U.S. GOVERNMENT PUBLISHING OFFICE

29–991 WASHINGTON : 2019

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 

( 

Printed for the use of the Committee on Energy and Commerce 

energycommerce.house.gov 

(II) 

COMMITTEE ON ENERGY AND COMMERCE 

GREG WALDEN, Oregon 

Chairman 

JOE BARTON, Texas 

Vice Chairman 

FRED UPTON, Michigan 

JOHN SHIMKUS, Illinois 

MICHAEL C. BURGESS, Texas 

MARSHA BLACKBURN, Tennessee 

STEVE SCALISE, Louisiana 

ROBERT E. LATTA, Ohio 

CATHY MCMORRIS RODGERS, Washington 

GREGG HARPER, Mississippi 

LEONARD LANCE, New Jersey 

BRETT GUTHRIE, Kentucky 

PETE OLSON, Texas 

DAVID B. MCKINLEY, West Virginia 

ADAM KINZINGER, Illinois 

H. MORGAN GRIFFITH, Virginia 

GUS M. BILIRAKIS, Florida 

BILL JOHNSON, Ohio 

BILLY LONG, Missouri 

LARRY BUCSHON, Indiana 

BILL FLORES, Texas 

SUSAN W. BROOKS, Indiana 

MARKWAYNE MULLIN, Oklahoma 

RICHARD HUDSON, North Carolina 

CHRIS COLLINS, New York 

KEVIN CRAMER, North Dakota 

TIM WALBERG, Michigan 

MIMI WALTERS, California 

RYAN A. COSTELLO, Pennsylvania 

EARL L. ‘‘BUDDY’’ CARTER, Georgia 

JEFF DUNCAN, South Carolina 

FRANK PALLONE, JR., New Jersey 

Ranking Member 

BOBBY L. RUSH, Illinois 

ANNA G. ESHOO, California 

ELIOT L. ENGEL, New York 

GENE GREEN, Texas 

DIANA DEGETTE, Colorado 

MICHAEL F. DOYLE, Pennsylvania 

JANICE D. SCHAKOWSKY, Illinois 

G.K. BUTTERFIELD, North Carolina 

DORIS O. MATSUI, California 

KATHY CASTOR, Florida 

JOHN P. SARBANES, Maryland 

JERRY MCNERNEY, California 

PETER WELCH, Vermont 

BEN RAY LUJA ́ N, New Mexico 

PAUL TONKO, New York 

YVETTE D. CLARKE, New York 

DAVID LOEBSACK, Iowa 

KURT SCHRADER, Oregon 

JOSEPH P. KENNEDY, III, Massachusetts 

TONY CA ́ RDENAS, California 

RAUL RUIZ, California 

SCOTT H. PETERS, California 

DEBBIE DINGELL, Michigan 

(III) 

SUBCOMMITTEE ON HEALTH

MICHAEL C. BURGESS, TEXAS

Chairman 

BRETT GUTHRIE, Kentucky 

Vice Chairman 

JOE BARTON, Texas 

FRED UPTON, Michigan 

JOHN SHIMKUS, Illinois 

MARSHA BLACKBURN, Tennessee 

ROBERT E. LATTA, Ohio 

CATHY MCMORRIS RODGERS, Washington 

LEONARD LANCE, New Jersey 

H. MORGAN GRIFFITH, Virginia 

GUS M. BILIRAKIS, Florida 

BILLY LONG, Missouri 

LARRY BUCSHON, Indiana 

SUSAN W. BROOKS, Indiana 

MARKWAYNE MULLIN, Oklahoma 

RICHARD HUDSON, North Carolina 

CHRIS COLLINS, New York 

EARL L. ‘‘BUDDY’’ CARTER, Georgia 

GREG WALDEN, Oregon (ex officio) 

GENE GREEN, Texas 

Ranking Member 

ELIOT L. ENGEL, New York 

JANICE D. SCHAKOWSKY, Illinois 

G.K. BUTTERFIELD, North Carolina 

DORIS O. MATSUI, California 

KATHY CASTOR, Florida 

JOHN P. SARBANES, Maryland 

BEN RAY LUJA ́ N, New Mexico 

KURT SCHRADER, Oregon 

JOSEPH P. KENNEDY, III, Massachusetts 

TONY CA ́ RDENAS, California 

ANNA G. ESHOO, California 

DIANA DEGETTE, Colorado 

FRANK PALLONE, JR., New Jersey (ex 

officio) 

(V) 

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 

Page

VI 

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. 

(1) 

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. 

2 

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, creVerDate Nov 24 2008 10:21 Jan 16, 2019 Jkt 037690 PO 00000 Frm 00008 Fmt 6633 Sfmt 6633 I:\MY DOCS\HEARINGS 115\HEARINGS\115-96 CHRIS
3 

ating 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 

4 

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 

5 

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. 

6 

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 

7 

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 

8 

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 antiinfective agent. Also last year, three infants received a compounded morphine prepVerDate Nov 24 2008 10:21 Jan 16, 2019 Jkt 037690 PO 00000 Frm 00014 Fmt 6633 Sfmt 6633 I:\MY DOCS\HEARINGS 115\HEARINGS\115-96 CHRIS
9 

aration 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 

10 

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 

11 

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, 

12 

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 

13 

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:] 

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29991.001

TESTIMONY 

OF 

SCOTT GOTTLIEB, M.D. 

COMMISSIONER OF FOOD AND DRUGS 

FOOD AND DRUG ADMINISTRATION 

DEPARTMENT OF HEALTH AND HUMAN SERVICES 

BEFORE THE 

SUBCOMMITTEE ON HEALTH 

COMMITTEE ON ENERGY AND COMMERCE 

U.S. HOUSE OF REPRESENTATIVES 

"EXAMINING IMPLEMENTATION OF THE COMPOUNDING QUALITY ACT" 

JANUARY 30, 2018 

RELEASE ONLY UPON DELIVERY 
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29991.002

Introduction 

Mr. Chairman, Ranking Member, and Members of the Subcommittee, I am Dr. Scott Gottlieb, 

Commissioner of Food and Drugs at the Food and Drug Administration (FDA or the Agency), 

which is part of the Department of Health and Human Services (HHS). Thank you for the 

opportunity to speak with you today about drug compounding. 

Five years ago, Congress, FDA, state regulators, and practitioners across the country grappled 

with the largest healthcare-related outbreak in recent history. The 2012 fungal meningitis 

outbreak, resulting from a compounder that shipped contaminated compounded drugs throughout 

the country,led to more than 750 cases of illness and 60 deaths in 20 states. The tragic 

proportions of this case were largely attributable to the company's large-scale, multistate 

distribution of an injectable drug intended to be sterile that had been prepared under 

inappropriate conditions. This outbreak underscored the need for improvement in compounding 

practices, as well as the need for more robust oversight of compounders, close Federal and state 

collaboration, and a clear legal framework that would provide for lawful compounding to meet 

patients' medical needs, while also providing FDA with tools to address unlawful compounding 

practices that threaten the public health. 

The meningitis outbreak also made very apparent that there was a need to better define and 

separate the legitimate practice of pharmacy compounding from a growing number of enterprises 

that were acting as large-scale drug manufacturers seeking to operate outside of FDA's routine 

oversight, often creating substantial risk in the process by operating without adhering to good 

manufacturing practices, and evading proper oversight by inappropriately operating under the 

guise of a pharmacy under section 503A of the Federal Food, Drug, and Cosmetic Act (FD&C 

Act). 

Congress addressed these challenges in November 2013, by passing bipartisan legislation, the 

Drug Quality and Security Act (DQSA). The new law amended section 503A of the FD&C Act 

to remove its unconstitutional provisions (related to restrictions on the advertising of and 

solicitation of prescriptions for compounded drugs), thereby enabling FDA to fully implement 
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29991.003

and enforce the remaining provisions of section 503A. The law also created the new section 

5038, establishing the new category of outsourcing facilities, which often engage in larger-scale, 

nationwide distribution with the potential to expose more patients to the risks associated with 

compounded drugs, compared to more traditional pharmacy compounders that are regulated 

under section 503A. The new legislation was aimed at preventing future tragedies like we saw in 

2012 and in many cases before then. 

FDA's compounding program is a priority for the Agency. During the last five years, we have 

made great strides in DQSA implementation through policy development, oversight, and 

stakeholder outreach. FDA has produced a body of policy documents on a scale that clearly 

indicates the importance of this issue for the Agency; we have convened advisory committee 

meetings to obtain advice on scientific, technical, and medical issues concerning drug 

compounding; we have engaged in robust inspection and enforcement; and we have closely 

collaborated with state regulators and interested stakeholders. 

Going forward, we are committed to issuing a series of additional policy documents to continue 

to implement the law. As the framework matures, we will address additional challenges, such as: 

• How do we reduce regulatory burden without sacrificing minimal public health 

protections so that pharmacies that want to engage in larger-scale compounding across 

state lines, or undertake compounding for "office stock," to supply healthcare sites can 

more easily transition to 5038 outsourcing facilities? 

• How can we take steps to enable pharmacies that register as 5038 outsourcing facilities 

to create a more high-quality supply of compounded drugs? 

• As we learn more about the opportunities and risks of this expanding industry, how do we 

more clearly define the boundary between products that should and should not be 

compounded? 

FDA already has taken many steps to implement the new framework created by DQSA. 

Specifically, since enactment ofDQSA, we have issued 24 draft and final guidances to provide 

clarity to compounders on compliance policies, four proposed and final regulations addressing 

products that can or cannot be compounded or used in compounding, and a draft memorandum 

2 
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29991.004

of understanding (MOU) with the states addressing certain distributions of compounded drugs. 

We will be updating that MOU soon, taking into consideration the feedback we received from 

stakeholders. Before developing revised draft or final guidances, we have similarly considered 

thousands of stakeholder comments on the prior drafts. In addition, we have held eight meetings 

of the Pharmacy Compounding Advisory Committee where we have sought the Committee's 

advice on 48 bulk drug substances nominated for use in compounding, six categories of drugs for 

the "Difficult to Compound" list, and 31 substances for the "Withdrawn or Removed" list. We 

have held numerous stakeholder listening sessions, engaging with over 75 different organizations 

annually to hear their feedback on our proposed policies and oversight efforts. We have held six 

intergovernmental meetings with pharmacy regulatory bodies from all 50 states to discuss 

continued Federal and state collaboration and other matters of mutual concern. 

While engaging in policy development and stakeholder outreach initiatives, we have maintained 

robust oversight. We have conducted close to 500 inspections of503A and 503B facilities 

between the passage ofDQSA and the end of fiscal year 2017. We have observed problematic 

conditions during the vast majority of these inspections and have overseen more than 150 recalls 

of compounded drugs and issued more than 180 warning letters. We also have 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 and working with the 

Department of Justice on civil and criminal enforcement actions. 

We will continue to engage in a robust level of oversight and enforcement activity in 2018, as we 

take new steps to make sure .that we are fulfilling FDA's goal to assure the quality of human 

drugs, while also meeting the needs of patients for compounded products. We also will take 

measures that preserve lawful pharmacy compounding practices, while reducing regulatory 

burden without sacrificing critical public health protections for pharmacies that intend to engage 

in large-scale compounding and become 503B outsourcing facilities. 

It is clear to me that our policy development, oversight, and collaboration initiatives have had a 

significant public health benefit. Since embarking on these efforts, we have, in many cases, 

observed improved compliance with the law. For example, since issuing our final guidance 

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29991.005

concerning the prescription requirement under section 503A, we have observed that many 

pharmacies obtain valid prescriptions for individually identified patients. This is consistent with 

the statutory requirement for compounding under section 503A and many state laws and 

enforcement policies that now align with this provision ofFederallaw. 

Collabomtion with states has also improved our ability to address rapidly potential outbreaks and 

emerging quality problems before they cause widespread harm. Likewise, our inspection and 

enforcement efforts have, in many cases, prompted compounders to implement corrective actions 

to address egregious conditions and practices at their facilities before they result in patient injury. 

These initiatives also have fulfilled another critical objective: preserving access to compounded 

drugs for patients who have a medical need for them. In enacting section 503A in 1997 and 

section 503B in 2013, Congress recognized the value of compounded drugs to patient care and 

intended to give FDA necessary authorities to address unlawful compounding that could cause 

serious harm, while preserving access to lawful compounding as an important tool in healthcare 

providers' toolbox for patient treatment. To that end, the policies that we have developed in 

guidance attempt to achieve that balance between patient access to lawful compounding and 

addressing unlawful compounding that could cause harm. When we received comments 

suggesting that policies proposed in draft guidance could have an adverse impact on access to 

lawfully marketed compounded drugs, we have taken a close look at the policies and, when 

appropriate, made revisions. 

Our commitment to preserving needed access to compounded drugs is also evident from our 

oversight approach. We are encouraged by the recent increase in our letters closing out 

inspections of pharmacies that comply with the law, often after having received a warning letter, 

and our letters referring inspections to state boards of pharmacy regarding pharmacies that 

appear to meet certain conditions of section 503A and that have committed to correct readily 

addressable violations of Federal law. FDA is focusing its enforcement priorities on the subset of 

compounders that are most appropriately overseen primarily by FDA rather than the states. 

This progress notwithstanding, challenges remain. Unfortunately, there remain compounders 

whose practices present significant risks to patients. The risks are greater when it comes to sterile 

4 
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29991.006

drugs. For example, during our initial inspections, we have seen vermin, such as cockroaches, in 

the area where employees prepare for sterile processing; employees processing sterile drugs with 

exposed skin that sheds particles and bacteria; contamination, including bacteria and mold, in the 

environment where sterile drugs are produced; and much more. In some cases, pharmacies that 

produce drugs under these conditions ship them to healthcare facilities and patients nationwide. 

While we have seen problematic conditions at both 503A and 503B facilities, the majority of the 

most concerning findings were associated with those regulated under section 503A. 

These and similar violations have led to many cases of serious patient harm. Despite a 

heightened level of oversight activity, FDA has received a steady stream of reports of serious 

adverse events related to compounded drugs since 2012, mostly associated with pharmacies 

regulated under section 503A. 

5 
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29991.007

So""' 753 patients had fUngal meningitis and other infution• after recclvlng steroid injoctioos tlu!t 

weN! c.ontamlnatod wl!ll fungus. At !e"'t 54 patients d!OO. 

Reprinted from "Toward Better-Quality Compounded Drugs- An Update from the FDA/' by Woodcock, Janet, and 

Dohm, Julie, 2017, New England Journal of Medicine, 377, 2511. 

Just to name a few recent examples: this past year at least 43 patients experienced vision 

impainnent and vision loss after receiving eye injections of a compounded drug that was 

contaminated by a 503A phannacy. The year prior, three infants experienced serious adverse 

events after receiving a compounded drug manufactured by an outsourcing facility at a strength 

that was 20-fold greater than the strength indicated on the drug's prepared labeL In 2013, 

bacterial blood-stream infections developed in 15 patients, and two patients died, after receiving 

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29991.008

contaminated infusions that FDA subsequently found had been compounded by a 503A 

pharmacy under inappropriate conditions. Because the vast majority of 503A pharmacies do not 

report adverse events to FDA, our records probably include only a small proportion of the 

adverse events that actually occur. 

These problems emphasize the need to improve the quality of compounded drugs, and it is 

therefore critical that FDA continues to implement the authorities that Congress entrusted to the 

Agency to address compounders whose practices create serious patient risks, at the same time 

that FDA takes measures that preserve lawful pharmacy practices. Moving forward, we intend to 

expand and focus our DQSA implementation, oversight, and collaboration with state regulators 

and other stakeholders to continue to achieve the goals set out by DQSA. 

Policy Development 

I am personally committed to continuing to implement DQSA consistent with our Congressional 

mandate to protect the public health. FDA also plans to take steps that preserve lawful pharmacy 

practices and expand the opportunities for pharmacies that want to engage in larger-scale 

compounding to efficiently become 503B facilities. I hope that recent policy developments, as 

well as new steps that we will take in 2018, demonstrate my commitment to engaging with the 

stakeholder community to develop policies aimed at both preserving access to drugs produced by 

compounding facilities for patients who have a medical need for them, while protecting those 

patients from poor quality drugs that cause serious harm. 

In advance of today' s hearing, FDA announced that we issued three critical fmal guidances: one 

on certain manipulations of biological products by pharmacies and outsourcing facilities, and the 

other two regarding compounding drugs that are essentially copies of commercially available or 

approved drugs under sections 503A and 503B, respectively. The final biologics guidance marks 

the culmination of several years of thoughtful deliberation about how to strike the right balance 

between addressing the high risks for contamination and other product quality problems 

presented by biological products that are manipulated outside of their approved labeling, and the 

need to also preserve access to such products when they meet appropriate quality standards. The 

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final guidance reflects stakeholder input on both the initial draft guidance and revised draft 

guidance on this topic. 

The final guidances concerning compounded drugs that are essentially copies under sections 

503A and 503B describe how FDA intends to implement the statutory restrictions on 

compounding drugs that are essentially copies of commercially available or approved drugs. 

Receiving a compounded drug when a commercially available or approved drug meets the 

patient's medical needs puts that patient at unnecessary and unacceptable risk from receiving a 

drug that has not been proven safe and effective and that may have been produced under 

substandard manufacturing conditions. DQSA reflects the recognition that this practice can also 

undermine the new drug and abbreviated new drug approval processes in the United States. Why 

would sponsors seek approval of applications for life-saving treatments if compounders could 

simply produce copies of those drugs? These guidance documents reflect the careful 

consideration of input from stakeholders in the form of comments on the draft guidances and 

during stakeholder listening sessions. 

I expect that implementation of these three guidance documents, as well as other steps that FDA 

recently announced it will be taking in 2018, will further FDA's mission of reducing the risks 

that drugs produced by compounding facilities present to patients who have a medical need for 

them. At the same time, our policies will seek to expand opportunities for compounding 

pharmacies. Looking ahead, we intend to continue this momentum by issuing additional policy 

documents to implement the compounding provisions ofthe law in the coming months. While 

we have numerous policies in development, I'll discuss just three examples that I am prioritizing. 

Many of the members of this subcommittee are familiar with the provision of section 503A of 

the FD&C Act directing FDA to develop a standard memorandum of understanding (MOU) with 

the states addressing the interstate distribution of"inordinate amounts" of compounded drugs 

and providing for appropriate state investigation of complaints associated with compounded 

drugs distributed outside the state in which they are compounded. The statute provides that 

pharmacies and physicians located in states that have not entered into such an MOU cannot 

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29991.010

distribute more than five percent of their compounded drugs interstate and qualify for the 

exemptions under 503A. This provision of the statute is important for several reasons, including: 

Preventing compounders purportedly 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 (CGMP) requirements and other provisions intended to 

ensure the manufacture of quality drugs; 

Addressing the logistical, regulatory, and financial challenges faced by state regulators, 

such as difficulties states can face in investigating and responding to multi-state 

outbreaks associated with compounded drugs, when a substantial proportion of a 

compounder's drugs are distributed outside of a state's borders; and, 

Reducing the risk to patients that are being treated with drugs from a poor performing 

pharmacy located in another state with inadequate controls. 

It is important that FDA's implementation of this provision of the statute address these 

objectives, while also maintaining our commitment to preserve access to compounded drugs for 

patients who have a medical need for them. After issuing a draft MOU in 2015, FDA received 

more than 3,000 comments and has since heard feedback that the proposed policies could lead to 

access concerns. We have taken this input seriously and will soon issue a revised draft MOU for 

comment that we believe will address the most significant concerns that have been raised. 

Another important document that I would like to highlight is our guidance concerning CGMP 

requirements for outsourcing facilities. As previously noted, outsourcing facilities engage in 

larger-scale, nationwide distribution and are not subject to the conditions on interstate 

distribution or the requirement for compounding to be based on prescriptions for individually 

identified patients. As a consequence, outsourcing facilities have the potential to expose more 

patients to the risks associated with compounded drugs. Therefore, the statute importantly 

subjects outsourcing facilities to CGMP requirements. 

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FDA recognizes that there are differences between outsourcing facilities and conventional drug 

manufacturers that warrant certain differences in how manufacturing standards are applied to 

compounding. Outsourcing facilities can fulfill providers' needs for non-patient specific 

compounded drugs for "office use" or "office stock," which can range in volume, and sometimes 

may be produced in relatively small batches. Accordingly, our policies for CGMP requirements 

for outsourcing facilities, such as stability testing and product release testing requirements, 

should be sufficiently flexible to facilitate compounding in small batches. We need to make sure 

that our policies encourage appropriate compounding by 503B facilities on a small scale and are 

not overly burdensome so that it would be more feasible for pharmacies to become 503B 

outsourcing facilities. 

FDA issued a draft guidance on CGMP for outsourcing facilities in July 2014 that reflects FDA's 

intent to recognize the differences between outsourcing facilities and conventional drug 

manufacturers, and to apply CGMP requirements in a way that is tailored to the nature of the 

specific compounding operations conducted by outsourcing facilities, such as production in small 

batches. 

FDA is working on revising that guidance to incorporate changes that reflect comments we 

received on the 2014 draft, as well as additional feedback from stakeholders concerning the need 

for a policy that is sufficiently flexible to account for the production of small batches of 

compounded drugs for office use. We intend for this guidance to create a risk-based policy 

recognizing that one element of risk is the volume of a product being compounded. By 

considering volume and associated patient exposure, we believe we are able to take closer 

measure of some of the risks associated with the compounded drugs being made by a 503B 

outsourcing facility. 

A third example of a significant policy priority is implementation of the provisions of sections 

503A and 503B concerning bulk drug substances that can be used in compounding, in addition to 

those types of bulk drug substances the statute explicitly allows to be used in compounding. 

Section 503A directs the Agency to develop a list of bulk drug substances that can be used in 

compounding through notice-and-comment rulemaking, and section 503B directs FDA to 

10 
25 


29991.012

develop the list by issuing a Federal Register notice. Approximately 65 substances were 

nominated for the 503A bulks list, and approximately 200 for the 5038 bulks list, with adequate 

supporting information for FDA to evaluate them. Since enactment of DQSA, FDA has 

dedicated considerable Agency resources toward developing the framework for evaluating 

nominated bulk drug substances, conducting extensive scientific reviews, presenting 

recommendations to the Pharmacy Compounding Advisory Committee (the Committee), and 

considering input from the Committee and other stakeholders as it makes decisions regarding the 

disposition of the substances nominated for the section 503A bulk drug substances list. The 

Agency has evaluated and presented to the Committee nearly all of the bulk drug substances 

nominated for use in compounding under section 503A and has issued a proposed rule 

concerning the first ten. As we near completion of the initial phase of our evaluation of bulk 

drug substances nominated for use under section 503A, we are turning our attention to the 

substances nominated for use in compounding under section 5038. The subcommittee should 

expect to see considerable progress on the development of policies relating to the 5038 bulks 

list, and continued progress on the 503A bulks list, in the coming months. 

Oversight 

Next, I would like to discuss our oversight efforts. As I noted earlier, we have conducted 

hundreds of inspections of 503A pharmacies and 5038 outsourcing facilities, many of which 

have resulted in significant findings concerning risks to patients. Our inspections have resulted in 

recalls, temporary cessations of operations, warning letters, and civil or criminal enforcement 

actions. We believe that these regulatory efforts, instituted under the new framework Congress 

created, have prevented outbreaks and other cases of serious patient harm. We intend to continue 

these important efforts, and to continue to post all FDA inspectional findings and regulatory 

actions on our website so this important information is available to purchasers of compounded 

drugs and other interested parties. 

However, based on the experience we have acquired over the last five years in implementing 

DQSA, we are further refining and focusing our approach to compounding oversight. Our goal is 

to leverage our limited resources to achieve the greatest public health impact. Going forward, we 

11 
26 


29991.013

are focusing our oversight efforts on outsourcing facilities under section 503B and pharmacies 

under section 503A that are large-scale, multi-state distributors. 

Congress created the category of outsourcing facilities to serve as a source of higher-quality 

compounded drugs, particularly for office use, where providers may want to have a stock of 

drugs on hand in anticipation of procedures that they might perform in their offices. The 

outsourcing facility sector consists of about 75 entities and is growing. Most of the current 

registrants, who prior to registering as outsourcing facilities had been compounding drugs for 

years without routine federal oversight, and pursuant to production standards that did not meet 

CGMP requirements, are still adjusting to tighter production standards and routine, risk-based 

federal oversight mandated by DQSA. 

During this critical transition period, FDA is focusing our inspectional resources on helping 

outsourcing facilities comply with CGMP requirements. We are also engaging in pre-operational 

inspections and meetings to provide advice outside of the context of a formal inspection or 

regulatory action, as well as more frequent post-inspection correspondence and regulatory 

meetings. We see the growth of the outsourcing facility sector as a critical feature to enable 

patients and providers to access higher-quality compounded drugs. These endeavors should make 

it more efficient for outsourcing facilities to meet the requirements of DQSA, which, in turn 

should encourage pharmacies to register and re-register as outsourcing facilities. We believe this 

prioritization will yield greater voluntary compliance with CGMP requirements and other 

provisions ofthe FD&C Act. 

With respect to section 503A pharmacies, we are working with the states to obtain the necessary 

data to identify large-scale, multi-state distributors, to help focus our inspection and enforcement 

resources on the subset of pharmacy compounders that engage in compounding activities that 

merit FDA oversight. This risk-based prioritization is intended to: assist FDA in identifying 

compounders that may be distributing non-patient specific compounded drugs and should 

consider registering as outsourcing facilities; focus FDA oversight on facilities that, should 

quality problems occur, have the potential to affect the largest number of patients and create the 

greatest risk; and target FDA oversight in a manner that is helpful to the states, especially those 

12 
27 


29991.014

who are not able to conduct oversight of non-resident pharmacies. We are undertaking these 

efforts in close collaboration with our state partners. 

State and Stakeholder Collaboration 

And that brings me to my final topic: state and stakeholder collaboration. These efforts are 

critical to successful policy development and inspection and enforcement. Our state partners are 

critical to the success of the DQSA framework that Congress created. We carefully consider all 

feedback we receive from states and stakeholders, including in the context of comments on draft 

guidances and proposed regulations, stakeholder listening sessions, state and FDA 

intergovernmental working meetings, and many other forums for discussion. FDA has been 

extremely responsive to the feedback the Agency has received from its state partners and I am 

personally committed to making sure that we build on this collaboration. 

For example, we heard stakeholder concerns that we included on lists of inspectional 

observations issued to pharmacies, findings related to CGMP requirements from which the 

pharmacies might have been exempt. In response to those concerns, in 2016 FDA issued a notice 

announcing that the Agency would no longer include CGMP observations for pharmacies that 

meet the conditions of section 503A. We also recently heard that stakeholders had questions 

about the process and policies associated with becoming an outsourcing facility. To address these 

concerns, FDA recently issued an information guide for entities considering registering as 

outsourcing facilities, expanding on the resources available to them. 

In addition, in the past, stakeholders have commented that they would like additional 

opportunities to meet with FDA to share their concerns, outside of the larger annual listening 

sessions. Just after enactment of DQSA, due to the large number of such requests, FDA was 

unable to accommodate them. However, now we are in a different place. The Agency has begun 

to grant stakeholder meetings, and we will continue to do so going forward, as resources permit. 

We are also committed to continuing our close communication with our state partners, holding 

annual intergovernmental face-to-face meetings with representatives of the fifty states, inviting 

13 
28 


29991.015

states to accompany FDA on inspections and to participate in recall discussions with noncompliant firms, and answering questions about oversight and policy matters. We also routinely 

share inspection and enforcement information with state partners, including non-public 

information with those who have entered into information-sharing agreements that allow FDA to 

share such non-public information in accordance with Federal law. We will continue these 

efforts going forward, especially as we implement the MOU discussed earlier. 

Conclusion 

As my testimony describes, implementing the compounding provisions of the law in a manner 

that fulfills Congress' intent is often a balancing act. We must preserve access to compounded 

drugs for patients whose medical needs cannot be met by approved drugs while also taking steps 

to conduct appropriate oversight of compounding, particularly compounding on a larger scale 

and not in response to named patients and individual prescriptions. As we announced earlier this 

month, we are committing to taking a robust series of policy steps to continue to properly 

implement DQSA consistent with our public health mission mandated by Congress. We look 

forward to continuing to engage Congress and work with stakeholders, as we make sure that our 

efforts strike the right balance between patient safety and access. 

I look forward to answering your questions. 

14 
29 

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 indusVerDate Nov 24 2008 10:21 Jan 16, 2019 Jkt 037690 PO 00000 Frm 00035 Fmt 6633 Sfmt 6633 I:\MY DOCS\HEARINGS 115\HEARINGS\115-96 CHRIS
30 

try 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 

31 

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 twotiered 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. 

32 

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 

33 

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 interVerDate Nov 24 2008 10:21 Jan 16, 2019 Jkt 037690 PO 00000 Frm 00039 Fmt 6633 Sfmt 6633 I:\MY DOCS\HEARINGS 115\HEARINGS\115-96 CHRIS
34 

national 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 govVerDate Nov 24 2008 10:21 Jan 16, 2019 Jkt 037690 PO 00000 Frm 00040 Fmt 6633 Sfmt 6633 I:\MY DOCS\HEARINGS 115\HEARINGS\115-96 CHRIS
35 

ernment 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 

36 

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 

37 

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 

38 

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 manuVerDate Nov 24 2008 10:21 Jan 16, 2019 Jkt 037690 PO 00000 Frm 00044 Fmt 6633 Sfmt 6633 I:\MY DOCS\HEARINGS 115\HEARINGS\115-96 CHRIS
39 

factured. 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. 

40 

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? 

41 

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 luVerDate Nov 24 2008 10:21 Jan 16, 2019 Jkt 037690 PO 00000 Frm 00047 Fmt 6633 Sfmt 6633 I:\MY DOCS\HEARINGS 115\HEARINGS\115-96 CHRIS
42 

crative 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 

43 

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 proVerDate Nov 24 2008 10:21 Jan 16, 2019 Jkt 037690 PO 00000 Frm 00049 Fmt 6633 Sfmt 6633 I:\MY DOCS\HEARINGS 115\HEARINGS\115-96 CHRIS
44 

vide 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 

45 

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 

46 

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. 

47 

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. 

48 

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 

49 

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 

50 

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 riskbased 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 

51 

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 expecVerDate Nov 24 2008 10:21 Jan 16, 2019 Jkt 037690 PO 00000 Frm 00057 Fmt 6633 Sfmt 6633 I:\MY DOCS\HEARINGS 115\HEARINGS\115-96 CHRIS
52 

tation 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 

53 

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. 

54 

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 

55 

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. 

56 

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. 

57 

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 

58 

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 largerscale 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 

59 

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 

60 

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. 

61 

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 

62 

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 reguVerDate Nov 24 2008 10:21 Jan 16, 2019 Jkt 037690 PO 00000 Frm 00068 Fmt 6633 Sfmt 6633 I:\MY DOCS\HEARINGS 115\HEARINGS\115-96 CHRIS
63 

lations, 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:] 

64 


29991.016

0 AMERICAN ACADEMY'" 

OF OPHTHALMOLOGY 

Statement for the Record 

George Williams, MD 

American Academy of Ophthalmology 

U.S. House of Representatives Energy and Commerce Committee 

Subcommittee on Health 

Hearing 

"Examining Implementation of the Compounding Quality Act" 

January 30, 2018 

20 F Street NW 

Sulte400 

Washington DC 

20001·6701 

P.O. Box7424 

SanFrancisco,CA 

9412G-7424 

T: +1202.737.6662 

www.aao.org 

Chairman Burgess, Ranking Member Green, and members of the Committee, I am honored 

to be testifying before you on behalf of the American Academy of Ophthalmology on a topic 

critical to the practice of ophthalmology. My name is George Williams, MD, and I am a 

practicing retina specialist from Michigan. I am also the immediate past Secretary for 

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 the standards for ophthalmic education and advocating for our 

patients and the public. 

Background: 

Protecting Sight. Empowering lives."' 
65 


29991.017

Compounded drugs play a vital role in the treatment of patients across medical specialties, 

including ophthalmology, dermatology, allergy and immunology, otorhinolaryngology, and 

others. Ophthalmology is a unique specialty that uses drug dosage forms not commonly 

used in other areas of medicine. These dosage forms include ophthalmic topical solutions, 

suspensions, ointments, and treatments that are injected into the eye. In addition1 many 

drugs that are critical to the treatment of ophthalmology patients must be compounded or 

repackaged for concentration or dosage size, as drug manufacturers do not always make 

products appropriate for use in the eye. The use of compounded drugs is essential to the 

treatment of several ophthalmological conditions, including age-related macular 

degeneration, neovascular glaucoma, infectious endophthalmitis, bacterial corneal ulcers, 

and other potentially blinding infections and diseases. Compounded pharmaceuticals are 

also used in surgical settings, as well as for diagnostic office procedures. 

Because of the frequent need for these treatments, ophthalmologists rely heavily on access 

to drugs for 110ffice use" which is the provision and administration of a drug to a patient in 

the physician's office or other treatment setting without a patient-specific prescription. 

Having access to drugs for "office use" enables ophthalmologists to have these treatments 

readily available should patients arrive at the office in need of emergent care due to 

conditions such as severe infections. A delay in treatment~ even by a few hours, can result 

in permanent vision loss. In other cases, such as the treatment of age-related macular 

degeneration {AMD), ophthalmologists need to have drugs on hand because they do not 

know whether a patient will need treatment until an examination can be performed. 

The Academy actively engaged with Congress as it sought to create a new oversight 

structure for compounding pharmacies following the debacle with the New England 
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29991.018

Compounding Center. Since the passage of the Drug Quality and Security Act (DQSA), the 

Academy has been working with ophthalmic subspecialty organizations to ensure continued 

access to compounded and repackaged drug products for ophthalmology. The Academy and 

other physician organizations have also tried to engage with the Food and Drug 

Administration as it has worked to implement the DQSA to maintain access to the 

treatments that our physicians, and more importantly, their patients need, Despite years of 

effort, we continue to hear from our members about difficulties they have accessing 

important compounded drugs. Therefore, this issue remains a critical priority for the 

Academy and we appreciate the opportunity to share our perspective on DQSA 

implementation efforts. 

Repackaged Biologics: 

The Academy has been a vocal advocate for policy that ensures access to all three, current 

vascular endothelial growth factor (VEGF) inhibitor treatments used by ophthalmologists in 

the treatment of our patients. This includes the FDA-approved anti-VEGF treatments 

ranibizumab and aflibercept, as well as repackaged bevacizumab. Availability of these 

products is critical to patients facing sight-threatening eye disease. We know that individual 

patients respond differently and may have better outcomes with one treatment versus 

another. 

Since 2005, repackaged bevacizumab (Avastin) has been an essential treatment option for 

various blinding eye conditions such AMD, diabetic retinopathy, central retinal vein 

occlusion1 neovascular glaucoma, and others. Its use in terms of efficacy and safety is 

supported by rigorous federally-funded evidence-based clinical research. Ophthalmologists 

have administered millions of repackaged bevacizumab injections to patients. In fact, during 
67 


29991.019

2014 a loner the Academy estimates over four million injections were administered to 

patients. The Academy is aware of adverse event clusters associated with intravitreal 

injections of repackaged bevacizumab, including 2013 events in Georgia and 2014 events in 

Florida. Events like these, along with the passage of DQSA, have led to necessary changes at 

compounding pharmacies and improvements in the safety of repackaged bevacizumab. 

Since the passage of DQSA, the Academy has tracked endophthalmitis rates within 15 days 

of an injection among patients with AMD who received anti-VEGF treatments, including 

compounded bevacizumab. The American Academy of Ophthalmology utilized our IRIS0 

Registry (Intelligent Research in Sight), which is the nation's largest comprehensive eye 

disease clinical registry, to track adverse events associated with use of these products from 

January 2013 to June 2016. The data showed no statistically significant difference in adverse 

events among different anti-VEGF treatments, including repackaged bevacizumab. 

While we understand that the FDA does not factor cost considerations into its policy 

decisions, the potential financial impact of drugs is often an important consideration for 

patients. The price differential between the two branded products and repackaged 

bevacizumab is substantial. Patients may be financially unable to afford the co-insurance 

and deductible payments associated with the branded products. While the average 

Medicare beneficiary pays $11 (co-payment) for one treatment with repackaged 

bevacizumab, the same beneficiary would pay approximately $400 (co-payment) per dose of 

the FDA-approved alternatives. Many ofthese patients require monthly treatments. 

Patients who find it difficult to afford the more expensive alternative may have to make the 

choice to forgo treatment and will eventually lose vision. Currently, some patients lacking 

financial resources find access to the FDA-approved products through patient assistance 
68 


29991.020

programs set up by the manufacturers. It is unlikely that these programs could handle the 

increased demand for approved products created by loss of access to bevacizumab. 

If ophthalmology were to lose access to repackaged bevacizumab when medically 

appropriate, it could cost the Medicare program up to $2 billion per year as physicians are 

forced to use more expensive treatments. 

In February 2015, FDA released Draft Guidance for Mixing, Diluting. or Repackaging 

Biological Products Outside the Scope of an Approved Biologics License Application. The 

Academy expressed grave concerns over the impact of the policies included in the draft 

guidance on the ophthalmic use of bevacizumab. In its original draft guidance, the FDA 

proposed a maximum five-day beyond use date (BUD) for repackaged biologics. 

Traditionally, compounding pharmacies conduct sterility testing on each lot of repackaged 

bevacizumab for a period of roughly 14 days prior to shipment. The proposed 5-day BUD 

would have meant the repackaged drug would have expired before it left the facility or it 

would have required facilities to forego critical sterility testing which our members would 

have found to be unacceptable. The proposed 5-day BUD would have effectively ended 

ophthalmology's use of repackaged bevacizumab. 

Fortunately, FDA has listened to the concerns raised by the Academy and other 

ophthalmology subspecialties. In January 2017, the FDA released an updated draft guidance, 

which created a pathway to a longer BUD for repackaged biologics in accordance with 

additional sterility testing outlined by the agency. The new guidance represented a step in 

the right direction and was recently finalized by the agency. While optimistic about the 

updated policy, it is important that outsourcing facilities have clarity from FDA with respect 
69 


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to required testing to extend a repackaged biologic's BUD. The Academy will continue to 

engage with the agency, Congress and compounding facilities to ensure patient and 

physician access to repackaged bevacizumab is protected. 

Prescription Requirement for 503A 

The Academy is concerned about continued access to other, non-biologic, compounded 

drugs for "office-use. The FDA has issued final guidance on office-use that threatens 

access to compounded drugs for such use by requiring a patient-specific prescription 

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 their needs for office-use drugs. 

While we understand that outsourcing facilities can meet much of ophthalmology's needs, 

we know that the financial costs involved with testing and Current Good Manufacturing 

Practices (cGMP) compliance is an impediment to the production of all the compounded 

drugs ophthalmology relies on. These concerns stem directly from conversations with 

several outsourcing facilities that have conveyed doubts about their ability to prepare 

certain compounds that aren't traditionally ordered in bulk. Regardless of how critical 

these drugs are for patients; their business model is not to compound drugs at a financial 

loss, Facilities have also explained that in instances where they are willing to prepare small 

batch drugs to meet a given need, physicians and patients alike will face steep costs that 

may render many drugs unaffordable. The loss of access to these products is exceedingly 
70 


29991.022

problematic, especially if they are used to treat urgent or emergent conditions} as a 

treatment delay of even a few hours can result in a patient suffering permanent vision 

loss. 

As an example of the unintended consequences of this policy, I would like to share a story 

from one of our members treating patients in my home state of Michigan. 

The patient is a 31-year-old woman who resides in the state of Michigan. She is a soft lens 

wearer and having developed eye pain, she saw a local provider and given a diagnosis of 

Herpes simplex keratitis. Initial cultures were negative but over the next week she 

developed radial perineuritis of her cornea, a sign highly suggestive of Acanthamoeba 

keratitis. Cultures of her contact lens case grew Acanthamoeba and compounded 

polyhexamethyl biguanide (PHMB) was prescribed. Unfortunately, the local Michigan 

pharmacy was not then able to compound PHMB and another source, Leiter's pharmacy 

in San Jose, CA, could not ship it to Michigan. The Michigan ophthalmologists contacted 

the University of Illinois at Chicago (UIC) Eye and Ear Infirmary and their cornea fellow 

talked with their pharmacy, which is very experienced with PHMB compounding. They 

were willing to supply the drug, but only within Illinois, and only if the patient registered 

as a U!C patient. The patient. then having extreme light sensitivity and severe pain, was 

driven from Livonia, Michigan to Chicago, 225 miles each way, by her husband. 

Fortunately, she responded well to PHMB treatment and regained full vision over the 

course of three months. 

Stories like these are why the Academy has been so vocal on this issue and why we support 

policy that ensures access to drugs for office-use, such as H.R. 2871, the Preserving Patient 

Access to Compounded Drugs Act, introduced by Congressman Morgan Griffith. While we 

adamantly believe that compounded drugs must be manufactured safely and be subject to 
71 


29991.023

critically important testing, there is a point where policy becomes restrictive and in turn 

negatively impacts a physician's ability to properly and effectively treat our patients. It is 

also important that we point out that ramifications stemming from access issues are 

exacerbated in more rural parts oft he country. 

The Academy, as well as other physician groups, has highlighted availability concerns to FDA 

both through written comment and during the agency's 2017 listening session with 

physician stakeholders. In a step towards increasing awareness of drug availability, the FDA 

recently released a product list of compounded drug products currently being provided by 

outsourcing facilities. While the Academy appreciates the release and update of the product 

list, it did not alleviate our previously mentioned concerns as many compounded ophthalmic 

drugs remain absent from the list. 

In addition, I would note that according to the FDA's list, some of the compounded drugs 

used by ophthalmology are only being made by a single facility. This raises questions 

regarding the ability of that facility to meet ophthalmology's needs nationwide. We are 

concerned that dependence on a single facility leaves physicians and patients vulnerable to 

supply interruptions should that facility's production encounter technical difficulties or is 

perhaps impacted by a natural disaster. There is also the potential for inflated costs to 

obtain the drug. Ophthalmology's recent experiences with ophthalmic drugs in the generic 

market, including rapid price increases and shortages, have made the Academy sensitive to 

these types of problems. 

