are ways that you can apply the GMP standards
in a fashion that comports with the level of the volume and the
level risk you are creating. And that is what we are seeking to
do in the more flexible framework that we are contemplating.
Mr. Schrader. So, I guess the last question: what do you
see as the role with the state regulatory framework versus the
federal regulatory framework. The interstate commerce piece
would, obviously, be a federal purview. How do you juxtapose
the state regulatory framework on these 503A and, more
importantly, the 503B pharmacies?
Dr. Gottlieb. The MOU is going to define sort of the
interplay between the state and the federal scheme and the
level of activity that a 503A can engage in that might cross it
into being subject to federal oversight because it is engaging
in interstate commerce, interstate activity. And we have talked
about various thresholds, about how much product can cross a
state line before a compounder should or ought to be subject to
at least our attention, to make a decision on whether or not it
is subject to, should be subject to FDA oversight.
Here again, this is not going to be a fixed standard when
we are contemplating this. It is not going to be, if you ship
31 products, you are subject to the federal scheme, but if you
had only shipped 30, you would be fine. We are going to try to
take a risk-based approach here as well, and it is going to be
based on volume, percentage of products you are shipping across
the state line, the kinds of products you are shipping across
the state line, the manner in which you are doing it. And so,
we are going to have a threshold in which we want notification
by the states, but, then, we are still going to make an
independent decision whether or not it should be subject to a
federal inspection because of the activity.
And the essence is, if I could just close, the essence is
that, if a pharmacy is subject to state regulation, but is
shipping most of its product out of state, it can't be subject
to state regulation anymore. Because if you are in New Jersey
and you are subject to the New Jersey Board of Pharmacy and New
Jersey inspectors, but most of your products are going to New
York, the New York inspectors don't know. Then, they can't
provide the oversight that they need to in a trace-back. So, it
is important that the states be aware of what is going on
within their states.
Mr. Schrader. Very good. Thank you.
And I yield back.
Mr. Burgess. The Chair thanks the gentleman.
The Chair recognizes the gentleman from New Jersey, Mr.
Lance, 5 minutes for questions.
Mr. Lance. Thank you very much, Mr. Chairman.
And thank you for being here, Commissioner.
The district I serve provides innovative medicines for
patients across the country. Protecting these patients is, of
course, a top priority for all of us, and so is protecting the
FDA's gold standard. As the Drug Quality and Security Act is
implemented, we need to ensure that we provide the incentive
for innovator and generic manufacturers to go through the FDA
process. To do this, we need to make sure that commercially-
available drug products cannot be copied. How is the agency
protecting patients and the gold standard as you implement the
Drug Quality and Security Act?
Dr. Gottlieb. Well, Congressman, thanks for the question. I
would like to assert that we are protecting the interest of
patients by implementing this statute and making sure that we
continue to move through the regulatory steps to, for example,
finalize the 503B bulks list, finalize the guidance on sanitary
conditions, finalize the list on bulk substances that the 503A
facilities can compound from, make sure we get the MOU in
place, so we can provide proper oversight of 503B and 503A
facilities, in concert with the states, and work closely with
our state partners. And so, we are going to continue to work
through that.
With respect to the first part of your question about just
the sort of economic issues inherent in situations where a
compounder might be copying a drug that is otherwise an FDA-
approved product, we have asserted in the copies guidance
certain activities that we would believe fall outside the
scheme contemplated by DQDA. We are going to reassert those in
the guidance that we issue in March with respect to the
criteria for what should and shouldn't be on the bulk drugs
list. Then, it is going to be a question of taking enforcement
action where we see companies or compounders engaging in
activity that falls outside that scheme that we both
articulated in our guidance as well as Congress contemplated in
the statute. That is what we are going to be focused on doing.
I will say, though, our enforcement activities will be, as
they should be, guided by patient risk, first and foremost. But
we will be baking into our protocols in terms of how we take
enforcement action the kinds of considerations that you talked
about, because that is what Congress has asked us to do.
Mr. Lance. Thank you.
I was pleased to see that the agency's 2018 Compounding
Policy Priorities Plan--and I am interested to hear more about
the forthcoming flexible risk-based approach to current good
manufacturing practices. Recognizing the agency's goal to
increase the number of 503B outsourcing facilities, recognizing
the compliance costs for larger 503B facilities and the
investment necessary to satisfy the statute, is the agency
concerned that the multi-tiered 503B regulatory approach may
affect incentives for these facilities?
Dr. Gottlieb. Well, quite the opposite, we feel that we
hope that by taking a tiered approach based on risk, we might
provide the opportunity for more 503A pharmacies to step across
the line into being 503B pharmacies and consider it worth the
economic investment. Becoming a 503B pharmacy is not without
some investment in cost for most 503A facilities. They don't
have the kinds of facilities to be subject to GMP oversight.
And so, it is going to require some investment. But we are
hoping that we could provide a framework where more facilities
can find it, have the ability to make the capital investments
and raise the capital necessary to make those investments
because they see a better opportunity on the other side of that
in terms of trying to increase their volume and increase the
kind of activity that they are engaged in. We think by having
more 503A facilities converting to being 503B facilities, it is
going to facilitate access and, also, give them the ability to
grow.
A 503A facility that is trying to engage in some low level
of manufacturing, even if they can do it under the radar of
regulators, if they grow to a certain proportion, eventually,
they are going to pop up. And so, they are basically capped
under this legislation. If they step across that threshold and
become a 503B, they have much more latitude to engage in
broader manufacturing.
Mr. Lance. Thank you, Commissioner.
And, Mr. Chairman, I yield back 27 seconds.
Mr. Burgess. The Chair thanks the gentleman.
The Chair recognizes the other gentleman from New Jersey,
the ranking member of the full committee, Mr. Pallone, 5
minutes for questions.
Mr. Pallone. Thank you, Mr. Chairman.
I wanted to ask you about this issue of distribution versus
dispensing. Section 503A of the law prohibits a pharmacist,
pharmacy, or healthcare provider from distributing compounded
drug products across state lines that exceed 5 percent of the
total prescriptions distributed or dispensed unless the product
is compounded in a state that has entered into a memorandum of
understanding with FDA that addresses the distribution of
inordinate amounts of compounded drug products and provides for
investigation by the state into complaints associated with
compounded drug products that are distributed interstate. And
FDA released a draft MOU in February 2015 that proposed
defining inordinate amounts for purposes of interstate
distribution to no greater than 30 percent of all products
distributed or dispensed.
So, in terms of this distribution versus dispensing,
Commissioner, some have suggested that the MOU is only intended
to apply to drugs that are distributed without a prescription.
What is your view about the purpose of the MOU and the public
health purpose it serves? Are there some drugs, such as those
dispensed directly to patients, which could be excluded
consistent with that purpose?
Dr. Gottlieb. Well, in my weekend reading of pharmacy
bylaws, the other observation that I had is that the bylaws
make specific reference to the word ``dispense'' as part of
their definition of what constitutes the practice of pharmacy.
It is our view, and we feel strongly, that the practice of
pharmacy always contemplates the dispensing of the drug. Now in
certain circumstances the drug is going to be dispensed and,
then, distributed across state lines, and that is where the MOU
comes into play. The MOU contemplates drugs that are dispensed
and shipped across state lines, and shipping is a form of
distribution, as I think you all agree. But we think that
dispensing is part and parcel of the activity of practicing
pharmacy, and no compounded drug can be distributed without
first being dispensed, because dispensing is the act of
creating that patient-specific prescription.
And I will just say, and to address the elephant in the
room, because this has been contemplated as one of the beliefs
in terms of why DQSA might have contemplated something
different with respect to office stock than FDA's current
interpretation of how we perceive the law to have been written,
I don't think that redefining the practice of pharmacy, which
involves the activity of dispensing a product to a patient, is
a good way to try to create a framework for office stock. I am
open to the debate about office stock and the merits of it. I
think we have been clear from the agency's standpoint the risks
that we feel it creates if a 503A facility is getting engaged
in it. But I would hate to see the practice of pharmacy
redefined as a sort of backdoor into that. I think if we are
going to have a discussion about the merits of 503A facilities
engaging in some level of manufacturing and shipping, we ought
to just do that directly.
Mr. Pallone. All right. Then, let me get to my second
question. Recently, you announced the agency's intention to
modify the allowable percentage of compounded drug product
distributed into a state to effectively eliminate the 30-
percent threshold and, instead, implement certain reporting
requirements that will be triggered at a 50-percent threshold.
And this strikes me as a weakening of an important patient
protection and in contrast to what you have noted in your
testimony is the stated goal of this provision in the statute,
which says, ``Preventing compounders reportedly operating under
the exemptions in Section 503A from growing into conventional
manufacturing operations making unapproved drugs and operating
a substantial portion of their business interstate without
adhering to current good manufacturing practice requirements
and other provisions intended to ensure the manufacture of
quality drugs.'' So, would you explain how increasing the
allowable threshold for interstate distribution to 50 percent
is consistent with the goal of the statute of preventing
compounders from making unapproved drugs and operating a
substantial portion of their business interstate without
adhering to the CGMPs?
Dr. Gottlieb. Well, I appreciate the question, Mr.
Chairman. I don't see it as a weakening. I see it as a
strengthening, because we are going from a hard threshold of 30
percent to a risk-based threshold of 50 percent. It is not 50
percent--it is not 49 percent and you are all good, and 51
percent and you are now subject to a different scheme. There
are going to be other tests that we apply to make assessments
about what the appropriate scheme is for a particular facility.
It is the case, though, that there are facilities--for
example, a border-state pharmacy that develops TPN, total
parenteral nutrition; a home infusion company that provides
patient-specific, named patient products on a prescription
basis and might ship more widely that are engaging in the
traditional practice of pharmacy; they are doing it on the
basis of named patients in response to an individual
prescription, but they might be shipping more of those
products. They might be lower-risk, too, depending on what they
are doing.
And so, the reality is that there are a lot of different
kinds of pharmacies situated across the spectrum in terms of
the activity that they are engaged in. And we don't think a
sort of fixed standard where there is a fixed line based just
on volume makes the most sense. We want a volume-based
standard, but also a standard that allows us to make an
assessment about what the kind of activity is. And it is
another effort on our part to be risk-based. I think,
ultimately, our enforcement is stronger when we are taking a
risk-based approach.
Mr. Pallone. All right. Thanks a lot.
Thank you, Mr. Chairman.
Mr. Burgess. The Chair thanks the gentleman. The gentleman
yields back.
The Chair recognizes the gentleman from Virginia, 5 minutes
for questions, please.
Mr. Griffith. Thank you very much, Mr. Chairman. I
appreciate it greatly.
Let me get the record a little bit straight because I think
it was confused a little bit earlier. While we had criminal
conduct by NECC, we also had timid lawyers at the FDA. Ohio had
warned the FDA there was a problem. Colorado had outright
banned NECC from putting products into their state. And FDA was
aware of it and didn't even bother to seek a warrant to go in
and see what was going on. So, as we move forward, let's
continue on that.
Also, I think in the next panel there will be some question
about the intent, and you touched on that in your testimony
with Mr. Shimkus a little bit earlier. But I want to go back to
when the bill passed in September of 2013. At that time, now-
Ranking Member Green said, in part, ``While I believe the FDA
dropped the ball with regards to the NECC, with this law they
must succeed where in the past they failed.'' And I know you
are working hard on that.
This bill still lacks clarity in many important areas:
office use, how nuclear pharmacies are regulated, and
repackaging of sterile products. I look forward to working with
my colleagues to provide meaningful oversight of the FDA to
make sure another NECC-type outbreak never happens again, and
make sure they are using the type of enforcement discretion
necessary to preserve patients' access to critical medicine.
In that same press release--because it was a bipartisan
effort, as you heard earlier, Mr. Green, myself, and Ms.