The Academy hopes to discuss ways to improve future updates of the product list with the 

agency, including ways to include more real-time information, detailing contact information 

for facilities, pricing~ and other information that would improve awareness and timety 

acquisition of available products. 
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29991.024

Physician In-Office Compounding 

The Academy is also concerned about FDA policy that may infringe upon physician in-office 

activities, including reconstitution of botulinum toxin with an anesthetic. These are low risk 

activities that have been performed in physician offices for years without increasing odds of 

adverse events. The FDA, as well as the United States Pharmacopeia, has expressed concern 

over such activities elevating risks to patients but these concerns are not supported by 

credible data. In fact, the Academy tracked 91,623 botulinum injections between 2013 and 

2016 through its IRIS data registry with only 61 potential adverse events. 

While we understand that compounding activities, specifically sterile compounding, should 

not be undertaken in a physician's office, minor office preparation activities that have been 

a safe and effective part of patient care should not be considered compounding activities by 

regulatory bodies. The Academy believes that any efforts to include these activities under 

the definition of compounding are misguided and will be detrimental to patient care. 

Engagement with Physician Communitv 

As DQSA implementation efforts move forward, we urge the FDA to make additional strides 

in engaging with the physician community and for the agency to be more proactive in 

finding avenues to incorporate physician perspectives. While the FDA has convened 

stakeholder "listening sessions/' the limited time allocated to those sessions have not 

always allowed for substantive discussion of the issues of concern to the physician 

community. It has also been challenging for many stakeholders to engage the FDA in oneon-one discussions. The inability to communicate directly with agency leadership and DQSA 

implementation staff on these issues has been a major source of frustration for the 

stakeholder community. 
73 


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Additionally, given our specialty's heavy reliance on compounded and repackaged drugs, the 

Academy has been disappointed that an ophthalmologist has not been selected to serve on 

the FDA's Pharmacy Compounding Advisory Committee (PCAC). 

Closing Remarks 

Despite serious concerns about implementation policy, we remain tremendously supportive 

of efforts by Congress and FDA to improve the safety of compounded drug products. As 

implementation efforts move forward, we would urge a greater emphasis on ensuring policy 

that promotes patient safety does not do so at the expense of patient access to these vital 

treatment options. 

The Academy stands ready to work with any and all stakeholders on efforts to improve 

implementation of the law and ensure compounded drugs remain safe and effective 

treatment options for our patients. On behalf of the Academy and the ophthalmic 

community, I thank you for your time in allowing me to discuss this critically important 

issue. I look forward to your questions. 
74 

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. 

75 

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:] 

76 


29991.026

Introduction 

Statement for the Record 

Bruce A Bred, MD, FAAD 

American Academy of Dermatology Association 

Chair, Congressional Policy Committee 

Hearing 

Examining Implementation of the Compounding Quality Act 

Subcommittee on Health 

House Committee on Energy & Commerce 

U.S. House of Representatives 

January 30, 2018 

Thank you, Chairman Burgess, Ranking Member Green, and members of the Health 

Subcommittee for the opportunity to appear before the Committee at this hearing entitled "Examining 

Implementation of the Compounding Quality Act," and to speak about the importance of physician 

access to compounded medications to treat dermatology patients. My name is Bruce Bred. I am a 

board-certified dermatologist on staff at the Hospital of the University of Pennsylvania, and a clinical 

professor at the University's Perelman School of Medicine. I currently serve on the Board of Directors 

of the Pennsylvania Academy of Dermatology and Dermatologic Surgery, and as chair of the 

American Academy of Dermatology Association's Congressional Policy Committee. I was also in 

private practice for 22 years in Lancaster, Pennsylvania. 

Hll!nryW. U'", MO, fAAO 

Pr.,>idoml 

SyzaMe M. Olbricht, MD, fAAD i>w>l<l<>~l·EI.a:~1 

Brial'l Borman, MD, PhD, 'FMD 

Theodore Rosen, MD, FAAO 

Barbara M. Mntlles, MD, FAAO 

Marta Val'l Seek, MO, MPH, FAAD 

Elaine Weiss 

!i><e<:»twe DitOld<>r Md CEO 
77 


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Hearing: Examining Implementation of the Compounding Quality Act 

January 30, 2018 

Page 2 of 8 

My testimony will focus on ways the Drug Quality & Security Act (DQSA) has adversely 

affected the practice of medicine for dermatologists in two significant ways: first, (1) with respect to 

maintaining a small supply of office-use compounded medications for administration when patients 

present; and second, (2) when dermatologists prepare low-risk sterile and non-sterile medications 

in the office setting. 

The Academy appreciates the Committee's efforts to maintain the safety of compounded 

medications in wake of the meningitis outbreak from contaminated sterile drugs compounded by the 

New England Compounding Center that tragically resulted in dozens of deaths and hundreds of 

injuries. As physicians, we take an oath to "first do no harm." The well-being of our patients is our 

primary concern and responsibility, and having a safe supply of medications with which to treat our 

patients is of utmost importance. 

During the drafting process of the DQSA in 2013, the Academy engaged with staff from your 

Committee and the Senate HELP Committee so that a final legislative solution not only provided a 

safe drug supply, but also would not interfere with the practice of medicine. We appreciated the 

public statements of Chainnan Burgess, Ranking Member Green, and others that noted the 

importance of maintaining patient access to office-use drugs and ensuring that compounding 

regulations should not interfere with the practice of medicine. 

Dermatologists diagnose and treat more than 3,000 skin, hair and nail diseases, including 

many that are chronic and disabling. We rely heavily on compounded medications that are not only 

medically necessary, but life changing. For decades, dermatologists have safely and effectively 

prepared and administered low-risk topical and intralesional compounded medications to a wide 

range of patients, including individuals presenting with special and emergent needs, persons 
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Hearing: Examining Implementation of the Compounding Quality Act 

January 30, 2018 

Page 3 of 8 

suffering from rare diseases, and children. We have a long and consistent record of safely and 

effectively prescribing and administering compounded medications in a clinical setting. The 

administration of compounded medications is not only a common type of treatment, but it is an 

essential component of many dermatology practices. It is critical to a dermatologist's ability to provide 

proper and timely care for our patients, which can result in better outcomes and lower health care 

costs. 

Office-use Compounded Medications 

In accordance with state law, dermatologists have historically obtained compounded 

medications from section 503A compounding pharmacies prior to receipt of a patient-specific 

prescription for administration to patients within their own offices, a practice referred to as "officeuse." Dermatologists rely on and value the relationship with 503A compounding pharmacies to help 

meet our patients' needs. However, the Food & Drug Administration's (FDA) December 2016 final 

guidance on the Prescription Requirement under 503A of the Food, Drug and Cosmetic Act restricts 

503A compounding pharmacies from providing office-use compounded medications prior to receipt 

of a patient-specific prescription. This limits physicians' access to important compounded 

medications. 

While we understand the FDA intended for the newly created 5038 outsourcing facilities to 

be a meaningful resource for providing physicians' office-use stock, in practice, these outsourcing 

facilities have not been able to meet all the needs of physicians and our patients. Less than 75 

outsourcing facilities are registered with the FDA. The FDA's websitE;llists only the facilities that are 

registered, but with no contact information, no real-time product availability information, and no price 

list. Physician practices have the administrative burden of going on a scavenger hunt to seek this 
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Hearing: Examining Implementation of the Compounding Quality Act 

January 30, 2018 

Page 4 of8 

information. In addition, dermatologists have reported that the outsourcing facilities have quoted 

prices that are cost prohibitive. We also have no indication that 5038 outsourcing facilities will 

provide flexibility in the various concentrations that we use in our offices, flexibility that had been 

guaranteed by the 503A compounding pharmacies. 

Dermatologists rely on compounding pharmacies to produce compounded medications to 

meet their patients' needs. These compounded medications include non-sterile topicals used to treat 

warts, molluscum contagiosum, disfiguring birthmarks, skin cancer, alopecia areata, 

hyperpigmentation, psoriasis, and cutaneous T-cell lymphoma, among others, as well as 

intralesional drugs which are injected directly to areas of skin affected by skin cancer and sexually 

transmitted diseases. Recently, the FDA made public a list of compounded medications that entities 

listed as FDA-registered outsourcing facilities reported producing between December 2016 and May 

2017. The list is retrospective, and it does not indicate if these drugs will be produced in the future. 

Furthermore, as the FDA indicates, not all outsourcing facilities have submitted their product list, the 

list is not neither exhaustive nor even complete. 

The unintended consequence of the restrictive interpretation of the DQSA is limited and/or 

delayed access to needed treatments, which could ultimately result in increased patient morbidity. 

It can also result in unnecessary increases in health care expenses for both patients and the health 

care system, or no care at all. 

If a compounded drug is not available from an outsourcing facility, under the FDA's final 

guidance requiring a patient-specific prescription for access, what could previously have been 

treated in one office visit now requires: 1) a trip to the physician office for evaluation and diagnosis, 

2) a trip to the pharmacy to obtain the prescription, and 3) a follow-up visit to the physician office to 
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Hearing: Examining Implementation of the Compounding Quality Act 

January 30, 2018 

Page 5 of8 

finally have the treatment administered. These two additional steps are not only inefficient for the 

physician practice, but also impose new burdens on the patient and delays in patient care. The 

patient is now confronted with an additional co-pay for a specialist office visit, which may be difficult 

to schedule to begin with, as well as the possibility of further missed school for a child or work time 

for an adult. 

These hurdles undermine timely treatment and continuity of care. They increase the risk of 

non-adherence as well as the risk that patients will not attend follow up visits. The patient's condition 

could persist without the necessary care and treatment, which is safe and effective and, in most 

cases, inexpensive. 

When compounded medications are outside a provider's chain of control, there are safety 

concerns regarding the proper storage, handling, and application that need to be considered. Some 

compounded medications require certain temperature and storage restrictions. When a provider 

does not maintain control of the medication and cannot be sure how it has been stored between the 

time the patient picks it up at the pharmacy and then returns to the physician's office for 

administration, there is no guarantee regarding the integrity of the medication. For example, if stored 

at a high temperature, there are risks of inactivating the active ingredients of Betacaine-LidocaineTetracaine (BL T), a topical anesthetic. 

Many compounded medications should only be administered by a licensed health care 

professional in an office setting. As many of the compounded medications are used topically to 

destroy unwanted skin lesions, there are certain risks if accidentally applied to normal areas of skin. 

Patients may cause harm or permanent disfigurement should they administer these drugs 

themselves. As such, they should be administered by the dermatologist. For example, cantharidin 
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Hearing: Examining Implementation of the Compounding Quality Act 

January 30, 2018 

Page 6 of B 

can burn healthy skin and squaric acid can cause severe allergic contact dermatitis if applied 

improperly. A topical bleaching cream of hydroquinone, retinoid and steroid used to treat melasma, 

which is a pigmenatary disorder common in women, and other pigment disorders can cause 

permanent blue-black pigmentation if not stored or handled properly, and should be applied only for 

a limited duration. 

Another reason a health care provider should directly supervise the application of certain 

compounded medications is that systematic lidocaine toxicity can occur if a numbing cream is 

applied for too long or over a large surface area of the skin. Seizures, cardiac arrest, and death have 

occurred in otherwise healthy individuals who applied this numbing cream without proper supervision 

of a licensed medical professional prior to certain medical procedures. 

In-Office Preparations 

A second unintended consequence of the DQSA having an adverse impact on patient access 

occurs with in-office preparation of drugs. Because the FDA's definition of compounding --

"combines, mixes, or alters ingredients of a drug to create a medication tailored to the needs of an 

individual patient" -- is broad, many in-office preparations are considered compounding and are 

being subject to scrutiny though they are very simple and low risk. 

A widely used local anesthetic in surgical dermatologic procedures is lidocaine buffered in the 

clinical setting with epinephrine andfor sodium bicarbonate. Common practice is to add sodium 

bicarbonate to manufactured lidocaine with epinephrine to decrease the pain of delivery, especially 

for children and patients requiring extensive outpatient skin cancer surgery. This allows us to perform 

more extensive skin cancer surgeries in a more cost effective outpatient setting, also negating the 

need for higher volumes of anesthesia. We have buffered lidocaine syringes readily available, as 
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Hearing: Examining Implementation of the Compounding Quality Act 

January 30, 2018 

Page 7 of 8 

many are used each day when patients present and are in need of in-office surgical treatment and 

important diagnostic biopsies. Given the shortage of manufactured lidocaine with epinephrine, 

dermatology practices must resort to adding epinephrine to lidocaine and other local anesthetics 

themselves for pain control and vasoconstriction. 

Simple in-office preparations are considered "compounding" as opposed to mixing when the 

medication is not prepared pursuant to the manufacturer's labeling (e.g., reconstituting certain FDA 

approved neurotoxins with sterile saline for the treatment of hyperhidrosis). As a result, low-risk, lowvolume, in-office preparations are subject to the FDA's guidance on Insanitary Conditions at 

Compounding Facilities, which is currently in draft form. Under this draft guidance, the FDA proposed 

that physician offices be considered a "compounding facility" subject to the same equipment and 

process requirements as high-volume compounders. Many of these proposed requirements, which 

include International Organization for Standardization Class 5 (ISO 5) area (including laminar flow 

hood), and gowning apparel (e.g., sterile gowns, gloves, mask, foot covers), are simply unworkable 

for dermatology offices both structurally and financially. 

The activities we are performing should be considered the normal practice of medicine. While 

the FDA and U.S. Pharmacopeia are working with medical specialties to explore an urgent use 

exemption, we have real concerns that patient access will be harmed by an exemption based on a 

restrictive timeframe or that remains overly burdensome. For example, peer reviewed journal articles 

show that buffered lidocaine and reconstituted botulinum toxins are safe for patient use for up to four 

weeks, assuming that current aseptic practice is followed. 

We are appreciative that the FDA's 2018 Compounding Policy Priorities Plan mentions that 

the agency will publish revised draft guidance and address concerns we raised about these low-risk 
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Hearing: Examining Implementation of the Compounding Quality Act 

January 30, 2018 

Page 8 of 8 

practices. The FDA stated it plans to define the circumstances in which mixing drugs and applying 

them in a manner that is low risk would not be subject to the same requirements as its risk-based 

approach. We look forward to working with the FDA to ensure that requirements imposed on 

providers do not adversely impact patient access. 

On behalf of the American Academy of Dermatology Association and its member 

dermatologists, I thank you for holding this hearing, and for your commitment to maintaining timely 

access to safe and effective compounded medications. The Academy looks forward to working with 

you as you address the unintended interference on the practice of medicine and patient access. 
84 

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 1A1⁄2 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 

85 

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:] 

86 


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January 24, 2018 

The Honorable Dr. Michael Burgess 

Chainnan, Subcommittee on Health 

Energy and Commerce Committee 

U.S. House of Representatives 

Washington, D.C. 20515 

The Honorable Gene Green 

Ranking Member, Subcommittee on Health 

Energy and Commerce Committee 

U.S. House of Representatives 

Washington, DC 20515 

RE: Testimony Submitted for Health Subcommittee Hearing on DQSA Implementation 

Dear Chainnan Burgess, Ranking Member Green and Members of the Health Subcommittee: 

On behalf of the IACP Board and our members, we thank you for holding this subcommittee hearing on the 

important issues surrounding the Drug Quality and Security Act of 2013 (DQSA), and for the opportunity to 

submit our organization's input. 

IACP is an association representing more than 4000 phannacists, technicians, students, and members of the 

compounding community who focus on the specialty practice of phannacy compounding. Compounding 

phannacists work directly with prescribers including physicians, nurse practitioners and veterinarians to create 

customized medication solutions for patients and animals whose health care needs cannot be met by 

manufactured medications. 

Every day, compounding phannacists serve patients in a variety of areas including: autism, oncology, 

dennatology and pediatrics, in a variety of practice settings including hospice in-patient units, emergency 

rooms, surgical centers, physician clinics, and even Federal Facilities like the VA. Compounding phannacists 

also have served patients such as pre-term infants who require parenteral nutrition (PN). PN provides 

intravenous lifesaving therapy for patients whose gastrointestinal (GI) tracts are not functioning or cannot be 

accessed, or where nutritional needs cannot be met with oral or enteral diets. These are just a few examples of 

how compounding pharmacists are working with physicians to provide life-saving medications for patients. 

Again, we thank you for including IACP in this important hearing and for the opportunity to provide the 

subcommittee with our input. We look forward to working with you on compounding phannacy policies that 

protect both patient safety and patient access to critical medications. 

Sincerely, 

Erik Tosh, D.Phann, FIACP, FACA 

!ACP President 
87 


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Executive Summary: 

For over three years, lACP has worked with a coalition of over 30 prescriber and phannacy organizations (the 

"DQSA Coalition") on issues related to the Food and Drug Administration's implementation and enforcement 

ofthe Drug Quality and Security Act of 2013. IACP and the other member organizations of the DQSA 

Coalition have worked to provide stakeholder input directly to the FDA and through Congress to improve 

patient safety and patient access to compounded medications. In certain areas, we believe the FDA is 

overstepping the regulatory authority given to the agency by Congress in the Federal Food, Drug and Cosmetic 

Act as amended by the DQSA and infringing upon the traditional role of state boards of phannacy in the 

regulation of the practice of pharmacy. We strongly endorse bipartisan legislation, HR2871, the Preserving 

Patient Access to Compounded Medications Act, by Rep. Griffith (R-VA) and Rep. Cuellar (0-TX) as a needed 

clarification of the DQSA that will better delineate the practice ofphannacy from drug manufacturing. 

While encouraged by some of the intended policy changes announced in the "2018 Compounding Policy 

Priorities Plan" released by the FDA, IACP is hopeful that this hearing will result in improved dialogue between 

the FDA and stakeholders, and that future FDA compounding policies will better reflect the input the Agency 

has received from prescribers and pharmacists. Our written testimony for this hearing of the Health 

Subcommittee is focused on the following policy areas: 

Office-use compounding pursuant to state pharmacy laws and regulations; 

The draft sample MOU between FDA and states on interstate distributions; 

Appropriate inspection standards for compounding pharmacies; 

Compounding with dietary supplements; 

Policymaking through Guidance for Industry instead ofrulemaking; 

The Phannacy Compounding Advisory Committee (PCAC). 
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Introduction: 

IACP understands and supports the need to protect public health and safety through strong laws and regulations 

that provide appropriate oversight over both drug manufacturing and the practice of compounding pharmacy. It 

is also critical that those laws establish clear and definitive lines between compounding and manufacturing and 

whether state boards of pharmacy or the Food and Drug Administration (FDA) are the appropriate regulators 

over those distinct activities. Although it was a goal of Congress in passing the DQSA to better brighten this 

line and improve patient safety and access to compounded medications, in many ways the law has unfortunately 

had the unintended consequence of providing less clarity to pharmacists, state boards of pharmacy and medical 

providers, and in addition jeopardizing patient access to critical, often life-saving compounded medications. 

Rather than working with stakeholders through the formal rulemaking process to implement the DQSA and 

establish compounding policies that balance public safety with patient access and adhere to the law's statutory 

language and congressional intent, the FDA has instead issued draft guidance for industry (GFI) documents that 

are often in conflict with the statute and congressional intent, and then finalized without any reflection of the 

stakeholder input received from providers and pharmacists. These GFI documents are treated by the FDA as 

though they have the weight of law or regulation, which they do not, and are used by the FDA to establish 

federal violations that lead to state licensed and compliant "503A" pharmacies being inspected under drug 

manufacturer standards rather than standards established by state pharmacy laws and regulations. 

IACP was hopeful that a new Administration and new FDA Commissioner would lead to a reset of the agency's 

policies that stress the importance of compounding a high-quality preparation, rather than displacing the role of 

state boards of pharmacy in regulating the practice of compounding. Unfortunately, we have yet to see any 

significant movement away from the policies of the last Administration, nor have we seen a willingness to work 

with stakeholders towards improving the FDA's compounding policies to better reflect the practice of medicine 

and pharmacy in the real world, and the state laws and regulations that regulate those professions. 
89 


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For over three years, IACP has been working with a coalition of more than 30 pha!Jllacy and provider 

organizations (the "DQSA Coalition") on the issues our members and their patients are having with FDA's 

implementation and enforcement of the DQSA. The DQSA Coalition was pleased and encouraged when 

bipartisan legislation, HR2871, The Preserving Patient Access to Compounded Medications Act, was introduced 

by Rep. Morgan Griffith (R-VA) and Rep. Henry Cuellar (D-TX) in June of last year. This legislation, which 

now has 43 cosponsors, would address several of these issues and amend the DQSA in a way that would better 

clarify state and federal regulatory authority over compounding,. and better balance patient safety and patient 

access to critical medications. HR2871 has been endorsed by 50 national and state pharmacy and medical 

provider organizations. 

IACP strongly recommends that HR2871 be voted out of this committee and the full House and Senate this year 

and we look fmward to working with you on that process. In the meantime, and for purposes of this 

subcommittee hearing, we appreciate the opportunity to provide our input on several specific policies the FDA 

has adopted in implementing and enforcing the DQSA that we and other organizations believe is contrary to the 

language of the law and its congressional intent, and that is unnecessarily jeopardizing patient access to critical 

medications. 

Office-Use Compounding: 

"Office-Use Compounding" refers to a pharmacist, pursuant to state pharmacy laws that authorize the practice, 

compounding a limited quantity of a medication that medical necessity requires be administered in an office or 

clinical setting by the prescribing physician and transferring the drug to the physician for administration to the 

patient. The majority of state pharmacy practice acts and related state regulations authorize some form of 

office-use compounding, usually as an exception to the prescription requirement under state law. IACP and 

multiple other organizations representing pharmacists and the providers who prescribe and treat their patients 

with compounded medications have provided the FDA with input as to the medical necessity of the 

administration of compounded medications by providers in office or clinical settings. The Congress has 
90 


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weighed in on multiple occasions and in multiple ways (including statements in the congressional record, 

letters, and directives in appropriations bills that are enclosed in this submission) to remind the FDA that the 

DQSA was not intended to prohibit office-use compounding and does not preempt state laws that authorize 

office-use compounding. Indeed, appropriators have been very clear with the FDA in asserting congressional 

intent on the issue of office use. Relevant language in the House Reports accompanying the FY20 16 and 

FY2017 Omnibus Appropriations Acts, as well as House Report language in the FY2018 FDA/Ag 

Appropriations Act is as follows: 

Omnibus Appropriations Act: House Report 114-205, FY 2016: 

The Committee is concerned that, since passage of the Drug Quality and Security Act (DQSA) of 2013, 

the FDA has interpreted provisions of Section 503A of the FDCA in a manner inconsistent with its 

legislative intent and with the agency's own previous positions. Specifically, the FDA has taken the 

position that under 503A, a pharmacist may not compound medications prior to receipt of a prescription 

and transfer the drugs to a requesting physician or other authorized agent of the prescriber for 

administration to his or her patients without a patient-specific prescription accompanying the 

medication. This practice, which is often referred to as 'office-use' compounding, is authorized in the 

vast majority of states and was intended to be allowable under DQSA. The Committee is aware that in 

2012, prior to passage of the DQSA, FDA was working on a draft compliance policy guide for 503A of 

the FDCA that provided guidance on how 'office-use' compounding could be done consistent with the 

provisions of 503A. The Committee understands the intent of the DQSA was not to prohibit 

compounding pharmacists 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 before the receipt of a patient-specific prescription consistent with 

the provisions of 503A within 90 days after the enactment of this Act. (P.67) 
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Omnibus Appropriations Act: House Report 114-531, FY 2017: 

The Committee believes patient access to the right drug at the right time is of utmost imparlance, In 

instances where a commercially manufactured drug is not appropriate for a patient for a specific 

reason, a compounded drug may be the difference between life and death. Since passage of the Drug 

Quality and Security Act (DQSA) of 2013, the Committee has had concerns that the FDA interpreted 

provisions of Section 503A of the FDCA in a manner that might jeopardize the availability of 

compounded medications for ''office use''. The practice of ''office use'' occurs when a compounder will 

compound a batch of drugs in anticipation of receiving patient-specific prescriptions at a later time. It 

may also be the case of a doctor in his or her office maintaining compounded drugs on site because it is 

unsafe or impractical to issue a traditional prescription. This practice is authorized in the vast majority 

of states and was intended to be allowable under DQSA. The Committee is aware that on Apri/15, 2016, 

FDA released a new Draft Guidance on the issue of "office-use" compounding. The Committee directs 

the FDA to issue a Final Guidance that provides for ''office-use'' compounding of drugs, in appropriate 

circumstances as well as including drugs compounded in anticipation of a prescription for an identified 

individual patient. Such "anticipatory" compounded drugs must be based on the history of previous 

valid compound prescription orders, and on an established history between the prescriber and the 

patient and the compounder. (p 68-69) 

House Committee Report to FY 2018 FDNAg Appropriations Bill: 

The Committee continues to believe that patient access to the right drug at the right time is of utmost 

importance. In instances where a commercially manufactured drug is not appropriate for a patient for 

a specific reason, a compounded drug may be the difference between life and death. Since 

passage of the Drug Quality and Security Act (DQSA) of 2013, the Committee has had concerns that the 

FDA interpreted provisions of Section 503A of the FDCA in a manner that might jeopardize the 

availability of compounded medications for ''office use''. The practice of ''office use'' occurs when a 

compounder will compound a batch of drugs in anticipation of receiving patient-specific prescriptions 
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at a later time. It may also be the case of a doctor in his or her office maintaining compounded drugs on 

site because it is unsafe or impractical to issue a traditional prescription. This practice is authorized in 

the vast majority of states and was intended to be allowable under DQSA. The Committee directed the 

FDA to issue a Final Guidance that provides for ''office-use'' compounding of drugs, in appropriate 

circumstances as well as including drugs compounded in anticipation of a prescription for an identified 

individual patient. Such "anticipatory" compounded drugs is based on the history of previous valid 

compound prescription orders, and on an established history between prescriber, patient and 

compounder. Despite clear directives in previous reports accompanying FDA's appropriations bills 

for the agency to finalize guidance that authorizes office-use compounding, in December of 2016, 

the FDA finalized a Guidance for Industry (GFI) entitled "Prescription Requirement Under Section 

503A of the FDCA, ''which expressly prohibits office-use compounding. The Committee directs the FDA 

to rescind this GFI and issue a proposed rule, subject to the notice and comment provisions in the 

Administrative Procedure Act. The proposed rule should be consistent with Congressional intent as 

stated in both Appropriations Reports and the DQSA, and that also allows for office-use compounding 

as authorized by state law. In the proposed rule, FDA should lay out the means by which office use is 

permissible while addressing such critical safety matters, such as maintaining controls on quantity and 

safety issues such as those related to office stock shelf life. Lastly, FDA's clarification on the line 

between traditional compounding and outsourced compounding will support state regulators, 

outsourcing facilities, and traditional compounders in their efforts to ensure that patients have access to 

safe. compounded drugs while reducing the risks associated with sterile drugs produced in bulk. (page 

67) 

Yet, the FDA continues to ignore stakeholders and the Congress and substitute the agency's desired regulatory 

authority over compounding pharmacies for the authority actually given to the agency under the law. 

Stakeholders and the Congress have repeatedly reminded the FDA that in 2012, prior to passage of the DQSA, 

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the agency circulated a draft compliance policy guidance that would have allowed for office-use compounding 

under 503A of the FDCA, with some restrictions. The relevant statutory language of 503A was not changed by 

the DQSA, yet the agency now takes the position that the same statutory language prohibits office-use 

compounding by 503A pharmacies under all circumstances, even where expressly authorized by state law. 

Similar to most, if not all, state and federal statutes governing the practice of pharmacy, the statutory language 

of Section 503A of the FDCA requires that drug products compounded by pharmacies must be "for an 

identified individual patient based on the unsolicited receipt of a valid prescription order ... " However, this 

language does not speak to the timing of the prescription, and there are always statutory and regulatory 

exceptions to the prescription requirement based on the realities of medical practice and the needs of patients. 

Indeed, Section 503A also clearly allows for "anticipatory" compounding "in limited quantities before the 

receipt of a valid prescription order for such individual patient." Additionally, Section 503A gives the FDA 

regulatory authority over the "distribution of inordinate amounts of compounded drug products interstate ... " in 

the form of an FDA-developed MOU between states, or a default cap on interstate distributions equal to 5% of 

the "total prescription orders dispensed or distributed by such pharmacy or physician." Notwithstanding 

FDA's attempt to redefine the terms in Footnote 7 of the GFI on the Prescription Requirement Under FDCA 

503A, it is clear from the plain language of the statute that Congress intended for the terms "distributed" and 

"dispensed" to be treated as the distinct activities they are in law and in medical/pharmacy practice, and that 

Congress recognized there are limited instances where it is appropriate and medically necessary for a 

pharmacist to "distribute" compounded medications to a physician or other prescriber prior to the receipt of a 

valid prescription order, including for administration to patients in an office or clinical setting.4·5 

Given this context and the statute's plain language, together with the fact Congress did not in Section 503A of 

the FDCA expressly preempt state pharmacy laws and regulations that allow for limited quantity office-use 

compounding, we believe FDA has misinterpreted the law to prohibit office-use compounding. When 

inspecting 503A compounding pharmacies, FDA continues to use the fact that a pharmacy is doing office-use 
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compounding prior to receipt of a prescription, including where expressly authorized by state law, to remove the 

exemptions provided to pharmacies in the law and inspect them under current Good Manufacturing Practices 

(cGMPs) rather than under standards adopted by state pharmacy boards under state law. This is drastically 

reducing patient access to vital, and often life-saving, compounded medications. 

FDA, Pew and others have asserted that leaving the issue of 503A office-use compounding to state laws and 

regulations will mean that pharmacies will be able to do unlimited compounding without safety and 

recordkeeping requirements. However, a look at the laws and regulations of the states that still allow office-use 

compounding, shows that the vast majority of them have quantity limitations, sterility requirements, and 

recordkeeping requirements that state lawmakers and boards of pharmacy have determined are appropriate to 

balance the interests of patient safety and patient access to critical compounded medications. Unfortunately, 

FDA has worked diligently to convince several states who previously allowed office-use compounding to repeal 

their laws and regulations in this space due to FDA's assertion that these laws and regulations are now in 

conflict with or preempted by the FDCA as amended by the DQSA. However, a majority of the states still 

authorize some form of office-use compounding by 503A traditional pharmacies, a clear recognition of the 

medical needs of patients in those states. Below are some examples of states that still allow some form of 

office-use compounding under restrictions and requirements determined to be appropriate in those states by 

state lawmakers and boards of pharmacy. 

Office-Use Compounding Authorized: Yes 

Sterile: Yes 

Non-Sterile: Yes 

Statutory Reference: TX Occupations Code §562.152 

Rule or Policy Reference: TAC §291.131 

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Prescription Requirement: No 

Quantity Limitation: Yes 

Comments: Texas statutes and Board regulations specifically authorize the compounding of a ''reasonable 

quantity" of sterile and non-sterile drugs by pharmacies for office administration. The regulations further define 

reasonable quantity, require a written agreement between pharmacist and prescriber, and have strong 

recordkeeping and labeling requirements. 

Washington: 

Office-Use Compounding Authorized: Yes 

Sterile: Yes 

Non-Sterile: Yes 

Statutory Reference: RCW 18.64.270 

Rule or Policy Reference: WAC 246-878-020 

Prescription Requirement: No 

Quantity Limitation: Yes 

Comments: The statute and the Board rules authorize distribution of limited quantities of compounded 

medications to licensed practitioners for office administration. Distribution of inordinate quantities is 

considered manufacturing. 

Oregon: 

Office-Use Compounding Authorized: Yes 

Sterile: Yes 

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Non-Sterile: Yes 

Statutory Reference: No 

Rule or Policy Reference: OAR 855-045-0200 

Prescription Requirement: No 

Quantity Limitation: Yes 

Comments: Oregon pharmacies may provide non-patient specific, non-controlled compounded drugs to OR 

practitioners under a Shared Service arrangement with the Oregon Board of Pharmacy. 

Colorado: 

Office-Use Compounding Authorized: Yes 

Sterile: Yes 

Non-Sterile: Yes 

Statutory Reference: CO Code 12-42.5-118(6)(b) 

Rule or Policy Reference: Colorado BOP Rule 21.00.20 

Prescription Requirement: No 

Quantity Limitation: Yes 

Comments: Colorado resident pharmacies can compound and distribute to CO prescribers for office 

administration up to a I 0% cap. Any compounding for out of state must be patient specific. An accredited 

compounding pharmacy can register as such with the board and then dispense and distribute compounded meds 

in unlimited quantities to CO prescribers and other pharmacies. 

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The FDA's assertion that the creation of S03B "outsourcing facilities" that are authorized to compound without 

receipt of a patient-specific prescription eliminates the need for SOJA office-use compounding is inaccurate. 

S03B outsourcing facilities simply do not have the flexibility to meet these needs. These new entities must 

meet current good manufacturing practices ( cGMP), which are designed for making large amounts of a limited 

variety of medications. To compound an order for a particular formula, extensive testing and validation must be 

done that can take a minimum of 90 to 120 days before the medication can be made available to either a 

healthcare provider or a medical professional. In addition, there must be a need for large quantities of the 

medication in order to make the business practice sustainable given the cost of standardizing of processes as 

required by cGMP. On the other hand, traditional compounding pharmacies, also known as SOJA pharmacies, 

can provide necessary medication in a matter of days or even hours. In many cases, medications need to be 

prepared within hours to ensure a patient can transition from one site of care to another. Their flexibility allows 

them to quickly respond to the needs of patients and medical professionals for specialized medications that are 

not commercially available. For example, the majority of parenteral nutrition patients, especially those needing 

long-term therapy, need individualized formulations that are adjusted frequently. Customized parenteral 

nutrition compounds cannot be provided by S03B outsourcing facilities due to the lag time of dispensing created 

by the end-product testing requirements. 

S03B outsourcing facilities are restricted in the range of medications they can provide. They are able to 

compound medications that are on FDA's drug shortage list that is still under development, and can repackage 

finished product to customize dosage and delivery systems. However, when compounding from bulk 

ingredients (the most common form of compounding), they are limited by statute to a positive list developed by 

FDA. FDA has yet to develop the positive list and has been using enforcement discretion to allow S03 B 

facilities to compound from bulk ingredients without the limitations of a list. But as soon as the agency 

develops the positive list, most bulk ingredients are likely to be excluded from what is allowed. Further, FDA 

is interpreting the statute authorizing outsourcing facilities as requiring an extensive documentation of clinical 

need before compounding of a medication is allowed. If FDA enforces this interpretation, a simple prescription 

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or medical order will no longer suffice and the required medication could not be obtained from a 503B 

outsourcing facility. 

FDA claims that the demand for office use of compounded medications, which medical professionals depend on 

for emergency situations and other appropriate uses as allowed under most state laws, can be met by 

outsourcing facilities. With the prospects of a limited positive list, a requirement for documented clinical need, 

and a limited demand of many of these medications, outsourcing facilities simply will not and cannot meet the 

needs of patients and medical professionals. Furthermore, the greatest demand for office use is for non-sterile 

compounds (capsules, creams, tablets, powders, etc.). Establishing an outsourcing facility requires meeting 

extensive and costly sterile compounding regulations, and only a small number of outsourcing facilities are 

doing non-sterile compounding. 

503B facilities will play an important role in our health care system, and are designed to meet the needs of 

hospitals and others in dealing with drug shortages. This should help alleviate some of the patient access 

problems in those settings; however, the requirements and cost of complying with cGMP prevents the 

compounding of small batches and limits the role they can play in meeting the needs of patients for 

compounded drugs in smaller office and clinical settings. This gap in patient access to compounded 

medications for office administration has been experienced by prescribers in a broad range of practice areas, but 

has had a particularly negative impact on the patients of dermatologists and ophthalmologists. Enclosed in our 

submission is a chart showing compounded medications needed by prescribers that they report they are unable 

to obtain from 503B facilities. 

On Friday, January 19, FDA released a "2018 Compounding Policy Priorities Plan" that describes the agency's 

intention to issue a revised draft guidance document with a "new flexible, risk-based approach to requirements 

for outsourcing facilities." The policy is intended to make it easier for smaller pharmacies to register with the 

FDA as outsourcing facilities, and compound with or without patient specific prescriptions, including for office 

administration. While IACP will wait to see the actual language of the revised GF! and eventual proposed rule 

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before commenting in detail on this new policy proposal, we do have strong concerns about any proposal that 

could negatively impact patient access to compounded medications and are wary of FDA policies that would 

lead to the further federalization of the regulation of the practice of pharmacy, and weaken the traditional role of 

state boards of pharmacy as the appropriate regulatory authority over the profession. 

We join the 65 Members of Congress who wrote to the FDA in May of 2017 asking that the final GF1 on the 

503A prescription requirement be rescinded, and that the agency work with stakeholders to develop a proposed 

rule that authorizes office-use compounding by 503A compounding pharmacies where authorized by state law 

in a way that protects both patient safety and patient access to the compounded medications they need.' 

Definitions of the terms "Distribute" and "Dispense": 

Section 503A of the Food, Drug and Cosmetic Act (FDCA) gives the FDA limited regulatory authority over the 

"distribution" of "inordinate quantities" of compounded medications across state lines in the form of a sample 

MOU between states to be established by the FDA in consultation with the National Association of State 

Boards of Pharmacy, or a default cap contained in the FDCA. The relevant section of the FDCA (21 U.S.C. 

§353a (b)(3)(B)) establishing the default cap on compounded medications shipped interstate, says that it applies 

to pharmacies in a state "(ii) that has not entered into the memorandum of understanding described in clause (i) 

and the licensed pharmacist, licensed pharmacy, or licensed physician distributes (or causes to be distributed) 

compounded drug products out of the State in which they are compounded in quantities that do not exceed 5 

percent of the total prescription orders dispensed or distributed by such pharmacy or physician." (emphasis 

added). This section of the FDCA was not amended by the DQSA and was part of the 1997 Food and Drug 

Modernization Act that established Section 503A of the FDCA. 

The draft MOU, in its Appendix, defines "distribution" to include the dispensing of compounding medications 

directly to a patient for the patient's use. In December of 2016, the FDA issued a Final Guidance for Industry 

(GFI) entitled "Prescription Requirement under 503A of the Federal Food, Drug and Cosmetic Act" that, in a 

footnote, also defines "distribution" to include dispensing a drug directly to a patient. The terms 

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29991.048

"distribution/distributed" and "dispensing/dispensed" are clearly distinct and commonly understood terms in 

both medical practice as well as throughout federal and state law.4 

The "dispensing" of medications, commonly understood to mean the transfer of a drug product to a patient or an 

agent of the patient for that patient's use, is the very essence of the practice of pharmacy, something 

appropriately regulated by state boards of pharmacy under laws established by state legislatures. The term 

"distribution" is commonly understood in medical practice and defined throughout federal and state law to 

mean the sale, transfer or storage of a drug product that does not include "dispensing" to a specific patient. 

The very section of the FDCA (21 U.S.C. §353a(b)(3)(B)) giving the FDA regulatory authority over the 

"distribution of inordinate quantities of compounded medications" clearly distinguishes distribution and 

dispensing as the distinct activities they are by creating a default cap on interstate distributions that is based on 

a percentage (5%) of the total amount of prescriptions "dispensed or distributetf' by the pharmacy or physician. 

(emphasis added). By redefining these key terms in the sample draft MOU and in a GFI, the FDA is asserting 

regulatory authority over the "dispensing" of compounded medications over state lines in a way that Congress 

never intended and that will jeopardize patient access to critical compounded medications. The FDCA was not 

intended to give FDA the authority to limit the patient specific "dispensing" of compounded medications, only 

the "distribution" of "inordinate quantities" of compounded medications shipped over state lines. 

It is highly unusual and inappropriate for the FDA to, in a GFI and a sample MOU, attempt to redefine key 

statutory terms to meet their policy interpretation of the statute, especially those that are defined elsewhere in 

federal state laws and regulations and with clearly understood meanings in practice. FDA, in the Notice of 

Availability for the MOU acknowledges the fact that these terms are defined elsewhere in federal law. In the 

notice the FDA asserts that because Congress did not provide a definition of"distribution" in this section of the 

FDCA that does not specifically exclude "dispensing". Congress intended for FDA to ignore the multiple 

federal and state statutory and regulatory definitions of these terms, as well and the medical and pharmacy 

15 
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communities' common understanding of those terms, and instead use the "ordinary meaning" of those terms, 

which they analogize to manufacturers of other goods distributing those goods to their customers. 

Congress has, through multiple letters to the FDA and in report language in the last two FDA appropriations 

bills (FY16 and FY17) told FDA their re-defining of these terms in a sample MOU and in a GFI is an 

"overreach," and is "unprecedented" and inconsistent with congressional intent of the statute. A copy of the 

congressional letter referenced above and dated May 23, 2017, is enclosed as an attachment to this testimony 

and the relevant report language is quoted below, including language from the House Report accompanying the 

FY 2018 bill. However, FDA continues to move forward with implementing compounding policies in a way 

that is inconsistent with the statutory language of this section of the FDCA and the definitions of these terms 

throughout federal and state law and congressional intent, which will threaten patient access to critical 

compounded medications. The access problem will be especially felt by patients served by compounding 

pharmacies near state Jines that would, under FDA's interpretation of the FDCA, be subject to an arbitrary cap 

on the compounded medications they can "dispense" to specific patients across state lines. 

Examples of definitions of the key terms "distribution" and "dispensing" can be found throughout state and 

federal health care and pharmacy law. For FDA to redefine these key terms in the MOU and GFI would not 

only expand the agency's regulatory authority over patient specific dispensing of compounded medications in a 

way Congress never intended, it would conflict with the commonly understood medical and legal definitions of 

those terms throughout state and federal health care statutes causing unnecessary confusion and legal 

uncertainty at both the state and federal levels. Below are some examples of how these key terms are currently 

defined in state and federal law: 

Federal Law Definitions: 

21 CFR208.3 

Specifically, in 21 CFR §208.3, 

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§208.3 Definitions. 

For the purposes of this part, the following definitions shall apply:~Ir] 

(a) Authorized dispenser means an individual licensed, registered, or otherwise permitted by the 

jurisdiction in which the individual practices to provide drug products on prescription in the course 

of professional practice.[,}~} 

(b) Dispense to patients means the act of delivering a prescription drug product to a patient or an agent 

of the patient either:~~~} 

(1) By a licensed practitioner or an agent of a licensed practitioner, either directly or 

indirectly, for self-administration by the patient, or the patient's agent, or outside the licensed 

practitioner's direct supervision; or[s}~} 

(2) By an authorized dispenser or an agent of an authorized dispenser under a lawfol 

prescription of a licensed practitioner.[,~~} 

(c) Distribute means the act of delivering, other than by dispensing, a drug product to any person.;}~} 

(d) Distributor means a person who distributes a drug product. 

21 u.s.c. §802(10)-(11) 

In addition, the Controlled Substances Act defines "dispense" and "distribute" to mean two different things, 

and expressly excludes "distribute" from the act of dispensing. Specifically, the CSA states that a pharmacy 

which is: 

registered to dispense a controlled substance may distribute (without being registered to distribute) a 

quantity of such substance to ... another practitioner for the purpose of general dispensing by the 

practitioner to patients" unless the pharmacy's "total number of dosage units of all controlled 

substances which will be distributed by him" does not "exceed 5 percent of this total number of dosage 

units of all controlled substances distributed and dispensed by him during that calendar year." 

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21 u.s.c. 581 

In section 581 of the FDCA, the term "distribute or distribution" is defined: 

§581 Definitions. 

In this subchapter: 

(5) Distribute or distribution--The term 'distribute' or 'distribution' means the sale, purchase, trade, 

delivery, handling, storage, or receipt of a product, and does not include the dispensing of a product 

pursuant to a prescription executed in accordance with section 503(b)(1) or the dispensing of a product 

approved under section 512(b). 

State Law Definitions: 

Indiana: 

IC 25-26-13-2 

Definitions 

Sec. 2. As used in this chapter: 

"Dispensing" means issuing one (1) or more doses of a drug in a suitable container with 

appropriate labeling for subsequent administration to or use by a patient. 

IC 25-26-14-4.7 

"Distribute" defined 

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Wisconsin: 

Sec. 4. 7. As used in this chapter, "distribute" means to sell, offer to sell, deliver, offer to deliver, 

broker, give away, or transfer a legend drug, whether by passage of title or physical movement, 

or both. The term does not include the following: 

(I) Dispensing or administering a legend drug. 

(2) Delivering or offering to deliver a legend drug by a common carrier in the usual 

course of business as a common carrier. 

(3) The provision of a legend drug sample to a patient by a: 

(A) practitioner; 

(B) health care professional acting at the direction and under the supervision of a 

practitioner; or 

(C) hospital's or other health care entity's pharmacy that received the drug 

sample in accordance with this chapter and other applicable law to 

administer or dispense and that is acting at the direction of a practitioner; 

licensed to prescribe the legend drug, 

Statute 450.01 

(7) "Dispense" means to deliver a prescribed drug or device to an ultimate user or research subject by 

or pursuant to the prescription order of a practitioner, including the compounding, packaging or 

labeling necessary to prepare the prescribed drug or device for delivery. 

(8) "Distribute" means to deliver, other than by administering or dispensing. 

The Congress has been clear that its intent on this issue is for these terms to be treated as the separate and 

distinct activities that they are and has expressed that intent in the reports accompanying the final versions of 

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the FDA's appropriations legislation for FY2016 and 2017, as well as the House Report for the 2018 bill. 

Below is the language in each of those House reports. 

Omnibus Appropriations Act: House Report 114-205, FY 2016: 

The Committee is very concerned with the draft MOU that the FDA has proposed under Section 503A of 

the FDCA. The proposed MOU would complicate patient and prescriber access to compounded 

medications, and may have a deleterious effect on small pharmacies. Under the draft MOU, the FDA 

attempts to describe "distribution" as occurring when "a compounded human drug product has left 

the facility in which the drug was compounded." In the DQSA, Congress only allowed the FDA to 

regulate "distribution." But the MOU appears to exceed the authority granted in the statue by 

redefining "distribution" in a manner that includes dispensing-something unprecedented. This 

overreach could generate exactly the kind of costly and confusing litigation that Congress intended to 

avoid when it amended and rein- stated Section 503A. The Committee expects that, when a final MOU 

is proposed as a model agreement for the states to consider, that distribution and dispensing are treated 

as the different and separate activities that they actually are. 

Omnibus Appropriations Act: House Report 114-531, FY 2017: 

The agreement remains concerned with the draft MOU that the FDA proposed under Section 503A of 

the FDCA. Section 503A distinguishes between "distribution" and "dispensing" for the purposes of the 

MOU. In the DQSA, Congress only allowed the FDA to regulate "distribution." The MOU appears to 

exceed the authority granted in the statute by redefining "distribution" in a manner that includes 

dispensing. Congress did not intend to include dispensing of compounded drugs over state lines 

within the scope of the MOU. The MOU should not address dispensing of compounded drugs to a 

patient over state lines if all other requirements of 503A are met. 

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House Committee Report to FY 2018 FDA/Ag Appropriations Bill: 

The Committee is also very concerned with the draft MOU issued February 13, 2015, entitled "Draft 

Memorandum of Understanding Addressing Certain Distributions of Compounded Human Drug 

Products Between the State of () and the Food and Drug Administration'' as it applied to Section 503A 

of the FDCA. The proposed MOU would complicate patient and prescriber access to compounded 

medications, and may have a deleterious effect on small pharmacies. Under the draft MOU, the FDA 

attempts to describe "distribution" as occurring when "a compounded human drug product has left 

the facility in which the drug was compounded." In the DQSA, Congress only allowed the 

FDA to regulate "distribution." But the MOU appears to exceed the authority granted in the statute by 

redefining "distribution" in a manner that includes dispensing-something unprecedented. This 

overreach could generate exactly the kind of costly and confusing litigation that Congress 

intended to avoid when it amended and reinstated Section 503A. The Committee expects that, when 

a final MOU is proposed as a model agreement for the states to consider, that distribution and 

dispensing are treated as the different and separate activities that they actually are. (pages 67-68) 

We were encouraged to read in FDA's "2018 Compounding Policy Priorities Plan" issued Friday, January 19th 

that the agency, in the coming months, intends to pull down the current draft sample MOU and issue a 

"significantly revised draft MOU" that is intended to "address many of the concerns (they) have heard" in the 

thousands of public comments on the current draft sample MOU. The plan states the FDA's intention to raise 

the current MOU's 30% cap on the distribution of inordinate quantities of compounded medications interstate to 

50% and indicates the new cap will trigger enhanced reporting requirements and FDCA violations that would 

lead to pharmacies being regulated like drug manufacturers. The new draft sample MOU will also purportedly 

relax some of the requirements on the states that sign the MOU. While we are pleased that the FDA has 

acknowledged the serious deficiencies in the current MOU that we and other stakeholders have been pointing 

out since its release, IACP will wait to see the actual language of the new draft sample MOU before 

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commenting in detail. However, we do have strong concerns that as described in the plan, the new draft sample 

MOU would still apply to interstate patient specific dispensing in violation of the plain language and 

congressional intent behind the FDCA, and pharmacists in states that do not sign the MOU would still be 

subject to a true 5% cap on these prescriptions that could lead to pharmacies that go over that arbitrary cap 

being regulated by the FDA like drug manufacturers.5 

We join other stakeholders and the Congress in asking that FDA rescind the GFI and issue a proposed rule and 

final MOU that treats the distribution and dispensing of compounded medications as the distinct activities they 

actually are in medical and pharmacy practice and under the plain language of the statute. 

Inspection Standards for 503A Pharmacies: 

IACP would also like to raise the issue of FDA inspecting 503A compounding pharmacies under cGMP 

standards rather than under USP or other applicable pharmacy inspection standards adopted by state law or 

regulation. Often, FDA will cite a pharmacy for not obtaining patient-specific prescriptions before compounded 

medications leave a pharmacy and assert that the pharmacy has therefore lost its exemptions from cGMP 

standards, even when inspecting pharmacies in states where office-use compounding is specifically authorized 

by state law and/or regulation. FDA also routinely attempts to deny compounding pharmacies the records 

exemptions provide in 21 USC 374 (a)(2)(A) without citing any statutory authority to do so. 

IACP believes that when inspecting state-licensed 503A pharmacies, the agency should work with state boards 

of pharmacy and use inspectors trained in USP or other applicable state pharmacy inspection standards. We 

believe that the FDA should cease using the agency's misinterpretation and misapplication of the prescription 

requirement under 503A as a pretext to conduct pharmacy inspections under manufacturer standards. As the 

Congress has attempted to remind the agency on multiple occasions, compounding pharmacies are not drug 

manufacturers, and should not be inspected under cGMP standards absent a clear showing of violations of 503A 

of the FDCA. This congressional intent was clearly expressed to the agency in the following House report 

language from the 2017 Omnibus Appropriations Act. 

22 
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Omnibus Appropriations Act: House Report 114-531, FY 2017: 

The Committee understands that the FDA is interpreting provisions of Section 503A of the FDCA to 

inspect state-licensed compounding pharmacies under current Good Manufacturing Practices (cGMPs) 

instead of under the standards contained in the United States Pharmacopeia/ Convention (USP) for 

sterile and non-sterile pharmaceutical compounding or other applicable pharmacy inspection standards 

adopted by state law or regulation. The Committee reminds the FDA that compounding pharmacies are 

not drug manufacturers, but rather, are state licensed and regulated health care providers that are 

inspected by state boards of pharmacy pursuant to state laws and regulations that establish sterility and 

other standards for the pharmacies operating within their states. Compounding pharmacies are more 

appropriately inspected using USP standards or other pharmacy inspection standards adopted by stale 

law or regulation in the state in which a pharmacy is licensed. (p. 69) 

Compounding with Dietary Supplements: 

Section 503A of the FDCA authorizes drug compounding by pharmacists and physicians using components of 

FDA approved drugs, or that appear on a positive list to be established by the FDA. In a June 2016 guidance for 

industry document on their interim policy on bulk ingredients, and later in the Final GFI on the Prescription 

Requirement Under 503A issued in December of 2016, FDA formally took the position that only a drug 

substance monograph met this requirement, without citing any statutory authority or legislative intent to back 

up this interpretation. The FDA's interpretation would eliminate compounding using dietary supplements, 

including those with USP dietary supplement monographs. This interpretation is inconsistent with the common 

23 
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29991.057

meaning attached to the term "monograph" and will limit patient access to compounded preparations using 

ingredients with a dietary supplement monograph. This interpretation of the law by FDA will mean that patients 

will have to rely on over the counter dietary supplements rather that allowing the prescribing physician and 

compounding pharmacist to work together to determine appropriate dosage levels and other medical 

considerations when dietary supplements are part of the recommended course of treatment. Again, this was 

done not through formal rulemaking but through a GFI. FDA should rescind the GFI and issue a proposed rule, 

or alternatively, the statute should be amended to clarity that either a drug substance or a dietary supplement 

monograph meets the statutory requirement as an ingredient that may be compounded under Section 503A of 

theFDCA. 

Pharmacy Compounding Advisory Committee (PCAC): 

The PCAC was originally created in 1997 under the Food & Drug Administration Modernization Act of 1997 

(FDAMA); however, due to judicial rulings that held portions of §503A invalid, PCAC was dissolved. The 

PCAC Charter was re-established in 2012, and referenced in the Drug Quality and Security Act (DQSA) in 

2013. PCAC held its first meeting in 2014. The committee is comprised of 14 members- 12 voting and two 

non-voting - who provide advice on scientific, technical and medical issues concerning drug compounding 

under sections 503A and 503B of the Federal Food, Drug, and Cosmetic Act. Members and the Chair are 

selected by the Commissioner or designee from among authorities knowledgeable in the fields of 

pharmaceutical compounding, pharmaceutical manufacturing, pharmacy, medicine, and related specialties. 

The statue requires that members will include representatives from the National Association of Boards of 

Pharmacy (NABP), the United States Pharmacopeia (USP), pharmacists with current experience and expertise 

in compounding, physicians with background and knowledge in compounding, and patient and public health 

advocacy organizations. 

1ACP is concerned that although we and other organizations have nominated multiple pharmacists with 

compounding experience and expertise, none of them have been selected to serve as voting members of the 

PCAC. There is currently one non-voting member who is a practicing compounding pharmacist. The nominees 

24 
110 


29991.058

are often informed by the FDA that their financial interest in a compounding pharmacy creates a conflict of 

interest that precludes their service on the PCAC. 

By contrast, The Pew Charitable Trusts (Pew), a huge charitable entity with a significant lobbying/advocacy 

component has an employee who serves as a voting member of PCAC, including making recommendations to 

FDA on ingredients and medications that can be used in human compounding. These decisions can have a 

significant effect on competition and the profitability of large pharmaceutical companies that see compounded 

medications as competition to their commercially available drugs. As a result, recommendations by PCAC can 

affect the products of drug companies that have billions of dollars at stake for their high priced and market 

protected medications. It is often these pharmaceutical companies or those associated with them make 

nominations of ingredients to the PCAC's "difficult to compound" list and oppose nominations to the positive 

list of bulk ingredients that can be used in pharmacy compounding under 503A of the FDCA. 

In addition to the financial conflicts arising from Pew's joint activities with the pharmaceutical industry, Pew 

has advocated for restrictions on the access of compounded medications that would be difficult - if not 

impossible - for their employee to ignore. These restrictions benefit the very pharmaceutical companies whose 

interest Pew lobbies for in jointly signed documents and efforts, and creates a conflict of interest that should 

preclude their participation in the PCAC. IACP recommends that PEW be removed from the PCAC and 

replaced with a voting member with experience and expertise in pharmacy compounding. 

Guidance For Industry vs. Rulemaking: 

IACP and other organizations have expressed concern with the FDA's policy of using Guidance For Industry 

(GFI) documents to implement and enforce the DQSA, rather than going through notice and comment 

rulemaking pursuant to the Administrative Procedures Act. As has been noted throughout this testimony, IACP 

has serious concerns that many of the policies that FDA has finalized and is enforcing through GFI do not 

adhere to the statutory language of the FDCA as amended by the DQSA, nor to its clear congressional intent. 

IACP believes the FDA should rescind the GFI that have been developed pursuant to the DQSA to date, and 

25 
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29991.059

issue proposed rules to be published in the Federal Register, seek and incorporate stakeholder input, and then 

finalize those rules consistent with the underlying statute. Unlike GFJ, which do not have the weight of law and 

are merely FDA's current interpretation of the law, final agency rules are subject to judicial review and must 

adhere strictly to the laws they are based on. Given the serious consequences on patient safety and access, as 

well as the economic and regulatory burden the FDA's policies are having, it is appropriate that their policies be 

developed through the rulemaking process. 

Conclusion: 

Again, we thank you for holding this important hearing, and for seeking !CAP's input on the many issues 

surrounding FDA's implementation and enforcement of the DQSA. We strongly support HR287! as a muchneeded clarification and strengthening of the DQSA, and again urge the Congress to pass the bill this year. We 

stand ready to work with you to establish laws and regulation that protect patient safety, including access to 

critical compounded medications. 

26 
112 


29991.060

1

(2017, May). Congressional Support Letter [Letter to Commissioner Gottlieb]. Washington, D.C. 

2

Representative Griffith (VA), Representative Burgess (TX), and Representative Green (TX). "Drug Quality and Security Act." 

Congressional Record p.H5963. Available from: Thomas.gov. 

3

Representative Griffith (VA).~'Preserving Patient Access to Compounded Medications Act of2017." Congressional Record p.H2871. 

Available from: Thomas.gov. 

4

United States. Department of Health and Human Services. Food and Drug Administration. Prescription Requirement Under Section 

503A of the Federal Food, Drug, and Cosmetic Act. Final Guidance. Washington, DC: n.p. December 2016. Print. 

5

United States. Department of Health and Human Services. Food and Drug Administration. Draft Memorandum of Understanding 

Addressing Certain Distributions of Compounded Human Drug Products between the State of [insert State]and the U.S. Food and 

Drug Administration. Washington, DC: n.p. February 2015. Print. 

Accompanying Materials (Attached) 

See attached far state office-use laws and chart. 

See attached for office-use drug chart. 

27 
113 

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 

114 

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 FDAregistered 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:] 

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29991.061

WWW.MCPAIIIf,OaO 

United States House of Representatives Energy and Commerce Committee 

Subcommittee on Health 

Hearing: "Examining Implementation ofthe Compounding Quality Act" 

Written Testimony of: 

Jacob Olson, Pharm.D., R.Ph. 

President & CEO, Skywalk Pharmacy 

On Behalf of the National Community Pha'rmacists Association (NCPA) 

January 30, 2018 

Chairman Burgess, Ranking Member Green and Members of the Subcommittee: 

Thank you for conducting this hearing on compounding and providing me the opportunity to share my views and 

personal experiences. My name is Jake Olson and I am a pharmacist owner of four pharmacies located in the 

Children's Hospital of Wisconsin and their outlying specialty clinics in the greater Milwaukee area. 

In 2003 I opened Skywalk Pharmacy as the first independently owned community pharmacy located in a 

children's hospital in the United States to serve the unique needs of pediatric patients. My pharmacies specialize 

in patients with cystic fibrosis, oncology, and organ transplants with a focus on specialty and compounded 

medications. On average, we fill 500 prescriptions amongst my 4 locations, only for children. 

TI-lE VOICE OF TH£ COM.MU~ll'Y PHAf!.MI'C!SP. 

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Akxmulria. VA 12~14·281!8. 

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29991.062

Page 2 

Of those 500 prescriptions, we compound roughly l 00 of those per day by primarily taking tablets and capsules 

approved for adults, and making them into a liquid to be dosed correctly for a child. I am a member of the 

National Community Pharmacists Association (NCPA) and serve on NCP A's Compounding Steering 

Committee. 

NCPA represents America's community pharmacists, including the owners of more than 22,000 independent 

community pharmacies. Together they represent an $80 billion health care marketplace and employ more than 

250,000 individuals on a full or part-time basis. 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, focusing on quality 

compounded preparations and patient access. 

In this statement, NCPA would like to present our thoughts on important issues surrounding implementation of 

the Compounding Quality Act. According to a NCPA member survey, over 88% of our members provide some 

form of compounding services. Also, over 95% of survey respondents stated they do not plan to register as a 

503B outsourcing facility. Therefore, most of our members are held to the laws and regulations of section 503A 

of the Food, Drug, and Cosmetic Act. 

Compounding is a backbone of pharmacy practice and for many decades independent community pharmacists 

have provided millions of adults, children, and animals with access to safe, effective and affordable medications 

through compounding services. When manufactured drugs aren't an option, independent community pharmacists 

provide traditional pharmacy compounding to prepare customized medications for patients. 
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Page 3 

Independent community pharmacies perform a wide variety of compounding services including hormone 

replacement medications, making suspensions out of tablets and capsules to allow for pediatric patients to receive 

correctly dosed medications, different dosage forms for patients suffering from intractable nausea and vomiting, 

and removing allergy causing excipients from commercially available products, to name a few. Compounding 

services can help bridge the gaps during times of prescription drug shortages, such as those occurring now with 

oral suspensions used for flu patients. 

It is important to note that pharmacist compounding is an integral part of the pharmacy profession and that 

compounding occurs in many pharmacy settings, including hospitals. All compounding pharmacies should be 

held to the same standards so that patients have assurance that they are receiving the same quality regardless of 

whether the compounded medication is from a hospital or community pharmacy. 

It is essential that patient access to vital compounded medications is preserved in the patient-physician-pharmacist 

triad. Providers must be able to choose the best medication for the patient's well-being. 

Along with every American, NCPA member pharmacists were horrified by the tragic consequences of the fungal 

meningitis outbreak triggered by the reckless actions ofNECC. We appreciate the thorough, bipartisan approach 

that this committee undertook to examine what changes, from both the regulatory enforcement and legislative 

fronts, were necessary to help prevent such an epidemic from recurring, while preserving patient access to 

essential, customized medications. NCPA subsequently endorsed the bipartisan law that emerged from those 

efforts, the Compounding Quality Act. 
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Page4 

However, because of the FDA's implementation and enforcement of the Compounding Quality Act, providers 

lack much needed clarity and access to compounded medications has been negatively impacted. 

For providers to gain clarity and for access to be ensured, NCPA strongly supports bipartisan legislation, H.R. 

2871, the Preserving Patient Access to Compounded Medications Act, by Reps. Morgan Griffith (R-Ya.) and 

Henry Cuellar (D-Tex.). 

We greatly appreciate this opportunity to provide our input on these important issues. 

1. State Board of Pharmacy Oversight of Pharmacy Compounding is Critical 

NCPA has always and will continue to advocate that pharmacy compounding is best regulated by the state Boards 

of Pharmacy while manufacturing is overseen by the FDA. Pharmacy compounding of medications is an 

important part of medical care that allows for the dispensing of custom-made medications and should continue to 

be regulated by state Boards of Pharmacy, as all other medical licensed professional practices are. If the FDA has 

a concern about an appropriately-licensed pharmacy, then the FDA has the authority to ask the state Board of 

Pharmacy to work with them to address the issue. If it is found that an entity acting under the guise of a pharmacy 

has exceeded their state-regulated authority, then the state Boards of Pharmacy should suspend the license of the 

pharmacy until it complies with state laws and regulations governing compounding or meets FDA standards and 

registers with the FDA. 
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Page 5 

2. FDA Must Reverse Stance on Office-Use Compounding 

Office-use compounding occurs when a pharmacist compounds a limited quantity of a medication that due to 

medical necessity must be administered in an office or clinical setting by the physician. By prohibiting all officeuse compounding by 503A pharmacies, FDA disregards the plain language of Section 503A and the fact that 

Section 503A permits office-use, as well as disregards Congressional intent that states should continue to oversee 

traditional compounding practice, including office-use compounding. 

The majority of pharmacy practice acts and state regulations authorize some form of office-use compounding. In 

addition, Congress has weighed in on multiple occasions and in multiple ways reminding FDA that office-use 

compounding should still be allowed in states that authorize its use. This includes several Statements for the 

Record that were given and floor speeches that were made during passage of the Drug Quality & Security Act. 1 

Appropriators have also been clear with FDA on the issue of office-use and its allowance in the House Reports 

accompanying the FY20 16 and FY20 17 Omnibus Appropriations Acts, as well as House Report language in the 

FY20 18 FDA/ Agriculture Appropriations Act. 

' Senator Coburn (OK). "Drug Quality and Security Act" Congressional Record 159: 162 (November 14, 2013) p. S8029. 

Senator Boozman (AR). "Drug Quality and Security Act" Congressional Record 159: 164 (November 18, 20 13) p. S8073. 

Representative Griffith (VA). "Drug Quality and Security Act." Congressional Record 159: 131 (September 28, 20!3) p. H5963. 

Representative Green (TX). "Drug Quality and Security Act." Congressional Record 159: 131 (September 28, 2013) p. H5963. 
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Unfortunately, FDA continues to prohibit all office-use compounding by 503A pharmacies, ignoring the plain 

language of Section 503A, Congressional intent, current state laws or regulations, and even contradicting the 

FDA's own current draft guidance document "Hospital and Health System Compounding Under the Federal 

Food, Drug, and Cosmetic Act," as well as FDA's previous rationale regarding office-use compounding. This 

previous rationale includes the FDA circulating in 2012 a draft compliance policy guidance that would have 

allowed for office-use compounding under 503A, with some restrictions. The relevant statutory language of 

503A was not changed by the DQSA, yet FDA is taking the position that the same language now prohibits officeuse compounding, even where expressly authorized by state law. 

Section 503A limits interstate "distribution" of compounded medications to quantities that do not exceed 5 

percent of the total prescription orders dispensed or distributed unless a state enters a MOU with the FDA 

addressing the distribution of compounds above the 5% threshold. 2 Based on the statute, this 5% rule is meant to 

limit what constitutes "distribution" under Section 503A, that is compounding for office-use. Other Federal laws 

support this construction. For example, the Controlled Substances Act (CSA) permits pharmacies to distribute for 

office-use without a distributor's license so long as their office-use distribution does not exceed 5%. 1 

2 21 U.S.C. §353a(3)(B) 

) 21 u.s.c. §802(10)-(11) 
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Page 7 

The permission contained within the CSA is the same statutory approach set up by Section 503A permitting 

pharmacies to distribute up to 5% of their compounded medications interstate, e.g., compounds for office-use. 

Many State laws also adopt a similar 5% rule permitting office-use distribution. 4 

NCPA contends that Congressional intent is very clear in that compounding for office-use is permitted under 

Section 503A. We fully support the 65 Members of Congress who wrote the FDA in May of2017 asking that the 

final office-use guidance be rescinded and that the FDA work with stakeholders to develop a proposed rule that 

authorizes office-use compounding by 503A pharmacies when authorized by state law. 

3. Not All Office-Use Compounding Needs Can be Met by Outsourcing Facilities 

NCPA is very concerned that FDA has taken the position that health care providers can easily obtain all needs for 

office-use compounds via Section 503B outsourcing facilities. 503B outsourcing facilities provide an important 

function in meeting the needs ofhealthcare 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 traditional compounding pharmacies 

practicing under Section 503A. 

4 Wise. Stat. §450.01(23)(e); Wise. Admin. Code Pharm. §13.02(1l)(e); 12 Alaska Admin. Code §52.695(5)(A); Ariz. Stat. §32-

1981(7)(d) 
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Page 8 

Because of the requirements placed on outsourcing facilities (limited to positive list, clinical need, cGMP 

validation procedures) and the cost of complying with cGMP, outsourcing facilities are not able to compound in 

small batches, thus limiting the role they can play in meeting immediate patient needs for compounds. As an 

example, outsourcing facilities have told us that when an ophthalmologist or urologist needs a sterile compound 

which is not a common formula for that facility they must refer the clinic to a 503A pharmacy. 

NCPA has continually offered FDA input regarding compounded medications that are needed by providers in 

office settings. 

The following is a non-exhaustive list of both non-sterile and sterile compounded office-use products that 

community healthcare providers rely on from our members. As discussed above, 503B outsourcing facilities are 

not able to provide many commonly needed office-use products, and by prohibiting 503A pharmacies to 

compound for office-use, FDA is severely limiting access to these products. 

Anesthetic gels/creams for dental, ENT and dermatology practices. In the past, practices could keep a 

jar/pump or tube of these available in the office for when patients needed them. The patient-specific 

requirement has created several issues. MDs may not know what the patient needs until they are seen. If 

they need to do a procedure, now the patient must schedule a second visit because they don't have the 

anesthetic available in the office. This creates waste. Many patients only need a small amount, but when 

a patient-specific prescription is generated it is typically for 30 to 60 grams. Depending on the procedure 

the MD may only use 5 grams for the patient. 
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29991.069

Page9 

• E=tile Dysfunction inje<:tions (Tri-mix, Quad-mix). The lint dose of these medications is always given 

in the office to detcnnine the best fonnulation and dosage. Now patients are forced to buy it before the 

physician has tried it and they must transport it (sometimes refrigerated) to the office for their first 

dose. If it doesn't work, they must buy another prescription. The importance of the physician-patient 

interaction, including counseling and education, at the time of the office visit necessitates the medication 

be on hand to ensure access 10 the right dosage of med.ication at the right time. 

• Phenol and Cantharidin both used in podiatry and dennatology. These are items that like anesthetic gels 

are easily kept in office for when a patient presents and needs them. They use a very small amount on 

each patient. Having a patient-specific prescription for a whole bottle is wasteful and again causes delay 

in treatment . 

• Ophthalmic injections and "emergency" eye drops. The physician does not know when a patient will 

present with a need for these items. Phannacies ofien get frantic phone calls at the end of the day for 

these medications. Literally waiting until the next day could cause loss of vision. Many times, the MD is 

fon:ed to admit the patient to the hospital if they cannotloeate these items within a few hours. 

• Iontophoresis solutions for use in physical therapy (Potassium Iodide, Dexamethasone). 

Pain creams for hand therapists in a Hand, Shoulder & Elbow Surgical group. Mostly Ketoprofen, 

Gabapcntin, and Lidoeaine. 
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Children's dentistry (Hydroxyzine Pamoate Suspension for anxiety). 

Chemical peels for dennatologists. 

Anesthetics for numbing prior to laser resurfacing. 

Lidocaine/Oxymetazoline for nasal rinsing in office. 

Phenol for inner ear procedure. 

4. FDA Must Clearly Differentiate Between "Distribute" and "Dispense" In the MOU 

NCPA remains concerned that FDA continues to use the tenn "distribute" and "dispense" in an interchangeable 

manner, when in fact these tenns are distinct and clearly defined in both Federal and State law. In Section 503A, 

Congress did use the words "distribute" and "dispense" as mutually exclusive categories, in the same sentence, 

and separated them by "or."5 Congress used the two words in the same sentence to mean two different things, as 

they have repeatedly used these two tenns to mean different things. 6 NCP A requests that FDA follow the intent 

of Congress and treat these two tenns as separate and distinct activities. 

'21 U.S.C. §353a(3)(B)(ii) 

'FDCA §581(5), 21 U.S.C. §802(10)·(11), and 21 CFR §208.3 
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By defining "distribution" to include dispensing in the MOU, FDA disregards the plain language of Section 503A 

and the fact that Section 503A pennits office-use, as well as disregards Congressional intent that states should 

continue to oversee traditional compounding practice. In the availability notice of the draft MOU, FDA states 

"interstate distributions of compounded drug products would count toward the 30 percent limit whether or not the 

compounded drug products satisfied the prescription condition, or other conditions, in section 503A of the FD&C 

Act." 7 FDA also states, "under our draft standard MOU, a distribution occurs when a compounded drug leaves 

the facility where it was made, regardless of whether the drug is also deemed to be dispensed." 8 

NCPA disagrees with FDA's inclusion of"dispensing" in the definition of"distribution," as the plain language of 

Section 503A does not support this conclusion. Section 503A states that the MOU should address the 

"distribution of inordinate amounts of compounded drug products interstate and provide for appropriate 

investigation by a State agency of complaints relating to compounded drug products distributed outside such 

State." 9 There is no allowance in the statute for FDA to address dispensing in the MOU. 

NCPA also disagrees with FDA's reasoning behind including "dispensing" in the definition of"distribution." 

That is, Congress did use the words "distribute" and "dispense" as mutually exclusive categories, in the same 

sentence, and separated them by Hor." 10 

7 80 Fed. Reg. 8877 8 Id 

9 21 u.s.c. §353a(3)(B)(i) 10 21 u.s.c. §353a(3)(B)(ii) 
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Therefore, FDA's assertion that there is nothing "to suggest that Congress understood distributed and dispensed 

to be mutually exclusive categories rather than overlapping categories" is not persuasive. Congress used the two 

words in the same sentence to mean two different things, as they have repeatedly used these two terms to mean 

different things. 11 

FDA should follow the plain language of the statute when developing the final MOU as directed by Congress, and 

ensure that the MOU only addresses "the distribution of inordinate amounts of compounded drug products 

interstate." 12 FDA should not include the interstate dispensing of compounded drugs in the definition of 

distribution, and instead leave the practice of dispensing compounded drugs to oversight by the States, as 

Congress intended. 

By not allowing SOJA pharmacies to compound for office-use, the current MOU eliminates all non-sterile officeuse compounding and severely limits access to sterile office-use compounding. 

NCPA is very concerned that FDA is attempting to regulate traditional compounding pharmacies and the patientspecific compounds they dispense through the MOU process. FDA, with the proposed MOU, would have the 

authority to oversee traditional compounding pharmacy practice based solely on the location of a patient. 

11 FDCA §581(5), 21 U.S.C. §802(10)-(11), and 21 CPR §208.3 12 21 U.S.C. §353a(3)(B)(i) 
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Many pharmacies specialize in specific treatment areas and because of their expertise, these pharmacies have 

relationships with doctors and patients in wide geographic areas, are registered in multiple states, and ship their 

medications. Under the draft MOU, most would involuntarily be deemed an outsourcing facility by FDA. In some 

cases, these pharmacies may not compound sterile products, and therefore would not be eligible to become an 

outsourcing facility. 

Also, based on the current proposed threshold and how it's calculated, pharmacies that provide only compounds, 

and no general non-compounded prescription products, will always be at a great disadvantage when calculating 

what constitutes an "inordinate amount of compounded human drug products interstate". Some NCPA members 

are compounding-only pharmacies, and do not dispense any non-compounded prescriptions, and therefore would 

be at a mathematical disadvantage to their colleagues who have "hybrid" pharmacies, i.e. those that provide both 

traditional prescription services in addition to compounds. 

Specifically, we are concerned that the arbitrary cap provides no protections for patients who live in different 

parts of the country throughout the year or those that may live in states with smaller populations. They and the 

physicians who treat them would potentially not be able to obtain the compounds they need simply because they 

do not live in the same state with the pharmacy that they need to provide their medication. 

The lack of any protections for border pharmacies is also of great concern to NCPA. FDA does not consider 

location of the pharmacy in the proposed MOU. 
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Many NCPA members are in areas, both urban and rural, that border one or more states and by not providing 

exceptions for these circumstances, FDA is punishing these pharmacies that may ship medications to their 

patients over state lines. While we appreciate FDA trying to account for some of these situations by allowing for 

an exemption for patients who drive or walk across state lines to pick up their own medications, this scenario is 

oftentimes not an option, especially for frail, elderly patients. 

5. FDA Must End Inspection Reporting Discrepancies Between Manufacturers and Compounding 

Pharmacies 

When inspected by the FDA, our members pharmacies potentially receive an FDA Form 483. This form is issued 

after an inspection when the investigator(s) observed any conditions that in their judgement may constitute 

violations of the Food Drug and Cosmetic Act and related Acts. It is important to note that the compounding 

inspections that have been conducted to date by the FDA are focused on community-based compounding 

pharmacies. FDA has inspected only I physician compounder and no federal facilities, to our knowledge. We are 

also unsure how many compounding pharmacies residing in health systems have been conducted but believe this 

number to be very small or none. 

NCP A feels strongly about the quality of compounded medications and after learning of several of our members 

experiences with FDA inspections and subsequent public posting of Form 483s we sought information on how the 

inspections were like those of FDA-registered manufacturers. The observations being documented at FDAregistered facilities are very similar to those that FDA publicly reports as unsafe in a compounding environment. 
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When a Form 483 is presented to a compounding pharmacy, it is also posted by the FDA to the FDA website. 

Conversely, when perusing the FDA website to search for any Form 483s given to FDA-registered manufacturers, 

all that can be found are inspection citations and inspectional observation summaries. We have been unable to 

find any Form 483 for a FDA-registered manufacturer facility posted to the FDA website. 

The manufacturer inspection citations are on an excel spreadsheet and list a brief description of the general nature 

of the violation. The inspectional observation summaries summarize the number of 483s in various fields and 

you can expand a specific field to see the frequency of the violation. The manufacturers found on these 

spreadsheets are well-known. 

The information posted to the website pertaining to inspections of compounding pharmacies are much more 

detailed and in depth than those posted for FDA-registered manufacturers. Many of the observations found in 

compounding pharmacies are the exact same ones found in FDA-registered manufacturing facilities. However, 

FDA presents the findings of inspections of compounding pharmacies in a much more intense manner than those 

of registered manufacturers. 

While FDA publicizes Form 483s and photographs from compounding pharmacy inspections, we have 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 to be afraid of compounding. 
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The observations from inspections of compounding phannacies have been over generalized as applying to the 

entire profession. This has led some to believe most of compounding is done in substandard conditions, when 

this is not the case. These overgeneralizations are detrimental to pharmacies and patients. 

Violations do occur in even the most advanced manufacturing processes. Unfortunately, the public is unable to 

see more details of violations found in FDA-registered facilities as manufacturer 483s are not public infonnation. 

At the same time, 483s from compounding facilities are publicized. 

6. FDA Must Make Key Changes to the Pharmacy Compounding Advisory Committee (PCAC) and 

Associated Activities 

As the FDA and PCAC members continue to consider which drugs nominated will be considered for inclusion on 

the 503A "positive" list, among other responsibilities, NCPA is committed to working with the FDA and 

stakeholders on these critical issues. However, we have concerns with the creation, oversight and operation of the 

PCAC and associated processes. 

Among these concerns are the following: 

Inadequate member selection and renewal processes. NCPA remains concerned that none of our nominees to the 

PCAC were ever contacted. Unfortunately, there is currently not one voting member of the PCAC who 

compounds for human use daily. 
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NCPA finds this fact astounding 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, one of which specialized in sterile compounding. The FDA should select at a 

minimum one practicing human compounder on the Committee as a voting member. 

Despite Congressional intent and prior FDA actions to include voting members with current expertise and 

experience in compounding on the PCAC, it is our understanding the Agency has cited potential conflicts of 

interest in having compounding pharmacists as voting members of the Committee. However, the appearance of 

impartiality of the Committee could be questioned by voting members whose organizations actively lobby 

Congress on the very issues they vote upon while serving on the PCAC. We also ask that the FDA provide 

greater transparency throughout the process of selecting members to serve on the PCAC and make certain that the 

compounding pharmacy and patient voice of those who depend on these compounded medications are 

represented. 

FDA's insistence that any bulk drug substance not voted onto the positive list can easily be obtained via the 

investigational new drug (!NO) process. This is a cumbersome, timely and expensive process, especially for 

community health care practitioners who have previously presented their real-life concerns with the lND process 

to the Committee. 
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Unequal time allotted for nominators to defend substances and respond to Committee questions. Throughout this 

entire process, each nominated substance is given a total of I 0 minutes to be defended by nominating 

organizations, and oftentimes nominators will have to split this time up, all while the FDA has unlimited time to 

present their review and opinions related to the nominated substances. In addition, nominators have a limited 

time frame to organize their presentations (normally less than 3 weeks), where FDA has months to prepare. 

NCPA has concerns that FDA allows their own representatives and speakers to participate via conference calls for 

all PCAC meetings, but has refused our request that stakeholders be allowed to do the same. 

FDA's indication that it does not consider USP monographs for dietarv supplements to be "applicable" USP or 

NF monographs, therefore limiting compounding to only USP drug monographs when no basis exists for FDA to 

exclude USP or NF monographs for dietary supplements. This is of great trouble to NCPA as it defies logic that 

these substances can be easily obtained by the public at any Costco, Wal-Mart or CVS for example, but in the 

hands of health care practitioners are not to be trusted. The practice of compounding is built on the patientphysician-pharmacist triad, and there is no better way to oversee the use of these preparations than through this 

relationship. 

A confusing nominating and review process that leaves many unanswered questions for health care practitioners 

and patients who rely on compounds. NCPA contends that it was premature for the FDA to have solicited 

nominations for the 503A list, as well as selected six products to consider at the first PCAC meeting, before 

developing and agreeing on criteria used to develop the list. 
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In addition, when nominating we were asked for all possible uses of the substances, not the most likely. We are 

also concerned that the FDA has separated substances in the 503A bulk drug substances interim policy based on 

nothing more than if the Agency considers that adequate information to evaluate the substance was included as 

part of the nomination process. Not being able to compound with these substances (included on FDA's 503A List 

3) is causing impaired patient access. Not to mention that many of the substances included on List 3 are by 

FDA's own definition not active pharmaceutical ingredients that should even be under discussion. 

Lastly, NCPA has concerns regarding FDA's recommendations for the Difficult to Compound List. It is 

important that the PCAC keep in mind that while dosage forms under consideration for the List may not be 

utilized in compounding practices today, there may come a time when technology advances to the point where 

pharmacies could be able to make these dosage forms. NCPA strongly urges the PCAC to approach the Difficult 

to Compound List in a very limited way to not stifle future innovation, technology and research. 

The intent via Congress of this process was to increase appropriate access to bulk drug substances without a 

USP/NF monograph or from an FDA approved product. Unfortunately, quite the opposite is occurring. 
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Conclusion 

In summary, NCPA is committed to working with Members of the Health Subcommittee, the FDA, and other 

stakeholders regarding these important matters. NCPA strongly supports H.R. 2871, the Preserving Patient 

Access to Compounded Medications Act as a much-needed clarification and strengthening of the Compounding 

Quality Act. We appreciate your consideration of our statement. Thank you. 
135 

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 

136 

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 FDAapproved 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 

137 

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:] 

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WRITTEN TESTIMONY OF JENN ADAMS, 

PRESIDENT 

PharMEDium 

BEFORE THE U.S. HOUSE COMMITTEE ON ENERGY AND COMMERCE, 

SUBCOMMITTEE ON HEALTH 

EXAMINING THE IMPLEMENTATION OF THE COMPOUNDING QUALITY ACT 

January 30, 2018 

Full Committee Chainnan Walden and Ranking Member Pallone, Health Subcommittee 

Chainnan Burgess and 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 ofPharMEDium. On behalf ofPharMEDium, I wish to express our longstanding and 

continued support for the Drug Quality and Security Act (DQSA). I look forward to today's 

hearing and the Committee's continued work to ensure the faithful implementation of this 

important law. 

A subsidiary of AmerisourceBergen, PharMEDium is the leading provider of phannacyoutsourced, ready-to-use compounded sterile preparations. With over 20 years of experience, 

PharMEDium operates four outsourcing facilities registered with the Food and Drug 

Administration (FDA) pursuant to section 503B of the Food, Drug, and Cosmetic Act (FDCA), 

as established by the DQSA. PharMEDium was the first entity to register with FDA following 

the law's passage in 2013. 

PharMEDium's operation is exclusively "sterile-to-sterile" compounding, which means that all 

of our products are prepared using only FDA-approved (or otherwise legally marketed) drugs in 

finished dosage fonns and other FDA-cleared components, such as containers and diluents. 

Much of what we prepare for hospital and health system clients involves- as the name 

"outsourcing facility" suggests - outsourcing the very same production that they would have to 

do on site in order to prepare sterile drugs for administration to patients. We provide our hospital 

customers with an array of pre-admixed preparations for pain management, surgeries, and labor 

and delivery. For example, expecting mothers in labor are typically administered epidural and 

other compounded preparations of drugs for which the FDA approved versions are not 

manufactured in ready to administer fonns. PharMEDium serves thousands of hospitals across 

all fifty states, and our customers range from small community hospitals to the nation's largest 

and most prestigious health systems and academic medical centers. 