DeGette worked hard on trying to get this portion of the DQSA
right, and to the best of our ability, although we had some
disagreements with our Senate colleagues. I said on that
occasion that, ``The Drug Quality and Security Act leaves a
large portion of existing law intact. It also leaves many areas
of practice where clarification may still be needed,
particularly as it relates to office use, repackaging, and
nuclear pharmacies. Along with my colleagues, I will continue
working to oversee the FDA's interpretation and implementation
of this law.''
And I think that is what we are doing today. Some folks
have characterized this, because I am leading the push for
office use, as wanting to undo everything that DQSA stood for.
Obviously, I wouldn't have drafted it and fought hard along
with my colleagues to get it, if that was my intent.
But I do have questions. And one of those was raised by
your testimony to Mr. Shimkus in answering his questions where
you indicated that twice they had decided that you had to have
a prescription in order to issue a drug, and that Congress had
made that decision. But I am looking at 503A, little ``a'' to
big ``A'', and it says, as one of the things, it says, ``or is
by a licensed pharmacist or a licensed physician in limited
quantities before''--before--``the receipt of a valid
prescription order for such individual patient.''
Obviously, the law--and that was the old law, which was not
changed and which we were assured that the practices weren't
going to change at the times we were negotiating this by folks
in the Senate saying they didn't want to do this because the
FDA wasn't going to change anything. It clearly anticipates
that in some cases you won't have a prescription until
afterwards. We had debated making sure that a prescription was
written within 7 days at the time that we were negotiating it.
But this seemed acceptable at the time, and the reason that I
put that into my statement--and others may have put it into
their statement--and the statement on the floor was we were
given the assurance that office use was going to remain pretty
much the same, and for 503A pharmacies I think that is
important.
So, how do you rectify that you think there needs to be a
prescription with the actual wording of the law? There are also
other references, future-looking references, in the next
section.
Dr. Gottlieb. Yes, thank you, Congressman, for the
question. I appreciate your longstanding dedication to this
issue and your longstanding work on it. And you and I have had
the time to talk about this on many occasions.
With respect to the nuclear pharmacies, I will just say we
will be putting out a guidance that will specifically address
radiopharmaceuticals.
But, in respect to your specific question about the
language you quoted, I believe that that language and we
believe that language was contemplating anticipatory
compounding, basically, compounding on an expectation that you
were going to receive a certain volume of prescriptions.
Because we know, with the 503A pharmacies--and I know you are
very familiar with the practice of pharmacy--sometimes when you
mix up one batch, when you are mixing up a batch, you can't
just mix up one drug. You mix up 10 at a time or 15 at a time.
And you can do that if there is an expectation that you know
you get 30 prescriptions a month or 40 prescriptions a month.
So, we allow for that.
What we have said in guidance is that you can mix up a
level of volume in anticipation of what you your prescriptions
might be over the course of a 30-day period to provide that
kind of flexibility. That is what I believe the statutory
language that you referenced was anticipating and that we have
allowed for.
Mr. Griffith. And I disagree, just based on the debate that
we had when we were doing this a number of years ago in 2013,
because we anticipated there would be continued office use.
That is why we were looking at putting in the 7-day
requirement. And as Ms. DeGette said, there has got to be a
balance. As Mr. Shimkus said, we are worried about rural areas.
I do appreciate that you are concerned about the state
lines because, having now been made famous by the GEICO
commercial where the lizard jumps from Tennessee to Virginia
and back and forth, and back and forth, that is my district.
And so, you have got a pharmacy on either side of that state
line. You just turn around and you cross the state line.
The other day I was traveling in my district and I went
from Virginia to West Virginia, to Virginia, to West Virginia,
back to Virginia, then ended up the day going from Virginia to
Tennessee, back into Virginia, and back into Tennessee, and
then, back home in Virginia, just to try to talk to my
constituents and do what I needed to do.
So, I appreciate you paying attention to that as you look
at the flexibility side, but I really believe that the existing
law allows for some office use from the smaller folks. We were
trying to get to the big guys and the larger guys because of
the NECC problem, which was shipping into all the states, not
just across the Tennessee line or the Virginia line.
I yield back.
Dr. Gottlieb. I understand and appreciate concerns,
Congressman, the impact on small pharmacies.
Mr. Griffith. And I yield back. Thank you, Mr. Chairman.
Mr. Burgess. The Chair thanks the gentleman.
And the Chair recognizes the gentleman from a similar small
state, Maryland, for 5 minutes.
Mr. Sarbanes. Small, but powerful, and home to the FDA.
Welcome, Commissioner.
People have touched on kind of the partnership, regulatory
partnership between your agency and what happens at the state
level. I wanted to explore that a little bit more.
I was looking at your testimony on page 3, where you talked
about the 500 inspections that have been conducted, 503A and B
facilities, since the passage of the new law and the end of the
last fiscal year; how you have observed problematic conditions
during the vast majority of these inspections, overseeing more
than 150 recalls of compounded drugs, issued more than 180
warning letters. You have also worked in close coordination
with our Federal and state partners, sending more than 70
referral letters to state regulatory authorities for follow-up
on certain inspectional findings.
So, I am just curious how that is going. There must be some
states that are better partners than others. Obviously, you
have to rely to a certain degree on those follow-up
inspections. And maybe without naming specific states, you
could give me an example of a state that is engaged in this
partnership in a very productive and efficient way, and why
that is the case, what you would point to as indicating kind of
a high standard in terms of the partnership, and the follow-up,
and all the rest of it. And then, maybe give me an example,
again without naming the state, of a place where that is not
going so well. And what does the agency do, either because it
is required to in some element or just because you regard it as
your responsibility to help states to get to where they can be
the best possible partners in this effort at oversight?
Dr. Gottlieb. Congressman, thanks for the question. To your
point, there is a fair degree of variability. I think it would
be risky of me to try to characterize a good state and a not-
so-good state, because it is not something I have actually
asked the question of my folks, and I would want to contemplate
it in concert with them. Because the field people, the field
team that is engaged in these efforts are going to have the
best perspective. We could certainly get you that perspective,
but I wouldn't want to mischaracterize the state.
I will say, though, broadly, that what we are seeing
directionally is that the states are starting to conform more
to DQSA now. And so, there has been discussion, for example, of
states' pharmacy bylaws that might allow for certain practices
that DQSA we don't believe contemplates. We are starting to see
more of the states conform their practices, their inspectional
activity, as well as their laws, to be compliant with the DQSA,
be consistent with the principles of the DQSA.
For the states that might be moving in a different
direction or not moving as quickly in the direction that was
envisioned by DQSA, I think what it creates for us is more of a
resource burden. Those are the states that we might have to put
more resources into to make sure that we are providing the same
level of oversight that we would be to a state that is sharing
information with us very cooperatively and reporting to us, so
we can target our inspections better.
A lot of our inspections are for-cause inspections. A lot
of them are based on information we derive from the states. If
the states aren't reporting to us as efficiently, then we need
to do more work to try to derive that information on our own.
It is just a more resource-intensive process.
Mr. Sarbanes. Is there an opportunity to provide, I don't
know, technical assistance or other support to the states, as
they are trying to come into compliance with this effort?
Dr. Gottlieb. We do that. As the scheme contemplates, we
provide a lot of resources or technical assistance within the
context of the resources we have available to do this in terms
of training to state inspectors, training around inspectional
issues that they might need to be aware of as they start to
inspect, for example, 503B facilities and do their own GMP
inspections. We do dual inspections with the states. We invite
the states in on our inspections, so that they can both learn
alongside of us as well as dually inspect some of these
facilities and share information. So, there is a lot of stuff
that we are trying to do in concert with the states.
As I sunk deeper into this and understanding how we were
applying this framework when I re-arrived at FDA 10 months ago,
there were a lot of aspects of this that looked very similar to
FISMA, the framework envisioned in FISMA, where the regulatory
scheme is very much dependent upon a close Federal/state
partnership.
Mr. Sarbanes. Thank you. I yield back.
Mr. Burgess. The Chair thanks the gentleman. The gentleman
yields back.
The Chair recognizes the gentleman from Georgia, 5 minutes
for questions, please.
Mr. Carter. Thank you, Mr. Chairman.
And thank you, Dr. Gottlieb, for being here. I want to
commend you and thank you for your adherence to safety, and I
think it is very important.
It has been mentioned more than once during this hearing
that there has to be a balance between accessibility and
safety. I think that is perhaps one of the areas that I
struggle with. And you and I have had many conversations.
I want to ask you, first of all, about the rulemaking
process, because that is of great interest to me, being a
relatively new Member of Congress, only in my second term, my
third--I guess I am starting my fourth year now. So, I am
getting older, but I am still learning about the rulemaking
process.
I noticed that, since the passage of DQSA, that you have
used oversight guidance documents to really enforce this and to
really enforce what you want the agency to see out there.
Although we probably disagree, and we do disagree, you say it
is with stakeholder input; I say it has not been with
stakeholder input. And I am just wondering how you can justify
that, particularly in light of the fact that just recently the
Office of the Associate Attorney General issued a new policy to
DOJ that guidance policies will not be converted into
rulemaking. So, how are you justifying this, that you are going
to use guidance policy for rulemaking here?
Dr. Gottlieb. Thank you, Congressman.
We have a long history of issuing non-binding guidance in
many contexts. And our guidance practice--and this question has
come up in other contexts well outside this context--our
guidance practices, generally, have been used as a model for
other agencies and for OIRA as well in terms of what we do, how
we issue guidance, what we use guidance for under the
Administrative Procedures Act.
So, I feel confident that, on the whole--and we can have a
debate around any individual guidance--but I feel confident
that, on the whole, we have adhered to good practices in terms
of how we promulgated guidance in multiple----
Mr. Carter. I don't mean to interrupt, but you even
answered Representative Upton's question about the guidance,
that you expected it and that you were using the guidance for
enforcement. You are, essentially, saying that this guidance is
going to be enforced.
Dr. Gottlieb. There is----
Mr. Carter. Even though the DOJ has been told that, no, it
cannot be converted into rulemaking. Quite honestly, I have not
read this from the Associate Attorney General. Perhaps they
said this is going to apply to the DOJ, but not to the FDA. I
don't suspect that was the case; maybe it is.
Dr. Gottlieb. Well, we could take enforcement action now.
We don't need the guidance document in order to take the
enforcement action. The guidance document is a way to provide
public discussion around how we intend to take our enforcement
action. So, we can both inform the public as well as learn from
the public. The guidance document itself isn't the basis for
the enforcement action, you are absolutely right. We have
regulatory authority that has been given to us by Congress.
Mr. Carter. Well, what about stakeholder input? Because
that is something that is very concerning to me, that I don't
feel like we have had stakeholder input. I know that you are
coming out with a new MOU. My hope is that you are going to
have more stakeholder input into that. The existing MOU,
although I was not here at the time, I don't think there was
sufficient stakeholder input into that.
One thing, in particular, about this is the difference
between dispensing and distributing. As you know, the DEA has
said that distributing is going to be overseen by the FDA, but
the dispensing is going to be overseen by the state boards of
pharmacies. Yet, you seem to want to oversee dispensing as well
through the FDA.
Dr. Gottlieb. I am not familiar with the particular
definition of dispensing and distributing, probably under the
Controlled Substances Act, that you have derived from--I don't
know, is it a regulation or a guidance document? So, I can't
speak to how the DEA might have defined something in a certain
context, again under the Controlled Substances Act, which is my
presumption.
We believe that, under this law and under the practice of
pharmacy, with products that we regulate, and outside of the
context of controlled substances, the practice of pharmacy
involves the dispensing of a product, just like the practice of
pharmacy involves a patient----
Mr. Carter. But why is it that the FDA thinks that they
have to intercede the state boards of pharmacy? That has always
been something that the state boards of pharmacies----
Dr. Gottlieb. We need to work with them.
Mr. Carter. OK. I have got just a few seconds left. Now I
want to ask you about something that has been brought up by Ms.
DeGette, by Mr. Griffith, and that is office use. And that is
something that I think you have absolutely got wrong here.
But I want to ask you just from a perspective of a Member
of Congress. It is my understanding that not once, not twice,
but three times, through appropriations language, that the FDA
has been instructed to revisit this and to look at this. In
fact, in 2016, it said, ``The committee understands the intent
of the DQSA was not to prohibit compounding pharmacies from
operation under existing 503A exemptions. Therefore, the
committee directs the FDA to issue a guidance document on how
compounding pharmacists can continue to engage in office-use
compounding.''
Why do you ignore these? Why have you not ignored it once,
not twice, but three times? I don't get it.
Dr. Gottlieb. Congressman, those appropriation riders I
believe preceded my arrival at FDA. I would be happy to work
with this committee, or anyone in Congress, to contemplate if
they want to have a discussion around the statute and what we
can do to continue to improve this on this legislation.
But we have to keep patients in mind and make sure patient
safety drives the decision we make. And remember why we are
here. We are here because pharmacies were engaging in
manufacturing without any standards in place.
Mr. Carter. Dr. Gottlieb, I could not agree with you more.
I commend you on your dedication to safety. Again, we get back
to the balance between access and safety. And that is just you
and I live in different worlds. You are in a different world
than what I previously was in my career in pharmacy, and I saw
firsthand the access issue and how people struggled with it.
That is just a difference that we have and that I hope that you
will take into consideration in the future.
Thank you very much.
Dr. Gottlieb. Thank you, Congressman.
Mr. Burgess. The gentleman yields back.
So, Dr. Gottlieb, once again, I think we have gotten
everyone on the committee. I will just ask, Mr. Green, do you
have a follow-up question before we leave?
Mr. Green. No. Oh, I guess we do, Mr. Chairman.
[Laughter.]
Mr. Burgess. I could intuit that.
Mr. Green. OK. Commissioner, one of the most important ways
FDA is conducting oversight and ensuring compliance with the
DQSA has been through inspections. Since the enactment of the
Drug Quality and Security Act, FDA has conducted nearly 500
inspections, issued more than 180 warning letters identifying
significant violations of compounding pharmacies, issued more
than 70 letters referring to inspectional findings to state
regulatory bodies, and overseen more than 120 recalls of
compounded products.
Commissioner Gottlieb, as I noted, FDA has conducted
hundreds of inspections in compounding pharmacies and
identified numerous violations. Will you describe briefly for
us some of the violations and conditions FDA found when they
were inspecting both 503A compounding pharmacies or 503B
outsourcing facilities?
Dr. Gottlieb. I brought some slides with me, if the
chairman would let me use them, of some of the things that we
found. So, we can close on this, if that is OK. I don't know if
we have them teed up.
Thank you, Mr. Chairman.
This is visible microbial contamination on a ceiling tile
in a clean room.
If we go to the next slide, this is a HEPA filter located
immediately above an ISO5 workbench that was observed to have a
stained surface. The stain was due to a drug product which had
exploded due to excessive pressure when forcing non-sterile
product through a sterilizing filter, a device used to force
the product sterilizing, in other words, a stainless steel
caulking gun that was not sterilized.
Next slide. This is a sleeve used in the aseptic glovebox
for aseptic manipulation. You can see it is damaged where it is
circled.
Next slide. This is a toaster oven that was used to dry
heat sterilize glassware. The oven wasn't capable, as we can
probably presume, of reaching high enough temperature to be
effective for that purpose.
Next slide. This is a ceiling above the doorway to a clean
room with exposed insulation. This was supposed to be a clean
room that would store products manufactured.
Next slide is a kitchen dishwasher that was actually being
supplied with tap water and home detergent and used to clean
equipment, equipment and the utensils that come in contact with
products that were intended to be sterile.
And they jumped my bug. This was a bug.
But, we also saw things like coffee filters being used to
filter particulate matters. We find things that are deeply
concerning. And these are sterile, these are facilities that
are manufacturing sterile products, or at least intended to be
sterile products.
I appreciate the question.
Mr. Green. Thank you.
Mr. Burgess. The Chair observes that debate on the floor
has proceeded to the point where Mr. McGovern is making some
fairly significant gestures, which usually means he is
concluding and we will be voting shortly. So, I will advise the
committee that we will recess upon the votes that are called on
the floor.
But we thought Ms. McMorris Rodgers was coming back, and
she is. So, I will recognize her.
Mrs. McMorris Rodgers. Thank you, Mr. Chairman.
Mr. Burgess. But, again, I observe that the vote on the
floor is probably very close. Mr. McGovern is making smaller
and smaller circles with his hands, and that usually means we
are getting there.
[Laughter.]
Mrs. McMorris Rodgers. OK. Very good. OK.
Well, Commissioner, thanks for being here.
I wanted to ask about the 503As and the 503Bs, and just
what the intent is moving forward as far as preserving them
separately, or what your thoughts are.
Dr. Gottlieb. Well, thank you, Congresswoman, for the
question. On the 503A, are you talking about the bulks list or
just the different facilities?
Mrs. McMorris Rodgers. Well, I understand that you have
issued some guidelines related to 503As, 503Bs, and I wanted
just to understand better what you think the future is for the
503As.
Dr. Gottlieb. Well, the general question with respect to
the 503As is we believe that the 503As, which is a traditional
practice of pharmacy, should continue to flourish. We believe
it provides an important product for patients, the practice of
pharmacy being able to individualize products on the basis of a
prescription for an individual patient.
On the 503Bs, we do hope, and we always envisioned, that
there would be more facilities converting into being
outsourcing facilities. We also believe that more 503A
facilities would opt to become 503B facilities. Now, in full
disclosure, we have not seen the industry grow up the way we
had hoped. We still believe it is early. And we intend to try
to promulgate a set of policies that we believe that will,
hopefully, provide a flexible regulatory framework based on
risk that is going to allow more pharmacies to contemplate
becoming 503B facilities. Because there is an argument to be
made that, when a pharmacy can become a 503B facility and
engage in larger-scale manufacturing, under GMP compliance
standards, we are able to apply a level of oversight that
ensures the sterility of the products that are being
manufactured. That could, hopefully, provide for more patient
access.
But, with respect to the 503A facilities that were
contemplated in the statute, and always enshrined in statute,
that is the traditional practice of pharmacy that we believe
should be preserved and protected, and provides an important
opportunity for patients to get products that are tailored to
their unique clinical needs.
Mrs. McMorris Rodgers. So, you anticipate that they will be
preserved as you move forward, the 503A----
Dr. Gottlieb. Well, they are. They are being preserved. The
question becomes the scope of the activity and whether or not
503A facilities can and should be engaging in larger-scale
manufacturing, and manufacturing and distributing products. And
we believe that DQSA contemplated a scheme where that kind of
activity would move into the 503B facilities that would be
subject to GMP standards, if you were engaging in manufacturing
and wider-spread distribution.
That is what brought us here. It was the fact of pharmacies
like NECC engaging in manufacturing under the guise of a
pharmacy license, not subject to standards that ensure the
sterility of those products, that created the risks that
brought Congress to contemplate this new framework.
Mrs. McMorris Rodgers. OK. Well, I look forward to talking
further about this with you.
Dr. Gottlieb. Thank you.
Mr. Griffith. Will the gentlelady yield?
Mrs. McMorris Rodgers. Yes. Yes, I would be happy to yield.
Mr. Griffith. And I would just ask, in relationship to
503A, because we were talking about it earlier, if that didn't
contemplate office use, then why has FDA allowed it up until
this point in time? Because that is existing law and was
existing law before DQSA, and it was allowed.
Dr. Gottlieb. Yes, it is a good question, Congressman. And
I was at FDA over part of the time that we struggled with the
503A statute. As you know, after the Western States case
vacated certain aspects of that law, FDA was on shaky legal
ground with respect to trying to contain and implement that
statute----
Mr. Griffith. We know.
Dr. Gottlieb [continuing]. With the division in it.
Mr. Griffith. I know, and, yes, that was, again, timid
lawyering, because that just dealt with advertising. It didn't
have anything to do with anything else, and it was not ruled,
the question of severability was not ruled on by the Supreme
Court.
Dr. Gottlieb. Right. I think what the agency would have
said at the time was that it had a difficult time bringing
cases under that statute, and we also at the time faced a lot
of pressure from Congress on the implementation of 503A. I
think DQSA was not only a clarification of the statute and
removed the offending provision, but was a clear declaration
from Congress that you wanted the agency to be vigilant with
respect to these----
Mr. Griffith. No question about being vigilant. Just we
didn't anticipate eliminating something that had been in
practice under the existing law that we left as the existing
law.
But, that being said, also, you showed the pictures of
things you found as problems in compounding pharmacies, but you
also found problems, which is why you do your job, in large
manufacturers as well from time to time. Isn't that correct?
Dr. Gottlieb. Absolutely right.
Mr. Griffith. Thank you very much. I yield back.
Mr. Burgess. The gentleman yields back.
The Chair recognizes the gentleman from Texas for a
unanimous consent request.
Mr. Green. Mr. Chairman, I would also like to ask the
Commissioner to submit those slides for the record.
Mr. Burgess. Without objection, so ordered.
[The information appears at the conclusion of the hearing.]
Mr. Burgess. I do have one follow-up question that I feel
compelled to ask. Because we are going to hear from a patient
in the next panel, and Mr. Guthrie referenced--I think it was
Mr. Whitfield's constituent in several Congresses ago who came
and talked to us about losing a spouse after the Exserohilum
infection that they acquired.
Does the agency have an opinion on when it is the duty of a
physician or a surgery center or a hospital to inform a patient
that they are receiving a medication from a compounding
pharmacy as opposed to one of the other pharmacies?
Dr. Gottlieb. I don't have a view on that, Congressman. I
have seen survey data with respect to that, I think including
data that was developed by Pew. So, I know you have a witness
who can speak to that, the development of that data, on the
next panel.
As you know, there are labeling requirements for the
products that are produced by the 503B facilities that provide
warning information and certain disclosures, but not
necessarily that it was a compounded product.
Mr. Burgess. It doesn't escape me that the witness we had
several Congresses ago, and likely the one we are going to hear
from today, may very well tell us that they never had any idea
what a compounding pharmacy was; they never heard of it before.
And now, their lives have been seriously affected by----
Dr. Gottlieb. Well, I would say that, here again, I think
this gets to the question of the prescription as a line of
demarcation. Because if the prescription is the line of
demarcation, if you are going into a 503A facility and getting
a compounded product, you know that. If you are going into a
doctor's office and you are getting a product from that
doctor's office, and that was produced by a compounding
pharmacy, not subject to sterility standards, you don't know
that. That is why it is important, we believe, to have a
mechanism in place to make sure that, when those products are
being provided in that sort of de-identified way, because you
no longer have that relationship to the pharmacist and
understand where and how that product was manufactured, that
there are standards applied for sterility to how that product
was developed.
Mr. Burgess. I also appreciate your comments that this is
all about patient safety, and that is why we all want to get it
right. We may not agree on everything on the dais here, one
side or the other, but we do want to get it right. And we
appreciate your efforts in trying to help us get that right.
That will conclude the testimony from the first panel.
Again, we are very close to a series of votes on the floor.
So, I am going to ask that we actually not take a break between
panels. We will let Dr. Gottlieb gather his papers up and
leave, and just take a second to put the nameplates out. But we
probably better proceed directly into the second panel.
I call the subcommittee back to order.
Once again, as we transition to our second panel of
witnesses, I do want to thank all of our witnesses for being
here and taking time to testify before the subcommittee. Each
witness will have the opportunity to give an opening statement,
followed by questions from members.
Again, I will advise that we will recess when votes are
called on the floor.
But today we are going to hear from Dr. George Williams,
President-Elect of the American Academy of Ophthalmology; Dr.