As one of the first organizations to endorse the DQSA, we are fully committed to its successful 

implementation. We welcome policies to facilitate the success of the law through a vibrant and 

competitive marketplace for outsourced sterile drug preparations, and appreciate Congress' 

continued interest and oversight. However, a fundamental premise of the law that remains 

equally true today is that compounded drugs should only be used when FDA-approved drugs do 

not meet a patient's clinical needs. 
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NECC and the DQSA: Congressional Response to a Public Health Tragedy 

As Members of this Committee are acutely aware, in 2012, the interstate distribution of 

contaminated steroid injections by the New England Compounding Center (NECC) is reported to 

have resulted in over 750 cases of fungal meningitis and claimed the lives of 64 Americans. 

NECC had been the subject of multiple complaints, including warnings from PharMEDium. 

Thanks to the Energy & Commerce Committee's thorough investigation and sustained 

leadership, working in collaboration with the Senate HELP Committee, Congress passed the 

Compounding Quality Act (CQA) as Title I of the DQSA. The DQSA received broad bipartisan 

and bicameral support. Working through a transparent legislative process that engaged the full 

array of stakeholders, the authorizing Committees developed legislation that garnered 63 

endorsement letters from diverse organizations ranging from the National Community 

Pharmacists Association (NCPA), and American Society of Health-System Pharmacists 

(ASHP), the Pew Charitable Trusts, Biotechnology Industry Organization (BIO), and 

PharMEDium, among many others. 

The DQSA confirmed FDA's authority to enforce parameters of traditional pharmacy 

compounding under section 503A of the FDCA, centered on the prescription requirement. 

Additionally, it created a new section of the FDCA, section 503B, to regulate "outsourcing 

facilities." In exchange for the ability to compound drugs in larger volumes, without receiving 

patient-specific prescriptions as are necessary under section 503A, outsourcing facilities must: 

register with the FDA; submit to routine FDA inspections; pay annual fees; report all production 

and serious adverse events to the FDA; label products as compounded drugs "for office use 

only;" and most importantly, operate in accordance with current good manufacturing practices 

(cGMPs). 

cGMPs are vital for non-patient-specific compounding because these standards provide the 

highest degree of quality assurance and are designed for larger volume production, as opposed to 

prescription-by-prescription production. cGMPs are a series of guidelines and principles 

governing the preparation of drugs. In the context of section 503B, cGMPs are particularly 

focused on eliminating the potential for contamination of compounded medications and ensuring 

the uniformity of production, among other safety and quality issues. In our view, section 503A's 

prescription requirement is the lynchpin that makes the DQSA work. Specifically, it preserves 

the incentives for facilities to register as outsourcing facilities and provides a clear delineation 

for federal oversight. It utilizes a market-based approach that encourages entities wishing to 

engage in larger volume compounding to make the necessary investments in quality systems to 

submit to FDA oversight and routine inspections. 

FDA's significant progress toward enforcing the prescription requirement and implementing the 

fundamental rules of the road for the new outsourcing facility sector are critical to the success of 

the DQSA and to the ultimate goal of ensuring patients have access to a safe supply of medically 

necessary compounded medications. In just over four years, the agency has issued proposed and 

final regulations on numerous aspects ofthe DQSA, issued numerous final guidance documents, 

and is actively working to finalize a number of additional guidance documents currently in draft 

form. 

2 
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FDA has also conducted hundreds of inspections of registered outsourcing facilities, identifying 

areas of needed improvement in every inspection conducted. Speaking for PharMEDium, we 

have undertaken major investments in personnel, systems, and process enhancements pursuant to 

achieving the highest possible quality for our compounded products. Yet there is more work to be 

done, both in terms of outsourcing facilities fully meeting FDA's expectations for our respective 

operations, as well as FDA taking steps to fully implement the law. 

From PharMEDium's perspective, implementing final cGMP standards for outsourcing facilities 

is a critical and foundational step toward the successful implementation of the DQSA, so that we 

know exactly what requirements apply, and that states also have clarity and certainty as to 

governing standards for outsourcing facilities. We understand that the agency is working to 

finalize its 2014 draft guidance and proceed to rulemaking. In tailoring cGMPs to specific 

compounding operations, it is critical that final standards are oriented to the particular challenges 

presented by different types of compounding operations, their source (i.e., raw or starting) 

materials, sterile practices, and finished products. Although PharMEDium supports efforts to 

facilitate additional entities registering as outsourcing facilities, the very high bar on compliance 

with quality assurance must be maintained in any such initiative. 

Moreover, it is imperative that FDA continue to work with states to ensure that the ongoing 

patchwork of inconsistent state requirements is replaced by consistent, national standards for 

outsourcing facilities, as the DQSA envisioned. Harmonization of compounding standards is 

particularly important to ensuring uniform, safe products. Unfortunately, several states have 

rigidly followed alternative quality regimes such as the model act, and refuse to recognize FDA's 

pronouncements regarding how to apply the regulatory GMPs (i.e., 21 C.F.R Parts 210 and 211) 

to outsourcing facilities, while others have promulgated their own alternative standards for 

outsourcing facilities. In addition, some states have not yet updated their statutes and regulations, 

and thereby are unable to appropriately license and regulate outsourcing facilities. ln short, the 

lack of finalized cGMP regulations for outsourcing facilities has contributed to a patchwork of 

inconsistent requirements that in some cases conflict with FDA's expectations. 

Vague policies and lax enforcement of bulk drug substances undermine the DQSA and 

threaten patient safety 

While FDA has made commendable strides in implementing the DQSA, PharMEDium urges 

FDA to begin policing the DQSA's strict standards on compounding from bulk drug substances, 

which are typically the nonsterile raw materials that contain the active pharmaceutical 

ingredients (APls) used to make drugs. 

As the Committee knows, the DQSAprohibits compounding using bulk substances unless: (I) 

the drug is in shortage at the "time of compounding, distribution, and dispensing"; or (2) FDA 

determines that there is a "clinical need" that is not being met by approved products, and 

includes the substance on a list of such ingredients. 1 Unless one of these circumstances is 

present, outsourcing facilities are expected to compound using only FDA-approved drugs and 

cleared components. These restrictions were established based upon the fundamental reasons that 

1 FDCA § 503B(aX2). 

3 
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the use of bulk drug substances introduces additional safety risks, and their use in place of an 

approved drug undermines the integrity of the drug approval system. 

In several guidance documents, FDA has failed to clarify these provisions, which has 

inadvertently exacerbated the misuse of bulk drug substances. First, in its Interim Policy on 

Compounding Using Bulk Drug Substances, finalized in June of20 16, FDA announced openended enforcement discretion toward a list of nearly 200 substances, including more than I 00 of 

which are the active ingredients in one or more FDA-approved drugs. Therefore, these 

substances are being used in compounding even when there is no legitimate clinical need served 

by the bulk-compounded version that couldn't be served by the FDA-approved drug. Despite 

comments from PharMEDium and many others, FDA has declined to impose any restrictions on 

the use of these bulk substances. 

As noted, PharMEDium has seen a dramatic marketplace shift toward purchasing bulkcompounded versions of several critical drugs since these policies were issued. This trend 

threatens to undermine the federal drug approval system and adds additional safety risks for 

patients. Of particular concern, many of these bulk-compounded drugs appear to be unlawful 

copies of FDA approved drugs. For example, rather than starting with an FDA-approved finished 

vial of a particular drug, an entity can prepare simple dilutions or reconstitutions from bulk APis, 

enabling them to undercut the approved drugs and the drugs prepared by outsourcing facilities 

from approved drugs. In the above example of pain management epidurals, some compounders 

are substituting the FDA-approved finished drugs, such as a vial of fentanyl, with nonsterile API 

powders, despite the absence of a clinical rationale for doing so. Moreover, hospitals and other 

providers are not necessarily aware that they are receiving products compounded from bulk API 

rather than from approved drugs. 

Separately, the DQSA prohibits compounding what is "essentially a copy of one or more 

approved drugs."2 FDA has issued guidance describing section 503B's prohibition on copying 

approved drugs, but has misinterpreted the definition of "essentially a copy" in a way that fails to 

provide an appropriate check on compounding from low-cost bulk API when it is clinically 

unnecessary to do so. The statutory definition states that a compounded "drug, a component of 

which is a bulk drug substance that is a component of an approved drug" is an unlawful copy 

"unless there is a change that produces for an individual patient a clinical difference, as 

determined by the prescribing practitioner[.]"3 In implementing the requirement for 

documentation of a clinical difference, however, FDA has misstated the condition that the drug 

be compounded from bulk substances. The final guidance states that the prescriber determination 

requirement "applies to a compounded drug whether it was compounded from bulk drug 

substances or from drugs in finished form." 4 This creates the misperception that the clinical 

determination needed to justify combining FDA-approved fentanyl with FDA-approved 

ropivacaine in a pain management epidural might also satisfy the documentation requirement for 

starting with API powder for either drug (in place of using the FDA-approved versions). By 

2 Id. § 503B(a)(5). 

3 Id. § 503B(d)(2)(B). 

4 FDA, Compounded Drug Products That Are Essentially Copies of Approved Drug Products Under Section 503B 

of the FD&C Act, at 9 (Jan. 2018). 

4 
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misapplying the definition, the policy creates a disincentive to compound from drugs in finished 

form and thereby encourages the exact type of unnecessary copying Congress set out to prevent. 

The combined effect of these two ambiguous policies is to incentivize the rampant and 

widespread misuse of bulk drug substances, which are far riskier than compounding sterile drugs 

using FDA-approved drugs. Nonsterile APis introduce risks into the compounding process that 

simply cannot be justified when a sterile finished drug can be used to meet patients' clinical 

needs. For example, because current policies do not specify that outsourcing facilities must use a 

particular grade of API and testing is often limited to identity/potency, the resulting impurity 

profile is unknown and, therefore, uncharacterized. Further, terminal sterilization introduces 

additional complexities (e.g., endotoxins and pyrogens) that would not be expected in aseptic 

processing of already sterile finished drugs and components. 

FDA has announced its intention to issue new guidance in March clarifying that bulk drug 

substances may be used for compounding, "only when there is clinical need to compound drugs 

using these substances." FDA confirmed 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 drug can be used to meet patient 

medical needs."5 Statements to describe the limitations on compounding using bulk drug 

substances when there is not a legitimate clinical need are welcomed and long overdue. 

To protect the public health and preserve incentives to seek new drug approvals, however, FDA 

must also begin to enforce the DQSA's strict limitations on bulk substances. 

PharMEDium is concerned that future draft guidance could be an inadequate response to the 

rampant and ever-increasing misuse of bulk drug substances. We urge FDA to take the following 

actions: (I) implement changes to the Interim Policy to place guardrails around the use of 

substances that correspond to an FDA-approved drug on the enforcement discretion ("Category 

1 ") list; (2) revise the Essentially a Copy final guidance to accurately describe section 503B 's 

prohibition on copying approved drugs based on a faithful reading ofthe law's definition of 

copies, which further limit how bulk substances may be used; and (3) issue the announced 

forthcoming guidance describing restrictions on the use of bulk dug substances with FDAapproved drugs are available as soon as possible . 

.. .. * 

In summation, PharMEDium feels strongly that by preserving the regulatory clarity and certainty 

that the DQSA sought to create, FDA can best ensure patient safety. It is imperative that FDA 

faithfully enforce section 503B's restrictions on bulk drug substances to preserve the boundary 

between compounding and conventional drug making, and not allow compounders to become 

pseudo-manufacturers of drugs that circumvent the premarket approval process. This 

interpretation ofthe DQSA and corresponding enforcement is critical to protect patients. It is 

also essential to preserve the prescription requirement of section 503A as the clear line of 

demarcation between traditional pharmacies and federally regulated outsourcing facilities. 

5 FDA, 2018 Compounding Policy Priorities Plan, (Jan. 2018). 

5 
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Without this line of demarcation, the framework of the DQSA would not be sustainable. 

Although FDA has myriad other policies to tackle as part of its oversight of drug compounding, 

we believe that fidelity to these basic principles will go a long way to ensuring the success of the 

DQSA. 

Again, thank you for the opportunity to contribute to this important dialogue. Stakeholder 

engagement is vital to ongoing implementation efforts we welcome the opportunity to continue 

offering assistance in ensuring the success of this bipartisan public health endeavor. 

With that, I look forward to answering your questions. 

Thank you. 

6 
144 

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. 

145 

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:] 

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·-----

Introduction 

Testimony of Molly Ventrelli 

Vice President, Regulatory Affairs 

Fresenius Kabi USA. LLC 

U.S. House of Representatives Energy and Commerce Committee 

Subcommittee on Health Subcommittee 

January 30, 2018 

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. I am testifying today on behalf of Fresenius Kabi USA, a member of the 

Association for Accessible Medicines, or AAM, which represents companies that develop and market 

generic and biosimilar medicines. Fresenius Kabi is a leading provider of generic sterile injectable 

medicines in the U.S., and proud of the important role generic and biosimilar medicines play in helping 

patients and reducing costs in the U.S. health care system. 

AAM is the nation's leading trade association for manufacturers and distributors of FDA-approved 

generic and biosimilar prescription medicines. AAM members employ more than 36,700 individuals at 

nearly 150 facilities and manufacture more than 61 billion doses in the United States every year. AAM's 

core mission is to improve the lives of patients by advancing timely access to affordable generic and 

biosimilar medicines. Generic medicines represent greater than 89 percent of all prescriptions 

dispensed in the U.S., but only 26 percent of expenditures on prescription drugs, saving patients and 

payers nearly $5 billion every week. 

Fresenjus Kabj Background and Experience 

Fresenius Kabi is a global health care company- with more than 30,000 employees around the world -

specializing in lifesaving medicines and technologies for infusion, transfusion and clinical nutrition. 

Our portfolio consists of more than 400 injectable drugs administered predominately in hospitals and 

other clinical settings. These include chemotherapeutics, analgesics and anesthetics used in surgery, 

and a wide range of anti-infective and critical care drugs. We manufacture these products in three 

601 NEW JERSEY AVE. NW• SUITESSO WASHINGTON, DC • 20001• PHONE202-Z49-7100 • FAX 202·249-7105 l!lcct!SSiblemeds.org 0 0 rC) /accessibJemeds 
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·-----

states - Illinois, New York and North Carolina -and we employ approximately 3,000 people in the U.S. 

in research and development, manufacturing, distribution and other related functions. 

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 suburban Boston. It is from 

these various experiences that I share my perspective with you today. 

We commend FDA's implementation of the Drug Quality and Security Act of 2013 (DQSA). As you 

know, this bipartisan legislation was passed by Congress in response to a fungal meningitis outbreak 

that sickened over 700 Americans and killed 54. This was caused by the compounding of sterile 

medications under insufficient quality standards and in violation of federal law. In order to avoid future 

tragedies like this, FDA must continue to enforce the strong protections of the DQSA against illegal 

compounding activity, including federal prohibitions on compounding without an individual 

prescription by pharmacies that do not comply with FDA regulations and do not meet quality 

standards designed to better protect and ensure patient safety. 

Drug Compounding Background 

Drug compounding plays an important role in health care. In particular, it allows a pharmacist, through 

a patient specific prescription, to tailor a therapy for an individual's unique needs -for instance, to add 

flavor to a child's medication or provide the medication in a liquid instead of solid form. But it is critical 

for us all to ensure the safety of patients who receive compounded medications, specifically, 

outsourcing facility compounded products as the 2012 outbreak demonstrated. Compounding should 

not be used for widespread manufacturing and distribution as a substitute to the FDA generic drug 

review process gold standard. 

Congress recognized this when crafting the DQSA, and established two regulatory structures for the 

oversight of drug compounding: 503A and 503B. Pharmacies that operate under 503A are those that 

compound according to specific prescriptions unique to a patient ("one patient, one prescription") and 

under state board of pharmacy oversight. They do not compound large quantities of product in 

advance of a patient prescription. 

However, Congress also recognized that some hospitals and health care providers may need supplies 

of medications not made by pharmaceutical manufacturers, or not made in a specific form, 

combination, or strength that is medically required for patients. These products, which need to be on 

2 
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·-----

hand, often referred to as "office stock," present unique safety concerns due to the amount of tirne 

between compounding and administration of the drug to the patient This risk is increased as these 

products are typically rnade in large volumes. Therefore, if they do become contaminated, or are 

produced incorrectly, more patients are exposed to the risk. To mitigate the higher risk associated with 

producing stock supplies of compounded drugs, Congress created the outsourcing facility category, 

governed by section 5038 of the Food Drug and Cosmetic Act (FDCA). Congress required that these 

facilities adhere to current Good Manufacturing Practices (cGMP)-rigorous requirements enforced by 

FDA that describe a full-set of quality standards for the manufacturing, processing, packing, storage 

and testing of pharmaceutical products. Generic manufacturers are held to these robust standards to 

ensure the safety and efficacy of our products. To protect patients from another tragedy, outsourcing 

compounders must also be held to these rigorous standards as Congress intended. 

Quality Standards 

Compounded medications produced under conditions that guarantee potency and stability and are 

free of contamination can help patients in need and have a place in the U.S. health care system. 

Therefore, compounders registered under 5038 of DQSA must comply with standards consistent with 

cGMPs that apply to regulated drug manufacturers. Recent history has proven the need for clear and 

strong regulation of standards for this space. 

5038 facilities, called "outsourcing facilities", allow for appropriate FDA regulation of mass production 

of compounded products. If these outsourcing facilities elect to register with FDA, and agree to meet 

critical regulatory and quality standards, they may provide hospitals and clinics with standing supplies 

of non-patient-specific compounded medicines that are regularly prescribed, when an FDA-approved 

product is not available. It is important to note that compounders registered under section 5038 may 

not make a drug that is essentially a copy of an approved medicine except under certain highly limited 

circumstances. One of the primary reasons Congress was so clear in drafting 5038 this way was to 

preserve incentives for traditional manufacturers to continue to pursue FDA approval through the 

current NDA and ANDA process. It is critical that this standard be upheld. 

We support the FDA's efforts to ensure patient safety by inspecting compounders under the new 5038 

category in a timely fashion, and issuing guidance to make clear how 5038 facilities should comply 

with federal law. We also commend the FDA for its continued risk-based inspections of compounding 

pharmacies not registered with the FDA that may not be in compliance with the provisions of 503A or 

5038. One lesson learned from the fungal meningitis outbreak is that some licensed pharmacies 

operated outside the bounds of traditional, patient-specific compounding pharmacy practice. As 

·-----------·-----------------3 
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Congress has repeatedly noted, the FDA has the authority to address facilities that are illegally 

manufacturing drugs in violation of federal law. These facilities are not entitled to any of the 

exemptions that apply to compounding pharmacies; and are therefore subject to the requirements 

placed on manufacturers including adherence to cGMPs. FDA must be allowed to enforce federal law 

to prevent compounding activities that increase safety risks to patients. 

FDA's enforcement of 503A is also important to ensure that facilities that are essentially acting as 

outsourcers, i.e., selling significant amounts of commercially unavailable compounded sterile drugs in 

absence of patient prescriptions, register as FDA 5038 outsourcers. Congress' intent under DQSA was 

for this kind of larger-scale, non-patient specific compounding to be conducted not by traditional 

pharmacies but by 5038 registered facilities that meet higher quality standards and submit to FDA 

oversight. 

We also note that Congress did not alter the law prohibiting the repackaging or compounding of 

biologics without FDA oversight, and encourage FDA to include such activities in its enforcement 

priorities. 

Additionally, a compounding pharmacy that seeks to compound a copy of a commercially available 

drug on the drug shortage list should be overseen by the FDA and should not only notify FDA, but also 

be inspected by the FDA prior to beginning the compounding of that product. In the interest of 

protecting public health, the safety and manufacturing standards of compounders producing 

commercially available products on the drug shortage list should not be lowered below the standards 

required of pharmaceutical manufacturers. 

Protecting the FDA approval process 

Another key to protecting patients is safeguarding the FDA approval process for new drugs. To uphold 

patient safety, Congress sought to ensure that FDA-approved drugs would be used whenever possible, 

including in the rare circumstances in which FDA-approved ingredients might be necessary in the use 

of compounded formulations. Under the DQSA, compounders should not use an active pharmaceutical 

ingredient (API) from any source, except those available through an FDA-approved source, unless 

doing so would produce a clinical difference for an identified patient. This is commonly referred to as 

patient-prescription specific compounding. In addition, the DQSA prohibits the compounding of drugs 

that are essentially a copy of an FDA-approved medicine, unless FDA has placed that drug on the drug 

shortage list. It is critical that these provisions be enforced to avoid a disincentive to invest in new 

drug approvals and in the production of approved versions of drugs. While compounded drugs are an 

4 
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·-----

important option when approved drugs cannot meet a patient's clinical needs, products that have been 

evaluated and approved through FDA's approval process are the gold standard. 

State Boards of Pharmacy quality standards applied to pharmacies are appropriate for patient-specific 

preparations, but not for outsourcing facility operations at a larger scale, where significantly more 

individuals are exposed. We must ensure that flexibility for outsourcing facilities does not compromise 

patient safety. 

Drug Compounding is Not the Appropriate Response to Rising Drug Prices 

Despite what some might argue, drug compounding -whether conducted under 503A or 5038 - is 

not a solution to the issue of high drug prices. Congress has clearly recognized that the solution to 

high drug prices is greater competition from lower cost FDA-approved generic and biosimilar 

medicines. In the past year, Congress has taken important steps to encourage greater availability of 

generics - including in therapeutic areas without generic competition -through enactment of the 

Generic Drug User Fee Act. Moreover, FDA Commissioner Gottlieb continues to prioritize generic 

competition as part of the FDA Drug Competition Action Plan. And multiple legislative proposals are 

under consideration in Congress that would lead to greater competition through generic and biosimilar 

medicines. In contrast, seeking to use mass drug compounding as a solution for more drug 

competition ignores the tragic events of 2012-2013 and more recent warnings of the safety of 

compounded drugs - including some that FDA has called out even since the enactment of DQSA as 

having significant quality problems. 

Conclusion 

On behalf of Fresenius Kabi and member companies of AAM, I extend our gratitude to the 

subcommittee for holding today's hearing. I'd also like to thank the FDA and Commissioner Gottlieb 

for the steps the Agency has taken to-date to strengthen the oversight of compounding, and for 

clarifying today FDA's path forward. We recognize the role compounders play in delivering special care 

to patients, but as we know all too well, it should not be done at the expense of quality and patient 

safety. 

5 
151 

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 patientspecific 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 

152 

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:] 

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29991.092

'"' PE\V 2005 Mericat SU&!H, S\!!te 280!} 2Hi.~J5.9(150 f'h~V~e 

Phdsde!phlo, f'A 19103o7077 

901 E Street NW ZO:Z.$52.2000 Phor~a 

W&ihinlO!tOr'l, DC' 20004 

www.pawtrui)U;,(Irg 

Testimony of Elizabeth Jungman, The Pew Charitable Trusts 

before the Committee on Energy and Commerce 

Subcommittee on Health 

United States House of Representatives 

January 30, 2018 

Chairman Burgess, Ranking Member Green, and members of the Subcommittee: 

Five years ago, the full extent of the fungal meningitis outbreak caused by contaminated 

compounded injections was still being revealed. As the case count and fatality count went up 

day by day, this Committee took action. The Energy and Commerce Committee oversight team 

investigated the root causes, and then Committee members worked with your counterparts in the 

Senate, and across party lines, to pass legislation that is already making a difference: the Drug 

Quality and Security Act (DQSA). 

I am Elizabeth Jungman, director of public health programs at The Pew Charitable Trusts. Pew is 

an independent, nonpartisan research and public policy organization with a longstanding focus 

on drug quality issues, including pharmaceutical compounding. 

Weakening the DQSA would threaten patient safety. I am here today to convey Pew's strong 

support for the continued, robust implementation and enforcement of the law. I will also share 

findings from a not-yet-published study showing that the DQSA has also helped spur state-level 

improvements in compounding oversight. 

When this legislation was being developed, I worked for the Senate, and had the privilege of 

being a part of the negotiating team. As Members and other stakeholders who were here will 

recall, we knew that the changes in practice that experts told us were necessary to protect 

patients would not be universally popular. But each round of staff negotiations started with a new 

count of the illnesses and deaths discovered since we had last met, and that was a powerful 

motivator to persevere and create a bill that would protect patients. Years later, we cannot let 

ourselves forget the stories that created the imperative to act. 

Patients get hurt when compounding goes wrong 

While the meningitis outbreak is the most extensive known example of harm to patients from 

compounded drugs, there have been many other cases of serious illness, injury, and death 

associated with them. Appended to my testimony is information on more than 70 adverse events 

that have been publicly reported since 200 I, although we think our list probably underestimates 

the scale ofthe problem. 
154 


29991.093

For example, last year, 43 people in Texas were harmed after a compounded steroid antibiotic 

was injected into their eyes, including patients who suffered vision loss. 1 That is unacceptable; 

patients deserve access to compounded products that they can trust. 

Patients should receive the highest-quality product that meets their clinical need 

Poll data from the Pew Research Center indicates that the vast majority of Americans (87%) 

expect the government to play a "major role" in ensuring the safety of medicines and foods. 2 For 

most drugs, FDA fills that role by evaluating safety and effectiveness, and setting manufacturing 

quality standards. Compounded drugs are not subject to these protections. 

An FDA-approved drug is the gold standard, and should be the first choice whenever possible. 

But some patients have medical needs that approved products cannot meet. For them, 

compounded drugs can be an important tool. 

When a pharmacist tailors a drug for an individual patient who will use it immediately, the risks 

of any contaminants growing are limited, and the public health impact from any error is 

contained. States primarily oversee patient-specific compounding, which is called "traditional" 

compounding, and mandate quality standards appropriate to its risks. 

But sometimes, clinical circumstances require that providers keep compounded drugs on-hand, 

known as "office stock." These products carry distinct risks for patients, because rather than 

being used immediately, they are often stored for a period oftime before use, increasing the 

opportunity for any contaminants like bacteria and fungus to grow to dangerous levels. Also, 

they are frequently produced in bulk, multiplying the consequences of microbial contamination, 

adulteration, and under or over-potent products. 

To mitigate these risks, Congress created a special category of compounder to supply office 

stock- outsourcing facilities, established under section 503B of the DQSA. FDA's quality 

standards for outsourcing facilities are similar to those for approved drugs, called current Good 

Manufacturing Practice standards (cGMP). In exchange for investing in meeting these standards, 

outsourcing facilities can compound drugs without prescriptions. 

1 U.S. Food and Drug Administration, "Compounded Triamicinolone and Moxifloxacin Product for lntravitreal 

Injection by Guardian Pharmacy Services: Alert to Health Professionals- Serious Adverse Events Reported," 

accessed Nov. 14, 2017, 

https:Uwww.fda.gov/Safetv/MedWatch/Safetylnformation/SafetyAiertsforHumanMedicaiProducts/ucmS69123.ht 

ill· 

2 Pew Research Center, "Government Gets Lower Ratings for Handling Health Care, Environment, Disaster 

Response" (20 17), file:// /C:/Users/ acohen2/Downloads/12-14-17 -Government-release. pdf. 
155 


29991.094

FDA has indicated that forthcoming regulations will apply these quality standards flexibly, to 

allow compounders of varying sizes to register as outsourcing facilities. 3 But while tailoring 

standards to risk is sensible, and having more entrants to the outsourcing facility market could be 

a good thing, any flexibility in the standards that apply to outsourcing facilities must preserve the 

role that Congress created these facilities to fill: reliable sources for safe supplies of compounded 

office stock. 

The prescription requirement helps ensure that compounded drugs are produced under 

appropriate standards 

To ensure that all drugs are compounded under suitable quality standards and with appropriate 

oversight, it is essential that the two categories of business engaged in this practice - traditional 

compounders and outsourcing facilities- be clearly delineated and defined. To that end, 

Congress has twice determined- first 20 years ago, and then 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 

comply with cGMP. 

Furthermore, a clear dividing line helps ensure that both regulated facilities and regulators know 

who is responsible for overseeing any given compounder, and what rules apply. Congress 

considered a variety of ways to distinguish traditional compounders from outsourcing facilities, 

but the downside to other proposals, like designating categories based on production volume, 

was that the difficulty in enforcing them would have undermined accountability. The 

prescription requirement, in contrast, is very clear- you have a patient name on the pill bottle, or 

you don't. Congress decided- twice that the benefits of that clarity outweighed the downsides 

of prohibiting office stock by traditional compounders. 

States are important partners 

The vast majority of compounded drugs are produced by traditional compounders- pharmacists 

or physicians who dispense patient-specific drugs, and are primarily regulated by states- and so 

appropriate state oversight of compounding is an important component of a safe marketplace. 

In 2014, as many state officials sought to determine which reforms would help them oversee 

drug compounding most effectively, Pew convened an advisory committee of state pharmacy 

'Nate Raymond, "Exclusive: FDA Plans New Compounding Pharmacy Policy, Agency Head Says," Reuters, Sept. 15, 

2017, https:/lwww.reuters.com/article/us-usa-fda-pharmacies-exclusive/exclusive-fda-plans-new-compoundingpharmacy-policy-agency-head-says-idUSKCN1BQ2RV; U.S. Food and Drug Administration, "2018 Compounding 

Policy Priorities Plan," accessed Jan. 22, 2018, 

https:/lwww.fda.gov/Drugs/GuidanceComplianceRegulatorvlnformation/PharmacyCompounding/ucmS92795.htm 
156 


29991.095

regulators and other experts to identify best practices that were most achievable by states. 4 We 

then released an assessment of state policies, relative to those best practices, in 2016. 5 About two 

weeks from now, Pew, along with the National Association of Boards of Pharmacy, will release 

an update to that research, 6 but I can preview some findings today. They show that the majority 

of states now conform to best practices in two key areas. 

First, among the best practices was a recommendation that states adopt widely-recognized 

quality standards established by the United States Pharmacopeia! Convention (USP). The 

forthcoming report will show that the vast majority of state boards of pharmacy have adopted 

either those standards, or other strong quality standards, for the compounders they oversee. 7 

• Requ!t~ full c;omplianto • Requiro compUaoce with strong requlrBmBfltswlth US? <797> on st~ll-a. compculld!ng pract1ce, locludlng th~:~ 

10 sUites reporting standards ~equlvah.mt to or 

strict('!'" than~ USP Chapt:Olr<797>, even lf someekirrtQ.'llSWf!'falr9ssspeclfl~:.-

• Require othor qua lily standards Dot!s not require quality standanls 

(~} 2018 The Pl?w Charitable Trus-ts 

Fig. 1. State adoption of quality standards. Pew!NABP (forthcoming February 2018) 

4 The Pew Charitable Trusts, "Best Practices for State Oversight of Drug Compounding" (2016), 

http://www.pewtrusts.org/N /medi a/assets/2016/02/best practices forstate oversight of drug compounding.pdf. 5 The Pew Charitable Trusts, "National Assessment of State Oversight of Sterile Drug Compounding" (2016), 

http://www.pewtrusts.org/N/media/assets/2016/02/national assessment of state oversight of sterile drug co 

mpounding.pdf. 

6 The Pew Charitable Trusts and the National Association of Boards of Pharmacy, in press, "State Oversight of Drug 

Compounding" (2018). The report will be posted at the following URL on approximately Feb. 14, 2018: 

http://www.pewtrusts.org/statecompounding. 

7 Thirty-two state boards of pharmacy require traditional pharmacies that compound sterile drugs for humans to 

be in full compliance with the quality standards established by USP in its general Chapter <797> "Pharmaceutical 

Compounding-Sterile Preparations." An additionalll states have strong requirements on sterile compounding 

practice- which 10 states characterized as "equivalent to or stricter than" USP Chapter <797>, even if some 

elements were less specific. An additional four states have pending policy changes that, if passed, would require 

full compliance with USP Chapter <797> or other strong state requirements. 
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29991.096

Second, the best practices recommend that states align with federal law on the prescription 

requirement- and the forthcoming report will show that the vast majority of states now do. 

Thirty-nine states and the District of Columbia prohibit traditional pharmacies from 

compounding sterile office stock for humans- through their laws or regulations, state guidance, 

or by advising compounders to follow the federal law prohibiting the practice. 

• Prohlb!tsi«Heort'!cestockcornpoundlng 8 Altowster!teo1tlcestockcompoundlng 

for humans through their laws or Jl!8'Uiatlons, for humarts with limitations state gtJid.<w:a, or by adYislngcompoun<klrs 

to lollowthemor11- n!strlctlve federal law 

It' 20m The P't<W Charita~ Tr~s 

Fig. 2 State adoption of prescription requirement. Pew/NABP (forthcoming February 2018) 

While many states fall short of the best practice standard of annual inspections, which would 

ensure compliance with these policies, states' adoption of key policies regarding quality 

standards and the prescription requirement are promising steps in ensuring that states are doing 

their part to ensure the safety of compounded drugs. 

Congressional support for the federal compounding law will help ensure its effectiveness 

The DQSA was passed under the shadow of an unfolding tragedy. Congress- this committeeacted boldly, in the face of push back and controversy, to draw clear lines that help ensure drug 

quality. This hearing is an important reminder of why Congress passed federal compounding 

law, and what could happen if Congress doesn't protect it, and encourage its robust 

implementation. I am honored to have had the opportunity to be a part of it, and welcome any 

questions. 

29991.097

Appendix Adverse Events Chart 

Pew's drug safety project has identified 71 reported compounding errors or potential errors associated with 1A16 adverse events, including 114 deaths, from 2

2017, However, a 2015 survey found that only 30 percent of states (13 of the 43 that responded) require sterile compounding pharmacies to report serious adv

events. 1 Of the states that requlre reporting, the type of information that is required to be reported may vary, further contributing to an incomplete picture of a

€vents associated with compounded medications. Even ln states with strong adverse event reporting requirementsj illnesses and deaths caused by compounde

not alw8ys linked to the compounding error. 2

'

3

' 4 Because many such events go unreported, this chart an underestimation of the number of compounding erro

200L Contamination of sterlle products was the most common error; others were the result of compounders' mlscalcu!ations and mistakes in filling prescriptio

Drug compounding can be an interstate operation; compounders may prepare medicines in one state and ship them to another, States may encounter oversigh

challenges if an out-of-state compounder shipping into their jurisdiction is held to a different qu21.Hty or regulatory standard than in-state compounders, As a res

each row below, the state where the compounding error or potentia! error occurred and the state{s} where the adverse event{s) occurred are listed. Harmonize

minimum quality standards for anyone who compounds drugs- in any setting- across states would he!p address challenges in regulating out-of-state compoun

ensure that all compounding meets strong baseline criteria for preparing safe drugs and protecting patients. 

29991.098

41• 

2017 1• 

2"' 

2016 17 

2016 3 

2016 6'7 

2016 1" 

Zot6 ,,. 

2015 7"' Seven~!" 2015 5" "s.tven~l"~ 2014-15 "Severaf'M 

2" Fungal bloodstrl!am Infections 

Unspecified serious 

adverse events SeJ,t~ci.;.ru. Abscesses and 

osteomyelitis .~ Hepatitis C 

Redness, swelling. and 

pain at injection site 

Contaminationu 

Dose of morphine 

sulfate stronger than 

labeled concentratlonlS 

/ i:o~ / / / / 

Contamination ;~:pc.te11t Campounded di'Uil 

Contamination 

Contamination 

Injectable saline, heparin, 

vancomycin, and 

ceftazidime 

Injectable morphine sulfate Vls<oStiPI!~~ linee 

....... l!ijecta.bl~ Unknown Injectable .tciii:i~ilr'll ·;~~ Unknown injectable 

betamethasone phosphate 

and betamethasone 

NY NY 

IN IL.fNlfl 

Not reported NM 

CA CA 

AL Not reported 

United States Pharmacopeia

and were used past approp

use datirw. The two deat

within 12 weeks of the fun

but it is unclear whether 

Investigation revealed uns

and compounding pr

Investigation into the din

infection control breaches 

29991.099

2014 1" 

1 

2013 15 

6 

2013 5 

201346 

2012·'" 12 

2" 

Severe flushing. stinging. 

and dizziness 

aacterial bloodstream 

infection 

Serious bacterial eye 

infections 

pancreas 

I!Octenal bfoodslfe8m• •' 

sulfate 200 times 

stronger than labeled 

Contaminationl'.n.3JI. 

Contamination4L4l,4l 

Unknown47 

contamtnatJOn 

Compounded magnesium 

sulfate 

Injectable calcium 

gluconate 

Injectable bevaclzumab for 

administration in the eye 

Pan!irteialintil$toti 

TJ( Not reported TJ( TJ( 

GA 

GA, IN 

Not reported Not reported 

NotrePOrted I( 

. 

The Centers for Disease C

Preventton {CDC) has not 

linked the deaths to the co

The patient developed diff

digestion and metabolism 

kidney failure, which requi

FadlitV ''""'"'ed 

29991.100

iti:tlle 

< ;;;'!lni!l!iilldfiiiJ;

Skin and soft tissue infectio

Bacterial and fungal Injectable preservative--free after intramuscular inj

2012-13 26 infections in skin aod soft Contamination"" methylprednisolone TN AR, FL.Il. NC preservative-free product. 

tissue acetate votuntary recall of sterile p

76 

CA, CO, IL.IN, 

2012 47 ContaminaUon54 FL LA, NC, NV, 

cases administration in the eye NY, TX 

zou:: 7 .lnfectiOI\. NC. 

Flecalnide toxicity can cau

Dose of flecainide four heart rate and rhythms t

1 Overdose times stronger than Oral flecalnide liquid Not reported Not reported severe and life-threatenin

ordered-57 increased liver enzymes, w

an indicator of liver 

blood5treant dv<o: anesthetic zousa 10 1 jnrectlon . • ond steio1d Not repoi:ted 5taildOUP!i!tOUIIWIIY

. slni!hHiose W!ati 

... 

2011· Bacterial bloodstream 

Adverse events resulted fro

12'" 15 --·- Contamination Sterile products Not reported wv bulk saline bag for IV flu

1 

Bacterial eye infection, 

and one case of Injectable bevacizumab for 201163 9 meningftis and Contamination 54 Not reported TN 

encephalltis; four cases administration in the eye 

12 

2011 5 Blindness Unintended presence of Injectable bevacizumab for CA CA drug that is not intended 

another medicatlon 66 administration in the eye into the eye, were detected 

29991.101

19 

2010 

2010 

2009 

2009 1 

2009 

200873 1 

2008 

200l("' 

200771 

···~~am 

Fatal overdose ~.~~· Dose of sodium 60 times stronger than ordered 68 ·~OU!rl!ion 'ii•iblutl<ili'' Injectable sodium chloride 

;; . < . ' .·. ; .lloseof~ntt1.(1•· 

[ UII$J>eCllled,kie~' :/lltne$~gerttoan •· :•oio!~l\e(T3) ... , .. ·,:..,~ ... · . . ,, , .... ,,.., 

Fatality >~,OV<!rd~ Eye infection; at least 

one case of vision loss 

Fatal overdose 

P..-.istent.t!lflamllla!oty 

reaction 

Fatal acute respiratory 

distress syndrome 

Bacterial bloodstream 

Unknown10 

00:,~~~~ 

c;C>ritfi"""~~Wp!'l$ ·····~11·· Unknownn ~otbaclcit..i.7. perteiltofordefed dosage"' 

Dose of sodium chloride 

10 times stronger than 

ordered7S u~n Colistimethate sodium 

left in solution longer 

than recommended79 

Contamination8l 

Injectable preservative-free 

hyaluronidase for 

administration in the eye 

. ·~~~~;.,2~ 

adtnlniS'!allonlrt.lhe~IIIJ 

Injectable sodium chloride ~~Pv InjectiOnS 

Colistimethate sodium 

inhaled solution 

lnjectabJe fentanyl M~ IL ll A1;1' ).~~ TN Not reported symptoms ranging from flu

to seilures and coma, affec

organs including lungs and 

patient was eJCposed to a po

containing fluid that wa

incorrectty during the prepa

medication, resulting i

~J<oe~q,

·~l~t~71e,

Patients developed orbita

FL Not reported type of infection that r

NC Not reported Hot repor!ed .co Not reported Not reported Not reported CA,MO inflammation of the 

Th&~l(l#iofedJ

··1~~=:

.. ,.,~ 

Acute sodium overload 

symptoms ranging from flu

to seizures and coma, a

multiple organs including 

kidneys. Seve!iiiiOI)thsa

mesothe(apyl~. 

dl!veloped•""~'

mediafedl~..,.e

The prodrug of colistin 

tolerated than the active d

it converts. More than h

prodrug Is converted within 

solution at a certain tempe

premixed product was in 

fiVe weeks before further 

administration

29991.102

2006 

2006 

20QS;: 3 

zoos 19 

to04:a6. 80 

2004-05 

1l 

2002-04 

Redness, swelling. 

bruising, rash, fever, and 

ceUulltis 

Fatal overdose 

. fatal.~, clirdlaC 

. ·•.c~O$t .. 

Bacterial bloodstream 

infection 

saC!eriat j,JOOd.trea.. lr1fectioR 

Bacterial eye infection; 

all cases had partial or 

complete loss of vision; 

two patients had eye 

removals 

~!~l!'ii>~ 

!~~-

Fatal overdose 

Betamethasone made 

with Incorrect amount of 

preservativelll· 84 

Dose of zinc 1,000 times 

stronger than ordered llfi 

Injectable betamethasone 

Neonatal parenteral 

nutrit;ion solution 

bt>seoftidocal~~~>aitd. 

<><:rop~catcombinatl9<1 

. 

tetiaca~lilshet#lall: 

·~~Cteaft$ .. 

· : ""'atu, .. • . tndQcalrte am tetracar""l 

Contaminationn,90 

I;Otitah11natlonoi 

Contamination'2 

Injectable magnesium 

sulfate 

lnJeeiab!eltepatinlzed 

• sallnO 

Trypan blue eye drops 

/ . ,;;;/,; •·~~for 

~IJIIna~~~c 

• ,atf,it~dujfn(beiut 

Dose of lidocaine and Topical combination 

tetracaine higher than ane.rthetic cream (lidocaine 

usual 97·w and tetracaine) 

AL Not reported amount of preservative

inve.rtigation discovered 

complaints associated wit

\~[~~l~~'~fu

NV 

TX 

Tl( 

Not reported 

UT 

NV 

··ir;c 

CA, MA. NC, 

NJ, NY, SO 

-.,1; MO,_~HYt :, 

SO, TX;wt 

Not reported 

A2 

The dose was incorrectly 

pharmacy preparation as 

instead of microgr'ams, re

thow.cmdfold overd

29991.103

2002101 

2 

2002 1 

2001. 2 

2001108 

13 3 

2001 4 

Toxicity 

Fungal meningitis and 

sacroiliitis 

Bacterial bloOdstreall! 

.. . . . ; . 

Overdose 

Dose of clonidine 87 

times higher than 

orderedl02 

ContaminationtCiol,l05,t06 

Contaminatlonw 

Dose of clonidine 1,000 

times stronger than 

ordered109 

J:lVecase$ 

. • . ......... . . .. 

l>ltfl!ithad .•. 

lnfectedlllpJOint . 

Contamlnationlll 

Oral clonidine liquid 

· .admlnlsttat!oitll! tlt8 

Injectable 

methylprednisolone 

acetate for administration 

in the spine 

sc NC 

• N.,lreilotted /. · · • · ·· 

Oral clonidine liquid Not reported Not reported 

t'orll<lmlnlsttaiiOnlnsplne · 

"';Ioott< 

Injectable ranitidine Not reported Not reported 

During preparation of liquid 

from solid pills, milligram

substituted for micrograms, 

a thousandfold overdose. Pa

presentation included hyper

an unusual feature of clonid

Severe clonldine toxicity ca

low blood pressure, centra

system depression (letharg

status changes), and cardio

instability (heart and br

problems). 

Bacterial bloodstream 

infection 

This chart includes U.S. illnesses and deaths associated with compounded or repackaged medications from 2001 to the present. Adverse events were drawn from FDA and CDC r

as well as journal and news articles. 

In the total, ""several'" reported cases were counted as two adverse events, and an "'unknown" number of reported cases were counted as zero adverse events. 

29991.104

1 The Pew Charitable Trusts, "National Assessment of State OVersight of Sterile Drug Compounding" {February 2016), 

http:Uwww.oewtrusts.org!-/rnedla/assets/2016/Q2/national assessment of state oversight of sterile drug comDOUnding.odf. 

1 Allan Coukell, "Risks of Compounded Drugs/' JAMA Internal Medicine 174, no. 4 (2014): 613-14, http:lnamanetwortc.com/iournals!iamaintemalmedicine/fullarticle/1819570. 

l Marlya F. Farooqi et al.$ "Toxidty From a aonldine Suspension,"' The Journal of Medical Toxicology 5, no. 3 {2009): 130-33, https·/lflnk.sprlnger comlarticle/10.1007%2FBFQ3161223. 

• Rebekah W. Moehring et al., "'Outbreak of Bacteremia due to Buritholderla Contaminants linked to Intravenous Fentanyl From an Institutional Compounding Pharmacy/' JAMA Internal Medidne 174, no. 4 (2014}: 606-

http://dx.doi.org/10.1001/iamaintemmed.2013.13768. 

5 U.S. Food and Drug Administration, "Compounded Triamiclnolone and MoXifloxacin Product for lntravitreallnjection by Guardian Pharmacy Services: Alert to Health Serious Adverse Events Reported, .. a

2017, https:f/www.fda.goy/Safety/MedWatch/SafeMnformation{SafetyAlertsforHumanMedifa!PfOducts/ucm569123.htm. 

6 U.S. Food and Drug Administration, "Compounded Curcumln Emulsion Product for Injection by lmprimisRx: FDA Serious Adverse Events Associated with Use,"' accessed Jan. 22, 2018, 

httos·Uwww.fda.goy/Safety/MedWatchiSafetylnformat!on/SafetvAiertsforHumanMedicaiProducts!ucms70Q44.htm. 

1 News Channel tO, .. Amarillo woman claims local pharmacy paralyzed her face."' July 21, 2011, 

• Kathleen Ross et al., •outbreak of Septic Arthritis Associated with lntraNArtlcular Injections at an Outpatient Practice New Jersey, 2017," Morbidity and Mortality Weekly Report 66, no. 29 (2017): 

http://dx.dol.org/10.15585/mmwr.mm6629a3. 

9 U.S. Food and Drug Administration, "A case of hemorrhagic ocduslve retinal vasculitis (HORV) following intraocular injections of a compounded triamcinolone, moxtfloxacln, and vancomycin formulation,"' accessed No

https:Jiwww fda.gov/Drugs/GuidanceComelianceRegylatorvlnfonnatlonfpharmacyCompoundlng/ucmS?8514.htm. 

10 U.S. Food and Drug Administration, "FDA investigates two adverse events associated with United Pharmacy's compounded glutamine, arginine, and carnitlne product for injection," accessed Nov. 14, 2017, 

httos:Uwww.fda.gov/Drugs/GuidanceComplianceRegulatorylnfQW!ation(pharmacyCompouru:!inglugn584125.htfn 

11 Tile source explicitly states that It is unclear whether the reported deaths were related to tile compounding error or potential error. 

u Amber Vasquez et al., "Notes From the Field: Fungal Bloodstream lnfectionsAssoeiated Wrth a Compounded intravenous Medication at an Outpatlent Oncology Clinic-New York City, 2016;' Morbidity and Mortality W

6S, no. 45 (2016}: 1274-75, htto:/fwww.cdc.gov/mmwr/yoJumes/65/wr/mm6.54Sa6.htm?s cld=mm6545a6 w. 

13 The year soura: was published; information was not available about the timing of the adverse event. 

1-4 Elizabeth Hines et al., "Massive Intravenous Manganese Overdose due to Compounding Error: Minimal Role for Hemodialysis," Clinical Toxicology 54, no. 6 (2016): 523-25, http:l/dx.doi.org/10.1080/15563650.2016.1

15 u.s. Food and Drug Administration, "Morphine SUlfate 0.5 mg/ml Preservative Free in 0.9 Percent Sodium Chloride by Pharmakon Pharmaceuticals: Product." MedWatch: The FDA Safety Informa

Adverse Event Reporting Program, accessed Dec. 12, 2016, 

http://www.fda gov/Safety/MedWatch/Safetylnformation/5afetyAiertsforHumanMedlcaiProducts/ucm486431 htm1ytm medium=nl&utm source=internal&mkt tok=3RkMMJWWfF9wsRokugiMeu%2FhmjTEU5z17%2B

2EFve%2BUHETpodcM5MRIMb%2FVOBceEJhovQJxPr3HJdQN18RZRhHnM30%3D. 

16The drug product was distributed to Illinois and Indiana; information was not available about where adverse events occurred. 11 Patricia Kopp et al., "Septic Arthritis Outbreak Following Fluoroscopy Guided Vlscosupplementation Injections," (poster presented at the annual conference for the Society for Healthcare Epidemiology of America, St. 

31, 2017). 

15 Holly R. Simpson et al., "When Ignorance Is Not Bliss: Complications Associated with Homeopathic Injections from a Chiropractor,u (paper presented at the annual conference for the Council for State and Territorial Ep

Boise, June 4-8, 2017). 

a Janet Woodcock and Julie Dohm, "Toward Compounded Drugs- An Update from tile FDA/' The New England Journal of Medicine 377, no. 26 (2017): 2509-2512, http:l/dx.doi.org/10.1056/NEJMp1712

20 Monique A. Foster et al., "'Notes from the Field: Investigation of Hepatitis C Virus Transmission Associated with Injection Therapy for Chronic Pain -california, 2015,"' Morbidity and Mortality Weekly Report 65, no. 2

549, http:ljdx.doi.org/10.1558sJmmwr/mm6521a4. 

21 u.s. Food and Drug Administration, "Medisca Inc 11/25/15," accessed Jan. 22,2018, https:Hwww.fda.sovfiCECJ!EnforcementActlonsfWamingLetters/2015/uOM74892.htm. 

»Janet Woodcock. and Julie Dohm, "Toward Better-Quality Compounded Drugs- An Update from the FDA,"' The New England Journal of Medicine 377, no. 26 (2017): 2509-2512, http://dx doi.orgf10.1056/NEJMp1712

n The source explicitly states that the adverse events were potentially associated the compounded drug product in question. 1• U.S. Food and Drug Administration, •FDA Announces Glades Drugs' Nationwide Voluntary Recall of Compounded Multivitamins Containing High Amounts of VItamin Ds (Cholecalciferol);' accessed Feb. 17,2017, 

htto:Uwww.fda.g(AJ/drugs/drugsafetv/ucm474552.htm. 

25The drug product was distributed nationally; information was not available about where adverse events occurred. 26 Tile source explicitly states that the adverse events were potentially assodated with the compounded drug product in question. 

Food and DnJi Administration, ''Medlstat RX5terile Drug Products: Recall-Possible Contamination."' MedWatch: The FDA Safety Information and Adverse Event Reporting Program, accessed Dec. 12, 2016, 

http:IJwww.fda.gov/safety/medwatch/safetylnformatiQn!safetvalertsforhumanmedlcalproducts/ucm461850.htm. 

211 Tile drug product was distributed nationally; Information was not available about where adverse events occurred. 29 US. Food and Drug Administration, "Pharmakon Pharmaceuticals 5/21/15," accessed Dec.12, 2016, htto:l/www.fda.gov/ICECI/EnforcementActions!WaminglettersJ2015/ucm448642.htm. 

S1 Kevin Krause, "Patent pain creams that sold for up to $28K caused deaths, cost government millions," Dallas News, Nov. 12,. 2017, 

31 U.S. Food and Drug Admlnl$tration, .. Eastern Pharmacy, Inc. 10/29/14," accessed Jan. 22, 2018, httos:/Jwww.fda.gov/ICEO/EnforcementActions/Waminglettersfucm423249.htm. 

u Janet Woodcock and Julie Dohm, "Toward Better-Quality Compounded Drugs- An Update from the FDA," The New England Journal ofMed!dne 377, no. 26 (2017): .. 2

33 U.5. Food a!ld Drug Administration, "Walgreenslnfusion Services B/27/15/' accessed Jan. a, 2018, https:/Jwww.fda.gov/lgqJEnforcementActlons/Warnlnglettersf2015/ucm473497.htm. 

""U.S. Food and Drug Administration, "'FDA AnnouncesVol'untary Nationwide Recall of All Non·eKpired Sterile Drugs From Abrams Royal Compounding Pharmacy/' news release, Dec. 21, 2013. 

3STile source explicitly states that It is unclear whether the reported death$ were related to the compounding error or potential error. 

29991.105

)6 U.S. Food and Drug Administration_. "'Specialty Compounding Sterile Ptoducts: FDA Alert-Bacterial lnfectlon.s.," The FDA Safety Information and Ad1.1erse Event Reporting Program, Aug. 18, 2014, 

h.tte.JL....WW'N.fda.gov/Safety/Me(iWatch/Safetvlnformatign/safetyAiertsforHumanMedlcaiProducts/ucm.j6459S.htm. 

'fl United 5tatesv. Specialty Compounding LLC and Raymond L Solano and William L. Swail, "Complaint far Permanent Injunction/ Case 1:15·tv·0014fHY (United states Distrtct Court for the Western Oistrit;t otrexas. Fe

for Disease Control and Prevention, "Natianwld,e Voluntary Recall of All Products for Sterile Use From Compounding Pharmacy loc-ated in Cedar Park. Texas;' accessed Jan. 30,2017, 

http://emergency.(;dt.gov/HAN/han003S3.asp. 

Food and Drug Administration, "All Stelile Drug Products Made and Di-stributed by NuVislon Pharmacy Dallas Facility; Recall-Lack of Sterility Assurance/ MedWatch: The fDA Safety Information and Adven>e Even

Program, accessed Aug. 19,2015, http:/IWWN.fda.gov/Safety/MedWatch/SafeMnformation/SafetyAiertsforHumanMed!Cf!IProducts/utm3S2949.htm. 

40 u.s. Food and Drug Administration, "NuVislol'l Pharmacy 483 Report,n access-ed Aug.18, 2015, 

http://www.fda 

U.S. Food and Drug Administration> Statement of Janet Woodcock, M.O., director, Center for Drug Evaluation and Research, before the Committee on Health, Educatiofl,labor and Pensions, United States Senate, "Pha

Compounding: Ptoposed Legi.sJatilte SahJtlon," May 9, 2013, http:/ jwww.hefp.senate.gov/imo/medla/doc/Woodccx:IQ.pdf. 

U.S. Food and DrtJg Administration, "Clinical Spedalties Compouf'rding Pharmacy Prolfucts: Sterile Products Recal!ed dtJe to Lack of Sterility Assuram;:e," MedWatch:ThefDA Safety Jnf01"matlon and Advene 

Program, accessed Aug. B, 20131 http://www.fda.gov/Safetv/MedWatch{5afetvlnformatiof1/SafetyAiertsforHumanMedicaiProducts/ucm344B31.htm, 

43 S. Edison et aL, "Endophthalmltis OutbreakAss.oclated With Repackaged Emerging DiseClSet 21, no. 1 (Z015): doi:10.3101/eid2101.141040. 

""The y-ear source was published; information was not available about tfie timing of adverse events. 

45 Alan Sheyman et al., "An Outbreak of fungal Endophthalm!tis After lntravltreaf Injection of Compounded Combined Bevacizumab and Triamcinolone,."' lAMA Ophthalmology 131, no. 7 (2013}: 864-69, 

do!:10.1001/iamaophthalmoi.2D13.B-8. 

«The year source was published; informO'Ition was. not avaUabk:: about the timing of the adverse event. 

47 Brandon Libby eta!., "Muttisystem Organ Failure Fallowing LipoDi.ssatve Injections," Clinical Toxicology 3, no. 4 (2013); 171, doi:10.4172/2161·0495.1000171. 

BR Yablon eta!., "OUtbreak of Pantoea agglomerans Bloodstream lnfectlons.atan oncology C!ink:-lllinois, 2012-2013," Infection Contr-ol & Hospital Epidemlology 38, no. 3 (2017): 314-319, http#dx.doi.org/10.1017(jc

49 Centers for Cof'ltrol and Prevention, lrwestlgatlon tlfSuspected Inf-ections Following Steroid Injections/' Aug. lS, :2013, http://www.cdc.gov/hailoutbreaks/iN-pharmaMimiex.htmL 

F. Roche, "Meningitis outbreak tr!ai; Potentially deadly bacteria found in NECC drugs/' USA Today Network, oct. 12, 2011, https:l/www.tennessean.CQm/story/news/2017/10/1?./meningibHrial---ne-N-england-c

center/75945.9001/. 

51 Centers fat Disease Control and PrevE!f'ltian, "Multlstate Outbreak of !""ungal Meningitis and Other coont/ :accessed Dec. 21, 2016, http:ljwww.cdc.gov/halloutbreaks/r'Qeningitis·tnaP:!atg-e.html. 

5i Centers for Disease Control and Prevention, "Mu!tfstate Outbreak of Fungal Meningitis and Other Infections;' accessed De<;, :Zl, 21J16, 5" U.S. Food and Drug Admini!>tratlon, "Mult!state Outbreak of Fungal Meningitis and Other Infections- Archive of Updates," accessed May 1, 2017, 

54 Christina A. at, "-Fungal Endophthalmitis Associated With Compounded Products," (merging Infectious 20, no. 2 {2.014): 248-56, doi:1D.3201/Eid2002.131257. 

s$ Rebekah W. Moehringet at, "Outbreak of Bacteremia," 

year source was published; information was not available about the timing of the adverse event. 

57 George Wang et al., "f'-lecain1de Toxicity in a PediatricPatief'lt doe to Differi!nces ln Pharmacy compounding,:'' lntematJonaJJournol of Cardiology 161. no. 3 (2012}: 178-79, doi:l0.1016/i.llcard.201l.D6.028. 

Centers fa-r Disease CQntrol aM Prelo'ention, "Invasive Staphylococcus au reus Infections Assodated with Pain lnjecttons and R-euse of S1ng!e·Oose Vt.als- Ari:j:ona and Delaware, 2012./' Morbidity and Mortality Weekly R

27 {1012); 501-504, https:l/www.cdc.gov/mmwr/preview/mmwrhtmllmm512?a1.htm. 

59 Centers far control and Prevention, "Protect Patients Against Preventable Herm from Improper Us.e of Single-Dos.e/Sing!e-Use Vials," accessed Jan. 22:, 2018, 

singleusevlal.html. 

E<l Isaac See et at, "Outbrea!o: ofTsukamurella Species Bloodstream Infection among Patients at an Oncology Cltnic, West Virglnfa, 2011-2012/'lnfectlon Control & Hospital Epidemiology 3S, no. 3 {2014): 3D0-306, 

http:/fdx.dotorg/10.1086/675282. 

6} I he year sourte was published; information was not available about the timing ()f the adverse eveot. 

Q Eric Schwam, "'Seven:- Accidental of 4-Amlnopyrk!lne due to a compounding Pharmacy Error," The Journal of Emergency Medlcin.e 41, n-o.l {2.011); 51-54, dol:10.1016/j.iemermed.2009.04.037. 

ijs The year source was published; information was not availablE" about the timing of adverse events. 

Anne Frost and Marion A. Kainer, "Safe Preparation and A-dministration oflntravltreal Bevacizumab Injections: The New £ngfondJoumaf af Medicine 3-65, no-. 23 (2011): 2238, doi:10.1Q56/NEJMc1105759. 

65 R<Jger A. Goldberg et aL, "An Outbreak of 5treptococe;us-!ndopl1thalmitlsAfter Jntravitreal1f1jection of Bevadzumab," AmericanJoumalofOphthafmology 153, no, 2 (2012): 204-S.U, c;loi:10.1016/t.ajo.2Q11.11.035, 66 Department of Veterans Affairs, Office of Inspector Genera!, "Healthcare Inspection: Oversight Review of Ophthalmology Adverse Drug Events, YA Greater Los Angeles Heatthcare los Angeles, california," Repo

01515-151 (April 12.. 2012J, http:ljwww.v:a..go ... 

!17 Chery! A. thompson, "!iacteremla Outbreakiied to !tnproper Filtration by Compounding Pharmacy;" American Journul ofHeofth·System Pharmacy6S, no, 22 (2011): 2110 and 2112, doi:10.2146/newsl10075. 

611 Barbara Vitello, "lutheran General to Pay $8.25 Million in Baby's oeath." Daily Herald, AprilS, 2012, http://www.dal!vhera!d.comhlrticle/201204QS/news/704059806. 

ro Arizona State Board of Pharmacvv. Vick.i Graves, "Coi1Sent Agreement for Ch,.ll Penalty and Continuing Education," Board case {May 14, 2010)_. httos://oharm.acy.auovfsitgs/def.ault/fi!es/document.s/

0061.pdl. 

rou.S. Food and Drug Administration, "PharMEDium services, LLC4S3 Report/' accessed Oe-c. 21, 2016. 

71 North Carolina SOard of Pharmacy, "Consent Order: In the Matter of Deep River Drug.." accessed oec.ll, 2D16, http;/Jwww.ochoo.prg/Oisciplinarv%20Actions%2D-%20PHARMAC!£S/DeepRiverOrugp8944.pdt 

r2 U.S.. Food and DrugAdministratiarr, Responses for the record foltowittg heating on "Pharmacy JmpUcations of the 201Z Menillgitls Outb(eak," United Sta.tes committee on Health Education, labo

May 16, 7'The year source was published; information was not aboutthe·timing of the adverse event. 

29991.106

74 David Kanter et aL, "Acute Bac!ofen Withdrawal in a Patient Receiving Compounded Intrathecal Baclofen: A case Report," Archives of Physical Medicine and Rehabilitation 89 (2008): E123, accessed Dec. 12, 2016, 

http://www.archives-pmr.org/article/S0003·9993108)01152-Q/odf. 

15 North Carolina Board of Pharmacy, "Consent Order of Discipline: In the Matter of Jewel Freeman," accessed Dec. 12, 2016, http:jjwww.ncbop.org/Discipllnai)'%20Actions%2Q--%20PHARMACISTS/FreemanJewell0249.p

16 The year source was published; information was not available ahout the timing of the adverse event. 

n Jamison E. Strahan, Joel L. Cohen, and Joe A. Cherny, "Granuloma Annulare as a Complication of Mesotherapy: A case Report," Dermatologic Surgery 34, no. G (2008}: 83&-38, doi:l0.1111/j.1524-4725.2008.34156.x. 

711 The year source was published; Information was not available about the timing of the adverse event. 

79 Karen McCoy, "Compounded Collstimethate as Possible Cause of Fatal Acute Respiratory Distress Syndrome," The New England Journal of Medicine 357 {2007): doi:10.1056/NEJMc07171. 

80 Centers for Disease Control and Prevention, "Deaths From Intravenous Colchicine Resulting From a Compounding Pharmacy Error-Oregon and Washington, 2007," Morbidity and Mortality Weekly Report 56, no. 40 (2

http://www.cdc.govjmmwr/preview/mmwrhtm!/mm5640a3.htm. 

8l Lisa l. Maragakis et al., "Sphingomonos paucimobilis Bloodstream Infections Associated With Contaminated Intravenous Fentanyl," Emerging lnfecUous Diseases 15, no. 1 (2009): 12-18, doi:10.3201/eidl501.081054. 

82 U.S. Food and Drug Administration, "PharMEDium Services, LlC accessed Dec.12, 2016, http://www.fda.gov{tCEC1/EnforcementActions/Warningletters/l007/ucm076357.htm. 

SJ U.S. Food and Drug Administration, "Med-South Pharmacy Inc. 28-Sep-07t accessed Dec. 12, 2016, 

http://www.fda.gov/lCECI/EnforcementActions/Warningletters/2007/ucm076516 htm. 

80 Erik Greb, "FDA Censures Med-South Pharmacy for CGMP Violations," Pharmrech.com, Oct. 18, 2007, 

http://www.pharmtech.com/fda-censures-med-south-pharmacy-cgmo=violations. 

85 Jnstitute for Safe Medication Practices, Medication Safety Alert, "Fa lied Check System for Chemotherapy leads to Pharmacist's No Contest Plea for Involuntary Manslaughter," accessed January 9, 2013, 

http://www.ismp.org/newsletters/acutecarefartidesf20090423.asp. 

86 Matthew Grissinger, "A Fatal Zinc Overdose in a Neonate: Confusion of Micrograms With Milligrams," Pharmacy and Therapeutics 36, no. 7 (2011): 393-94,409, htt.p:lfwww.ncbl.nlm.nih.gov/pmdarticles/PMC317181

II7 Reid Paul, "Despite Court Ruling, FDA Still Warning Compounders," Drug Topics, Jan. 8, 2007, 

http://drugtopics.modernmedicine.com/drug-topics!content/despite-court·rullng-fda-still-warning-compounders. 

M ABC News, "Death Prompts Calls for More Drug Scrutiny," April 21, 2005, 

http://abcnews.go.com{Primetime/Health/storv?id-692826&page-1. 

M Rebecca Sunenshine et al., "A Multistate Outbreak of Serratia marcescens Bloodstream Infection Associated With Contaminated Intravenous Magnesium Sulfate From a Compounding Pharmacy," Clinical Infectious Dis

(2007): 517-33, dot:10.1086/520664. 

'iO u.S. Food and Drug Administration, "PharMEDium Services, llC 13-Apr-07 Warning Letter," accessed Aug. 18, 2015, http://www.fda.gov/ICECI/EnforcementActions/Warningletters/2007/ucm076357.htm. 91 Mark D. Gershman et al., "Multistate Outbreak of Pseudomonas fluorescens Bloodstream Infection After Exposure to Contaminated Heparinized Saline Flush Prepared by a Compounding Pharmacy," Clinical Infectious D

(2008): 1372-79, 

n Rebecca Sunenshine eta\., "An Outbreak of Postoperative Gram-Negative Bacterial Endophthalmitis Associated With Contaminated Trypan Blue Ophthalmic Solution," Clinical Infectious Diseases 48 (2009): 158D-83, 

doi:10.1086/598938. 

93 Ami 5. Patel et al., "Outbreak of Systemic Inflammatory Response Syndrome linked to a Compounding Pharmacy- Virginia, 2005" (poster presented at the 55th Annual Epidemic Intelligence Service Conference, 2006), 

http://www.cdc.gov/eis/downloads/2006.eis.conference.pdf. 

9ol Maryland State Board of Pharmacy, "Order for Summary Suspension: In the Matter of Central Admixture Pharmacy Services, Inc.;' accessed Jan. 9, 2013, 

http://www.dhmh.marvland.gov/pharmacy/docs/Forma!Orders/C/C.A.P.S%2011·15-0S.pdf. 

95 Melissa R. Held et al., "Life-Threatening Sepsis Caused by Burkho/deria cepacia From Contaminated Intravenous Flush Solutions Prepared by a Compounding Pharmacy in Another State," Pediatrics 118, no. 1 (2006): e2

http:!/pediatrics.aappublications.org/content/118/1/e212 long. 

!101 Arizona State Board of Pharmacy, "Amended Complaint and Notice of Hearing: In the Matter of Apothecary Shop of Phoenix, Inc.;' accessed Dec. 22, 2016, https://pharmacy.az.gov/sites/defaultlflles/documents/files/

0015%20B.Qdf. 

97 Paul, "Despite Court Ruling." 98 ABC News, "De.-ath Prompts Calls.'' 99 The year source was published; information was not available about the timing of the adverse event. 1w Jeffrey Suchard and Kimberlle Graeme, "'Pediatric Clonidlne Poisoning as a Result of Pharmacy Compounding Error," Pediatric Emergency Core 18, no. 4 (2002): 295-96, htt.p://joumals.lww.com/peconline/Cftatlon/2002/08000/Pediatric clonidine poisoning as a result of.14.aspx. 

101 The year source was published; information was not available about the timing of the adverse event. 

m Suchard and Graeme, "Pediatric Clonidine Poisoning." 

lin Nadine Shehab et al., "U.S. Compounding Pharmacy-Related Outbreaks, 2001-2013-Publlc Health and Patient Safety Lessons learned," Journal of Patient Safety (2015), doi:10.1097/PTS.OOOOOOOOOOD00188. 

104 Centers for Disease Control and Prevention, "E:<ophiala Infection From Contaminated Injectable Steroids Prepared by a Compounding Pharmacy-United States, July-November 2002," Morbidity and Mortality Weekly 

49 (2002}: 1109-12, http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5149al.htm. 

105 North Carolina Department of Health and Human Services, Division of Public Health, "Exophiala {Wangielfa) dermatitidis Fungal Infection Outbreak," Epi Notes 2002-4 (December 2002-February 2003): 4-6, 

http://epi.publichealth.nc.gov/odf/enl0024.pdf. 

106 David Brown, "'Previous Fungal Meningitis Outbreak a Decade Ago Resulted in No Oversight Changes," The Washington Post Nov. 5, 2012, 

outbreak-a-deal de-ago-reslJ !ted-in-no-oversight -ch anges/2012/11/05/B417d84e-1 faB-11 e 2-9cd5-b5Sc3838B962 storv. htm l?utm term= .2 ec5blbfe3 7 4. 

29991.107

107 Joseph F. Perz et al., "Pseudomonas putlda Septicemia in a Special Care Nursery due to Contaminated Flush Solutions Prepared In a Hospital Pharmacy," Journal of Clinical Microbiology 43, no. 10 {2005): 5316-18, 

doi:10.1128/JCM.43.10,5316-5318.2005. 

1oa The year source was published; information was not available about the timing of the adverse event. 

1ll!l Michael Romano and Ann Dinh, "A 1000-Fold overdose ofC!onidine Caused by a Compounding Error in a 5-Year-Otd Child With Attention-Deficit/Hyperactivity Disorder," Pediatrics 108, no. 2 (2001): 471-72, 

httos://www.ncbl.nlm.nih.govtoubmed/11483818. 

110 Rachel Chten et at, "Outbreak of Serratiamarcescenslnfections Fo!lowinglnjection of Betamethasone Compounded at a Community Pharmacy," Clinical Infectious Diseases 43 {2006): 831-37, 

http:ljcid.oxfordjournals.orglcontent/430/831.full.pdf-+htm!. 

111 California Board of Pharmacy, "Decision: In the Matter of the Statementofls.suesAgainst Robert Eugene Horwitz," Oct.l5, 2008. 

m Dejana Selenic et al., "Enterobaetercloacae Bloodstream Infections in Pediatric Patients Traced to a Hospital Pharmacy," American Journal of Health-System Pharmacy 60, no. 14 {2003}: 1440--46, 

https://www.ncbi.n!m.nih.gov/pubmed/12892028. 
169 

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. 

170 

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:] 

171 


29991.108

Testimony of Nancy Dargan 

before the Committee on Energy and Commerce 

Subcommittee on Health 

United States House of Representatives 

January 30, 2018 

Good morning, and thank you for allowing me to be here today to provide testimony 

regarding the Drug Quality Safety Act (DQSA). My name is Nancy Dargan, and I live in Brighton, 

Michigan. I am going to tell you about 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 the future. 

To begin my story, I have to travel back to early 2012. I was experiencing pain from 

arthritis in my back and my hip, and my primary physician referred me to a pain clinic, for 

periodic injections of a steroid called Methylprednisolone. The shots gave me some relief, and I 

continued my busy life as a grant writer and business consultant, until 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, though I didn't 

think 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 and spread 

down to my knee. The pain became so unbearable that I had to use my left foot for the gas and 

brake pedals. I arrived in Michigan, completely unable to bear weight on my leg, and my 

husband Mike took me to the hospital, to try to figure what was going on. 

The doctors ordered x-rays, a spinal tap, a biopsy, and 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 and sent me home. It was there that I got a call from the pain 

clinic that had administered my steroid injections. They said I'd potentially received 

contaminated drugs and should go to the emergency room immediately. By this time, the 
172 


29991.109

hospital staff were realizing that my case was not an isolated one. Other patients were showing 

up at the hospital with infections and pain similar to mine, and like several of them, I was 

ultimately diagnosed with a fungal infection. 

I underwent surgery and spent two weeks in the hospital. I was placed on the maximum 

dose of Voriconazole- a powerful antifungal medicine with side effects that seemed nearly as 

bad as death itself. I took it 4 times a day for 14 months, even waking in the middle of the night 

to receive a dose. 

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 a room and I would be carrying on a conversation with my 

daughter who died in 1979-the result of hallucinations caused by the antifungal medication. I 

would call out for our pet, Deuce, and would get frustrated when he wouldn't respond. We had 

put him down the year before due to cancer. 

Throughout this nightmare, Mike made sure I made it to every doctor's appointmentoften 3 or 4 per week-on top of other tests including blood draws every Friday. If something 

needed to be done, including all of our household chores, he did it. For 14 months, 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 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 held wonderful memories for my husband. I saw the grief in Mike's eyes every 
173 


29991.110

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 sinuses. I continue to suffer from short term memory loss, and it 

is getting worse year after 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 because 

sadly, there are many others who have endured as much suffering or more. I weep for the 79 

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 was not easy for Mike and I to get here today. We hope that 

by sharing our story, we can help prevent this from happening to anyone else. 

Thank you for allowing me to take some of your time today to allow me ta share my story. 
174 

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, 

175 

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. 

176 

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— 

177 

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. 

178 

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 FDAapproved 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 agenVerDate Nov 24 2008 10:21 Jan 16, 2019 Jkt 037690 PO 00000 Frm 00184 Fmt 6633 Sfmt 6633 I:\MY DOCS\HEARINGS 115\HEARINGS\115-96 CHRIS
179 

cy 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 

180 

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-tosterile 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 

181 

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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NACCHO 

~ion:rl~of'Courtl,.CitytlnkhOIJOO 

l11eNtdiona!COMKiionforl.ocriAibkHeallh 

~ ~ :::=":'v })] PharMEDium· 

Organization AmerlsourceBergen 

Joint Statement for the Record 

Hearing of the Energy and Commerce Committee, 

Subcommittee on Health 

on 

Examining Implementation of the Compounding Quality Act 

January 30, 2018 

The undersigned stakeholders from the public health, manufacturing, and outsourcing facility communities, 

appreciate this opportunity to submit a statement for the record outlining our recommendations on the full 

implementation and enforcement of the Drug Quality and Security Act (DQSA). 

We applaud the Energy and Commerce Committee's (Committee) bipartisan efforts to defend the DQSA and 

ensure its proper implementation', including by holding this hearing. We also commend the Committee's 

continued work with the Food and Drug Administration (FDA or Agency) as part of those efforts. We too look 

forward to continuing to work with the agency as it implements the DQSA, including the recently released 

Compounding Policy Plan and guidances.' 

As the Committee members know, millions of Americans rely on prescription medicines on a daily basis, and 

they expect and trust that those drug products will be safe and effective. Some of those Americans rely on 

receiving compounded medicines, whether it is because they are allergic to a dye in the original drug, 

because they are unable to swallow pills and need a liquid form, or for any other of the number of reasons 

that an FDA-approved drug might not meet a patient's medical need. Due to the leadership of this 

Committee, Congress enacted the DQSA in 2013, in response to a public health crisis associated with 

compounded drugs, where approximately 76 people died and 778 individuals in 20 states were stricken with 

meningitis or other infections.' The DQSA was intended to ensure that compounded drugs meet appropriate 

standards to ensure drug quality, and to protect patients. It is imperative that all members of the health care 

1 Such as the House vote against the Carter Amendment, which failed by recorded vote: 141-279. 2 FDA, "2018 Compounding Policy Priorities Plan" (January 2018); FDA, "Compounded Drugs That Are Essentially Copies 

of Approved Drug Products Under Section 503A ofthe Federal Food, Drug, and Cosmetic Act" (January 2018).; 

"Compounded Drugs That Are Essentially Copies of Approved Drug Products Under Section 5038 of the Federal Food, 

Drug, and Cosmetic Act" (January 2018).; and "Mixing, Diluting, or Repackaging Biological Products Outside the Scope of 

an Approved Biologics License Application" (January 2018). 3 Tennessean. "Meningitis Outbreak Trial: Potentially Deadly Bacteria Found in NECC Drugs" (October 2017). 

https://www. tennessean.com/story/ news/2017/10/12/meningitis-trial-n ew-england-compounding-center/759459001/ 

1 
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system work together to ensure that patients are protected, and that compounded drugs are made under 

appropriate quality standards. As Congress provides oversight over the implementation of the law, we 

recommend that the oversight follow these principles: 

Ensure compounding is performed under appropriate standards wherever it occurs' 

The foundation of the DQSA is a risk-based approach, ensuring that compounding takes place under quality 

standards appropriate to the level of risk of the drugs being produced. Current federal law, as amended by 

DQSA, will help prevent another tragedy- but only if compounding is performed in a way that is consistent 

with the law, and if FDA prioritizes the law's implementation and enforcement. 

Regulators should ensure that physicians can acquire compounded drugs produced under the appropriate 

standards, unless physicians are able to produce drugs under those standards themselves. Similarly, if 

current Good Manufacturing Practices (cGMPs) are tailored to the needs of smaller-scale producers, any such 

revision must preserve outsourcing facilities as a reliably safe supply of sterile office stock product. 

Ensure that patients who have a clinical need for a compounded drug have access to the highest-quality 

product 

Compounded drugs benefit patients who have a medical need for a particular drug formulation that is not 

commercially available. It is important that these drugs are produced in full compliance with applicable 

standards and under conditions that guarantee potency, stability and freedom from contamination. 

Encourage the implementation of an effective, robust "Section 5038" program 

The DQSA established the outsourcing facility category to ensure hospitals, other health care facilities, 

physicians, and patients have access to a safe supply of high-quality, sterile drugs. This category provides for 

the compounding of drugs under rigorous standards different than those that apply to traditional 

compounders, including adherence to cGMPs. 5038 outsourcing facilities can compound without patientspecific prescriptions, strongly differentiating 503B facilities from traditional compounders. This distinction is 

integral to the DQSA because it incentivizes compounding facilities to register with FDA and ultimately make 

the investments necessary to bring their facilities into compliance with the standards under Section 5038. 

DQSA also clearly restricts the use of bulk ingredients for 5038 compounding except when truly clinically 

necessary. This restriction must be enforced by FDA. 

Preserve the traditional role of pharmacy practice consistent with the DQSA prescription requirement 

A key distinction between Section 503A and Section 503B in the DQSA is the prescription requirement. While 

Section 503B allows for outsourcing facilities following cGMP standards to provide stock supplies of 

medications, Section 503A dictates that traditional compounders must obtain individual patient prescriptions 

to compound and dispense or distribute medications. Although limited quantities can be produced in 

advance of the receipt of a prescription in the case that a history for such prescriptions exists, a prescription 

4 Such as the enforcement of the MOU provision of Section S03A(b)(3)(B)(i), which establishes an agreement between a 

State and the FDA regulating the distribution of inordinate amounts of compounded drug products. The MOU provision 

ensures that there are adequate protections and regulations in place1 which makes states responsible for investigating 

complaints about compounded drugs made in the state and distributed outside of the state. This ensures that 

compounders shipping compounded drugs interstate are held to robust quality and safety standards. In their recently 

released "2018 Compounding Policy Priorities Plan", FDA stated that they intend to release a revised version of the 

current MOU, with language that would increase the amount considered to be "inordinate" from 30 to SO percent of 

total drugs distributed interstate, as well as putting a mechanism in place that would require reporting obligations on 

compounders that distribute more than SO percent across state lines. 

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must be received prior to distribution. The foundational aspect of a prescription requirement ensures the 

traditional practice of pharmacy is maintained, including the accountability of a patient care triad between a 

patient, a prescriber, and a pharmacist. 

Protect the FDA approval process (innovator and generic pathways) by ensuring that commercially available 

drug products cannot be copied 

Another key to protecting patients is safeguarding the FDA approval process for new drugs. Unlike 

compounded drugs, FDA approved drugs are supported by substantial evidence demonstrating safety and 

efficacy. To uphold patient safety, Congress sought to ensure that FDA-approved drugs would be used 

whenever possible, including in the preparation of compounded formulations. Compounders should not use 

an active pharmaceutical ingredient (API) from a bulk substance that is available through an FDA-approved 

medication unless doing so would produce a clinical difference for an identified patient. In addition, federal 

law prohibits the compounding of drugs that are essentially a copy of an FDA-approved medicine, unless FDA 

has placed that drug on the drug shortage list. It is critical that these provisions be fully implemented and 

enforced to avoid a disincentive for a drug maker to invest in new drug approvals and in the production of 

approved versions of drugs. While compounded drugs are an important option when approved drugs cannot 

meet a patient's clinical needs, only products that have been evaluated and proved through FDA's approval 

process meet the gold standard for safety and efficacy. 

In conclusion, the undersigned organizations' believe that enabling FDA to further implement and enforce 

the DQSA will create a clearer framework for compounded medicines and protect the patients who rely on 

them. We again thank the Committee's leadership and would like to offer our help in ensuring this bipartisan 

Jaw is successfully implemented so that the nation's patients are protected. 

Association for Accessible Medicines 

Biotechnology Innovation Organization 

National Association of County & City Health Officials 

Pew Charitable Trusts 

Pharmaceutical Research and Manufacturers of America 

PharMEDium 

Trust for America's Health 

5 Some of these organizations have joined together to form the Compounding Quality Coalition. 

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MICHAEL D. BISHOP 

""c.nucr, ~~CAN 

COMMJT'TlEON 

WAYSANDM~ANS 

4)1 CAHNON Hcuu DFI'ICI BUILOINCi 

W~GTON. DC 20615 120:1:1 %2&-4812 PG2)U~f.u <!1nngress nf tl}e 111ntteb &tates 

l{loll!e of 1\tpreuentatibeu 

Jllas}Jibgtllli,II<R 2US15-22UB 

The Honorable Michael Burgess 

Chairman, Subcommittee on Heulth 

Committee on Energy and Commerce 

2125 Rayburn House Office Building 

Wasltington, DC 20S IS 

Dear Chairman Burgess: 

January 30,2018 

Thank you for your leadership and for holding today's hearing entitled "Examining 

Implementation of the Compounding Quality Act." -

As you are well-aware, in 2012, the New England Compounding Center in Massachusetts 

manufactured and distributed contaminated steroids to clinics and hospitals across the country. It 

was a horrible tragedy. Hundreds of people developed fungal meningitis after receiving these 

tainted injections. Sadly, dozens died as a result and most others are still dealing with the terrible 

illness today. 

The epicenter of the outbreak was Michigan's 81

h District, which is the community I represent. 

More than 200 people became sick and IS people died after receiving this tainted NECC 

injection from a clinic in our district. My staff and I have talked with and remained in close 

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contact with many of the victims- including Mrs. Dargan, who is before the subcommittee today 

- as far ns updates on compensation and legislation goes. Because of the reckless disregard for 

the health and safety of the recipients of these drugs, the Department of Justice secured 

convictions against 14 individuals, and 25 counts of 2nd Degree Murder against the two main 

defendants for deaths occurring in 7 states. 

Although this outbreak happened live years ago, the consequences are still very real today. 

Whether it's someone who lost a loved one, or a victim now living with chronic pain and 

sickness, or a family member caring for an ill victim, this is a national tragedy- and these people 

need to be heard. 

Not only have the day-to-day Jives of these victims been irretrievably altered, they've also been 

financially ruined. Co-pays on some of the drugs and treatments for the fungal meningitis they 

contracted can cost up to $5,000/month. 

That's where Congress can piny a signilicaht role. Since I arrived in the House in 2015, I've 

been working with 18 of my colleagues- many of whom serve on your subcommittee- to help 

secure a separate victims compensation fund through the Department of Justice. We are pleased 

to report $40 million wns authorized through this fund and allocated to the Massachusetts 

Attorney General's office last year, which is now responsible for handling the disbursement 

process. As a result, many victims have received some much-needed additional financial help 

from this fund, and may be eligible to receive additional compensation beyond what has already 

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been paid. Additional information so can be found on my website, mikebishop.house.gov by 

searching the term "meningitis". 