Bruce Brod, the Chairman of the Congressional Policy Committee
for the American Academy of Dermatologists; Shawn Hodges, Vice
President, International Academy of Compounding Pharmacists;
Jacob Olson, the President and CEO of Skywalk Pharmacy, on
behalf of the National Community Pharmacists Association; Jenn
Adams, Senior Vice President, Clinical Product Solutions,
PharMEDium Services; Molly Ventrelli, Vice President,
Regulatory Affairs, Fresenius Kabi; Elizabeth Jungman, Director
of Public Health of the Pew Charitable Trusts, and Nancy
Dargan, a former patient of the New England Compounding Center.
We appreciate all of you being here today.
Dr. Williams, you are now recognized for 5 minutes for a
summary of your opening statement.
STATEMENTS OF GEORGE WILLIAMS, PRESIDENT-ELECT, AMERICAN
ACADEMY OF OPHTHALMOLOGY; BRUCE BROD, CHAIRMAN, CONGRESSIONAL
POLICY COMMITTEE, AMERICAN ACADEMY OF DERMATOLOGISTS; SHAWN
HODGES, VICE PRESIDENT, INTERNATIONAL ACADEMY OF COMPOUNDING
PHARMACISTS; JACOB OLSON, PRESIDENT AND CEO, SKYWALK PHARMACY,
ON BEHALF OF THE NATIONAL COMMUNITY PHARMACISTS ASSOCIATION;
JENN ADAMS, SENIOR VICE PRESIDENT, CLINICAL PRODUCT SOLUTIONS,
PHARMEDIUM SERVICES; MOLLY VENTRELLI, VICE PRESIDENT,
REGULATORY AFFAIRS, FRESENIUS KABI; ELIZABETH JUNGMAN, DIRECTOR
OF PUBLIC HEALTH, THE PEW CHARITABLE TRUSTS; AND NANCY DARGAN,
FORMER PATIENT OF THE NEW ENGLAND COMPOUNDING CENTER
STATEMENT OF GEORGE WILLIAMS
Dr. Williams. Chairman Burgess, Ranking Member Green, and
members of----
Mr. Burgess. And do be sure your microphone is on and pull
it close.
Dr. Williams. Is it working?
Chairman Burgess, Ranking Member Green, and members of the
committee, I am honored to be testifying to you on behalf of
the American Academy of Ophthalmology on a topic critical to
the practice of ophthalmology.
My name is George Williams. I am a practicing retina
specialist from Michigan. I am also the Immediate Past
Secretary of the American Academy of Ophthalmology; Secretary
of Federal Affairs, and current President-Elect for the
Academy.
As the world's largest association of eye physicians and
surgeons, the Academy seeks to protect sight and empower lives
by setting standards for ophthalmic education, advocating for
our patients and the public.
Access to safe and effective compounded repackaged drugs is
vitally important to the practice of ophthalmology. This is due
in large part to the uniqueness of our specialty, as we utilize
drugs in dosage forms that differ from other areas of medicine.
Effective treatment often requires that drugs be compounded or
repackaged in concentrations or doses that are tailored to a
patient's specific needs and unusual route of administration to
the eye. These drugs are used in the successful treatment of
several ophthalmological treatments, including diseases that
threaten sight such as age-related macular degeneration.
Ophthalmology's treatment of patients facing sight-
threatening diseases such as AMD requires access to drugs known
as vascular endothelial growth factor inhibitors, or VEGF
inhibitors. These include the FDA-approved anti-VEGF treatments
ranibizumab and aflibercept, as well as repackaged bevacizumab,
or Avastin. The Academy has long advocated for access to all
three treatments, as individual patients may respond
differently and have better outcomes with one treatment versus
another.
Since the passage of the DQSA, the Academy's advocacy
efforts have included focus on protecting access to repackaged
Avastin. The Academy is aware of adverse event clusters
associated with intravitreal injections of repackaged
bevacizumab, including events in Georgia and Florida. Events
like these, along with the passage of the DQSA, have led to the
necessary changes at compounding pharmacies and improvements in
the safety of this treatment.
Because of our efforts since 2013 to track outcomes of
patients who receive anti-VEGF therapies, we have been able to
gather data on effectiveness and safety of these treatments.
The American Academy of Ophthalmology utilized our IRIS
registry, which is the nation's largest comprehensive eye
disease clinical registry, to track adverse events associated
with the use of these products from January of 2013 to June of
2016. These data clearly showed no statistically significant
difference in adverse events among different anti-VEGF agents,
including repackaged Avastin.
Today repackaged Avastin remains a safe and effective
treatment option for patients facing sight-threatening disease,
and Academy efforts to protect access are ongoing. The new
guidance from FDA, which represented a step in the right
direction, was recently finalized by the agency. The Academy
will continue to engage with the agency, Congress, and
compounding facilities to ensure patient access to repackaged
bevacizumab.
The Academy is also concerned about continued access to
other non-biologic compounds or drugs for office use. The FDA
has issued final guidance on office use that we believe
threatens access to compounded drugs for such use, requiring
patient-specific prescriptions before a compounded drug can be
distributed by a traditional compounding pharmacy. We are
concerned that policy outlined in the final guidance forces
practitioners to rely solely on outsourcing facilities to meet
all of their needs for office-use drugs.
I would like to share a few examples of how implementation
of the DQSA is having some unintended consequences, is
impacting access to compounded and repackaged drugs. This is
why the Academy is supporting policy that ensures access to
drugs for office space use, such H.R. 2871, the Preserving
Patient Access to Compounded Medications Act, introduced by
Congressman Morgan Griffith.
I would like to discuss a patient from my state of
Michigan. She is a 31-year-old lady who wears soft contact
lenses and developed an infection in her eye. She was
eventually determined to have a serious infection known as
acanthamoeba keratitis. The standard treatment for this is the
use of a drug called polyhexylmethyl biguanide. Essentially,
this is pool cleaner. This was prescribed, but, unfortunately,
it was not available in the state of Michigan. As a result, the
patient's ophthalmologist in Michigan was forced to contact
doctors at the University of Illinois-Chicago and to obtain the
drug from Chicago. However, Chicago was unable to provide the
drug in Michigan, and the patient, suffering from severe eye
pain, was forced to drive 225 miles from Michigan to Chicago in
order to obtain this therapy. Fortunately, she responded well.
But this is an example of the type of problems we have when
patients cannot access immediately important therapies.
The Academy has other examples of this involving the use of
autologous serum drops that are given topically and have been
used for more than three decades. These drugs are critical to
the management of severe dry eye. However, due to compounding
regulations, many compounding facilities have stopped producing
these drops.
In closing, ophthalmology strongly believes that compounded
drugs must be produced safely and be subject to critically
important testing. We do believe that regulatory policy in this
arena can become restrictive and, in turn, negatively impact
physicians' ability to properly and effectively treatment
patients. It is important that, as implementation efforts move
forward, the FDA strives to find a more balanced approach. We
believe that increased direct engagement with the physician
community is a strong path forward, and we look forward to
future opportunities with FDA, Congress, and other stakeholders
on these important issues.
Thank you.
[The prepared statement of Dr. Williams follows:]
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
Mr. Burgess. Thank you, Dr. Williams.
Dr. Brod, 5 minutes for an opening statement, please.
STATEMENT OF BRUCE BROD
Dr. Brod. Thank you, Chairman Burgess, Ranking Member
Green, and members of the Health Subcommittee.
I am Dr. Bruce Brod. I am pleased to share with you my
perspective as a dermatologist, a view that is shared by the
American Academy of Dermatology Association.
Dermatologists rely heavily on compounded medications that
are medically necessary and life-changing. We safely and
effectively prepare and administer low-risk topical and
intralesional compounded medications to a wide range of
patients, including individuals presenting with special and
emergent needs and persons suffering from rare diseases,
including children.
Current policy adversely affects the practice of medicine
in two significant ways, the first being with respect to
maintaining a small supply of office-use compounded medications
for administration to patients in our offices. Dermatologists
have historically obtained compounded medications from 503A
compounding pharmacies for immediate use in the office without
the need for a patient-specific prescription. However, current
policy now restricts this. While we understand the FDA intended
503B outsourcing facilities to be a meaningful resource for
providing physicians with office-use stock, not all office-use
compounded medications used by dermatologists are produced by
503Bs, including non-sterile topicals as well as sterile
intralesional drugs used for injection in the skin.
The FDA's website reflects a partial list of drugs that
registered outsourcing facilities have reported producing,
starting December 2016, but ending May 2017. So, the list is
retrospective and it is incomplete, and it doesn't indicate if
these drugs will be produced in the future. Furthermore, we
have no indication that 503Bs will provide flexibility in the
various concentrations that we use in our offices.
The FDA lists only the facilities that are registered. Yet,
it doesn't contain any contact information, real-time product
availability information, or price listing. So, physician
practices literally must go on a scavenger hunt for these
needed compounds. In addition, dermatologists have reported
that the outsourcing facilities have quoted prices that are
cost-prohibitive.
If a compounded drug is not available from an outsourcing
facility, a patient now requires, first, a trip to the
physician office for evaluation and diagnosis, then a trip to
the pharmacy to obtain the prescription, and then, thirdly, a
followup visit back to the physician to finally have the
treatment administered. Those two additional steps impose new
burdens on the patient, delayed treatment, and create
inefficiencies in our practices.
When compounded medications are handled outside of a
provider's control, there are also major safety concerns
regarding proper storage, handling, and application. When the
dermatologist cannot be sure how it has been stored between
patient pickup at the pharmacy and administration in the
office, it calls into question the integrity of the medication.
An additional safety concern is the risk that patients may
be tempted to self-administer the drugs prior to returning to
the physician's office. Many of the powerful compounds in
dermatology are used to destroy unwanted malignant and benign
skin lesions. And so, if they are spilled on the skin by
patients, they will cause scarring and disfigurement.
The second way current policy adversely affects the
practice of medicine pertains to dermatologists' preparation of
low-risk sterile and non-sterile medications in the office
setting. Because of the FDA's broad definition of compounding,
many simple in-office preparations are considered compounding.
Buffering lidocaine, for example, is a widely-used local
anesthetic in dermatologic procedures. Without our ability to
buffer lidocaine with sterile sodium bicarbonate, patients,
including children, will endure painful injections of
lidocaine. Using the buffered lidocaine allows us to perform
very extensive skin cancer surgeries in an outpatient office
setting without the risks and costs of sedation.
Because the FDA considers reconstituting certain FDA-
approved neurotoxins with sterile saline to be compounding, the
FDA's proposed guidelines imply that physician offices are
compounding facilities, subject to the same equipment and
process requirements as high-volume compounders. Many of those
requirements are simply unworkable for dermatology offices,
both structurally and financially.
Accordingly, we are encouraged that the FDA mentions
routine clinical practice and negligible patient risk in its
2018 Compounding Policy Priorities Plan, which states that
providers would not be subject to the same compliance policy in
certain cases. The manner in which we routinely buffer and
dilute our injectable medications in dermatology is really part
of our normal practice of medicine.
While we greatly appreciate the FDA and U.S. Pharmacopeia
are working with medical specialties to explore an urgent-use
exemption, we have real concerns that an exemption based on a
restrictive timeframe will negatively affect patient access.
The well-being of our patients is our primary concern and
responsibility. On behalf of the American Academy of
Dermatology Association, I want to thank you for holding this
hearing, and I am happy to address any questions.
[The prepared statement of Dr. Brod follows:]
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
Mr. Burgess. Thank you, Dr. Brod.
Mr. Hodges, you are recognized for 5 minutes, please.
STATEMENT OF SHAWN HODGES
Mr. Hodges. Yes, sir. Yes, sir. Good afternoon, committee
members.
Mr. Chairman and members of the subcommittee, my name is
Shawn Hodges, a pharmacist and owner of Innovation Compounding,
a compounding-only pharmacy located in Kennesaw, Georgia, just
outside of Atlanta. I also serve as the Vice President of the
International Academy of Compounding Pharmacists, IACP, an
organization that represents more than 4,000 pharmacists,
technicians, students, and members of the compounding community
who focus on the specialty of pharmacy compounding. I would
like to express my gratitude and appreciate to the Health
Subcommittee for taking the time to understand compounding
pharmacy and patient access issues from a pharmacist's
perspective with the implementation of DQSA.
In 2012, a pharmacy owner who lost sight of his moral
compass and violated his oath as a practicing pharmacist
violated both state and Federal laws and regulations related to
quality and safety. As a result, more than 60 lives were lost
and hundreds more fell ill, some to this day, nearly 5 1A\1/2\
years later. As compounders, our top priority is adhering to
the highest-quality compounding standards to prevent something
like this from happening again.
Since NECC, all regulatory bodies have made a concerted
effort to improve the practice of pharmacy. In November of
2013, the DQSA was signed into law, somewhat clarifying the
FDA's joint authority with the state boards of pharmacy, to
monitor the quality of pharmacy compounding. State boards of
pharmacy also updated pharmacy regulations and hired additional
state inspectors to monitor and inspect compounding pharmacies.
USP, the organization that sets the standards for governing
compounding pharmacies, is revising its standards to continue
to ensure best practices of pharmacy compounding, which can
reduce the risk of harm to patients and compounding pharmacy
employees.
As DQSA is well into its fourth year, I would also like to
share with the committee what the professional compounding
pharmacy has experienced and provide suggestions on how all
pharmacies, state boards, and the FDA can actually strengthen
DQSA while protecting access to lifesaving compounded
preparations. As I rely the suggestions of IACP and other key
pharmacy stakeholders, please note that our overall goal is to
encourage an open, transparent dialog with all stakeholders,
public and private. We strive to work closely with FDA in
developing an appropriate balance between regulating quality
and safety without eliminating patient access.
Pharmacies which are compliant and meet USP guidelines and
state board of pharmacy rules fear that FDA overreach will
impact patient care. This fear has been substantiated by
actions of FDA investigators. My pharmacy team experienced this
firsthand in an FDA inspection that lasted for 11 days over a
period of 4 months.
It is important to acknowledge that the FDA investigations
were fulfilling their assigned duties and expressed a keen
interest in the quality of our preparations. For that, I had
the utmost respect for them. However, many requests about our
pharmacy had little to do with the quality of our compounded
preparations, but were, rather, in how we operated our pharmacy
practice that is regulated by the boards of pharmacy. Luckily,
our pharmacy team employed attorneys who are knowledgeable of
both state and Federal pharmacy laws and regulations to advise
FDA that they were inspecting outside the scope given to them
under the law. Many of our fellow compounding pharmacists have
had similar experiences.
I would also like to share IACP's concerns as it relates to
the memorandum of understanding between FDA and the states,
which could limit patient access for preparations that are only
available across state lines. Last week we were encouraged by
Commissioner Gottlieb's 2108 Compounding Policy Priorities Plan
that states he would rescind the current draft MOU and prepare
a new draft for public comment. However, we still remain
concerned that the FDA proposes to define distributing and
dispensing as one and the same. As noted in all other Federal
and state regulations, these are two distinct activities. If
this is not corrected, the impact on patient access to
medications will be detrimental, particularly for patients near
state borders who rely on compounded medications from
neighboring states.
Another of our primary considerations for review is the
role of office-use compounding. I regularly hear from
prescribers who need compounded medications for office use that
they cannot obtain from outsourcing facilities in small dosages
necessary to expeditiously meet patients' needs. The
fundamental concept of office use from 503A pharmacies offers
solutions to prescribers who are faced with unique challenges,
whether a dentist needs a fast-acting, liquid anti-anxiety drug
on hand in case an autistic child may have a panic attack or a
hospice nurse that suddenly needs a compounded nausea
medication because she has terminally-ill patient who is not
responding to a manufactured product. The purpose of office use
is to support prescribers who otherwise do not have access to a
GMP product.
In closing, we at IACP want to be clear that our goal isn't
to interfere with FDA's inspections on quality, but to ensure
that FDA investigators who inspect compounding pharmacies are
aware of and spec within the boundaries of FDCA. They also must
have a working knowledge of USP standards and relevant state
regulations. Likewise, we don't seek to weaken the DQSA in a
way that will allow pharmacies to operate as drug
manufacturers. Our goal is to have an open and consistent
dialog with Congress and the FDA to establish policies that
more effectively balance patient safety with patient access,
because patient access is a patient safety issue.
We thank you for the opportunity to appear here today and
provide our input, and we do look forward to continuing to work
with you on these common goals.
[The prepared statement of Mr. Hodges follows:]
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
Mr. Burgess. Thank you, Mr. Hodges.
Mr. Olson, you are recognized for 5 minutes. And because a
vote has been called, we will take your testimony, and then, we
will have to recess until after the votes. So, you may proceed.
STATEMENT OF JACOB OLSON
Mr. Olson. Thank you. Thank you, Chairman Burgess, Ranking
Member Green, and members of the subcommittee. Thank you for
conducting this hearing on compounding.
My name is Jake Olson, and I am the pharmacist and owner of
Skywalk Pharmacy. We have four locations in the greater
Milwaukee area, serving patients of Children's Hospital of
Wisconsin and clinics. I am testifying on behalf of the
National Community Pharmacists Association. NCPA represents
America's community pharmacists, including the owners of more
than 22,000 independent community pharmacies that dispense
nearly half of the nation's prescriptions.
In 2003, I had the unique opportunity to open Skywalk
Pharmacy as an independently-owned community pharmacy which
would serve as the outpatient pharmacy for the Children's
Hospital of Wisconsin, the first of its kind in the United
States. My pharmacies specialize in treating pediatric patients
with routine ear infections to cystic fibrosis, cancer, and
organ transplants. I compound only non-sterile preparations and
I am compliant with USP 795 standards. I am licensed only in
Wisconsin. I do not ship compounded medications across state
lines, and compounding comprises 20 percent of my business.
Many of my pediatric patients have health conditions that
require medications that have not undergone FDA approval. In
many cases drug manufacturers do not produce a commercially-
available product in the necessary dosage form or strength for
these patients' needs. Physicians call on me to help under
these circumstances when compounding is the only option for
their patients.
I am here today as a healthcare provider and small business
owner to present some of my experiences and those of my fellow
independent pharmacists regarding the FDA's implementation of
the Compounding Quality Act.
First, it is imperative the state boards of pharmacy retain
oversight of pharmacy compounding. I am not eligible to
register as an outsourcing facility, nor would it make sense
for me to do so. The dispensing of custom-made medications
should continue to be regulated by the boards of pharmacy, as
all other medical license profession practices are.
Second, physician office-use compounding needs are not
being met. We used to provide compounds for dentists to treat
pediatric patients who would present with urgent issues.
However, we stopped doing this in 2013 due to the uncertainty
caused by DQSA and conflicting Wisconsin state law. Dentists
still request this compounded medication to be on hand in the
event that a patient needs this treatment. Because I am no
longer providing dentists with this office-use compound, the
dentist now has to close up the tooth, have the patient leave,
come down to my pharmacy, pick up a prescription, and then
return to the dentist. This cannot happen in the same day. So,
the child will continue with an infected tooth until the
dentist can reschedule an appointment. Most of these patients
are innercity children with Medicaid. Transportation is a huge
issue, and sometimes it will take a week or longer to get them
to come back. All the while, the child is suffering.
Third, not all office-use compounding needs can be met by
outsourcing facilities. 503B outsourcing facilities provide an
important function in meeting the needs of healthcare providers
and patients. However, outsourcing facilities are not able to
meet the entire office-use market, nor are they able to replace
the role of the traditional compounding pharmacies.
Because of the requirements placed on outsourcing
facilities and the costs of complying with CGMP, they are not
able to compound in small batches; thus, limiting the role they
can play in meeting the immediate patient needs for compounds.
By prohibiting 503A pharmacies to compound for office use, the
FDA is severely limiting access.
Fourth, FDA needs to end inspection reporting discrepancies
between manufacturers and compounding pharmacies. I often hear
from my fellow compounders who have been inspected by the FDA
about the 483 reports that may be issued post-inspection and
posted publicly, like they were today, on FDA's website. I
don't understand why these same reports are not also publicly
posted for FDA-registered facilities. While FDA publicizes Form
483s and photographs from compounding pharmacy inspections,
there is evidence of several of the same observations from CGMP
manufacturers with no corresponding publicity. This treatment
suggests there is intent by the FDA to sway the public and
undermine the confidence that parents have in my ability to
take care of their child's medications.
Fifth, the FDA must make changes to the Pharmacy
Compounding Advisory Committee and related activities. I am
very concerned that not one of the voting members of the
committee compounds for human use on a daily basis, considering
the committee is making recommendations that can vastly impact
the practice of compounding. The previous FDA PCAC had at least
three pharmacists with current experience and expertise in
compounding. The FDA should select, at minimum, one practicing
human compounder on the committee as a voting member.
Lastly, it is very confusing for me, as a compounder, to
understand what I can or cannot compound with today because of
some of the conflicting information.
In summary, NCPA is committed to working with members of
the Health Subcommittee, the FDA, and other stakeholders
regarding these important matters for a balanced approach to
ensuring patient access to safe and effective compounded
medications. Thank you.
[The prepared statement of Mr. Olson follows:]
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
Mr. Burgess. Thank you, Mr. Olson.
And I apologize, we were only able to get through half the
panel. We will get to the rest of you immediately after this
series of votes. It will probably take us 30 minutes to
complete that task.
So, the committee stands in recess until immediately after
the votes.
[Recess.]
Mr. Burgess. I think to be respectful of everyone's time, I
am going to call the subcommittee back to order. We are
expecting other members to show up almost immediately.
But as we recessed for votes, we were about to hear from
Jenn Adams, the Senior Vice President, Clinical Products
Solutions from PharMEDium Services. So, Ms. Adams, you are
recognized for 5 minutes.
STATEMENT OF JENN ADAMS
Ms. Adams. Thank you. Chairman Burgess, Ranking Member
Green, and members of the subcommittee, thank you for the
opportunity to participate in today's hearing.
My name is Jenn Adams, and I am the President of PharMEDium
Services. On behalf of PharMEDium, I want to thank you for
holding this hearing on the implementation of the Compounding
Quality Act, which Congress enacted as a part of the Drug
Quality and Security Act of 2013.
PharMEDium, which is a subsidiary of AmerisourceBergen,
operates four 503B registered outsourcing facilities. I want to
briefly describe, as we begin, what PharMEDium does, as our
business models tracks exactly what Congress codified in the
Compounding Quality Act. Our four facilities prepare ready-to-
administer compounded sterile drugs for hospitals, so that they
don't have to prepare these medications at a patient's bedside
under conditions that could introduce more risks of
contamination.
Many sterile drugs, such as injectables, in their FDA-
approved form are not manufactured in ready-to-use doses.
Therefore, the drugs have to be prepared by diluting or
admixing the FDA-approved drug with diluents or other
components to achieve the appropriate dose for patient care. We
prepare these sterile drugs into customized preparations, as
ordered by our hospital customers. And this is the primary need
that outsourcing facilities fulfill. And PharMEDium exclusively
compounds using only FDA-approved sterile drugs obtained from
registered drug manufacturers. This practice fills a very
different role than that of traditional pharmacy compounding,
which involves filling an individual patient prescription as
required by law.
Based on our experience in serving the needs of hospitals
and healthcare systems, outsourcing facilities anticipate the
need for drug preparations. We compound those preparations on
behalf of our customers, and then, our customers dispense the
medications to their patients. The types of drug preparations
that are compounded are, by definition, not available from
manufacturers; therefore, requiring these more custom
formulations to meet the clinical needs of patients.
Both of these distinct types of compounding, by outsourcing
facilities and also by traditional pharmacies, we believe are
critical in ensuring that patients have access to safe
compounded medications when needed.