These funds can be helpful, but the work is not done. These are innocent Americans whose lives 

have been destroyed by criminals who will never meet them, .. will never hear the pain in their 

voices ... will never see the irreversible damage they have caused. Bull see it. And the 

colleagues of mine who have victims in their districts see it, too. 

1 was a former prosecutor in my local community, so 1 know victims of crime need an advocate 

to stand up for them. Nothing will reverse the damage that has been done, but at the very least, 

we must ensure justice for these people, and we must hold those responsible accountable for their 

actions. 

Above all, no one should have to worry if the medically "approved" injection they are about to 

receive is contaminated. People should not hltve to live in fear, or worry, or become ill, because a 

compounder didn't do their job properly. 

That'g why we cannot loosen our oversight over the industry responsible for mixing importantand potentially dangerous -drugs. The Drug Quality and Security Act was passed in the 

aftermath of the NECC fungal meningitis outbreak, and it serves as an important reminder for us 

all today. We must ensure these industry regulations are maintained: this Is about saving lives. 

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I will continue to do my part to preserve this legislation and support the victims of the NECC 

fungal meningitis outbreak. It is the job of Congress to fight for those who need a voice in the 

legislative process, and I stand ready to help all of you however I can 

Thank you again for your steadfast leadership. I stand ready to work with you. 

Sincerely, 

Member of Congress 

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Committee on Energy and Commerce 

Subcommittee on Health 

Hearing on: "Examining Implementation of the 

Compounding Quality Act" 

January 30, 2018 

Statement for the Record 

Submitted by ASHP 

----"' 

ashe,macists advancing healthcare• 

American Society of Health-System Pharmacists 

4500 East West Highway, Suite 900 

Bethesda, MD 2.0814 

Email: gad@ashp.org 

Phone: 301-664-8710 
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ASHP Statement for the Record 

January 30, 2018 

ASHP (American Society of Health-System Pharmacists) is pleased to offer the following statement for 

the record on pharmaceutical compounding. ASHP represents pharmacists who serve as patient care 

providers in acute and ambulatory settings. The organization's 4S,OOO members include pharmacists, 

student pharmacists, and pharmacy technicians. For more than 7S years, ASHP has been at the forefront 

of efforts to improve medication use and enhance patient safety. 

In the fall of 2012, the New England Compounding Center (NECC) was behaving more like a 

manufacturer than a state-licensed pharmacy. That year, as a result of NECC's lack of sterile practices, 

more than 700 people in 20 states were diagnosed with fungal meningitis and other infections after 

receiving contaminated medication. Sixty-four patients in 9 states died, making it the deadliest 

meningitis outbreak in U.S. history. 

To help prevent tragedies like the NECC meningitis outbreak, ASHP supports a compounding framework 

that not only balances safety with patient and clinician access to essential compounded medications, 

but that also recognizes the different distribution models in hospital and health-system pharmacies. 

ASHP advocated passage of the Drug Quality and Security Act (DQSA), and we remain committed to 

ensuring that it is implemented in a manner that protects its goals. 

ASHP believes that the current legislative language of the DQSA is sufficient for the FDA to implement an 

appropriate regulatory structure and that no additional compounding legislation is needed at this time. 

The use of a prescription for an identified individual patient is a key differentiator between pharmacy 

compounding and manufacturing. We remain concerned that loosening certain requirements of the 

DQSA would result in an environment not unlike the one that caused the meningitis outbreak to occur. 

To meet the needs of patients, hospitals prepare a vast array of compounded sterile preparations every 

day, the majority of which are prepared in-house by pharmacy departments. The compounded 

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ASHP Statement for the Record 

January 30, 2018 

medications that hospitalized patients need range from simple intravenous admixtures to complex 

customized medications that are not available off-the-shelf, such as multi-ingredient cardioplegia 

solutions for heart surgery, precisely measured combinations of epidural pain medication, and adult 

medications prepared in concentrations that can be safely administered to babies and children. 

Hospitals prepare or purchase compounded medications based on specific patient needs and individual 

medication orders or in anticipation of needs for patients under their direct care. It is important to note 

that in hospitals, no medication compounded or otherwise prepared- is administered to the patient 

unless there is a patient-specific medication order. 

ASHP believes that the FDA is an important partner in ensuring that pharmacists and the patients they 

serve can access safe and high-quality compounded medications. We have been working with the 

agency to ensure that guidances account for hospitals' and health systems' unique care delivery models, 

which differ significantly from traditional community pharmacy models in a number of ways, including 

the following: 

Patient responsibility: Hospitals and health systems are accountable for patient care outcomes. 

Thus, for the purposes of both quality and outcomes tracking, it is beneficial for hospitals and 

health systems to maintain full control over all elements of patient care, including pharmacy 

access. In-house compounding of medications facilitates tracking of adverse events as well as 

oversight of care quality. Further, it allows hospitals and health systems to arrange pharmacy 

operations to provide patients and clinicians with compounded medications when they are 

needed, without significant wait times. 

Safety and Quality Regulations: While aii503A compounding falls under the purview ofthe state 

Boards of Pharmacy, compounding in hospitals cannot be disassociated from, and is itself 

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ASHP Statement for the Record 

January 30, 2018 

subject to, other quality and safety standards applicable to hospitals and health systems. These 

include Centers for Medicare & Medicaid Services (CMS) regulations for reimbursement, Joint 

Commission (TJC) standards, U.S. Pharmacopeia (USP) chapters <797> and <800>, quality 

metrics (e.g., for accountable care organizations, patient-centered medical homes, etc.), and 

state and local department of health regulations. Hospitals and health systems are strongly 

incentivized to ensure that all facets of a patient's treatment, including medications, are as safe 

and effective as possible. Strong 503A compounding programs are essential to this effort. 

limited Compounding: Hospital pharmacists seek to avoid compounding medications when an 

FDA-approved, commercially available therapeutic alternative is available. Compounding 

consumes resources and time, and it introduces additional risk into the medication-use process. 

Further, hospitals and health systems are not incentivized to compound on a large scale. Drugs 

are often bundled and, therefore, are not reimbursed separately, reducing or eliminating any 

financial incentive associated with compounding. Thus, in the hospital and health-system 

context, compounding volume has some built-in limitations that are not applicable in other 

settings. 

These differences underlie FDA's creation of tailored compounding guidances for hospitals and health 

systems. Such targeted oversight decreases the chances of creating unintended access limitations for 

hospital and health-system patients, while still allowing FDA and clinicians to protect patient health and 

safety_. Thus far, ASHP has supported FDA's efforts to craft tailored compounding regulation for hospitals 

and health systems. In particular, we look forward to the forthcoming hospital/health system-specific 

guidances related to repackaging, mixing, and diluting biologics, and 503B documentation requirements. 

Regarding published guidance, FDA has promulgated a draft hospital and health-system guidance 

regarding hospital compounding generally. Although we believe this guidance is a reasonable starting 

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ASHP Statement for the Record 

January 30, 2018 

point, we have asked the agency to revisit and revise certain facets before finalizing it. Specifically, 

although ASHP agrees that non-patient-specific compounding must be subject to reasonable limitations, 

we oppose using an arbitrary 1-mile radius in which distribution (not dispensing) of non-patient-specific 

medications is allowed. Imposing a geographic distance requirement could push compounding out of 

the pharmacy and back to the bedside, with negative consequences for patients. In order to comply with 

FDA's proposed hospital and health system guidance, hospitals and health systems would need to 

reconfigure existing care delivery models- many which have been heavily vetted by various accrediting 

bodies and regulators, and all of which are designed to maximize patient health and safety. To avoid 

disruption offunctional delivery systems, ASHP supports retaining the requirement that hospitals and 

health systems distribute compounded medications only to healthcare facilities under common control 

for use within the four walls of those facilities. We believe removing and replacing the geographic 

distribution limitation proposed by FDA with a time-based standard is more appropriate and in the best 

interests of patients. 

In place of an arbitrary limitation, ASHP urged the FDA to consider allowing hospitals and health systems 

to use the USP Chapters <797> and <800> beyond-use date (BUD) time frames for handling of nonhazardous and hazardous sterile compounding. USP Chapter <797> delineates the procedures and 

requirements for compounding sterile preparations. It focuses on ensuring that compounding 

pharmacies provide the conditions and institute practices to prevent harm to patients from microbial, 

chemical, or physical contamination; excessive bacterial endotoxins; variations in product strength; or 

poor-quality ingredients. Further, in order to meet USP Chapter <797> standards, all personnel involved 

in sterile compounding must undergo specific training and testing. Similarly, USP Chapter <800> 

describes the standards for the handling and administration of hazardous drugs with patient safety, 

worker safety, and environmental protection taken into consideration. 

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ASHP Statement for the Record 

January 30, 2018 

We anticipate that FDA will release a revised version of this guidance with an opportunity to comment. 

5038 Outsourcing Facilities 

FDA suggested that, should the geographic limit create difficulties, 503B outsourcing facilities 

(hereinafter, "503Bs" or "outsourcing facilities") can fulfill hospital and health-system needs. ASHP 

considers 503Bs essential to a strong compounding framework, but we remain concerned that, at 

present, 503Bs do not have the capacity to meet all system needs. Specifically, the wait times and longer 

turnaround times that some of our members have encountered when purchasing from 503Bs suggests 

that they are already straining to meet demand. Outsourcing facilities typically make large batches of 

compounded drugs and are not equipped to provide tailor-made products to hospitals and health 

systems. While many of our members rely on 503Bs, they also recognize that these outsourcers are 

limited in what they can produce. As a result, hospitals and health systems compound products to meet 

their own unique patient needs and do so in quantities significantly below a 503B's volume. 

CONCLUSION 

ASHP thanks the subcommittee for the opportunity to submit this statement. As noted earlier, ASHP 

believes that the DQSA established a sufficient regulatory framework for the FDA to implement the law 

and that no further legislation is needed at this time. ASHP remains committed to working with Congress 

and industry stakeholders to ensure that patients have affordable access to lifesaving and life-sustaining 

medications. 

6 
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ACfltS American College 

of Mohs Surgery 

Fdlows/Up lnlincd skiit cauo:r unclll!'COOStrnctio.·-e Ju.rgt'Ons 

Committee on Energy and Commerce 

Subcommittee on Health 

"Examining Implementation of the Compounding Quality Act" 

Statement of the American College of Mohs Surgery 

2123 Rayburn Hause Office Building Washington, D. C. 20515 

January 30, 2018 

Thank you for organizing this hearing to examine the U.S. Food and Drug Administration's (FDA) 

implementation of Title I of the Drug Quality and Security Act (DQSA), which was enacted nearly 

five years ago in the wake of the fungal meningitis outbreak caused by the New England 

Compounding Center (NECC). 

The American College of Mohs Surgery (ACMS) represents more than 1,400 Mohs micrographic 

surgeons who have successfully completed extensive fellowship-training in Mohs micrographic 

surgery following their dermatology residency training. Mohs micrographic surgery is the most 

effective and efficient treatment for advanced or difficult to treat skin cancers. In line with its 

mission, ACMS sets and promotes the highest standards of patient care relating to Mohs 

micrographic surgery. 

Skin cancer is the most common form of cancer in the United States and a growing epidemic. 1

• 2 

There are more new cases of skin cancer diagnosed each year than the combined incidence of 

cancers of the breast, prostate, lung and colon.3 One in five Americans will develop skin cancer 

in the course of their lifetime. 4 

We appreciate that the subcommittee will hear testimony from physician compounders, 

including a dermatologist. The ability to prepare local anesthetics in our offices is critical to the 

continued provision of integrated, coordinated, high quality and cost-effective skin cancer care. 

Preparation of Local Anesthetics by Mohs Surgeons is Safe, Effective, and Poses No 

Documented Risk to Patient Safety 

Mohs surgeons prepare local anesthetics in their offices within 24 hours of Mohs micrographic 

surgery. Specifically, Mohs surgeons prepare buffered or diluted lidocaine to ease pain and 

discomfort during Mohs micrographic surgery by adding commercially purchased sodium 

bicarbonate solution to commercially purchased 1% lidocaine hydrochloride with epinephrine. 

This simple step significantly decreases the painful/burning sensation at the time of injection and 

speeds up the onset of anesthesia. 5 The enhanced tolerability of the local anesthetic achieved 

1 https:Uwww.cdc.gov/cancer/skin/statistics/index.htm 

2 https://www.cdc.gov/cancer/skin/call to action/index.htm 3 Stern RS. Prevalence of a history of skin cancer in 2007: results of an incidence-based model. Arch Dermatol. 

2010;146(3):279-282. 

4 https:/lwww.skincancer.org/skin-cancer-information/skin-cancer-facts 

5 McKay W, Morris R, Mushlin P. Sodium bicarbonate attenuates pain on skin infiltration with lidocaine, with or 

without epinephrine. Anesth Analg. 1987;66(6):572-574. doi: 10.1213/00000539-198706000-00015. 
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allows the procedure to be performed without the need for systemic anesthetics, thereby greatly 

reducing cost and risk of complications. 

To achieve the proper anesthetic mixture or concentration, Mohs surgeons prepare buffered or 

diluted lidocaine using the aseptic technique-- a practice that has been proven safe and effective 

for decades. 6• 7• 8 Mohs surgeons only prepare buffered or diluted lidocaine for use in their offices 

for their own patients - not distribution or resale. This process is required, as buffered and 

diluted lidocaine with epinephrine, while remaining safe, begins to lose its vasoconstrictive 

efficacy after 7 days. 9 Thus, it would be difficult to receive the compounded drug through a large 

distributor, such as an outsourcing facility. 

The Scientific Advisory Committee of ACMS, composed of leading Mohs surgeons who practice 

at highly regarded institutions across the country, with many who serve on the National 

Comprehensive Cancer Network Guideline panel for Non-melanoma Skin Cancer, agree that use 

of the aseptic technique for preparing buffered or diluted lidocaine in the office is safe, 

appropriate, and consistent with the current literature. 10 

We emphasize that the practice of medicine includes preparing local anesthetics. State boards 

of medicine are responsible for regulating the practice of medicine. However, from the viewpoint 

of the FDA, Mohs surgeons would generally be preparing buffered or diluted lidocaine in 

accordance with section 503A of the Federal Food, Drug and Cosmetic Act (FD&C Act) and with 

patient specific prescriptions. 

Impact of FDA Guidance on Physician Office Compounding 

In August 2016, FDA released draft guidance-- "Insanitary Conditions at Compounding Facilities" 

-- that sets forth new standards for physician offices that compound under section 503A. For 

example, physician offices would be required to have engineering control devices capable of 

maintaining an ISO Class 5 environment or be deemed "insanitary." The FDA and Centers for 

Disease Control and Prevention {CDC) have yet to produce any scientific evidence to suggest 

there has been a problem to warrant this level of precaution with respect to physician office 

preparation of compounded medications. 

Because Mohs surgery is overwhelmingly performed in the office setting, Mohs surgeons would 

need to equip their offices as ifthey were compounding pharmacies to comply with the guidance, 

if finalized as currently drafted. The expense and impracticality would prohibit most Mohs 

surgery practices from making such a conversion, despite the current safety record of the use of 

6 Kimyai-Asadi, A., Goldberg, L., Peterson, R., Silapint, S., and Jih, M. The incidence of major complications from 

Mohs micrographic surgery performed in office-based and hospital-based settings. JAm Acad Dermatol 

2005;53:628-34. 

7 Melman, D., & Siegel, D. (1999). ?refilled Syringes: Safe and Effective. Dermatologic Surgery, 492-493. Retrieved 

May 29, 2017, from http://www.ncbi.nlm.nih.gov/pubmed/10469100 

' Larson PO, Ragi G, Swandby M, Darcey 8, Polzin G, Carey P. Stability of buffered lidocaine and epinephrine used 

for local anesthesia, J Dermatol Surg Oneal. 1991 May;17(5):411-4. 9 Pascuet E, Donnelly RF, Garceau D, Vaillancourt R. Buffered lidocaine Hydrochloride Solution With and Without 

Epinephrine: Stability in Polypropylene Syringes. The Canadian Journal of Hospital Pharmacy. 2009;62(5):375-380. 10 Letter to USP from Christopher Bichakjian, MD, Chair, ACMS Scientific Advisory Committee dated January 27, 

2016 
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buffered lidocaine among Mohs surgeons. This means patient access to Mohs micrographic 

surgery would be severely hindered. Instead, patients would be directed to hospital outpatient 

departments (HOPD) for skin cancer care and treatment, significantly increasing costs to patients 

and insurers, including the Medicare program, unnecessarily. We note that some health plans 

have attempted to limit Mohs micrographic surgery to the office setting because costs in the 

HOPD are high, which means some patients may not have access to the procedure at all. 

While we remain deeply concerned with this draft guidance, FDA recently announced its 2018 

Compounding Policy Priorities Plan11 that the agency will take a step back from the previous 

position and re-examine these issues. Specifically, FDA stated: 

"This guidance will address concerns raised by some providers who compound 

small quantities of drugs in their offices for patient use, and as part of their routine 

clinical practice. This came up in the setting of certain dermatological procedures, 

for example. The FDA plans to better define the circumstances under which we 

believe drugs are being mixed and applied in a manner that creates negligible 

patient risk, and therefore wouldn't be subject to the same compliance policy 

under the agency's risk-based approach to implementing these requirements." 

We believe the FDA can help prevent future problems, such as those associated with the New 

England Compounding Center (NECC), without imposing a one-size-fits-all approach. We have 

urged FDA to either exclude physician offices from the definition of "compounding facilities" in 

any finalized guidance or provide a meaningful exemption that does not impede Mohs surgeons' 

ability to safely prepare buffered or diluted lidocaine, which is the standard of care and within 

the scope of Mohs surgical practice. Any exemption would ideally be consistent with the current 

literature, which demonstrates that prepared buffered lidocaine is safe and effective for patient 

use for periods not less than two weeks. ACMS is unable to accept an "immediate use" exemption 

of less than 24 hours given the safe anesthetic preparation practices and long-standing safety 

record in Mohs micrographic surgery, coupled with the need for patient access. 

ACMS is cautiously optimistic that FDA's forthcoming revised draft guidance will maintain patient 

access to important, medically necessary medicines prepared in the physician-office setting. 

The Role of USP in Physician Office Compounding and Recent Engagement 

According to its website, the US Pharmacopeia (USP) is a scientific nonprofit organization that 

sets public standards for identity, strength, quality and purity of medicines. USP standards are 

recognized in various provisions of the federal Food, Drug and Cosmetic Act (FDCA), and in laws, 

regulations and policies promulgated by states. These standards are enforced by the U.S. Food 

and Drug Administration (FDA), states and other oversight organizations (such as The Joint 

Commission). Under the DQSA, Congress clarified FDA's authority over drug compounding and 

reaffirmed USP's role under Section 503A. FDA subsequently released guidance specifically 

referencing USP's General Chapter <797> Pharmaceutical Compounding- Sterile Preparations, 

including enforcement approaches. 

11https:/!www.fda.gov/Drugs/GuidanceComplianceRegulatorylnformation/PharmacyCompounding/ucm592795.ht 

rn 
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In September 2015, USP proposed revisions to General Chapter <797>. According to USP, based 

on the nature and significance of the public comments received, the chapter will be revised and 

is anticipated to be published in the Pharmacopeia! Forum 44(5) Sept./Oct. 2018 for a second 

round of public comment. General Chapter <797> is expected to become official on December 1, 

2019. 

Recently, USP initiated a process whereby "expert consultants" selected from the physician 

community have been invited to provide advice and guidance as USP's Compounding Expert 

Committee (CEC) continues to revise and refine Chapter <797>, addressing key issues and 

definitions. ACMS' nominee, Allison Vidimos, RPh, MD, has been appointed as an expert 

consultant. 

Request for Congressional Oversight to Ensure Patient Access to Medically Necessary 

Medicines 

The unfortunate events associated with tainted intrathecal steroids and the resultant fungal 

meningitis outbreak in 2012 that prompted significant scrutiny over drug compounding in the 

United States, including passage of the Drug Quality and Security Act of 2013, is completely 

unrelated to how Mohs surgeons utilize local anesthetic mixed in their offices. And, while 

significant progress has been made with the FDA and USP, Congressional oversight is essential to 

ensure patients have continued access to physician-compounded medicines. 

We look forward to working with the Members of this Subcommittee and the Congress, serving 

as subject matter experts on physician-office compounding, to safeguard the safety and health 

of our patients. 
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Statement for the Record of Avella 

Energy and Commerce Health Subcommittee Hearing 

"Examining Implementation of the Compounding Quality Act" 

January 30, 2018 

Avella of Deer Valley, Inc. and affiliated entities including Advanced Pharma Inc., D/B/A Avella of 

Houston (collectively, "Avella") are pleased to submit written testimony to the "Examining 

Implementation of the Compounding Quality Act" hearing before the Energy and Commerce Health 

Subcommittee. Avella has been, and continues to be, a strong supporter of the Compounding Quality 

Act ("the Act"). However, as a currently registered 503B, and as an entity that also dispenses 

compounded prescriptions under 503A, Avella would like to raise some concerns with the current 

implementation and enforcement landscape in the compounding world. 

Avella currently serves the needs of thousands of patients and providers by providing both dispended 

and office use, through its 503B facility, compounded medications throughout the United States. 

Founded in 1996 as a single pharmacy located in Phoenix, Arizona, Avella has since expanded to 

include two national distribution facilities and community-based pharmacies in eight states while 

serving patient and/or provider needs in all SO states. In February 2014, Avella's Deer Valley location 

was an early registrant with FDA as an Outsourcing Facility in accordance with Section S03B the Food, 

Drug and Cosmetic Act ("FFDCA"). Today, Avella is a national specialty and compounding pharmacy 

with unique expertise in ophthalmology treatments, and was the first ophthalmology pharmacy in 

the nation to earn the Pharmacy Compounding Accreditation Board's Seal of Accreditation. Because 

of the unique nature of ophthalmology and our hospital clients, a large portion of the medications 

Avella provides are customized to meet specific patients' unique medical needs. 

As this Subcommittee is well aware, patient safety and product quality are a top priority for the 

industry. Avella, and others, are working tirelessly to lead the industry in such standards to help 

ensure that a health crisis, like that of the New England Compounding Center ("NECC"), which 

resulted in 64 deaths and hundreds of injuries due to contaminated sterile injectables, never happens 

again. For this reason, Avella expresses a number of concerns related to FDA's current 

implementation and enforcement pathways that could have an impact on patient safety. 

I. Varying cGMP Standards Will Impact Product Quality and Put Patients at Risk 

FDA's recently published a 2018 Compounding Priorities Plan ("2018 Plan") outlines a risk-based 

approach for the applicability of current Good Manufacturing Practice ("cGMP") standards for 503B 

facilities. Specifically, in the 2018 Plan, FDA stated that it wanted to encourage traditional 

compounders operating under Section 503A of the FFDCA to register as outsourcing facilities by 

applying varying degrees of cGMP standards to a facility based on the size and scope of the 

outsourcing facility's operations. Thus, "smaller compounders that compound limited volumes of 

drugs, and presumably present lower risks, may decide to register as outsourcing facilities." 

Avella disagrees with this approach and advocates that instead, one, consistent cGMP standard 

should apply to all outsourcing facilities no matter the size of the entity or the volume of products 
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24416 North 19th Avenue 

Phoenix, AZ 85085 

main (623) 742-1700 fax (623) 434-3661 

A Avella 

Health via excellence· 

that the entity compounds. Application of varying cGMP standards will only create confusion within 

the industry, stress the FDA's already limited resources, and significantly raise potential risk to 

patients. Most importantly, a lesser cGMP standard for small facilities has the potential to impact 

the quality of drug produced by those entities, and could result in patient harm. For example, if 

smaller entities are exempt from certain product testing requirements, a sub-standard product may 

be produced and administered to a patient in the same manner that caused NECC. In turn, an 

outsourcing facility subject to the higher cGMP standards would have the testing processes in place 

to identify such an issue. In reviewing this issue, Avella asks that Congress take the time to ask 

themselves a simple question: if the medication was being injected into your family member, would 

you want to have the assurance that the preparation was appropriately tested or to take a chance 

because the facility is a smaller one and not required to have a rigorous testing program? 

For this reason, Avella believes that varying cGMP standards will only serve to create more risk in the 

marketplace and could result in another NECC-Iike tragedy. 

II. A Risk-based Approach to FDA Oversight Could Prevent Future Patient Harm 

Section 503B of the FFDCA mandates a risk-based inspection frequency, including consideration of 

certain risk factors such as compliance history, compounding risk level, and previous inspection 

history. Avella advocates that this portion of the statute be fully implemented as inspections are a 

key way to identify non-compliance and risky operations. If the most high-risk outsourcing facilities 

are identified, and inspected on a more frequent basis, there is a better likelihood that high-risk 

behavior will be corrected and patient harm may be prevented. 

Ill. Memorandum of Understanding 

In its 2018 Plan, FDA indicated that it planned to loosen the MOU standards to make it more feasible 

for states to sign the MOU, including altering the draft definition of "inordinate amount" from 30 

percent or more of all drug dispensed to greater than 50 percent during the calendar month. In 

addition, distributing inordinate amounts would no longer trigger state action, but would instead 

trigger certain reporting requirements. Although the 30 percent and 50 percent thresholds appear 

to be arbitrarily determined, Avella advocates for clarification as to how such a calculation will be 

made on patient scripts (as opposed to office use). Further, FDA has expressed its goal to encourage 

more compounders to register as outsourcing facilities, so those entities that believe they will 

distribute inordinate amounts have an opportunity to does so as FDA-registered outsourcing facilities 

and should be held to the proper cGMP standards established and regulated by FDA. 

Our mission Is to optimize patient health through 

a relentless devotion to clinical excellence. avella.com 

611962738.1 
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SAFE • EFFECTIVE • SOLUTIONS 

1111 ii Lee H. Rosebush 

OUTSOURCING FACIUTIES ASSOCIATION Chairman I OfA 

Statement for the Record of the Outsourcing Facilities Association 

Energy and Commerce Health Subcommittee Hearing 

"Examining Implementation of the Compounding Quality Act" 

January 30, 2018 

The Outsourcing Facility Association (OF A) appreciates the opportunity to provide written 

testimony for the Energy and Commerce Health Subcommittee hearing titled "Examining 

Implementation of the Compounding Quality Act." OF A's members are strong supporters of the 

Compounding Quality Act. With that said, OFA members have concerns related to the Food and 

Drug Administration's recently released 2018 Compounding Policy Priorities Plan, as well as with 

current FDA guidance documents related to Outsourcing Facilities and compounding. 

About OFA and 503B Outsourcing Facilities 

OF A is the trade association representing FDA-registered 503B Outsourcing Facilities whose goal 

is to provide patients and healthcare providers with high quality and safe compounded 

medications. OF A members continuously work with patients, healthcare providers, and hospitals 

on a daily basis to ensure the specific needs and access, of both providers and patients, for 

compounded medications are satisfied. 

FDA oversight of Outsourcing Facilities was authorized by Congress in the wake of the 2012 New 

England Compounding Center (NECC) scandal, in which 64 people died and hundreds more were 

harmed by NECC's fungal-contaminated sterile-injectable drugs. Patient advocacy groups, 

healthcare providers, and the pharmaceutical industry worked with Congress for a year to enact 

legislation that balanced the safety risks posed by batch compounding with the clear need for these 

products. 

Outsourcing Facilities exist in the space between small pharmacies that compound drug products 

for individuals (subject to section 503A of the FD&C Act) and large pharmaceutical 

manufacturers. There are currently more than 70 FDA-Registered Outsourcing Facilities, located 

in 24 states, and the number is rapidly growing. These businesses must be registered with FDA as 

Outsourcing Facilities and must comply with all of the requirements of section 503B of the FD&C 

Act. 

OF A's Specific Concerns 

OFA supports the FDA's overall implementation and enforcement of the Compounding Quality 

Act as written and intended by the Congress. However, OFA has four areas of specific concern: I) 

the impact FDA's risk-based current good manufacturing practices (cGMP) standards will have 

on product quality and safety; 2) patient access to 503B compounded medications; 3) FDA's 

consideration of cost; and 4) the use of bulk drug substance for compounding. These topics are 

discussed in greater detail below. 
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SAFE • EFFECTIVE • SOLUTIONS 

Lee H. Rosobush 

OUTSOURCING FACIUTIES ASSOCIATION Chairman I OfA 

FDA's risk-based cGMP Standards will adversely impact product quality and safety 

FDA announced in its 2018 Compounding Policy Priorities Plan that a risk-based approach will 

be utilized for the applicability of compounding standards, which will essentially allow FDA to 

permit a new, more flexible cGMP standard for smaller compounders. This policy will result in 

detrimental effects to current 503B Outsourcing Facilities and would allow a lesser standard of 

cGMP that would have a negative effect on the quality standards for compounded medications. 

Specifically, the 2018 Plan notes that FDA plans to draft proposed regulations on cGMP 

requirements for Outsourcing Facilities. While OFA applauds FDA for moving forward with 

regulations, FDA's proposal, in the interim, is to revise the current 503B Outsourcing Facility 

cGMP draft guidance to describe a new flexible, risk-based approach to cGMP requirements for 

Outsourcing Facilities based on the size and scope of an Outsourcing Facility's operations. For the 

FDA to allow a "less rigid" cGMP standard simply because a compounding facility is smaller or 

produces limited volumes unnecessarily exposes patients to higher-risk compounded medications 

that could lead to patient injury or illness, the exact area that Congress and FDA sought to prevent 

after the NECC scandal. For example, "less rigid" cGMP standards might allow an entity to 

compound without requiring certain testing or meeting other standards, which would put patients 

at unknown risk for harm, as those drugs may not have undergone testing to ensure they are sterile, 

potent, and/or stable or be made in proper conditions. This is exactly why and how NECC 

occurred. 

In addition, FDA has stated many times, both in administrative actions such as 483s and Warning 

Letters and in various public statements and testimony, that the current cGMP Standards are 

necessary to ensure patient access to quality compounded medications. By allowing a lesser cGMP 

standard, FDA would be reversing this position that Congress established in the DQSA to address 

NECC just a few years ago. Accordingly, OFA believes that one consistent cGMP standard should 

be utilized for 503B Outsourcing Facilities regardless of the volume of drug products compounded 

by the facility in order to ensure consistent quality of compounded drugs for patients and ultimately 

assuring patient access. 

Patient Access to Compounded Medications 

OFA and its members are committed to patient care and ensuring access to compounded drugs. In 

striving to meet this goal, OF A members work closely with prescribing practitioners and patients 

to compound drugs that serve the needs of patients and providers. At this time, OF A is not aware 

of issues limiting access to compounded drugs that are typically produced by Outsourcing 

Facilities. OFA is committed to an open dialog with FDA and patient advocacy groups about any 

known patient access issues with specific compounded medications that could otherwise be safely 

compounded. 
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FDA's Consideration of Cost 

In its 2018 Plan, and recently released draft guidance documents, FDA stated that cost will not be 

taken into consideration in FDA's determinations relating to whether a compounded drug is an 

essential copy of an approved drug product. FDA has communicated various reasons for this, 

including that it seeks to preserve the new drug application and abbreviated new drug application 

process. Yet, FDA proposes to utilize cost as a consideration as to whether 503B Outsourcing 

Facilities are meeting patient access concerns. For example, FDA states that cost is one reason 

why FDA wants to offer flexible cGMP standards to pharmacies that are compounding in limited 

batches, to encourage them to register as 503B Outsourcing Facilities. Therefore, the question 

must be asked, why is cost being eliminated as a consideration when 503B Outsourcing Facilities 

are compared to drug manufacturers, but used as a consideration when comparing 503B 

Outsourcing Facilities and compounding pharmacies? 

Bulk Drug List- Clinical Need Requirement 

According to the Compounding Quality Act, 5038 Outsourcing Facilities cannot compound with 

a bulk drug substance unless: 1) the bulk drug substance appears on a list developed by the FDA 

for which a determination of a clinical need has been made; or, 2) the drug compounded from the 

bulk drug substance is on the drug shortage list. According to FDA's 2018 Priorities Plan, FDA is 

still in the process of developing a Clinical Need list applicable to 503B Outsourcing Facilities. 

OF A, in reviewing the criteria that would possibly permit the FDA to make a determination of a 

clinical need, believes that the criteria utilized by FDA should actually define a clinical need. In 

the new drug approval process, FDA already reviews whether there is a clinical need for a drug 

substance. Specifically, during the new drug approval process FDA reviews the efficacy of a drug 

substance. Accordingly, FDA would not approve a drug if there was no "clinical need" for the 

drug. Therefore, OFA advocates that all drug substances used to make products listed in the FDA's 

Orange Book should be eligible for nomination on the clinical need list, as the FDA has already 

determined that there is a clinical need for those products. FDA has already determined that these 

products are both safe and efficacious for a patient to use for a specific disease. Accordingly, 

every component of a product that is listed in the Orange Book has a clinical need and, therefore, 

should be included on the clinical need and bulk drug substance list. To the legitimate concern of 

FDA to protect the new drug application process, the essential copy protection still exists. But the 

use of a bulk substance to compound, and the essential copy protection, should not be conflated. 

These are separate areas that must be reviewed accordingly. 
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ASCRS 

Written Statement for the Record 

Energy and Commerce Subcommittee on Health 

"Examining Implementation of the Compounding Quality Act" 

American Society of Cataract and Refractive Surgery 

4000 Legato Road, Suite 700 

Fairfax, Virginia 22033-4055 

Tuesday, January 30, 2018 

Chairman Burgess, Ranking Member Green, and members of the Subcommittee, the American 

Society of Cataract and Refractive Surgery (ASCRS) would like to thank the Energy and 

Commerce Subcommittee on Health for the opportunity to provide written testimony for the 

January 30,2018, hearing titled "Examining Implementation ofthe Compounding Quality Act." 

ASCRS is a medical specialty society representing nearly 9,000 ophthalmologists in the United 

States and abroad who share a particular interest in cataract and refractive surgical care. ASCRS 

members annually perform the vast majority of cataract procedures in the United States. 

We are very concerned that the Food & Drug Administration (FDA) is implementing Title I of 

the Drug Quality and Security Act (DQSA), the Compounding Quality Act, in a way that 

severely impacts patient access to compounded medications and creates an unnecessary burden 

on physician practices to secure compounded drugs. The practice of ophthalmology relies 

heavily on compounded drugs, and it is vital that physicians have an immediate supply of 

compounded drugs available in their offices to treat patients who present with emergent 

conditions. However, through the use of guidance documents-mostly in draft form, the FDA is 

restricting physicians' access to medications, which ultimately denies patients timely and 

effective treatment options. 

The FDA's implementation ofthe DQSA and use of draft guidance documents has created an 

environment of uncertainty for stakeholders. While draft guidance documents are not legally 

binding, many stakeholders feel pressured to comply because it represents the agency's current 

thinking for policy enforcement. As a result, many compounding facilities are abiding by the 

polices set forth in draft guidance documents, especially compounding regulations. This has 

significantly impacted physician and patient access to compounded drugs. 

When the DSQA was enacted, its sponsors indicated that it was not their intention to restrict the 

use of compounded drugs for office-use. However, since the implementation of the DQSA, 

physicians may only access compounded drugs from a 503A traditional compounder for officeuse if they have a patient-specific prescription. For patients who present with an emergent 

condition and require immediate treatment, this is not an effective pathway to quickly secure 

compounded medications. As an alternative, physicians may procure compounded drugs from a 

503B outsourcing facility without a patient-specific prescription; however, many 503B 
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outsourcing facilities are not producing drugs in the required quantities needed for ophthalmic 

care. Therefore, physicians' practices are experiencing difficulties in securing necessary drugs 

for patient treatment. 

ASCRS remains committed to ensure patients and physicians have timely access to safe and 

effective compounded medications, and therefore, we strongly support and urge Congress to pass 

H.R. 2871, the Preserving Patient Access to Compounded Medications Act, bipartisan legislation 

sponsored by Reps. Morgan Griffith (R-VA) and Henry Cuellar (D-TX). This bill will amend the 

Federal Food, Drug, and Cosmetic Act and allow physicians to obtain compounded drugs from 

503A traditional compounding pharmacies without a patient-specific prescription to treat patients 

that present emergent conditions. 

Our chief recommendations to the Subcommittee include: 

• Limit the use of guidance documents, often still in draft form, because of the 

uncertainty of whether the described policies will be enforced; and 

• Enact H.R. 2871, the Preserving Patient Access to Compounded Medications Act, 

bipartisan legislation sponsored by Reps. Morgan Griffith (R-VA) and Henry 

Cuellar (D-TX), to secure compounded medications for office-use compounding and 

safeguard patient access to treatment by allowing compounding in small quantities 

for office-use without a patient-specific prescription. 

Additionally, the FDA's 2015 draft guidance related to repackaged biologics would have made it 

very difficult for ophthalmic practices to access repackaged biologics. In this guidance, the FDA 

recommended a Beyond-Use Date (BUD) that would have severely impacted the ability of 

patients and physicians to access and use Avastin, a commonly used sight-saving drug in 

ophthalmology. ASCRS and the ophthalmic community advocated heavily against this proposal. 

Fortunately, the FDA took our concerns into account and amended the draft guidance to allow 

for extended BUD if in accordance with additional sterility testing. 

Limit Use of Guidance Documents 

As indicated above, ASCRS is concerned that FDA's routine use of guidance documents, 

often remaining in draft form for several years, creates significant confusion among 

physicians, pharmacies, and other stakeholders and an environment in which they feel 

forced to comply even though the documents are not finalized. The FDA's implementation of 

the DQSA showcases a larger pattern of regulatory overreach by the FDA that has involved the 

use of guidance documents, often still in draft form, that are not finalized. These guidance 

documents, while neither nonbinding or technically enforceable, create an environment of 

ambiguity, as new requirements are often cited in these documents without the benefit of notice 

or comment from the public. As a result, physicians and other stakeholders feel forced to comply 

due to the weight the agency and courts give these guidance documents. 

Furthermore, these guidance documents create significant financial and administrative burdens 

on physicians and other stakeholders. The Administrative Procedure Act's (APA) rulemaking 
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process does not apply to "interpretative rules, general statements of policy, or rules of agency 

organization, procedure, or practice." Therefore, guidance documents do not consider estimates 

of costs, economic burdens, and administrative burdens before expecting stakeholders to comply. 

We believe that policy decisions by the FDA should be conducted through the formal APA 

rulemaking process, should be consistent with the intent of Congress when the law was passed, 

and should not create additional burdens. We urge the Committee to review FDA's use of 

guidance documents to ensure the agency is following congressional intent related to the 

DSQA, and incorporating appropriate public input from all stakeholders. 

Patient-Specific Prescription Requirement for Office-Use Compounding 

ASCRS is concerned with the final guidance on "Prescription Requirement Under Section 503A 

of the Federal Food, Drug, and Cosmetic Act," as it will create further access issues to 

compounded drugs for office-use by requiring a patient-specific prescription for any drug 

compounded by a 503A traditional compounder. Before the enactment ofthe DQSA, it was very 

common for ophthalmic practices to routinely stock small quantities of compounded drugs to 

treat patients who present with emergent conditions in the office setting. However, this guidance 

prohibits physicians from keeping small quantities of compounded drugs for office-use, even to 

treat patients with emergent conditions that may cause blindness. Physicians may access 

compounded drugs from 503B outsourcing facilities, but many of these facilities do not 

produce the drugs in the limited quantities or in ophthalmic solutions required by 

ophthalmologists. 

Timely Access to Compounded Drugs Needed for Emergent Cases 

To reiterate, it is vital for patient care that ophthalmologists have immediate access to small 

quantities of compounded drugs for office-use to provide treatment to patients presenting 

emergent conditions. If an ophthalmologist does not have access to needed compounded drugs, 

this could have lasting negative consequences on a patient, such as extreme ocular damage or 

even complete blindness. For instance, if a patient presents a bacterial endophthalmitis-an 

infection where bacteria has reached the inside of the eye-and is not treated within 24 hours 

with the injection of compounded antibiotics, he or she will almost certainly experience the loss 

of an eye. 

We appreciate that the FDA acknowledged the medical necessity of patients' access to 

compounded drugs in their physician's office in the final guidance, "Prescription Requirement 

Under Section 503A of the Federal Food, Drug, and Cosmetic Act," while even highlighting an 

example from our specialty: 

"If a patient presents at an ophthalmologist's office with a fungal eye infection, timely 

administration of a compounded antifungal medication may be critical to preventing 

vision loss. In such a case, the ophthalmologist may need to inject the patient with a 

compounded drug product immediately, rather than writing a prescription and waiting for 

the drug product to be compounded and shipped to the prescriber." 

However, in the footnote of this example, the FDA states, "such compounding would be subject 

to all of the conditions of section 503A or 503B .... "This is particularly alarming, as the 
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agency has recognized the importance of the availability of compounded medications for officeuse, yet releases final guidance on prescription requirement under section 503A that does not 

ensure patients' timely access to medications. For example, the FDA acknowledged in this final 

guidance that "writing a prescription and waiting for the drug product to be compounded and 

shipped to the prescriber," also known as a patient-specific prescription, is not effective for 

patients experiencing a critical ophthalmic condition. Physicians have the alternative to obtain 

compounded medications from a 503B outsourcing facility. However, physicians experience 

many barriers in accessing necessary compounded medications to treat patients from a 503B 

outsourcing facility. In addition, many outsourcing facilities do not produce compounded drugs 

in the quantity needed by ophthalmology practices or in ophthalmic solutions, such as eye drops. 

This is not only an avoidable delay, but an additional burden on the practice to secure drugs to 

treat patients with emergent conditions. 