PharMEDium was, and remains, an active supporter of DQSA
because we felt strongly that more oversight of our industry
was needed. The premise of the DQSA is that outsourcing
facilities are subject to FDA oversight and more stringent
quality requirements. And as our industry shifts more toward
manufacturing quality standards, significant investment has
been and is required in our facilities, personnel, and
equipment to comply with these heightened standards. At
PharMEDium our investment has, indeed, been quite significant,
and the enhancements we have made have been challenging to
implement, but we are confident that these improvements are in
the best interest of patients and we are committed to
continuing on this path in cooperation with the FDA.
Unfortunately, the successful implementation of Section
503B is under a separate threat; namely, from the misuse of
bulk drug substances. I mentioned earlier that PharMEDium only
compounds from FDA-approved drugs, as opposed to starting from
bulk drug substances, which are sometimes referred to as bulk
active pharmaceutical ingredients, or API powders.
There are, indeed, circumstances in which it is sometimes
necessary to compound from bulk drug substances, such as when
an individual patient requires a dose that cannot be achieved
when using the FDA-approved manufactured drug as a starting
point. But using bulk powders and outsourcing facilities should
be the rare exception versus the rule, as it requires using a
version of the drug that has not gone through the FDA approval
and, therefore, has not benefitted from all of the safeguards
that are inherent to FDA's drug approval process, which are
designed to mitigate the risks of contamination.
As a result, under the law, bulk powders are only to be
used when clinically necessary and not simply substituted for
the FDA-approved version of the drug. Nevertheless, right now
we are witnessing rampant compounding from bulk drug substances
in the marketplace, usually lacking any clinical justification,
even for sterile drugs. This is particularly concerning because
using bulk drug substances is much less expensive for the
compounder; therefore, undercutting demand for the actual
approved drugs and creating a loophole for compounders to
circumvent the drug approval process.
In light of these and other risks, we remain concerned
about the rapid uptake of bulk drug substance powders in place
of FDA-approved drugs. As we have learned from history, which
demonstrated the tragic impact of poor compounding practice,
FDA should make every effort to implement the DQSA in a manner
that preserves patient access to important compounded
medications and that eliminates opportunities to perform an
end-run around clear restrictions of the law.
While we commend FDA's overall efforts to implement DQSA,
the agency has not tamped down on this rapidly growing abuse of
bulks. Its release of an overly broad interim list of
permissible drug bulk substances and its final guidance on what
amounts to impermissible copies of approved drugs fail to call
out these practices and will not curb these abuses. We
appreciate, however, that FDA announced that it would be
releasing a separate draft guidance in March clarifying that
bulk drug substances may only be used for compounding when
there is a clinical need to compound drugs using these
substances. FDA conformed that this restriction protects
patient health and the drug approval process, for example, by
helping to ensure that outsourcing facilities do not compound
using a bulk drug substance when an FDA-approved version can be
used to meet patient medical needs.
While this acknowledgment is important, it is even more
important that FDA follow this statement up with the promised
guidance as soon as possible, revise the guidance on copies,
communicate this message to providers who may not be aware of
the undisclosed use of bulks, and to rigorously enforce these
restrictions. In order to ensure that patients have a reliable
and safe source of sterile compounded preparations, it is also
important that FDA continue to move forward as quickly as
possible in finalizing other 503B policies that will provide
certainty and clarity to the outsourcing industry providers and
patients. In particular, the lack of final GMP standards for
outsourcing facilities has exacerbated ongoing confusion among
state regulators, many of whom continue to impose expectations
that differ from that of FDA's.
Key congressional proponents champion the DQSA as
clarifying the role of the states in regulating traditional
compounding, and outsourcing to be regulated at the federal
level. That vision has not yet been fully realized.
Again, thank you for the opportunity to contribute to this
important dialog. I appreciate it, and I look forward to your
questions.
[The prepared statement of Ms. Adams follows:]
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
Mr. Burgess. Thank you, Ms. Adams.
Ms. Ventrelli, you are recognized for 5 minutes, please.
STATEMENT OF MOLLY VENTRELLI
Ms. Ventrelli. Thank you. Chairman Burgess, Ranking Member
Green, and members of the subcommittee, thank you for the
invitation to testify today.
My name is Molly Ventrelli, and I am Vice President of
Regulatory Affairs for Fresenius Kabi USA. Fresenius Kabi is a
global healthcare company specializing in lifesaving medicines
and technologies for infusion, transfusion, and clinical
nutrition. We manufacture most of these medicines in Illinois,
New York, and North Carolina, and we employ more than 3,000
people in the U.S. Additionally, Fresenius Kabi operates 18
compounding centers around the world, and we are in the process
of launching our first U.S.-based 503B compounding center in a
suburb of Boston.
We commend FDA's implementation of the DQSA, and we believe
that FDA must continue to enforce the strong protections of the
DQSA against illegal or improper compounding activity. Patient
safety requires strict FDA oversight on outsourcing facility
compounding by pharmacies that do not comply with FDA
regulations and do not meet the highest standards for quality
and CGMP.
Drug compounding plays an important role in the delivery of
health care by allowing a pharmacist, by a patient-specific
prescription, to tailor a therapy for an individual's unique
needs. But it is critical to ensure the safety of patients
receiving these compounded medications. Congress recognized
this in drafting the DQSA and established the two regulatory
structures, both 503A and 503B. Pharmacies that operate under
503A are those that compound according to specific
prescriptions unique to a patient under state board of pharmacy
oversight. They do not compound large quantities in advance of
a patient prescription.
However, Congress also recognized that some hospitals and
healthcare providers may need supplies of medications not made
by pharmaceutical manufacturers or not made in a specific
dosage form, combination, or strength that is medically
required for patients. These products, which need to be on
hand, represent unique safety concerns, as they are typically
made in larger volumes. So, if they become contaminated or are
produced incorrectly, more patients are exposed to harm.
Congress required that these 503B facilities adhere to CGMP,
rigorous requirements enforced by the FDA, with a full set of
quality standards for the manufacturing, processing, packing,
release, testing, and storage of pharmaceutical products.
It is important to note that 503B outsourcing facility
compounders may not make a drug that is essentially a copy of
an approved medicine except under certain highly limited
circumstances like drug shortages. One key reason Congress
included this was to preserve incentives for traditional
manufacturers to continue to pursue FDA approval through the
current NDA and ANDA review process. This protects patient
safety and should be upheld.
We support the FDA's efforts to ensure patient safety by
timely inspecting 503B compounders and issuing compliance
guidance. Fresenius Kabi is currently addressing this now at
our site in Massachusetts.
We also commend the FDA for its continued risk-based
inspections of unregistered compounding pharmacies. FDA's
enforcement of 503A is also important to ensure that facilities
that are essentially acting as outsourcers by selling
significant amounts of commercially unavailable compounded
sterile drugs in the absence of patient prescriptions should
register as 503B outsourcers. In the interest of public health,
the safety and manufacturing standards of compounders should be
held to rigorous standards to ensure patient safety.
Additionally, to uphold patient safety, Congress sought to
ensure that FDA-approved drugs would be used as source material
by compounders whenever possible. Under the DQSA, compounders
should not use bulk active pharmaceutical ingredients as an
alternative to compounding from an FDA-approved medicine unless
doing so would produce a clinical difference for an identified
patient. Fresenius Kabi believes that there could be instances
where several 503B outsourcing compounders are doing exactly
this in contravention of federal law. It is our strong
recommendation that the committee support FDA's rigorous
oversight of pharmaceutical compounding.
Thank you for holding today's hearing, and I welcome any
questions you may have. Thank you.
[The prepared statement of Ms. Ventrelli follows:]
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
Mr. Burgess. Thank you, Ms. Ventrelli.
Ms. Jungman, you are recognized for 5 minutes, please.
STATEMENT OF ELIZABETH JUNGMAN
Ms. Jungman. Good afternoon. I am Elizabeth Jungman,
Director of Public Health Programs at the Pew Charitable
Trusts. We are an independent, nonpartisan research and public
policy organization with a longstanding focus on drug quality,
including compounding. I want to thank you for holding this
important hearing.
This committee has a long history of working to protect
Americans from the risk of substandard compounded drugs. Five
years ago, even before we knew the full scope of the fungal
meningitis outbreak, your oversight team investigated how the
crisis began, and you worked with the Senate and across party
lines to pass the DQSA. This legislation is making a
difference.
Today I will stress the importance of preserving it.
Efforts to weaken the DQSA pose very real risks for patient
safety. I will also share some new findings showing that DQSA
is spurring better compounding oversight in the states.
I was privileged to be among the Senate committee staff
that helped develop the DQSA. We knew then the provisions would
be met with resistance, but each round of negotiations started
with a new count of illnesses and deaths, and it was a powerful
motivator to push past that controversy and get the job done.
The meningitis outbreak is, of course, not the only case of
harm. As we have heard today, just last year 43 people in Texas
had contaminated antibiotics injected into their eyes and
several suffered vision loss. Also, last year 41 patients
received contaminated injections in a New Jersey clinic. They
developed joint infections caused by microorganisms that should
only be found in human mouths.
Americans expect their government to play a major role in
making food and drugs safe. Eighty-seven percent of Americans
think that, according to a Pew Research Center survey.
FDA evaluates the safety and effectiveness for most drugs
and sets manufacturing quality standards, but compounded drugs
are not subject to those protections, and, thus, should only be
used when commercial alternatives won't work. There is a big
difference between drugs prepared for a single patient who will
use it immediately and drugs prepared in bulk quantities for
use at some undetermined future date.
Compounding for a single patient is a traditional part of
pharmacy practice. The risks of dangerous contamination are
relatively low and the impact for errors is contained. States
oversee patient-specific compounding and mandate quality
standards.
But, if compounded drugs are going to be kept onhand, so-
called office stock, the risks are greater. They are often
stored for some period of time, increasing the chance that
contaminates like bacteria and fungus can grow. And since they
are not tailored to specific patients, they products are
frequently produced in bulk, multiplying the consequences of
any error.
That is why Congress created outsourcing facilities. In
exchange for meeting appropriate manufacturing standards,
outsourcing facilities can compound drugs without
prescriptions. Congress has decided twice, first 20 years ago
and again in 2013, that traditional compounding should require
a patient-specific prescription. If compounders want to sell
stock supplies, they must invest in the equipment, training,
and specialized personnel necessary to mitigate the risk. That
dividing line between stock supply and individual prescription
creates accountability.
This committee's investigation demonstrated the importance
of clear and enforceable lines, so that facilities and their
regulators know who is responsible for oversight and what rules
apply. The prescription requirement is very clear. Either a
patient's name is on the product or it is not.
While FDA regulates outsourcing facilities, states are
still the primary regulator of traditional pharmacies, and they
play an important role in ensuring the safety of compounded
drugs. In 2014, Pew convened an advisory committee of pharmacy
regulators, state pharmacy regulators, and other compounding
experts to identify best practices for states. Next month, Pew,
together with the National Association of Boards of Pharmacy,
will release a 50-state assessment.
I am happy to say that most states now conform to best
practices in two key areas. First, states are widely adopting
quality standards that have been established by the USP, the
United States Pharmacopeia. And second, states are aligning
with Federal law on the prescription requirement.
However, there is more work to be done. Ideally, states
should inspect compounding pharmacies every year, but our study
showed that we haven't met this mark. That is why state and
Federal regulators must prioritize the most risky operations.
To wrap up, since the DQSA became law, states have made
important changes, and other stakeholders like outsourcing
facilities have made significant investments, too. To avoid
undermining that progress, Congress and the FDA must continue
to protect, implement, and enforce the DQSA.
Five years ago, this committee acted boldly to draw clear
lines that protect patients from another tragedy. This hearing
reminds us of why we need that law and what could happen if it
is weakened.
I welcome any questions.
[The prepared statement of Ms. Jungman follows:]
[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
Mr. Burgess. Thank you, Ms. Jungman.
Ms. Dargan, you are recognized for 5 minutes, please.
STATEMENT OF NANCY DARGAN
Ms. Dargan. Thank you. Good afternoon, and thank you for
the opportunity to be here today.
My name is Nancy Dargan and I live in Brighton, Michigan. I
am going to tell you how a contaminated compounded medication
permanently harmed my health, putting a premature end to my
career and ruining my family's finances and plans for our
future.
To begin my story, I have to travel back to early 2012. I
was experiencing pain from arthritis in my back and hip, and my
primary physician referred me to a pain clinic for periodic
injections of a steroid called methylprednisolone, which is a
compounded product.
The shots gave me some relief and I continued my busy
career, my life as a grant writer, a business consultant. And
everything changed that August. I had driven from my home in
Michigan to West Virginia to meet with a new client and help
them set up a nonprofit organization. During my stay I began to
feel sick, but I didn't think very much of it at first. But the
symptoms steadily worsened and I realized I had to cut my trip
short.
As I drove home, an excruciating burning sensation
developed in my right hip spreading down to my knee. The pain
became so unbearable that I had to use my left foot for gas and
brakes. I arrived in Michigan completely unable to bear weight
on my leg, and my husband took me immediately to the hospital
to figure out what was going on.
The doctors ordered x-rays, a spinal tap, a biopsy, and
several other tests and expressed that my condition was
something they had not seen before. They worked to treat my
pain, but, initially, had no clear diagnosis. So, they sent me
home.
It was there that I got a call from the pain clinic that
had administered my steroid injections. They said I potentially
received contaminated drugs and should go to the emergency room
immediately.
By this time, the hospital staff were realizing that my
case was not an isolated incident. Other patients were showing
up at the hospital with infections and pains similar to mine,
and like several of them, I was ultimately diagnosed with a
fungal infection.
I underwent surgery and spent 2 weeks in the hospital. I
was placed on a maximum dose of a drug called Voriconazole, a
very powerful antifungal medicine with severe side effects that
seemed nearly as bad as death itself. I took it four times a
day for 14 months, even waking in the middle of the night for
doses.
After I was discharged, my husband Mike became my
caretaker, at great personal expense to him, both mentally and
physically. His job was one of the worst a care partner can
experience, dealing with the unknown effects of a major medical
event. I can't tell you how many times Mike would come into the
room and I would be carrying on a conversation with my
daughter, who had died in 1979. That was the result of
hallucinations caused by the antifungal medication. I would
call out for our pet, and I would get frustrated because he
wouldn't respond, and we had had him put down the year before
due to cancer.
Through all this nightmare, Mike made sure that I made it
to every doctor's appointment, even often three or four per
week, on top of other tests, including blood draws every
Friday. If something needed to be done, including our household
chores, he did it. If something needed to be done around the
house, he never left my side unless I was napping and he could
get errands run. He was not only my caregiver, but my constant
advocate.
Of course, all of this has had a devastating impact on our
lives and plans for the future. Financially, we have lost
everything to this event. The hospital and doctor bills were
astronomical. I lost my ability to maintain self-employment
and, regrettably, had to close my business and refer my clients
to others.
We had partial ownership in a cabin left to my husband and
his sister by his father, but had to sell our interest in this
treasured family property which we enjoyed so much and which
had such wonderful memories for my husband. I saw the grief in
Mike's eyes every time we had to sell something he loved. The
financial toll has threatened our retirement and our
independence as we grow older together.
Today, 5 years after this tragedy began, I still have
recurring symptoms and numerous side effects. I walk with a
limp and cannot get an orthopedic surgeon to consider replacing
my right hip because there are still fungal pockets on my
bones. My pain levels are always elevated. My disease and
treatment have made me vulnerable to opportunistic infections
that have attacked my kidneys and my sinuses, and I still
continue to suffer from short-term memory loss, and it is
getting worse every year.
Before this happened to me, I had never heard of drug
compounding, and I never would have imagined coming to
Washington to speak about it. But I feel obligated to do so.
Sadly, there are many others who have endured as much suffering
and more. I weep for the 60-plus families who lost their loved
ones to this deadly and preventable outbreak and for the
hundreds of patients who live every day with the lasting
consequences of illnesses caused by contaminated compounded
drugs. Many of these people are friends and neighbors who live
in our community, and I am here to speak up for them, too. I
don't want another soul to experience what we have.
As a result of contaminated drugs and a failure to oversee
them, I am now a person who will spend the rest of my days
dealing with a complex illness. It wasn't easy for Mike and I
to get here today. We hope that by sharing our story we can
help prevent this from happening to someone else or anyone
else.
Thank you for allowing me to take some of your time, and I
welcome any questions you might have.
[The prepared statement of Ms. Dargan follows:]
Mr. Burgess. Thank you, Ms. Dargan. We appreciate your
testimony, and appreciate all of you for spending so much time
with us today.
I am going to yield to Mr. Griffith 5 minutes for
questions, since he was the Representative who was instrumental
in moving this legislation along several years ago. So, Morgan,
you are recognized for 5 minutes.
Mr. Griffith. Thank you, Mr. Chairman. I appreciate it very
much, and appreciate all of you being here.
I think sometimes we are talking at cross-purposes because
I don't think any of us want to see somebody like NECC coming
back, because they were operating in a couple of dozen states,
if I remember correctly, in my state and your state, Ms.
Dargan----
Ms. Dargan. California.
Mr. Griffith [continuing]. And California. They have been
kicked out of Colorado. They were national manufacturers who
were lying about what they were doing. They weren't your
traditional small pharmacy that was doing even small batches.
And so, what we have to do, as Ms. DeGette says, we have to
try to find that balance, because we have situations that, in
all fairness, I wasn't aware that one of the solutions to
resolve the problem was that we were going to have folks going
and picking up drugs. I forget who it was. I think a couple
folks were talking about the dentist. Mr. Olson? And I think
somebody, maybe Dr. Brod mentioned it, too, that they are
having the patients have to go to pick up the drug from the
pharmacist because of the new interpretation on 503A. I think
we all think 503B and the new stuff is good stuff. It is a
question of that balance.
And so, if you could, first, Mr. Olson, and then, Dr. Brod,
just tell me quickly about you and your testimony, but what
other situations besides the dentist who has to send somebody
in and, then, a child has to go through or an adult has to go
through pain for a day or two, until the dentist can get them
back in?
Mr. Olson. Thank you for the question, Congressman.
The dentist is the most critical one to my office. We have
other dental products that we had provided in the past. But I
think the other situation that we have is we are having to
teach parents to do this themselves at home, instead of me
providing it now. So, it is not necessarily an office-use
situation, but because I am not able to compound it--for
example, insulin dilutions, we are having to teach parents to
dilute their own insulin at home. We are having to teach
patients to draw up their own medications at home because we
are not allowed to perform that in our pharmacy. And we are
just unsure, if we do that, whether we will be violating
anything.
Mr. Griffith. Dr. Brod, you had some other examples?
Dr. Brod. Yes, several instances. So, we use cantharidin
quite a bit. It is not commercially available. So, we are
relying upon getting it from a compounding pharmacy. It is used
to treat predominantly children and, also, genital warts, too.
So, you can envision a situation where a child comes in.
They are a little scared to begin with. We recommend
cantharidin. It is painless. Other treatments that we have,
such as freezing or burning, to get rid of warts and molluscum,
common skin infections, are very painful and intimidating.
The parent took off of work. The child is out of school. We
say, ``You need a patient-specific prescription.'' The 503Bs,
these are small batches, so we are having trouble getting them
at any reasonable cost. So, the parent, then, has to go to the
pharmacy, schedule another appointment back into the office.
The other problem, too, is we treat a lot of genital warts
which carry oncogenic viruses. Patients with that don't want to
come in in the first place. A lot of the other treatment
alternatives, especially in patients with skin of color, can
cause dyspigmentation and scarring. Things like cantharidin or
podophyllin are really good options. And diminishing access
creating inefficiencies I think is actually a public health
issue.
Mr. Griffith. Do you find that some people, when they find
out they have got to go to the pharmacist and, then, make
another appointment, that they just don't do the treatment at
all?
Dr. Brod. Yes. Sometimes they don't do the treatment at
all; they don't come for follow-up visits, yes.
Mr. Griffith. Does anybody disagree that we all think that
the 503B program as it was originally intended for those medium
to larger folks is a good thing? Anybody disagree with that?
[No response.]
So, we have got to find that balance. Dr. Williams, do you
have examples of where that balance is askew right now?
Dr. Williams. I do, I believe. One of the most devastating
conditions that can occur in your eye is an acute bacterial
infection. This can either be on the surface of the eye, as I
discussed with that patient with a corneal problem, or in the--
--
Mr. Griffith. I am running out of time. So, if I could get
you to cut to the chase?
Dr. Williams. The answer to your question is, yes, we need
office-based access to specific antibiotics that are not
available through the 503B mechanism.
Mr. Griffith. And you don't need a big batch? You just need
a couple of small batches, isn't that correct, from time to
time?
Dr. Williams. I just need enough to have on the shelf, so
when that one patient a week comes in, I can take care of him.
Mr. Griffith. And I worry about my rural areas and my folks
who have a problem, suddenly an emergency late at night or on
the weekend, and there is no compounding pharmacy readily
available in that small, rural community. Is that a concern for
your doctors as well?
Dr. Williams. Absolutely. That is one of the most common
scenarios that we hear.
Mr. Griffith. That is what I am hearing, too.
I appreciate all your testimony. I think everybody had some
valid points. I figure we have got to figure out a way. Our job
is to help work with the FDA and find that proper balance.
And with that, Mr. Chairman, I yield back.
Mr. Burgess. Thank you, Mr. Griffith.
I am going to proceed with my 5 minutes for questions. Mr.
Green, I will come to him next. I was going to give him time to
collect his thoughts since he just rushed in here.
Dr. Williams, several references have been made to an
ophthalmic preparation that was injected after cataract
surgery. Now a patient comes in for cataract surgery in an
outpatient facility. They are coming in with the expectation
that they are either going to need drops or injection after the
surgery, is that correct?
Dr. Williams. That is correct.
Mr. Burgess. So, in that instance, could they not come in
with the prescription already in hand or having picked it up
themselves at a pharmacy? What would prevent that from being
the way this would be administered?
Dr. Williams. So, for an elective procedure such as
cataract surgery, that would be a possibility. The drug that
the specific episode, it is still not exactly clear what
happened. It does not appear to be a contamination in the sense
of a microbial or infectious cause. It seems to be that there
was a toxicity involved when the two drugs were mixed. And so,
it is still not entirely clear exactly what happened. But, even
if those patients had had a prescription and brought that in,
it probably would not have changed the outcome in this
particular case.
Mr. Burgess. Correct. The compounds would have been the
same and the doses and the route of administration would have
been the same, and the outcome you would predict would be the
same. So, I think that is a point well-taken. Just having a
prescription does not necessarily protect you in all instances
from an untoward event.
In the case of the methylprednisolone acetate--and I do
remember that so vividly from our hearings a couple of years
ago--so, here you have got a compound that has to be
preservative-free because it is going into the epidural space
and you don't want to damage a nerve with a preservative. And,
of course, being a steroid, it reduces the body's ability to
fight infection. So, it is like everything culminated in these
cases to really create literally one of the worst things that I
can recall having ever seen.
In addition to all the sympathy I have for everyone else,
the sympathy for the emergency room doctors--I know we had a
patient here in the previous hearing, and it was so difficult
for the attending physicians in the emergency room to really
get a grasp of what was going on, similar to other events that
have happened in this country. When there was anthrax in the
post office here in suburban Washington, the same thing, the
emergency room doctors, seeing those patients out of context,
it made it very, very difficult for them.
Ms. Adams, you referenced the bulk active pharmaceutical
ingredients. Can you give us an idea of which bulk
pharmaceutical ingredients you are talking about?
Ms. Adams. Yes, I can. Thank you.
So, when we look at the list, as an example, of the 200
permissible substances in Category I for bulk compounding right
now, as we cross-reference that list, we feel that almost half
of them have an FDA-approved vial that could be used rather
than bulk substances. So, it is a long list that we think needs
much revision.