Barriers to Access from 503B Outsourcing Facilities 

This lack of access to compounded drugs from 503B outsourcing facilities, since the enactment 

of the DQSA, is evident in the dozens of reports from our members describing access issues to 

certain drugs for office-use from outsourcing facilities. It is clear from the final guidance and the 

proposed 503B pathway, that the agency has ignored comments from outsourcing facilities, 

specifically smaller facilities expressing their inability or lack of willingness to compound in the 

small quantities needed by many ophthalmologists to have on hand for emergent cases. Since 

drugs for emergent conditions are not used in ophthalmic practices on a regular basis, physicians 

generally order smaller quantities, which make it less cost-effective for the outsourcing facilities 

to produce. As a result, many outsourcing facilities do not produce in the requested quantities as 

indicated in recent FDA reports, thus limiting physician and patient access to these drugs. 

503B Outsourcing Facilities Compounding Production Report 

Not only are ophthalmologists reporting a lack of access to drugs from 503B facilities, FDA's 

own reports demonstrate it. Last year, the FDA finalized guidance, "Electronic Drug Product 

Reporting for Human Drug Compounding Outsourcing Facilities Under Section 503B of the 

Federal Food, Drug, and Cosmetic Act Solution," which requires 503B outsourcing facilities to 

submit reporting data on drug production. While ASCRS appreciates the FDA's steps toward 

transparency in drug availability, we remain very concerned that the most recent report finds that 

a number of ophthalmic drugs are missing from the list of available drugs or are not being 

produced in the small quantities needed by an ophthalmologist.' Additionally, the report 

indicates that some ophthalmic compounded drugs are being produced by only one facility. The 

dependence on one facility to produce compounded drugs needed in ophthalmology is 

particularly alarming, as it leaves the patient and physician community without access to the 

drug if there is any disruption in production. 

To demonstrate the limited supply of compounded drugs from 503B facilities, please see 

Appendix A of this written statement, which includes a list of more than 100 ophthalmic 

drugs produced by a 503A traditional compounder before the enactment of the DSQA. 

Today, that same pharmacy has been converted to a 503B outsourcing facility and now 

produces just a handful of ophthalmic drugs. 

' Upon request, ASCRS will provide a list of ophthalmic compounded drugs not being produced by 5038 outsourcing facilitates. 
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Therefore, we strongly urge Congress to ensure that the FDA prioritize the needs of patients with 

emergent conditions by preserving physician access to compounded drugs for office-use from 

503A compounding pharmacies. It is not effective for patients experiencing a critical ophthalmic 

condition to have to wait for a physician to write a prescription and for the drug product to be 

compounded and shipped to the prescriber to be treated. We urge Congress to prioritize the needs 

of patients and enact the Preserving Patient Access to Compounded Medications Act that would 

allow physicians' access to compounded drugs without patient-specific prescriptions for officeuse from 503A traditional compounding pharmacies. 

Repackaged Biologics: 

ASCRS supports the provisions made in the final guidance, "Mixing, Diluting, or Repackaging 

Biological Products Outside the Scope of an Approved Biologics License Application," which 

would allow 503B outsourcing facilities to extend the BUD of repackaged biologics, such as 

Avastin, if additional sterility testing is undertaken. ASCRS applauds the FDA's recognition of 

the importance of repackaged products to ophthalmology, and thanks the agency for creating 

provisions within this draft guidance that allow for the extension of BUDs for repackaged 

biologics beyond 24 hours with additional testing. The previously released draft guidance, in 

February 2015, proposed strict BUDs that would have severely impacted the ability of patients 

and physicians to access and use repackaged pharmaceuticals from outsourcing facilities and 

treat patients before drugs' expired BUDs. This was especially true for biological products 

repackaged for office use, such as A vastin. Avastin is a commonly used sight-saving drug that 

ophthalmologists use to treat age-related macular degeneration. The time involved in sterility 

testing of Avastin is 14 days, as it must be plated and left to incubate in an incubator. In addition, 

it takes the outsourcing facility two days to package, label, and review the drug to ensure it is 

clear with no particles. We applaud the FDA for recognizing the time constraints and for revising 

the guidance to ensure that patients have timely access to treatments. 

Conclusion 

We encourage Congress to intervene with the FDA's implementation of DQSA to ensure 

patients and physicians have continued access to compounded medications. Currently, 

ophthalmologists cannot access an immediate supply of some compounded drugs to treat patients 

who present with emergent conditions. We urge Congress to pass the Preserving Patient Access 

to Compounded Medications Act, which will secure compounded medications for office-use 

compounding and patient access to treatments. 

We thank the Committee for the opportunity to bring these matters to your attention. We would 

be pleased to provide further input or clarification of our comments, as needed. Please contact 

Nancey McCann, director of government relations, at 703-591-2220 or nmccann@ascrs.org if 

you have any questions or would like to arrange a meeting. 
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APENDIX A: list of ophthalmic drugs/ injections being compounded before and after the 

enactment of the DQSA from same facility. 

Ophthalmic drugs/ injections being compounded in a 5038 outsourcing facility available in 

2018: 

lntravitreal Antibiotic Injections 

Cefuroxime 10 mg/ml in 0.9% Sodium Chloride (Preservative-free) $34.SOI1 ml in a 2 ml Vial 

Moxifloxacin 1 mg/ml in Sterile Balanced Salt Solution (BSS) $34.50/1 ml Vial 

Ophthalmic Injections 

Lidocaine HCI1%/Phenylephrine HCI1.5% in sterile water for injection (Bisulfite-Free) $23.0011 ml Vial 

Ophthalmic Solutions 

Atropine Sulfate 1% in 0.9% Sodium Chloride (Preservative-Free) $40.0014 ml in an 11 ml Dropper Bottle 

Edetate Dis odium 3% in sterile water for Injection $161.00/10 ml in a 15 ml Dropper Bottle 

Mitomycin 0.02% (0.2 mglml) in sterile water for injection $69.00/1 ml in a 2 ml Vial 

Topical Dilation Agents 

Cyclopentolate HCI I Tropicamide I Phenylephrine HCI 

1 ml Bottle Cycle HCI1% I Trap 1% I Phenyl HCI 2.5% in sterile water for injection $30.00IPreserved 1 ml 

Dropper Bottle 

5 ml Bottle Cycle HCI1% I Trap 1% I Phenyl HCI2.5% in sterile water for injection $4S.DOIPreserved 5 ml 

Dropper Bottle 

10 ml Bottle Cycle HCI1% I Trap 1% I Phenyl HCI 2.S% in sterile water for injection $74.50 Preserved 10 ml 

Dropper Bottle 

Tropicamide 1%/Phenylephrine HCI 2.5% in sterile water for injection $74.55 each 10 ml in a 15 ml Dropper 

Bottle 

Sterile Repackage 

Avastin (bevacizumab) 2.5 mg/0.1 ml (25 mg/ml) (repackaged, Injection) 

Ophthalmic drugs/ injections being compounded in a 503A pharmacy available before the 

enactment of the DQSA: 

Anti Allergy Solutions 

Cromolyn 4% Preserved or Preservative Free Ophthalmic Solution $73.05/10ml 

Naphazoline HCL Preservative Free Ophthalmic Solution $6S.6S/10ml 

Naphazoline/Pheniramine Preservative Free Ophthalmic Solution $65.65l10ml 

Pheniramine 0.3% PF Ophthalmic Solution $65.65/10ml 

Zinc Sulfate 0.2S% Preservative Free Ophthalmic Solution $S0.8S/10ml 

Anti-lnfectives 

Antibiotics 

Amikacin Ophthalmic Solution 10-50mg/ml $97.20I10ml 

Azithromycin 2mglml PF Ophthalmic Solution $102.60I10ml 

Azithromycin 1% PF Ophthalmic Solution $102.60I10ml 
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Bacitracin 400u/gm/Dexamethasone 0.05% Oph Ointment $63.20/4gm 

Bacitracin Ophthalmic Solution 5,000 or 10,000 u/ml $53.30/10ml 

Cefazolin Ophthalmic Suspension $77.95/lOml 

Ceftazidime Ophthalmic Solution $82.90/10ml 

Chloramphenicol 0.5% Preservative Free Ophthalmic Solution $82.90/10ml 

Chloramphenicoll.O% Ophthalmic Ointment $77 .95/4gm 

Chlorhexidine Ophthalmic Solution $63.20/10ml 

Clindamycin Preservative Free Ophthalmic Suspension varies 

Clindamycin 1% Ophthalmic Ointment varies 

Ciprofloxacin 0.3% Preservative Free Ophthalmic Solution $65.65/10ml 

Clarithromycin 1% Ophthalmic Suspension $90.30/10ml Doxycycline 0.025% 

or 0.1% Oph Solution $53.30/10ml 

Fortified Cefazolin Ophthalmic Suspension $77.95/10ml 

Fortified Gentamicin Ophthalmic Solution (also available Preservative Free) $64.40/7ml 

Fortified Tobramycin Ophthalmic Solution (also available Preservative Free) $64.40/7ml 

Fumidil B (bicyclohexylammonium fumagillin) $103.10/10ml 

Gentamicin Preservative Free 3mg/ml Oph Solution $53.30/5ml 

lmipenium/Cil5mg/ml Pf Oph Solution $102.60/10ml 

Kanamycin Ophthalmic Solution 40mg/ml $44.15/10ml 

levofloxacin 5-25mg/ml Ophthalmic Solution $53.30/10ml 

Metronidazole 0.5% Preserved or Preservative Free Ophthalmic Solution $66.15/10ml 

Metronidazole 0.75% Ophthalmic ointment $68.10/4gm 

Neomycin 15mg/ml Ophthalmic Suspension $41.00/10ml 

Paromycin 15mg/ml Ophthalmic Solution $102.60/10ml 

Penicillin G Potassium Ophthalmic Solution $83.40/10ml 

Piperacillin 10mg/ml Pf Oph Solution $117.40/10ml 

PHMB 0.01% or 0.02% $92.75/15ml 

Polymixin/Trimethoprim Preservative Free Ophthalmic Solution $102.60/10ml 

Sodium Sulfacetamide 10%-30% Preservative Free Ophthalmic Solution $82.90/10ml 

Sulfamethoxazole/Trimethoprim Ophthalmic Solution $65.65/10ml 

Vancomycin 20mg/ml, 25mg/ml or 50mg/ml Ophthalmic Solution $77.95/10ml 

Vancomycin 14mg/ml preservered (60 day exp date) $35/10ml 

Tobramycin 0.3%/Dexamethasone 0.1% Oph Solution $65.65/5ml 

Tobramycin 0.3% Preservative Free Oph Sol $77.95/10ml 

Tetracycline 1% Preservative Free Oph Ointment $82.90/4gm 

Anti-virals 

Acyclovir 3% Ophthalmic Ointment $92.75/4gm 

Cidofovir Ophthalmic Solution (Release is required) $225.85/3ml 

ldoxuridine 1% or 0.1% Ophthalmic Solution $75.40/8ml 

ldoxuridine 0.5% Ophthalmic Ointment $73.05/4gm 

Trifluridine 1% Preservative Free Ophthalmic Solution $108.15/Sml 

Trifluridine 0.5% Compounded Ophthalmic ointment $73.60/4gm 

Vidarabine 3% Ophthalmic Ointment $92.35/4gm 

Antl-fungals 

Amphotericin 0.1-0.5% Ophthalmic Solution $77.35/10m 
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Clotrimazole 1% Ophthalmic Suspension $77 .95/10ml 

Fluconazole 2mg/ml Ophthalmic Solution $90.30/10ml 

Flu cytosine 10mg/ml Ophthalmic Solution $65.65/10ml 

ltraconazole 1% Ophthalmic Suspension $78.95/10ml 

Ketoconazole 5% Oph Suspension in Peanut oil $77 .95/10ml 

Micafungin 0.1% Oph Solution $144.25/5ml 

Miconazole Nitrate 1% Ophthalmic Suspension $90.30/10ml 

Natacyn Ophthalmic Suspension $231.52/15ml 

Voriconazole 1% Cmpd Ophthalmic Solution $157.50/10ml 

Cytotoxic Agents 

Fluorouracil Ophthalmic Solution 1% $53.30/10ml 

Thiotepa 1:2000/ 1:1000 Oph Solution $77 .95/Sml 

Mitomycin Injection or Ophthalmic Solution (all strengths) $45.52/1ml 

Diagnostic Agents 

Cocaine Ophthalmic Solution 4% & 10% Varies 

Fluorescein Oph Solution 0.2% 2% Preserved or Preservative Free $41.00/15ml 

Glycerin 99.5% PF or Preserved Ophthalmic Suspension $32.06/10ml 

Gonioscopic Gel (various strengths) $32.06/10ml 

Hydroxyamphetamine 1% Preserved or PF 5ml $53.30/Sml 

lissamine Green 1% Preservative Free or Preserved Ophthalmic Solution $32.06/10ml 

Rose Bengal Solution 1% Pres. Free or Preserved Ophthalmic Solution $41.00/10ml 

Saccharin Sodium 10mg/ml $41.00/10ml 

Sodium Saccharin 2% Ophthalmic Solution $41.00/10ml 

Dry Eye Compounds 

Albumin 5% Ophthalmic Solution $53.30/10ml 

Aquasol A Ophthalmic Suspension $83.45/1Sml 

Calcium Carbonate 10% Ophthalmic Ointment $41.00/30gm 

Castor Oil 2% Ophthalmic Suspension $32.06/10ml 

Cyclosporine 0.2% Ophthalmic Ointment $62.65/4gm 

Cyclosporine 0.05% in Cyclodextran Solution $83.35/10ml 

Cyclosporine 0.05% /Dexamethasone 0.01% in Cyclodextran Solution $90.30/10ml 

Cyclosporine 0.05-2% Ophthalmic Suspension in Gum Cellulose varies 

Dehydroepiandrosterone (DHEA) Ophthalmic Suspension 0.5% or 1% $90.30/10ml 

Dextran Ophthalmic Suspension $32.06/10ml 

Estradiol 0.01-0.03% Ophthalmic Suspension $93.7S/10ml 

GumCellulose Preservative Free Ophthalmic Solution 0.3% to 2.S% $16.00/15ml 

Hyaluronic Acid PF Ophthalmic Suspension 0.5% $144.55 /10m I 

Methylcellulose Preservative Free Ophthalmic Solution $16.00/15ml 

Poly.Vinyl Alcohol/ Povidone Ophthalmic Solution $32.06/10ml 

Rapeseed Oil 2% (Alpha Omega Drop) Suspension $32.06/10ml 

Retinoic Acid (all trans) 0.01% Ophthalmic ointment $78.35/4gm 

Retinoic Acid (all trans) 0.01% or 0.005% Ophthalmic Suspension $78.35/10ml 

Serum Ophthalmic Drops varies 
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Sodium Carboxy Methylcellulose Ophthalmic Gel $16.00/15ml 

Tacrolimus 0.02% Cmpd Ophthalmic Suspension $32.06/5 ml 

Tacrolimus 0.02% Cmpd Ophthalmic Ointment $67.00/4 gm 

Trehalose 3.78% Ophthalmic Solution $73.05/lOml 

Vaseline Preservative Free Ophthalmic Ointment $78.55/4gm 

Vitamin A 0.01% Oph Suspension (All Trans Retinoic Acid) $77.95/10ml 

Vitamin A 0.01% Ophthalmic Ointment (All Trans Retinoic Acid) $78.35/4gm 

Glaucoma 

Acetazolamide 1% Preservative Free Ophthalmic Suspension $102.60/10ml 

Apraclonidine Preservative Free •• Ophthalmic Solution $77.95/5ml 

Betaxolol 0.125% Preservative Free•• Ophthalmic Solution $53.30/Sml 

Bimatoprost 0.015% PF•• Ophthalmic Solution $107.55/3ml 

Brimonidine 0.1% or 0.075% Preservative Free .. Ophthalmic Solution $102.60/lOml 

Brinzolamide 0.5% PF .. Ophthalmic Solution $45.95/5ml 

Carbachol1.5%, 2.25% & 3% Preservative Free Ophthalmic Solution $90.30/10ml 

Clonidine Preserved or Preservative Free Ophthalmic Solution $65.65/10ml 

Dipivefrin 0.1% Pres'd or pf Oph Solution $55/5ml, $75.00/10ml Dorzolamide 1% 

PF .. Ophthalmic Drops $102.60/10ml 

Dorzolamide 1%/Timolol 0.25% PF •• Ophthalmic Solution $97.2010ml 

Epinephrine Bitartrate Preservative Free Ophthalmic Solution $74.35/10ml 

Epinephrine Borate Preservative Free Ophthalmic Solution $97.20/10ml 

Epinephrine HCL 1% Preserved Ophthalmic Solution $77.95/10ml 

Latanoprost 0.0025% Preservative Free .. Ophthalmic Solution $90.07/3ml 

Levobutanol 0.25% PF .. Ophthalmic Solution $53.30/5ml 

Phospholine Iodide (all strengths) varies 

Pilocarpine Preservative Free Ophthalmic Solutions 0.1% to 6% $65.65/10ml 

Pilo 1%/Epi 1% Cmpd Ophthalmic Solution $41.00/5ml 

Travoprost Z 0.002% Cmpd PF .. Ophthalmic Suspension $83.35/3ml 

Preservative Free Steroids 

Dexamethasone Na Phos Injection 4-24mg/ml PF varies 

Dexamethasone Sodium Phosphate Preservative Free Solutions $58.00/10ml 

Dexamethasone 0.05% Ophthalmic Ointment $82.90/4gm 

Dexamethasone 0.05% Lanolin Free Ophthalmic Ointment $82.90/4gm 

Fluorometholone 0.1% PF Ophthalmic Suspension $55.00/5ml 

Loteprednol 0.25% PF .. Opthalmic Solution $74.35/ml 

Methylprednisolone Na Succinate Preservative Free Ophthalmic Solution $77.95/10m 

Prednisolone Acetate Preservative Free Ophthalmic Suspension $92.75/10ml 

Prednisolone Sod Phos Preservative Free Ophthalmic Solution $82.90/10ml 

Rimexolone 0.5% Cmpd PF •• Ophthalmic Solution $102.60/10ml 

Triamcinolone 80mg/ml Preservative Free Compound Injection $20.00/1ml 

Misc. Agents 

Acetyl Cysteine 5-20% Ophthalmic Solution pf $77.95-97.70/10ml 

Aminocaproic Acid 30% Ophthalmic Suspension $85.85/10m 

Ascorbic Acid 10% Ophthalmic Suspension $87.85/10ml 
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Bevacizumab (Avastin) Cmpd lnj (various doses available) varies 

Bevacizumab (Avastin) Topical Drops varies 

Benoxinate 0.4% PF or Preserved Oph Solution $32.06/Sml 

Boric Acid Ophthalmic Ointment $82.90/4gm 

Brilliant Green 2% Ophthalmic Stain $32.06/lOml 

Brilliant Blue G 0.25mg/1ml $10.00/1ml 

Cysteamine 0.55% Cmpd Ophthalmic Solution $83.90/10ml 

Diclofenac Sodium 0.1% Preservative Free Ophthalmic Solution $77.95/lOml 

EDTA Preserved 0.4% to 3% varies 

Ethanol (all concentrations) Ophthalmic Drops or Injectable $53.30/lOml 

Indomethacin 0.5 or 1% Ophthalmic Suspension $92.75/15ml 

Glutathione 6% Ophthalmic Solution $59.50/15ml 

Glycerin 50% oral solution $55.60/220ml 

Glycerin 50% Ophthalmic Solution $30.53/10ml 

Guanethidine Preservative Free Ophthalmic Solution 2%,5% or 7.5% varies 

Heparin PF Ophthalmic Solution $32.06/10ml 

Hyaluronidase Injection 150u/ml $15.00/1ml, $31.25/5 ml, $46.25 /10ml 

lbopamine 2% Ophthalmic Solution $65.00/Sml,$85.00/lOml 

Interferon Alfa 2B Ophthalmic Solution (1-3mu/ml) $235.73/3-10ml (depends on strength) 

lsosorbide 45% Cmpd Oral Solution $128.75/llOml 

Medroxyprogesterone Acetate 0.5% or 1% Ophthalmic Suspension $40.91/10ml 

PABA 10% Cmpd Ophthalmic Ointment $60.03/4gm 

Phentolamine 0.083% Ophthalmic Solution $41.00/Sml 

Physostigmine Salicylate 0.03%, 0.125% 0.25% or 0.5% Oph Solution $77.95/10ml 

Physostigmine Salicylate Ophthalmic Ointment $87.85/4gm 

Povidone-Iodine Ophthalmic Solution $53.30/10ml 

Silver Nitrate Ophthalmic 0.5% or 1% Solution $53.30/10ml 

Silver Protein 10% Ophthalmic Solution $44.15/lOml 

Sodium Chloride 5% Ophthalmic Solution PF $53.30/10ml 

Sodium Chloride 5% Preservative Free Ophthalmic Ointment $63.20/4gm 

Sodium Citrate 10% Ophthalmic Solution $69.10/10ml 

Tetrahydrolazine 0.05% PF Ophthalmic Solution $53.30/lOml 

Vision Blue 0.06% Singles $52.00/each 

Vitamin A 1%/ Vit C 1% /Glutathione 1%/DMSO 5% Ophthalmic Sol $98.70/10ml 

Topical Anesthetics, Reversal Agents and Combo Dilating Agents 

Atropine Sulfate Ophthalmic Solution 0.125% to 1% PF $50.90/10ml 

Benoxinate 0.4% PF or Preserved Oph Solution $32.06/Sml 

Cyclopentolate 0.5% to 1% P.F. $77.95/lOml 

Cyclopentolate/Phenylephrine/Bupivicaine Combo Ophthalmic Solution varies 

Cyclopentolate/Phenylephrine/Diclofenac Combo Ophthalmic Solution varies 

Cyclopentolate/Phenylephrine Combo varies 

Cyclopentolate/Proparacaine Combo varies 

Dapiprazole 0.5% Topical Drops (compare to Rev-Eyes-Lyopholized) $40.00/6ml kit 

Homatropine Preservative Free Ophthalmic Solution 5% $43.45/lOml 

Lidocaine Ophthalmic Solution 0.5-0.4% $53.30/lOml 
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Phenylephrine Preservative Free Ophthalmic Solution 2.5% or 10% $53.30/10ml 

Proparacaine Preserved or PF (0.03%, 0.05%, 0.1%, 0.25%) Ophthalmic Solution $43.35/10ml 

Proparacaine 0.05% PH Adjusted Preserved Ophthalmic Solution $32.06/10ml 

Proparacaine/Tropicamide/Cyclopentolate/Phenylephrine Combo Oph Sol varies 

Scopolamine 0.25% Preservative Free Ophthalmic Solution $65.65/lOml 

Tetracaine 0.5% PF Cmpd Ophthalmic Solution $32.06/5ml 

Tetracaine 0.5% Ophthalmic Ointment $82.90/4gm 

Tetracaine HCL 0.05% Preserved and Stabilized Oph Solution (Comfort Drops) $7.50/3 or 5ml 

Tropicamide Preservative Free Ophthalmic Solution $53.30/10ml 

Tropicamide 0.5%/Cyclopentolate 0.5%/PHN 2.5% Combo Spray $48.30/10ml 

Tropicamide 1%/ Cyclopentolate 1% Ophthalmic Solution $53.30/10ml 

Tropicamide 1%/ Phenylephrine 2.5% Preserved Ophthalmic Solution $53.30/lOml 

Tropicamide 1%/ Phenylephrine 5% Preserved Ophthalmic Solution $53.30/10ml 

Tropicamide 0.25%/ Phenylephrine 5% Preserved Ophthalmic Solution $53.30/10ml 

Topicamide 1%/Cyclopentolate1%/Phenylephrine 2.5% Preserved Ophthalmic $54.80/10ml 
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NACDS NATIONAL ASSOCIATION OF 

CHAIN DRUG STORES 

Statement 

of 

The National Association of Chain Drug Stores 

for the 

United States House of Representatives 

Committee on Energy and Commerce 

Subcommittee on Health 

Hearing on: 

"Examining Implementation of 

the Compounding Quality Act" 

January 30,2017 

11:00 a.m. 

2123 Rayburn House Office Building 

National Association of Chain Drug Stores (NACDS) 

1776 Wilson Blvd. Suite 200 

Arlington, VA 22209 

703·549-3001 

www.nacds.org 
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NACDS Statement on "Examining Implementation of the Compounding Quality Act" 

January 30, 2017 

Page I 

The National Association of Chain Drug Stores (NACDS) thanks Chairman Burgess, 

Ranking Member Green, and Members ofthe Energy and Commerce Committee 

Subcommittee on Health for the opportunity to submit a statement for the hearing on 

"Examining Implementation of the Compounding Quality Act." 

NACDS and the chain pharmacy industry are committed to partnering with Congress, the 

Food and Drug Administration (FDA), state boards of pharmacy, and others in the 

pharmacy community on policies that support the delivery of high quality, affordable 

healthcare services that meet the diverse healthcare needs of patients across the country. 

NACDS represents traditional drug stores, supermarkets and mass merchants with 

pharmacies. Chains operate over 40,000 pharmacies, and NACDS' nearly 100 chain 

member companies include regional chains, with a minimum of four stores, and national 

companies. Chains employ nearly 3 million individuals, including 152,000 pharmacists. 

They fill over 3 billion prescriptions yearly, and help patients use medicines correctly and 

safely, while offering innovative services that improve patient health and healthcare 

affordability. NACDS members also include more than 900 supplier partners and over 70 

international members representing 20 countries. Please visit www.NACDS.org. 

As the face of neighborhood health care, chain pharmacies and pharmacists work on a 

daily basis to provide the best possible care to patients and to meet their medication 

needs. Where some patients require medicines that are not otherwise available as 

commercially-manufactured preparations, chain pharmacists perform prescription drug 

compounding to ensure that patients have access to medications necessary to treat their 
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NACDS Statement on "Examining Implementation of the Compounding Quality Act" 

January 30, 2017 

Page 2 

medical conditions. These types of pharmacist compounding services have been offered 

by pharmacies since the early days of the pharmacy profession. Over the years, these 

services have remained a valuable and important component of our nation's healthcare 

system. 

When Congress enacted the Drug Quality and Security Act ("DQSA), lawmakers 

recognized the importance of allowing pharmacists in retail community pharmacies to 

continue to provide traditional compounding services and maintained pharmacists' ability 

to do so under Section 503A of the Food, Drug, and Cosmetic Act. The chain pharmacy 

community supports the implementation of the DQSA in a manner that is consistent with 

the intent of Congress to maintain access to compounding services historically provided 

by retail community pharmacies. 

Among its various actions to implement the DQSA, FDA published a draft memorandum 

of understanding (MOU) in 2015 outlining the responsibilities of FDA and individual 

state boards of pharmacy with respect to investigation and response to complaints related 

to interstate distribution of compounded drugs, and interstate distribution of inordinate 

amounts of compounded drugs. Like other pharmacy stakeholders, the chain pharmacy 

community is concerned that certain provisions in the draft MOU -if finalized and 

implemented- could impede retail community pharmacists' and pharmacies' ability to 

provide traditional compounding services that are permitted under Section 503A of the 

Food, Drug & Cosmetic Act. 
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NACDS Statement on "Examining Implementation of the Compounding Quality Act" 

January 30, 2017 

Page3 

Notably, Section 503A of the Food, Drug & Cosmetic Act clearly distinguishes the act of 

dispensing as separate from the act of distribution. 1 However, the language of the draft 

MOU defines the term "distribute" to include the act of"dispensing." In doing so, the 

draft MOU fails to maintain the important distinction between compounded products that 

are distributed versus compounded products that are dispensed. 

Before finalizing the MOU, it is imperative that FDA remedy the inconsistency between 

the language of law and the MOU. Given that Section 503A establishes that the scope of 

the MOU is to "address the distribution [emphasis added] of inordinate amounts of 

compounded drug products," the language of the MOU should address distribution only. 2 

Otherwise, the MOU may impede retail community pharmacies' ability to dispense 

compounded medications to their patients pursuant to a prescription. 

Additionally, we are concerned that the draft MOU imposes an arbitrary cap on what 

constitutes an "inordinate amount" of compounded product distributed interstate. 

Imposing this arbitrary limitation is problematic for a number of reasons. It fails to take 

into consideration regional and geographic issues, individual pharmacy volume, and other 

factors that may necessitate higher rates of interstate distribution in certain circumstances. 

Furthermore, it is concerning that the cap on interstate distribution would be calculated 

using both compounded drug products that are distributed and dispensed [emphasis 

added] in and out of state. As we discussed above, the law establishes that the scope of 

1 21 U.S.C. §353a(3)(B)(ii) 2 21 U.S. C. §353a(3)(B)(i) 
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NACDS Statement on "Examining Implementation of the Compounding Quality Act" 

January 30, 2017 

Page 4 

the MOU is limited to distribution only. Including compounded drug products that are 

dispensed would be inconsistent with the language ofthe law. 

Overall, the limitations established in the draft MOU regarding what constitutes an 

"inordinate amount" of compounded product may impede patient access to compounded 

products by restricting the supply of compounded products that may be distributed out of 

state. We believe that defaulting to any arbitrary cap is contrary to the overall goal of the 

MOU, which is to facilitate communication among the states and FDA on how to best 

trigger investigation of a compounding pharmacy where appropriate. For these reasons, 

the language establishing these specific limits should be eliminated from the MOU 

entirely. 

We note that the 2018 Compounding Policy Priorities Plan published by FDA earlier this 

month acknowledges that because ofthe many stakeholder concerns with the draft MOU, 

FDA plans to substantially revise the MOU to address many of the concerns raised. We 

are hopeful that the concerns we highlighted in our comments above will be among the 

issues that FDA addresses before finalizing the MOU, as these are central to maintaining 

patient access to the important pharmacist compounding services provided in retail 

community pharmacies across the nation. 

NACDS thanks the Committee for your consideration of our comments. We look 

forward to working with policymakers and stakeholders on these important issues. 
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-APbA AMERICAN 

_____ PHARMACISTS ASSOCIATION 

..... 

U.S. HOUSE ENERGY AND COMMERCE 

HEALTH SUBCOMMITTEE 

"Examining Implementation of the Compounding Quality Act." 

Tuesday January 30,2018 

ll:OOAM 

Statement for the Record 

The American Pharmacists Association 

The American Pharmacists Association (APhA) appreciates the opportunity to submit the 

following Statement for the Record for today's U.S. House Energy and Commerce Health 

Subcommittee hearing "Examining Implementation of the Compounding Quality Act." 

APhA, founded in 1852 as the American Phannaceutical Association, represents more than 

64,000 phannacists, phannaceutical scientists, student phannacists, phannacy technicians, and 

others interested in improving medication use and advancing patient care. APhA members 

provide care in all practice settings, including community phannacies, hospitals, long-tenn care 

facilities, community health centers, physician offices, ambulatory clinics, managed care 

organizations, hospice settings, and the unifonned services. 

APhA would like to thank Subcommittee Chair Burgess and Ranking Member Green for holding 

a hearing to gather Agency and stakeholder input on drug compounding as part of the 

Committee's ongoing oversight of the FDA's mission to ensure drug quality and security as the 

provision of safe, effective medications, including compounded medications, which is of 

paramount importance to APhA members and a goal shared by everyone here today. APhA 

would also like to note that legislation 1 providing appropriations to the federal agencies was 

recently signed into law. This legislation included report language clarifying congressional intent 

with regard to the Drug Quality and Security Act (DQSA), which aligns with APhA and other 

phannacy organizations' interpretation and our comments. The language specifically: 

• Calls on FDA to draft a Memorandum of Understanding (MOU) that addresses the 

"distribution" of compounded products over state lines; 

• Calls on FDA to draft final guidance to allow phannacists to compound for "office use" 

"in anticipation of receiving patient-specific prescriptions at a later time;" and 

• Reminds FDA that pharmacies that compound under 503A are under the purview of state 

boards of pharmacy and are not to be held to current Good Manufacturing Practices 

(CGMPs). 

MOU 

APhA supports FDA finalizing an MOU which aligns with the congressional intent of the 

DQSA. The plain language of the Food, Drug and Cosmetic (FD&C) Act directs FDA to develop 

1 See, H. Rept. 114-531- AGRICULTURE, RURAL DEVELOPMENT, FOOD AND DRUG ADMINISTRATION, AND RELATED 

AGENCIES APPROPRIATIONS BILL, 2017. Available at: https·//www.congress.gov/consressionai~report(ll4th-eongressfhousereport/53l/l ?q::o/i7B%22search%22%3A%5B%22H +Rent +114:531o/o22%5D%7D&r-1 
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an MOU that addresses "the distribution of inordinate amounts of compounded drug products 

interstate."2 While DQSA does not explicitly define "distribution," the statutory text 

differentiates between "distribution" and "dispensing" in a number of places-a clear indication 

that Congress ascribed different meanings to the two terms. 3 Historically, the terms "dispense" 

and "distribute" refer to two different activities. In both FD&C4 and the Controlled Substances 

Act,5 Congress and FDA expressly recognized the different usage of "dispense" and "distribute," 

defining "dispensing" as something that is intrinsically clinical in nature, while defining 

"distribution" as the act of shipping or delivering a medication outside of the patient-provider 

relationship. To treat "distribution" and "dispensing" as interchangeable only in the context of 

DQSA not only creates confusion, it also implies that FDA is entering into the regulation of 

clinical decision-making related to prescribing-an area meant to be governed by states. Thus, in 

keeping with congressional intent, we believe that a final MOU should only address 

"distribution" of compounded medications across state lines and should have no effect on 

dispensing of prescriptions for identified patients by pharmacies compounding under section 

503A. Congress noted that for the MOU, "inordinate" amounts or quantities refers to "amounts 

typically associated with ordinary commercial drug manufacturing."6 It would be helpful for the 

Committee to clarify congressional intent with the FDA during today's hearing. 

Office Use 

APhA reiterates its concern with FDA's position in its recent final guidance prohibiting 

pharmacies from compounding for office use, despite existing federal law which states that a 

licensed pharmacist can compound "in limited quantities before the receipt of a valid 

prescription order for such individual patient" and a long history of the Agency allowing the 

practice. 7 While the FDA has indicated that office use compounded products should be fulfilled 

by outsourcing facilities, due to the cost and/ or time to comply with CGMP, 503B facilities 

cannot meet all the product demands of patients and providers. This is why many 503B facilities 

have defined formulary lists.8 CGMP requirements include: procurement of bulk drug product(s) 

which meets CGMP; authoring procedures to compound the medication which meet CGMP; 

proper testing (validation, release testing, stability testing) and other requirements.9 APhA 

members' conversations with 503B facilities have confirmed the inabilitv of these facilities to 

supply many small batch medications commonly associated with office use (e.g., numbing 

creams/sprays, etc.). In addition, because of the time required to meet CGMPs, including, but not 

limited to the testing requirements, 503Bs are unable to immediately meet the needs of providers 

and patients unless facilities are currently compounding the product(s). Therefore, APhA 

1 See 21 U.S. C. § 353a(3)(B). Available at https://www.law.come1Ledu!us£ode/text/2l/353a 1 See e.g .. id. at (3)(B)(ii} (differentiating the "dispensed" and "distributed" through the use of the disjunctive "or", indicating that the terms are 

not interchangeable). 4 Drug Supply Chain Security Act, §581(5) (2013) (defining distribute as "the sale, purchase, trade, delivery, handling, storage, or receipt of a 

product", but stating that it "does not include the dispensing of a product pursuant to a prescription executed in accordance with section 503(b)(l) 

or the dispensing of a product approved under section 512(b)"). 

s See 21 U.S.C. §802(10)-(l I). Available at: http:/fwww.deadiversion.usdoi.gov/21cfr/21usc/802.htm; See also 21 CF.R. §208.3 defining 

"distribute" as "'the act of delivering other than by dispensing a drug product to any person", thereby expressly excluding dispensing from the 

act of distribution). Available at: httos·//www law.corneH.edu/cfr/text/21/208.3 

'See, S. Rept 105-43 ·FOOD AND DRUG ADMINISTRATION MODERNIZATION AND ACCOUNTABILITY ACT OF 1997. Available 

at httns:l/www.congress.gov/congressional-report/105th-congress/senate-report/43ll 

7 See. 21 USC 353a. SEC. 503A PHARMACY COMPOUNDING. Available at 

https:lfwww.fda.gov/drugs!guidancecomplianceregulatoryinformation.lpharmacycompounding!ucm376733.htm 

11 See SCA Pharmaceuticals. Product Catalog. 2016; Cantrell Drug Company. Product Catalog. 2016; and Leiter's Compounding Product C~talog, 

2016. 

9 See FDA Guidance for Industry Current Good Manufacturing Practice- Interim Guidance for Human Drug Compounding Outsourcing 

Facilities Under Section 503B of the FD&C Act. July 2014. Available at 

http:J/www.fda.gov/dovmloads!drugs/guidancecomplianceregulatorvinformationlguidanceslucm403496.pdf 

2 
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strongly urges Congress to ensure that FDA follows its previous long-standing policy, as well as 

existing statute and the intent of Congress, and continue to allow pharmacies compounding under 

section 503A to compound "limited quantities" without a patient-specific prescription and defer 

to states for statutory or regulatory authority over pharmacies' office use compounding. 

Anticipatory Compounding 

Section 503A(a)(2) of the FD&C Act, allows a licensed pharmacist or licensed physician to 

compound "limited quantities" 10 before the receipt of a valid prescription order when there is a 

relationship between the prescriber and pharmacist or physician receiving the prescription, or the 

patient and pharmacist or physician receiving the prescription. In final guidance, FDA defined 

"limited quantity" as "a 30-day supply of a particular compounded drug" if that supply "is based 

on the number of valid prescriptions that the compounder has received for an identified 

individual patient in a 30-day period over the past year" (i.e., referred to as "anticipatory 

compounding"). While APhA appreciates FDA acknowledging "larger batch sizes can increase 

efficiency and reduce the likelihood of human error,"11 because FDA is now attempting to define 

"limited quantity," we believe it is minimizing the value and benefit of anticipatory 

compounding. 

Inspections 

Finally, APhA was initially pleased with FDA's recent July 2016 "Notice" that starting August 1, 

2016, FDA inspectors would make a "preliminary assessment" of whether pharmacies are in 

compliance with 503A before applying 503B standards in "Form FDA-483" investigations and 

would not include observations in its Form-483 based "solely" on CGMP under section 503B. 12 

However, APhA has received multiple Form FDA-483s dated post-July 2016 regarding 

inspections of pharmacies compounding under section 503A, which indicate that FDA inspectors 

continue to inspect pharmacies, not outsourcing facilities under 503B, and cite CGMP 

noncompliance. APhA continues to have serious concerns that the pharmacies being cited are not 

503B and are incorrectly being cited by FDA for CGMP. Accordingly, we are pleased that the 

2017 appropriations legislation signed into law also requires FDA to recognize that federal 

oversight of pharmacies compounding under section 503A was not the intent of Congress, and 

that compounding pharmacies are not drug manufacturers-rather, they are "state licensed and 

regulated health care providers that are inspected by state boards of pharmacy pursuant to state 

laws and regulations that establish sterility and other standards for the pharmacies operating 

within their states." 13 We strongly urge the Committee to clarify to FDA the congressional intent 

of this language during today's hearing. 

In addition, we have heard from nuclear pharmacies, which are exempt from the DQSA for the 

preparation of radiopharmaceuticals, 14 that FDA is inspecting these facilities based on these draft 

10 See 21 U.S. Code § 353a ·Pharmacy compounding. Available at: https://www.law comell.eduluscode/text/21/353a 11 In addition, compounding larger supplies of products often encourages quality control testing because costs can be spread out among a larger 

number of products. 12 See FDA. Notice of Change in Process for Inspections of Certain Compounders. July 12,2016. Available at 

http·//www.fda.gov/downloods/Drugs/GuidanceComp!ianceRegulatoryJnformation!PharrnacyCornpounding/UCM510684.pdf 

lJ See, II. Rept. 114-531 • AGRJCULTIJRE, RURAL DEVELOPMENT, FOOD AND DRUG ADMINISTRATION, AND RELATED 

AGENCIES APPROPRJATIONS BILL, 2017. Available at: https://www.congress.gov/congressionaJ.reoort/114th-congresslhousereport/53I/l?q=%7B%22search%22%3A%5B%22H.+Rept.+l 14-53l%22%5D%7D&r=l 14 See 21 U.S.C §353a(e). "''(e) Application.-This section shall not apply to-- ''(l) compounded positron emission tomography drugs as 

defined in section 201(ii); or "{2) radiopharmaceutiya1s." Available at: httos://www.gpo.gov/fdsyslpkgiUSCODE-2010-title21/pdfJUSCODE20 l O-title21-chap9-subchapV -partA-sec353a. pdf 

3 
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guidances, not statutes, and then issuing Fom1 FDA-483s for observations that are not applicable. 

While compounding creates what are essentially new drug products designed to meet patient 

needs, most nuclear pharmacies are preparing radiopharmaceuticals from kits that are FDAapproved-activity that falls outside of the FD&C's definition of compounding. We would 

appreciate the Committee inquiring why FDA is inspecting nuclear pharmacies as compounders 

when Congress specifically exempted them from the DQSA. 

APhA would like to close by thanking the Committee for continuing to work with APhA and 

other pharmacy stakeholders to construct a framework in accordance with current statutory 

authority and congressional intent that ensures patients have access to safe and effective 

compounded medications. APhA looks forward to being part of future discussions on this topic. 

We hope to be a resource for Congress and FDA and are happy to be of assistance in any way 

possible. 

Thank you again for the opportunity to provide comments on this important issue. 

4 
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American Academy of Allergy, Asthma, & Immunology 

American College of Allergy, Asthma, and Immunology 

American Academy of Otolaryngic Allergy 

Joint Statement for the Record 

Before the House Energy and Commerce Health Subcommittee 

Hearing Entitled 

"Examining Implementation of the Compounding Quality Act" 

Tuesday, January 30, 2018 

Chairman Burgess, Ranking Member Green, and members of the Subcommittee, on behalf of the 

American Academy of Allergy, Asthma, & Immunology (AAAAI), the American College of Allergy, Asthma 

and Immunology (ACAAI), and the American Academy of Otolaryngic Allergy (AAOA), thank you for the 

opportunity to share our views on the implementation of the Compounding Quality Act. We hope you will 

consider our comments regarding efforts to establish heightened safeguards for compounded 

medications. The AAAAI and the ACAAI are the premier specialty societies representing more than 6,000 

allergist-immunologists and related professionals worldwide dedicated to advancing allergy and 

immunology health care. The AAOA is the premiere otolaryngology (ENT) society focused on diseases of 

the respiratory tract, including allergy, and represents over 2000 members impacting over 8000 

otolaryngologists. 