Mr. Burgess. OK.
Ms. Adams. And I think important to note, revising the list
is something that for sure needs to happen. But, in addition to
that--that is not a holistic approach--we also think that,
really, to address the issue beyond just that list of 200
substances, essentially copy needs to be revised to
differentiate between compounding that starts from FDA-approved
vials and compounding that starts from bulk substances.
Mr. Burgess. And are you assisting the agency in revising
that list?
Ms. Adams. We are. We have got a good dialog going with the
agency. We have got an opinion, which we have documented for
them, and we are happy to continue to serve as a resource in
that regard.
Mr. Burgess. Very well.
Mr. Olson, again, thank you for being here for the people
that you represent. Let me just ask you, on the FDA's draft
memorandum of understanding, they decided to rescind the
original draft and they are going through significant
revisions. States are going to be required at some point,
though, to sign onto this memorandum of understanding, is that
correct?
Mr. Olson. Yes, Congressman, that is my understanding.
Mr. Burgess. And what will be the consequences if a state
decided we are not going to sign onto that memorandum of
understanding? How would that leave you?
Mr. Olson. It would leave us very conflicted as to what we
are supposed to do. Because if we abide by our state laws, that
is what we should be abiding by. But in my situation I am only
licensed in Wisconsin, so I wouldn't have to worry about the
situation specifically. But I would think it would put
pharmacies in bordering towns or bordering areas in a
precarious position to figure out, well, wait, if the state I
am in signed it, but the state I am shipping into didn't, then
where does that leave me, or vice versa. Even though, to be
fair, most of the time if you are shipping into another state,
you have to be licensed in that other state as well. So, there
is a state license that you would have in both states. It would
just be the conflicting memorandum of understanding about
whether you can ship and how much you can ship into that state.
Mr. Burgess. Thank you.
And, Dr. Brod, just as an observation, years ago I remember
discovering that a little bit of bicarbonate in a vial of
lidocaine could make a tremendous difference as to what your
patients thought about you. And I didn't realize I was
compounding when I was doing that. I just thought I was being a
nice guy. But in your testimony you reference that as an
episode of compounding, is that correct?
Dr. Brod. A tremendous difference. And in speaking with
colleagues who haven't been able to buffer in the office, they
say that the patients note a distinctive difference. We are
very reliant on it. We perform extensive surgeries, but we do
it in the outpatient setting, Mohs surgery with reconstruction.
Having the bicarb to buffer the lidocaine, so that injections
in multiple areas of the face are tolerable, it really allows
us to do surgery outpatient instead of going into a surgical
facility with sedation and those types of things. So, it is a
world of difference and our patients really appreciate it very
much.
Mr. Burgess. Before I yield to Mr. Green, let me just echo
the comments of Mr. Griffith again. We appreciate so much you
all being here. We recognize that there are some issues that we
are going to have to work through, and we appreciate your help
in getting there.
Mr. Green, you are recognized for 5 minutes, please.
Mr. Green. Thank you, Mr. Chairman.
I apologize to the panel about being late, but I had a
medical that I couldn't do. I couldn't have any of my great
staff deal with that.
But I want to thank you for being here. And you know that
Congressman Griffith and Congressman DeGette and the chairman,
we want to fix it because we want to make sure the system
works. And that is what we did after the tragedies in
Massachusetts with 65 people dying. But we appreciate you all
being here and giving your stands on it, so we can actually
work through and see what the solutions will be.
Ms. Jungman, I know the Pew Charitable Trust has done a lot
of research on compounded drugs and was actively engaged in
this issue before the DQSA was signed into law and since. I
think it would be helpful to take a step back and get an
understanding of why this law was necessary and how we can
support its implementation in a manner that strikes the right
balance between access and safety.
Ms. Jungman. I would be delighted to answer that question,
and thank you.
So, as you know, the history of compounding has a long and
complicated legal history, right? It has been a part of
traditional pharmacy practice for as long as pharmacy has
existed. But over time businesses grew up; they were
compounding at a larger scale. And Congress first tried to
tackle that in the nineties, met some legal challenges that Dr.
Gottlieb referred to. And NECC I think really brought to the
forefront of everyone's mind the scale of the patient risk that
was there.
We have done a lot of work trying to capture the adverse
events that have happened in all sorts of facilities from
compounding pharmacies, but there is really not a comprehensive
way to know what the risks, what the scale of the impact is.
And so, what the DQSA does is draw really clear lines that
are designed to ensure that patients have access to the highest
quality product that meets their clinical need. So, if you can
use an FDA-approved product, that is great. If you can't use an
FDA-approved product, then you want a product that is made
under appropriate quality standards. And so, there is a balance
there that is about both ensuring that the quality standards
are appropriate, but that the lines are really clear, so that
everyone knows which side of the line they have to be on.
Mr. Green. I was a state legislator in Texas and we worked
with our pharmacy board and trusted them. I know, typically, we
have these national legislative groups that have standard
pieces of legislation from state to state. So, we do have some
kind of commonality between Texas and Louisiana, or whatever.
But is there anything like that, so we wouldn't have such 50
different? Is there any agency that does that, and say, ``This
is the standard way you pharmacy boards deal with it.''?
Ms. Jungman. The National Association of Boards of Pharmacy
does have a model law that does talk about some of these
issues. There is, of course, still state variation. But the
research that we will publish in about 2 weeks, not quite in
time for this hearing, will show that states are really
beginning to align with, really kind of come into compliance
with each other and in line with DQSA.
Mr. Green. What is the history of responsibility between
the state boards of pharmacy and the FDA? And how did DQSA
change that defining line?
Ms. Jungman. At the time that the NECC outbreak happened
there was a lot of confusion. And I think we saw that in the
hearings that happened at that time, where there was a lack of
clarity about who was supposed to be taking charge of these
institutions. And so, the DQSA really stressed accountability
and clear lines for that reason. So, it was, of course, about
improving the safety of the products, but it was also about
making sure that everyone knew who was, to use the phrase that
kept being used at the time, ``on the flagpole''. Which
regulatory agency was in charge of any type of activity?
And so, the Congress at the time--and you gentlemen know
this better than anyone--considered a lot of different ways of
drawing those lines. Could you do it based on volume? Could you
do it based on geographic reach? But, ultimately, the
prescription requirement was the line that was clear and
enforceable, and that was considered to be really important for
ensuring that the right quality standards were applied.
Mr. Green. When we had the hearings earlier on the tragedy
in Massachusetts, I remember we had FDA and the Massachusetts
Pharmaceutical Board, and they looked at each other. Here we
were sitting up here and saying, somebody has got to be minding
the store, and that is what we are looking for.
States are critical partners in the effort to ensure
patient access to safe compounded drugs. And I understand Pew
will soon release a report with our National Association of
Boards of Pharmacy which assesses best practices that are more
achievable by the states. Hopefully, we can have that
coordination. Again, we just want somebody to make sure,
whether it is the state level or across border lines, the FDA,
somebody needs to be minding the store to make sure we don't
have an incident like we did in Massachusetts, well, literally
countrywide, but it originated there.
Thank you.
Ms. Jungman. Thank you.
Mr. Guthrie [presiding]. Thank you.
And I will now recognize myself for 5 minutes for
questions.
Dr. Williams, your testimony has been about the critical
need for office use of compounded drugs. How do we ensure
office use is allowed while protecting patient safety?
Dr. Williams. Well, I think that is the critical issue we
have been discussing all day. We do not think that the patient-
specific prescription contributes to safety in any way. It
would allow us to track the use of drugs perhaps. But, for the
incidents where timely treatment is critical--and as I
mentioned earlier, infections of the eye, even a delay of an
hour or two will have adverse effects. So, we need to be able
to have these drugs available in office. We can just pull them
off the shelf. And it is just absolutely critical.
I alluded earlier to the pool cleaner for this type of
infection. And it sounds crazy that we would use a pool cleaner
for an infection in the eye, but I can assure you, if you had
that infection, you would want immediate access to that
treatment.
Mr. Guthrie. Thank you very much.
Ms. Adams, some compounded drugs for ophthalmology are
being done only be a single facility. Do you why this is and
was this the case before DQSA?
Ms. Adams. Thank you.
I don't have specific knowledge of where ophthalmology
drugs are compounded and in what scale. PharMEDium is strictly
sterile-to-sterile compounding in our 503B facilities. And as
we stand right now, we do not serve the ophthalmology patient
population. So, I don't have specific knowledge of that.
Mr. Guthrie. Would you know anything about that, Dr.
Williams? Is it done by a single facility and why is that the
case? Was it the case before DQSA?
Dr. Williams. So, before the DQSA, it was done by a single
facility, so-called traditional or 503As. There are many
ophthalmic drugs that are available through 503Bs, and we
encourage our members to use those. It is these relatively rare
conditions, but, yet, very potentially catastrophic, where we
need immediate access. And simply writing a prescription and,
then, having the patient have to go get it, if, in fact, they
can get it--these are drugs that are not typically manufactured
or compounded at a high rate. So, for a rural population, it
could be literally hundreds of miles, as I stated in my
statement.
Mr. Guthrie. Yes, absolutely. Thank you very much.
I am going to yield the time, my remaining time, to Mr.
Griffith of Virginia.
Mr. Griffith. Mr. Hodges, I am going to ask you a question.
It is getting down a little deeper in the weeds, and we still
want to reach a balance. But the committee has heard, much to
their chagrin, all about my family's allergy issues. And some
pharmacies specialize in serving patients with specific needs,
such as a drug without a particular dye or ingredient for those
patients who do have allergies to those particulars. And they
do it because they specialize. They do it in multiple states.
If the shipment of a patient-specific compounded
prescription is limited by the memorandum of understanding,
will patients be able to get all of these medications from
local pharmacies?
Mr. Hodges. Thank you, sir.
Simply put, no, they will not. Not all pharmacies make all
products for every type of patient population. So, for
instance, we engage in allergy immunotherapy. There are only a
handful of pharmacies in the country that offer that. And so,
it is particularly a concern for us that we cannot meet these
patients' needs because we are not able to provide it, in fear
of the MOU, if it is implemented.
And so, what we want to do is work closely with the FDA. We
have some ideas about what we can do to ensure the quality and
access. We have ideas. But we are looking for a sit-down with
the Commissioner. We have requested this year and years prior
we have sent letters, and we are not getting a response. And
so, what we would like to do is ask that the Commissioner have
a sit-down with us. We have some ideas on what we can do.
But, to answer your question, it would be a problem if the
MOU went into effect, especially for patients that live across
state borders.
Mr. Griffith. All right. I appreciate that.
I will tell you that Commissioner Gottlieb, of all the
folks that we have dealt with at that level, is probably the
most responsive that the committee has found. And so, we will
work towards that. But he is very responsive, tries to listen,
tries to pay attention. And so, it is a good working
relationship. Hopefully, together we can find a balance to the
issues that have been raised by today's hearing.
I appreciate all of you very much.
And I yield back, Mr. Chairman.
Mr. Guthrie. Thank you. The gentleman yields back, and I
yield back my time.
Seeing that there are no further members wishing to ask
questions, I would like to thank all of our witnesses for being
here today.
I would like to submit the statements from the following
for the record: American Society of Health-System Pharmacists;
American College of Mohs Surgery; Avella; Outsourcing
Facilities Association; American Society of Cataract and
Refractive Surgery; National Association of Chain Drug Stores;
American Pharmacists Association; a joint statement from the
American Academy of Allergy, Asthma & Immunology and the
American College of Allergy, Asthma and Immunology.
[The information appears at the conclusion of the
hearing.:]
Mr. Guthrie. Pursuant to committee rules, I remind members
they have 10 days to submit additional questions for the
record, and I ask that the witnesses submit their response
within 10 business days upon receipt of the questions.
Without objection, the subcommittee is adjourned.
[Whereupon, at 2:43 p.m., the subcommittee was adjourned.]
[Material submitted for inclusion in the record follows:]
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