Our written statement will discuss the recent proposed changes by the U.S. Pharmacopeia (USP) and the 

Food and Drug Administration (FDA) that would transform allergen immunotherapy (AIT)- a currently 

proven safe and effective disease modifying therapy- into a higher risk and less accessible treatment 

option. 

Allergen Extracts and Allergen Immunotherapy 

Allergen extracts are prepared based on the allergist's written order specifying the content, 

concentration, and dosing schedule. When a patient begins immunotherapy, he or she begins with highly 

diluted doses and the concentration gradually increases over time. Injections are typically between 0.5 

and 1.0 ml and are administered subcutaneously. Usually, by the end of a year, a patient is on a 

maintenance dose and receives injections once or twice every month. For some patients, such as those 

with life-threatening stinging insect allergies, this course of treatment can create a change in the body's 

immune response that is potentially life-saving. 

The mixing of allergen immunotherapy treatment sets begins with FDA approved allergenic extracts. 

Most, but not all, commercial allergenic extracts are 50% glycerinated. The allergenic extracts or 

"concentrates" are combined in a sterile vial using sterile syringes. Serial 5-fold or 10-fold dilutions are 

then made from the vial of concentrate using sterile saline (either normal saline or HSA saline) typically 

containing 0.4% phenol. Aseptic technique based on current USP Ch. <797> guidelines or the standards 

set forth in specialty-developed Practice Parameters is followed, and vials are labeled and stored in 

refrigerated conditions accordingly. Beyond-use dates (BUDs) are assigned based on the most recent 

expiration date of any of the component antigens. The inclusion of preservatives deters many infectious 
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concerns while allowing treatment to proceed safely by use of consistent extract over many months while 

the immune response to the allergens present increases. 

A typical multi-dose vial of maintenance extract contains 10 doses designed to last over a 10-12 month 

period. Dilutions, which are given at the onset of treatment, are also prepared in 10 dose vials but storage 

time is less because the injections are given more frequently (e.g., weekly to bi-weekly). 

Allergen extracts are uniquely situated compounded products. Allergen extracts require close monitoring 

at the time of the injection, and patients are closely monitored in the physician's office for reactions for 

at least 30 minutes post-injection. Additionally, patients receiving immunotherapy come to the physician's 

office at least monthly for injections. Before each new injection, patients are queried regarding any issues 

with the previous injection including any lesser reactions. The injection site is also physically examined. 

Any problems are reported to the physician. Based on the patient history and well-being, modifications 

are implemented to protect patients. For example, dose reductions or a postponed administration might 

be adopted if a patient has suffered an asthma flare. It is important that the allergist be able to make 

these changes on a timely basis so that the course of treatment is appropriate for the patient's current 

condition and not delayed. Anaphylactic reactions are always a possibility throughout immunotherapy 

treatment, and are the primary risk to allergen immunotherapy patients. The ability to compound and 

consistently monitor the use of allergen extract is fundamental to minimizing this risk. 

Allergen immunotherapy has been safely compounded and administered in allergists' offices for over 100 

years. This precision medicine technology is life altering and at times lifesaving. And unlike many other 

compounded treatments, All is administered subcutaneously and not parenterally or intrathecally, 

essentially eliminating any risk of systemic infection. Indeed, there is no documented evidence of an 

infectious risk from compounding allergen extracts in the office setting. 

Current Standards 

Current U.S. Pharmacopeia (USP) <797> standards, which are recognized by the FDA in regulation and 

guidance as required by statute, distinguish the unique nature of allergen extracts from other 

compounded drugs and provide specific requirements for their use. However, allergen extracts as 

compounded sterile preparations (CSPs) are not subject to the personnel, environmental, and storage 

requirements. 

FDA Guidance 

In February 2015, the Food and Drug Administration (FDA) issued draft guidance titled "Mixing, Diluting, 

or Repackaging Biological Products Outside the Scope of an Approved Biologics License Application 

Guidance for Industry." Those FDA draft guidelines suggest in-office allergen extract compounding should 

follow the USP <797> instructions specific to allergen extracts and specified policies which provided 

special exceptions recognizing the unique nature of AlT. We previously submitted comments generally in 

support of the FDA draft guidance, and we are pleased that the final guidance released in January 2018 

retains the special exemptions for allergen extracts. 

Given that Congress has statutorily required the FDA defer to the USP for some key regulatory questions, 

we urge you to maintain oversight not only overt he FDA process but also the USP process. As you may be 

aware, USP is in the process of crafting a significant revision to the <797> chapter that, if approved as 

proposed, could significantly alter the process of All compounding and administration that could 

significantly decrease access to this treatment. 

2 
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In the fall of 2015, USP published a proposed revision of Chapter 797 that significantly altered the 

standards for sterile compounding, moving from a risk assessment-based series of requirements to one 

that treated all sterile compounding as equally and inherently dangerous, regardless of the contents or 

administration site of the compounded material. The proposed changes to the USP for allergen 

compounding are not based on published scientific data in which any infectious clinical problem(s) with 

allergen extract compounding has occurred. However, these proposed changes have the potential to 

significantly decrease the safety of AIT and place patients at increased risk for adverse outcomes. 

Under the proposed revisions, allergen extracts would no longer have specific requirements for their use 

but would instead be treated similar to all other CSPs. The proposal would require that all sterile 

compounding, including allergen extract compounding, be performed in an ISO Class 5 environment. This 

contradicts current USP <797> guidelines and current FDA guidelines, without providing any evidence that 

such an approach is necessary to avoid infectious risk from mixing and administration of AlT. Therefore, 

we reject that the current standards (as previously agreed to by the USP and FDA) are insufficient to safely 

provide these services in the physician's office. 

The USP proposal would also require discarding of all preparations after either 28 or 42-days regardless 

of manufacturer beyond use dates (BUDs). This change would require more frequent mixing of allergen 

extracts, significantly increasing the risk of an adverse event due to an allergic reaction because of extract 

lot variability with respect to content and potency, which can cause allergic reactions. In addition to safety 

concerns, shorter BUD requirements would impact the efficacy of therapy. This potential lack of efficacy 

relates to immunotherapy induction of tolerance developed when maintenance dosing is achieved, and 

the linkage to the timing of injections that are typically given monthly once the maintenance dose is 

reached. If the allergen preparation for maintenance therapy must be remade every month, it would 

prevent the patient from reaching the maintenance dose (and desensitization) because the schedule 

would have to be restarted with each newly prepared allergen extract material. 

The proposed changes to USP <797> are not indicated by the medical literature, which supports the 

conclusion that allergen extract preparation following current <797> guidelines is safe and does not place 

patients at risk for infectious complications related to AlT. The over-reaching and dangerous USP proposal 

was met with almost 8,000 comments. The volume, intensity and extraordinary level of concern expressed 

in those comments reflects significant consideration from health care providers and patients, as well as 

an expectation that evidence supportive of this overreaching, "one-size-fits-all" approach should be 

provided before such draconian measures should be considered. 

Recently, USP invited a private practicing allergist, Andrew Murphy, MD, FAAAI, to serve as an expert 

consultant, providing important input as the USP Compounding Expert Committee (CEC) completes work 

on its second draft of USP <797> for public comment (expected September 4, 2018). However, there is no 

opportunity for ongoing feedback from the national specialty organizations while this work is underway. 

FDA Position 

In August 2016, the FDA issued draft guidance on insanitary conditions at compounding facilities. The 

draft guidance duplicates USP's inappropriate proposal that would require an ISO class 5 environment 

(among other things) or otherwise declare mixed products insanitary. This is a broad over-reach, given 

that these environmental standards have not previously been applied to the much-broadened category 

of "compounding facility" cited in the FDA's proposal. 

3 
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Additionally, we are concerned that through this draft guidance, FDA is fundamentally attempting to 

undermine the processes in place at the USP regarding the Chapter 797 proposed revision. 

Recently, the FDA announced as part of its 2018 Compounding Policies Priority Plan' that the Agency plans 

to revisit some of these key issues in light of concerns raised by providers. Specifically, the document 

states {with respect to the insanitary conditions guidance): "This guidance will address concerns raised by 

some providers who compound small quantities of drugs in their offices for patient use, and as part of 

their routine clinical practice. This came up in the setting of certain dermatological procedures, for 

example. The FDA plans to better define the circumstances under which we believe drugs are being mixed 

and applied in a manner that creates negligible patient risk, and therefore wouldn't be subject to the same 

compliance policy under the agency's risk-based approach to implementing these requirements." 

Therefore, we look forward to receiving more information from the FDA. Previously, we requested that 

the FDA withdraw this draft guidance, but we appreciate the FDA taking an initial step of recognizing the 

valid concerns we have presented. We urge Congress to continue to maintain oversight of the regulatory 

process to ensure that patient access is not unnecessarily hampered. 

Impact of Proposed Changes 

If the USP and FDA proposals are finalized, as initially drafted, patient access to AIT will be drastically 

reduced, if not eliminated, because allergists will no longer be able to prepare AIT vials for their patients 

in their offices. Moving allergen extract preparation to large compounding laboratories or pharmacies is 

not a viable alternative due to safety considerations. Patients experiencing allergic reactions to their 

immunotherapy injections require the allergist to change the content or dilution of the vials before they 

can receive the next injection. Failure to do so could result in a life-threatening systemic allergic reaction. 

These adjustments need to be done while the patient is in the office if the patient's treatment schedule 

is to continue without significant interruption or delay. Compounding pharmacies, located off-site from 

the allergist's office, would not be able to make these adjustments in a timely fashion. 

Again, anaphylaxis is the major risk in an AIT treatment. This risk is carefully managed under current 

requirements by having the extract mixed onsite by physicians and staff with a personal knowledge and 

experience with each and every patient. Outsourcing extract preparation removes this important 

safeguard and severely limits a physician's ability to respond to any adverse allergic reactions to AIT or 

other considerations impacting treatment. The proposed revisions would require patients to start new 

extract vials every month, most likely changing source material in the extract, and thus significantly 

increasing risk for adverse and potentially fatal allergic reactions. These changes therefore decrease the 

safety and increase the risk to the patient, forcing physicians and patients to decide if the newly increased 

risk is actually worthwhile, all based on a hypothetical but undocumented risk of infection. 

Conclusion 

To date, neither the FDA nor the USP has provided any scientific data, case reports or anecdotal evidence 

that AIT compounding, following current USP guidelines and in accordance with section 503A of the FD&C 

Act, has resulted in an infection. 

Members of Congress have previously weighed-in on this issue, urging the Secretary of the Department 

of Health and Human Services {HHS) to carefully weigh proposed regulations and the impact that they 

https://www.fda.gov/Drugs/GuidanceComplianceRegulatorylnformation/PharmacyCompounding/ucm592795.htm 

4 
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have on patient care. The FDA has recognized the important and vital role of allergen immunotherapy in 

managing patients with allergic diseases. In addition, proposed changes in USP <797> decrease the safety 

of allergen immunotherapy and increase documented risk of anaphylactic reactions, in an effort to 

prevent what is no more than a hypothetical risk. Proposed changes are overreaching, not based on any 

data suggesting a risk of infectious complication from allergen extract compounding, and ignore the 

scientific data that supports the safety of allergen extract compounding. Failure to keep the current USP 

<797> guidelines for allergen extract compounding will significantly increase the risk/benefit ratio of AIT 

and needlessly place patients in danger of medical complications and potential death. 

We urge Members of this Subcommittee and the Congress to actively oversee FDA's efforts to revise its 

compounding guidance documents. Forthcoming revisions should recognize that AIT compounding is a 

safe and unique compounding procedure that can continue following current <797> guidelines. 

Thank you again for taking into consideration our written comments. I encourage you to contact Sheila 

Heitzig, JD, MNM, CAE, AAAAI Director of Practice and Policy, at (414) 272-6071 or sheitzig@aaaai.org. 

Jim Sublett, MD, ACAAI Executive Director of Advocacy and Governmental Affairs, at 

jsublett@familyallergy.com, or Jami Lucas, AAOA Executive Director and CEO, at lucas@aaoaf.org if you 

have any questions. The American Academy of Allergy, Asthma, & Immunology, the American College of 

Allergy, Asthma and Immunology, and the American Academy of Otolaryngic Allergy look forward to 

working with the Subcommittee to address issues of importance to our patients and ways in which we 

can promote public health. 

5 
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GREG WALDEN, OREGON 

CHAIRMAN 

ONE HUNDRED FIFTEENTH CONGRESS 

FRANK PALLONE, JR., NEW JERSEY 

RANKING MEMBER 

C!Congrc!)!) of tbc ltnitcb ~tate!) 

~ouge of ll\epregentatitJeg 

COMMITIEE ON ENERGY AND COMMERCE 

2125 RAYBURN HousE OFFICE BuiLDING 

WASHINGTON, DC 20515-Q115 

The Honorable Scott Gottlieb 

Commissioner 

U.S. Food and Drug Administration 

10903 New Hampshire Avenue 

Silver Spring, MD 20993 

Dear Dr. Gottlieb: 

Majority (202)225-2927 

Minority 1202)225--3641 

February 16, 2018 

Thank you for appearing before the Subcommittee on Health on January 30, 2018, to testifY at the 

hearing entitled "Examining Implementation of the Compounding Quality Act." 

Pursuant to the Rules of the Committee on Energy and Commerce, the hearing record remains 

open for ten business days to permit Members to submit additional questions for the record, which are 

attached. To facilitate the printing of the hearing record, please respond to these questions with a 

transmittal letter by the close of business on March 3, 2018. Your responses should be mailed to Zack 

Dareshori, Legislative Clerk, Committee on Energy and Commerce, 2125 Rayburn House Office 

Building, Washington, DC 20515 and e-mailed in Word format to z.ack.dareshori@mail.house.gov. 

Thank you again for your time and effort preparing and delivering testimony before the 

Subcommittee. 

cc: The Honorable Gene Green, Ranking Member, Subcommittee on Health 

Attachment 
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Attachment- Additional Questions for the Record 

The Honorable John Shimkus 

IV compounding automation has potential for improving safety, consistency, and compliance 

with best practices in many types of compounding pharmacies and settings. Although the FDA 

has embraced safety through automation in other contexts, the FDA has been silent on the issue 

of automation in compounding pharmacies and on how it will regulate, inspect, and audit 

compounding pharmacies that adopt IV compounding automation. Given the potential of 

technology to better address safety concerns and potentially drive down healthcare costs, as it 

does it other healthcare applications, what policy or regulatory considerations might facilitate 

adoption or further exploration of automated compounding technology? 

The Honorable Morgan H. Griffith 

1. Regarding essential copies, are you requiring physicians to document clinical need on 

every prescription, is this right? 

a. How does this requirement work with state laws that govern what constitutes a 

valid prescription? 

2. At the hearing you stated that redefining the practice of pharmacy is not the best way to 

address office-use compounding. Can you please elaborate on what you meant by 

redefining the practice of pharmacy? 

3. With the flu epidemic hitting the country particularly hard, I've heard reports that 

pharmacists are experiencing shortages of generic Tamiflu suspension. I've been told 

Medicaid only reimburses for the generic, which means pharmacists are faced with the 

choice of either giving their patients the brand medication at a loss to their business or 

compounding the generic formula. However, when pharmacists recently contacted FDA 

to ask if they would be in compliance should they choose to compound the generic they 

were told past guidance allowing for this was no longer current. I'm sure you can 

appreciate the urgency in getting an answer to this question and how confusing this can 

be to pharmacies especially in light of your agency's recently released "essential copies" 

guidance. Do you have an update for us today as to whether or not pharmacists can 

compound Tamiflu suspension? 

4. Given the financial investment required for small town, lower volume 503A 

compounding pharmacies to become 503B outsourcing facilities, what steps is the agency 

taking to ensure that the prescription requirement won't be harmful to patients in rural 

communities needing immediate treatment with a compounded drug? 
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5. The agency put out its final guidance on repackaged biologics recently, which outlines 

additional testing required to extend the beyond-use date for drugs such as bevacizumab 

(Avastin). Have you worked with the outsourcing facilities directly to make sure they are 

able to meet these testing requirements to establish longer beyond-use dates? 

6. The physician community and other stakeholder groups have expressed a desire for more 

direct discussion with the agency about implementation efforts and their concerns. Do 

you believe a greater emphasis on stakeholder input could be beneficial as 

implementation moves forward? What additional steps will the agency consider taking to 

better engage with the physician community and other stakeholders about compounding 

issues? 

7. The FDA's 2018 Compounding Policy Priorities plan mentions "circumstances under 

which we believe drugs are being mixed and applied in a manner that creates negligible 

patient risk, and therefore wouldn't be subject to the same compliance policy." 

Physicians, like dermatologists, must perform simple and low-risk dilutions and mixing 

of manufactured drugs in the clinical setting, such as buffered lidocaine and reconstituted 

botulinum toxin, which falls under the FDA's broad definition of"compounding." 

a. Can you share any details about insanitary conditions equipment that the FDA is 

considering that will affect the physician community, specifically equipment or 

process requirements? 

8. By statute, compounding from bulk ingredients at a 503B outsourcing facility is limited 

to a positive list developed by FDA. To date, this positive list has not been developed 

and the agency is using enforcement discretion to allow compounding from many bulk 

ingredients. The assumption is that FDA will eventually develop a positive list as 

mandated by the statute that it will enforce. If a compounding pharmacy does not have 

an assurance that the bulk ingredients it uses to compound will be on this eventual 

positive list, why would they invest the necessary capital and risk their business to 

convert to a 503B outsourcing facility when so much uncertainty exists? 

9. FDA has indicated it will withdraw its draft MOU and issue a new one that will not have 

a hard cap on interstate distribution. The agency, however, is also insisting that it will 

include patient specific dispensing in the definition of distribution despite statutory 

language and precedent that does not support this definition. Regardless of how flexible 

FDA is with its proposed cap on interstate distribution, isn't it correct that if a state 

refuses to sign an MOU the default be a 5 percent limit on out-of-state distribution? And 

as long as FDA insists on defining distribution as including patient specific dispensing, 

won't patient access to medications from the pharmacy of their choice be disrupted if 

some states refuse to sign the MOU? 

10. Please describe the process by which the FDA's Pharmacy Compounding Advisory 

Committee will consider substances nominated for the Difficult to Compound List. Will 
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every nominated substance be considered? What is the timeframe for doing so? Will 

FDA continue to provide approximately three weeks notice to private sector participants 

ahead of the PCAC meetings, or will additional time be provided so that they can more 

thoroughly prepare their presentations to the Committee? 

II. Many of the policies surrounding the DQSA have been developed by the FDA under 

Guidance for Industry (GFI) documents rather than through the rulemaking process. It 

would seem that these policies affecting patient safety and access to critical medications 

warrant the stakeholder input, legal status and judicial review afforded to rules rather than 

GFis which are not legally binding and merely represent the "current thinking of the 

FDA" on a given policy matter. Why has FDA has chosen this path for these important 

policies? 

a. Do you believe some of these policies would be more appropriately developed 

under the rulemaking process? 

12. On Thursday, January 25th, the Associate Attorney General issued a memorandum that 

prohibits the Department of Justice from using civil enforcement authority to "convert 

agency guidance documents into binding rules." I am under the belief that you are 

required to follow this directive from the Department of Justice. Can you provide me 

with court opinions, rulings, and/or memorandums which indicate that you are not? 

13. Most pharmacies don't compound sterile medications- only about 15% of pharmacies 

do. The statute states that you must compound sterile medications to be a 503B. The vast 

majority of pharmacies will therefore never register as a 503B with FDA. How will the 

new proposal referenced in your 2018 Compounding Priorities Plan improve access to 

nonsterile office use medications? 

14. I appreciate recent explanations provided by FDA for their thought process on dietary 

supplement monographs for 503A pharmacies. Section 503A of the FDCA does not 

distinguish between groups ofUSP and NF monographs, but FDA policy has sought to 

restrict access to those monographs that reside in the Dietary Supplement section of 

USP. Does the FDA intend to change this guidance and if not, how does the guidance 

comply with the plain language of the statute? 

15. FDA's current interpretation that a monograph is limited to drug monographs, and not 

dietary supplement monographs is concerning for many reasons. The statute does not 

distinguish between groups ofUSP and NF monographs. The effect of the policy is that 

FDA is requiring patients to purchase and take the supplement separately, rather than 

trust the medical judgement of the doctor and pharmacist as to dosage, interactions and 

other factors? Does this not have the effect of having the FDA insertig itself into the 

doctor- patient relationship? 

16. The Pharmacy Compounding Advisory Committee is appointed by the FDA and 

considers substances that have been nominated for inclusion on the positive and negative 
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lists of bulk ingredients used in human compounding. Can you comment on why, to date, 

there has not been a voting member of the PCAC that is a compounding pharmacist with 

contemporary human compounding experience? Will you work to see that the FDA 

appoints a compounding pharmacist with human compounding experience to the 

PCAC? 

17. FDA informs consumers about their inspections of all compounding pharmacies by 

posting Form 483 inspection findings and any subsequent warning letters on the agency 

website. Is this the same level of transparency in place for manufacturing facilities? If 

not, will FDA commit to equal transparency for all inspections? 

18. Automation technology has recently entered the compounding space. Given the potential 

of technology to better address safety concerns and potentially drive down health care 

costs, is FDA considering implementing regulations that facilitate the adoption of this 

automated technology? Does FDA have the authority to do so or would they need 

additional authority from Congress? 

19. What data do you have that, four years after DQSA was enacted, patients who receive 

compounded medications are safer than before? Do you believe innovation, particularly 

automation, in the way medications are compounded would help reduce human errors 

that can lead to contaminated drug products? 

20. FDA Final Guidance on Mixing, Diluting and Repackaging of Biologics issued last 

month allows for preparation of allergen extracts that meet criteria for "prescription sets" 

including that they are prepared in accordance with USP standards. Yet pending FDA 

draft guidance on insanitary conditions would impose additional standards for allergen 

extracts that go far beyond what is required by USP. This seems inconsistent. Will FDA's 

Insanitary Conditions final guidance acknowledge the unique nature of allergen extract 

preparation for prescription sets consistent with its Final Guidance on Biologics? 

21. Dr. Gottlieb, we appreciate your leadership and the previous leadership to establish the 

FDA's Office of Laboratory Science and Safety to serve as the single point of 

accountability for all laboratory science, and safety functions across the FDA. However, 

this office still lacks direct funding and permanent staffing. The External Laboratory 

Safety Working group recommended that this office should be directly funded to carry 

out its critical mission, and the CDC has followed this recommendation. There is really a 

need for oversight of all lab science research activities at FDA. In the area of drug 

compounding, FDA labs conduct microbiology testing in compounded drugs to detect 

bacterial and fungal contamination. In addition, you announced last Friday that the FDA 

closed a nicotine addiction study at an FDA lab after the death of four squirrel monkeys. 

When will the FDA Office of Laboratory Science and Safety be funded independently 

and staffed appropriately to provide critical oversight of the FDA laboratories? 

22. How can we help you to ensure that this office is appropriately resourced and staffed in a 

timely manner to carry out its critical work? 
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23. It is my understanding that mixing and compounding are distinct acts. According to the 

ACAAI, when an allergist prepares an allergen extract, they mix several commercially 

manufactured, FDA approved antigens in a sterile vial using sterile syringes, following 

FDA standards specific to the mixing of allergen extracts. These patient-specific vials are 

then labeled and stored in refrigerated conditions. This produces a combination of 

different- naturally occurring- pollens or allergens into a single mixture. Compounding 

is functionally different in that it involves the combining of different drugs into a single 

new drug for an individual patient or into large lots for many patients. Unlike the mixing 

of naturally occurring allergens, when you combine different drugs, a biochemical effect 

often occurs that can bind these drugs together into a new, compounded drug. 

Based on these distinctions, I believe the preparation of allergenic extracts, which are 

biologics, constitutes mixing and not compounding, as defined by the FDA. Can the 

FDA confirm that preparation of allergen extracts is not compounding but rather mixing? 

The Honorable Gus M. Bilirakis 

I. DQSA was allows for compounded drugs from bulk drug substances when FDAapproved drugs are not commercially available or FDA has determined there is a clinical 

need for the substance. What precautions is the agency taking to ensure there is a 

legitimate clinical need for the bulk drug substances currently being used by 

compounders, and how is FDA enforcing this important provision ofDQSA in the 

marketplace? 

2. As I recall, Outsourcing Facilities can bulk compound drugs that are on an FDA list of 

approved bulk drugs, or are on a list of drugs that are in shortage, or have been 

discontinued commercially. How often or rapidly, does FDA plan to update this list so 

that patients never have an access problem obtaining medication they need? 

3. Has FDA thought about ensuring a competitive marketplace in the outsourcing facility 

market? What happens if only one Outsourcing Facility is bulk compounding a specific 

medication? Could we have a situation like we have in the pharmaceutical market when 

there is no generic or a sole-source generic, and this leads to pricing spikes due to a lack 

of competition? 

The Honorable Richard Hudson 

I. As you know, for a drug to be lawfully compounded under Section 503B of the DQSA, 

the drug must not be "essentially a copy of one or more approved drugs," which means 

that the drug may not be identical or nearly identical to a drug that has been approved by 

FDA. Congress never intended for minor modifications of an approved drug-such as to 

a drug's dosage strength or inactive ingredients--to allow for the compounding of that 

drug. Instead, Congress intended to protect the public health, and to preserve the 

integrity of the FDA approval process, by permitting the compounding of a drug only in 
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connection with a particular patient medical need that cannot be met by an FDAapproved drug. Can you confirm that FDA agrees with this interpretation of the 

"essentially a copy" provision of the DQSA and that this interpretation is consistent with 

the Agency's thinking laid out in its January 2018 503B guidance? 

2. Likewise, under Section 503B, there must be either a drug shortage or a demonstrated 

"clinical need" for compounding with bulk substances. A showing of"clinical need" 

requires a legitimate patient need that could not otherwise be met by compounding with 

the FDA-approved drug. The simple "convenience" of compounded product, such as a 

"pre-diluted" and packaged version of an approved drug, does not satisfy this 

requirement. Can you confirm that the Agency agrees with this interpretation of "clinical 

need," and confirm that this interpretation will be reflected in the Agency's forthcoming 

guidance in March 2018? 

3. During the hearing, you said that, in its forthcoming March 2018 guidance, the Agency 

will reiterate that the DQSA does not permit the bulk compounding of drug substances 

when FDA-approved drugs can be used. You provided the example that when a 

compounder is diluting or otherwise changing the concentration of an FDA-approved 

drug, they have to begin with the approved drug and could not compound from bulk 

substances. Can you confirm that the Agency's forthcoming March 2018 guidance will 

explicitly address this statutory requirement and example? Additionally, can you provide 

insight into how FDA will proactively apply its risk-based enforcement approach against 

compounders who violate this requirement? 

The Honorable Earl L. "Buddy" Carter 

1. Regarding essential copies, are you requiring physicians to document clinical need on 

every prescription? 

2. How does this requirement work with state laws that govern what constitutes a valid 

prescription? 

3. At the hearing you stated that redefining the practice of pharmacy is not the best way to 

address office-use compounding. Can you please elaborate on what you meant by 

redefining the practice of pharmacy? 

4. Most compounding pharmacies compound only non-sterile medications, and perhaps as 

high as 80 to 90 percent of these pharmacies do not engage in sterile compounding. FDA 

has consistently presented the 503B option as the easy way to address both the office use 

issue and limitations that would be imposed by an MOU that includes dispensing in the 

definition of distribution. Doesn't this argument fail since the vast majority of 

compounding pharmacies simply would not be eligible to convert to a 503B outsourcing 

facility since they do not engage in sterile compounding? 
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5. By statute, compounding from bulk ingredients at a 503B outsourcing facility is limited 

to a positive list developed by FDA. To date, this positive list has not been developed 

and the agency is using enforcement discretion to allow compounding from many bulk 

ingredients. The assumption is that FDA will eventually develop a positive list as 

mandated by the statute that it will enforce. If a compounding pharmacy does not have 

an assurance that the bulk ingredients it uses to compound will be on this eventual 

positive list, why would they invest the necessary capital and risk their business to 

convert to a 503B outsourcing facility when so much uncertainty exists. 

6. FDA has indicated it will withdraw its draft MOU and issue a new one that will not have 

a hard cap on interstate distribution. The agency, however, is also insisting that it will 

include patient specific dispensing in the definition of distribution despite statutory 

language and precedent that does not support this definition. Regardless of how flexible 

FDA is with its proposed cap on interstate distribution, isn't it correct that if a state 

refuses to sign an MOU the default be a 5 percent limit on out-of-state distribution? And 

as long as FDA insists on defining distribution as including patient specific dispensing, 

won't patient access to medications from the pharmacy of their choice be disrupted if 

some states refuse to sign the MOU? 

7. The two members of the Pharmacy Compounding Advisory Committee (PCAC) who 

represent compounding pharmacy and the pharmaceutical industry cannot vote, 

apparently because of potential conflict of interest issues. Yet, at least one voting 

member of the committee is from an organization that co signs letters and actively lobbies 

with pharmaceutical interests that could potentially benefit financial from the 

recommendations ofPCAC. Can you tell the committee what the conflict of interest 

rules are that govern voting status of PCAC members, and whether direct advocacy with 

drug companies that have a direct financial interest in PCAC decisions is a conflict of 

interest? 

8. Please describe the process by which the FDA's Pharmacy Compounding Advisory 

Committee will consider substances nominated for the Difficult to Compound List. Will 

every nominated substance be considered? What is the timeframe for doing so? Will 

FDA continue to provide approximately three weeks notice to private sector participants 

ahead of the PCAC meetings, or will additional time be provided so that they can more 

thoroughly prepare their presentations to the Committee? 

9. Many of the policies surrounding the DQSA have been developed by the FDA under 

Guidance for Industry (GFI) documents rather than through the rulemaking process. It 

would seem that these policies affecting patient safety and access to critical medications 

warrant the stakeholder input, legal status and judicial review afforded to rules rather than 

GFis which are not legally binding and merely represent the "current thinking of the 

FDA" on a given policy matter. 
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Page 8 

10. Can you tell us why FDA has chosen this path for these important policies and whether 

you believe some of them would be more appropriately developed under the rulemaking 

process? 

11. On Thursday, January 25th, the Associate Attorney General issued a memorandum that 

prohibits the Department of Justice from using civil enforcement authority to "convert 

agency guidance documents into binding rules." You are required to follow this directive 

from the Department of Justice, correct? 

12. To my knowledge, FDA has not recently contacted compounding pharmacy stakeholder 

groups, specifically the stakeholders who have been most active in the PCAC process to 

discuss the Agency's new ideas on incentivizing "a larger swath of pharmacies" to 

register as 503B outsourcing facilities, or recently issued final Guidance documents. Dr. 

Gottlieb, will you commit to meeting with stakeholders to discuss these important issues? 

13. Most pharmacies don't compound sterile medications- only about 15% of pharmacies 

do. The statute states that you must compound sterile medications to be a 503B. The vast 

majority of pharmacies will therefore never register as a 503B with FDA. How will the 

new proposal referenced in your 2018 Compounding Priorities Plan improve access to 

nonsterile office use medications? 

14. Many provider groups are expressing patient need for access to office-use medications 

from 503A pharmacies. 503Bs cannot provide immediate access to medications and/or 

will not provide the limited quantities needed by some prescribers. Congress has 

provided clarification for FDA through multiple sets of appropriations report language 

and other written communications. Why does FDA continue to put up roadblocks to 

prescribers obtaining the medications they need from 503A pharmacies to treat patients in 

their office, while at the same time maintaining a limited exemption for hospitals? When 

does FDA intend to make a change in policy allowing needed office use medications to 

come from 503A pharmacies consistent with the intent of the law? 

15. I appreciate recent explanations provided by FDA for their thought process on dietary 

supplement monographs for 503A pharmacies. Section 503A ofthe FDCA does not 

distinguish between groups ofUSP and NF monographs, but FDA policy has sought to 

restrict access to those monographs that reside in the Dietary Supplement section of 

USP. When will FDA correct this guidance to comply with the plain language of the 

statute? 

16. FDA's current interpretation that a monograph is limited to drug monographs, and not 

dietary supplement monographs is concerning for many reasons. The statute does not 

distinguish between groups ofUSP and NF monographs. The effect of the policy is that 

FDA is requiring patients to purchase and take the supplement separately, rather than 

trust the medical judgement of the doctor and pharmacist as to dosage, interactions and 

other factors? Isn't this FDA inserting itself into the doctor- patient relationship? 
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17. There has been an organized process in terms of how FDA would proceed related to 

compounding from bulk substances, and no similar framework has been put forward by 

the agency related to the difficult to compound list. This lack of direction has caused 

uncertainty and confusion in the profession, and for those who depend on compounded 

medications to live healthier, better lives. Does FDA intend to lay out a similar 

framework for the difficult to compound list, and if so, when will additional information 

be available from the agency? 

18. The Pharmacy Compounding Advisory Committee is appointed by the FDA and 

considers substances th.at have been nominated for inclusion on the positive and negative 

lists of bulk ingredients used in human compounding. Can you comment on why, to date, 

there has not been a voting member of the PCAC that is a compounding pharmacist with 

contemporary human compounding experience? To provide a more informed 

perspective for FDA and the PCAC, can you commit that the FDA will appoint a 

compounding pharmacist with human compounding experience to the PCAC? 

19. FDA informs consumers about their inspections of all compounding pharmacies by 

posting Form 483 inspection findings and any subsequent warning letters on the agency 

website. Is this level of transparency in place for manufacturing facilities? Specifically, 

does FDA post each and every Form 483 and warning letter for manufacturers of 

commercially available drug products? Will FDA commit to equal transparency for all 

inspections? 

The Honorable Frank Pallone, Jr. 

Memorandum of Understanding 

At the hearing we discussed further FDA's draft Memorandum ofUnderstanding and the 

agency's recently announced plans to revise this MOU. One of the announced changes would be 

the elimination of the 30 percent threshold and instead implementing certain requirements that 

would be triggered at a 50 percent threshold. When asked about this, you noted that "There are 

going to be other tests that we apply to make assessments about what the appropriate scheme is 

for a particular facility." 

I. Will you elaborate further on what other tests or assessments, in addition to volume, that 

FDA will be applying towards oversight of compounded drug products across state lines? 

2. The draft MOU released in February 2015 would require that states that entered into the 

MOU to investigate complaints related to the compounded drug products compounded in 

the state and then distributed outside of the state, including complaints about adverse 

events. States would also be required to take action to determine the root cause of the 

problem, to notify FDA within 72 hours of complaints, and to maintain records related to 

complaints and investigations. It appears under the revisions to the MOU that have been 

announced, that exceeding the proposed 50 percent threshold would only trigger certain 
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reporting requirements for the state instead of a hard limit for state action. Under the 

proposed revised MOU, how do you intend to protect against the kind of race to the 

bottom in state regulatory oversight that helped lead to the NECC tragedy? 

Economic Analysis 

3. At the hearing you noted that FDA has undertaken an economic analysis regarding the 

costs for different entities to comply with current good manufacturing practices (cGMPs) 

for compounded drugs. You noted that you thought it is "still a little bit too expensive to 

see some of the smaii503A pharmacies" opting into compliance with cGMPs as 

outsourcing facilities are required to do. Will you please provide FDA's economic 

analysis regarding compliance with these requirements for the record? 

Resources 

At the hearing that implementation activities ofthe Compounding Quality Act, such as 

inspections and examining potency issues, are dependent on what additional resources the 

agency can put towards it, and unlike other product areas that rely on user fees, the compounding 

program operates by "begging, borrowing, and stealing from other aspects of the agency, other 

parts ofthe agency." 

4. What resources have been dedicated to implementation of the Compounding Quality Act 

since enactment? 

5. What resources will be available under the President's proposed budget for fiscal year 

2019 for implementing of the Compounding Quality Act, and in particular for additional 

inspections of compounding pharmacies and outsourcing facilities? 

Access to Office Use Stock 

One area of continued concern for many stakeholders is access to office use stock. FDA has 

generally taken the position that 503A pharmacies may not compound for office-use, and that 

this role is better is better filled by outsourcing facilities under 503B as they are subject to 

increased oversight and quality standards that may help to reduce the risk of quality problems 

such as contamination. Health care providers in particular have raised issue with this perspective 

as they are concerned that this prohibition on office stock may impact their ability to prepare and 

administer low-risk compound products in office, or to prepare compounded products in the case 

of an emergency such as a severe infection. 

6. My understanding is that Section 503A of the Federal Food, Drug, and Cosmetic Act 

does allow for compounding in anticipation of a prescription in limited quantities if 

certain conditions are met. When is anticipatory compounding permitted under 503A? 

One of the common complaints we have heard from 503A pharmacies is that registered 503B 

outsourcing facilities are unable to meet the needs of physicians and patients, and further it is 

difficult to identifY outsourcing facilities that can meet their needs. On the second panel we heard 
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from Dr. Brad, chair of the American Academy of Dermatology Association, that "FDA's 

website lists only the facilities that are registered, but with no contact information no real-time 

product availability information, and no price list." He argues this results in physicians 

undertaking a scavenger hunt to identify 503B outsourcing facilities that can fit their needs. 

7. What assistance has FDA provided to help 503A pharmacies access office use stock of 

necessary products? Further, what are your thoughts on requiring FDA to maintain 

additional information on 503B outsourcing facilities, such as contact information, 

product availability, and price lists? 

8. One of the requirements of outsourcing facilities under section 503B is the submission of 

product lists to the FDA semiannually. FDA has noted that not all outsourcing facilities 

have been complying with this requirement, resulting in the posting of incomplete 

product lists. What steps, if any, is FDA taking to ensure compliance with this 

requirement? 

Inspections 

9. FDA's inspection authority is a critical tool to ensuring that pharmacies are compounding 

in accordance with the law, and to continue to be afforded the exemptions provided under 

the law. Since enactment of the Drug Quality and Security Act, FDA has conducted 

nearly 500 inspections, issued more than 180 warning letters identifying significant 

violations at compounding pharmacies, issued more than 70 letters referring inspectional 

findings to state regulatory bodies, and overseen more than 150 recalls of compounded 

drug products. 

10. There has been much debate over whether or not FDA is the appropriate entity to be 

inspecting compounding pharmacies. Will you clarify for the Committee where FDA 

derives its authority to inspect compounding pharmacies? 

11. Some stakeholders have argued that inspections of compounding pharmacies should be to 

USP standards or other pharmacy inspection standards adopted by the states rather than 

to good manufacturing practices. Will you explain why a compounding pharmacy may be 

inspected to cGMPs rather than USP standards? 

12. Further, will you also discuss what outreach and education efforts FDA has undertaken to 

ensure that 503A compounding pharmacies understand the inspection process? 
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Patient Access 

Critics ofDQSA have argued that FDA's definition of compounding- the combining, mixing, or 

altering ingredients of a drug to make a medication tailored to the needs of an individual patient 

-is overly broad and has resulted in patient access issues to low-risk compounded drug products. 

For example, we heard from one of the witnesses on the second panel how some simple in-office 

preparations are now considered "compounding as opposed to mixing" when the medication is 

not prepared pursuant to the manufacturer's labeling subjecting them to the guidelines outlined 

in FDA's guidance on insanitary conditions. 

13. Can you respond to this concern? What would be the potential risk of not requiring health 

care providers to meet the same standards as compounding facilities? 

Patient Safety 

While passage of the Compounding Quality Act was a strong step forward to addressing the 

safety issues associated with NECC and other largely unregulated compounding pharmacies that 

were compounding in bulk, safety issues associated with compounding pharmacies still persist. 

FDA has received adverse event reports of patient harm including contamination in drugs that 

need to be sterile because they are entering the bloodstream, the eye, or the spine. There have 

also been reports of drug products that are superpotent, for instance in the example in 2016 of 

three infants received a compounded morphine sulfate preparation at a strength that was greater 

than 20 times than that indicated on the label. One infant had to be taken by helicopter to a 

nearby children's hospital. 

14. It seems that there is an incomplete picture of the whole problem- there are likely more 

events or deaths than we know of, attributable to compounded drugs given that the vast 

majority of 503A pharmacies do not report on adverse events. How does the FDA plan to 

work with states, which also have a large regulatory role, to increase reporting and reduce 

safety events that harm patients from these pharmacies? 

The Honorable Anna G. Eshoo 

1. Is FDA considering policies or regulations that facilitate the adoption of automation 

technology in the compounding space? 

2. If yes, what is the timeline for this guidance or regulation? 
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GREG WALDEN, OREGON 

CHAIRMAN 

ONE HUNDRED FIFTEENTH CONGRESS 

FRANK PALLONE, JR., NEW JERSEY 

RANKING MEMBER 

QI:ongte55 of tbe Wniteb ~tate5 

J!)ouse of ~epresentatibes 

COMMITIEE ON ENERGY AND COMMERCE 

2125 RAYBURN HousE OFAcE BuiLDING 

WASHINGTON, DC 20515-6115 

Dr. George Williams 

Chair of the Board of Directors 

American Academy of Ophthalmology 

20 F Street, N.W.; Suite 400 

Washington, DC 20001 

Dear Dr. Williams: 

Majority (202)225-2927 

Minority (202) 225-3641 

February 16, 2018 

Thank you for appearing before the Subcommittee on Health on January 30, 2018, to testify at the 

hearing entitled "Examining Implementation of the Compounding Quality Act." 

Pursuant to the Rules of the Committee on Energy and Commerce, the hearing record remains 

open for ten business days to permit Members to submit additional questions for the record, which are 

attached. The format of your responses to these questions should be as follows: (I) the name of the 

Member whose question you are addressing, (2) the complete text of the question you are addressing in 

bold, and (3) your answer to that question in plain text. 

To facilitate the printing of the hearing record, please respond to these questions with a 

transmittal letter by the close of business on March 3, 2018. Your responses should be mailed to Zack 

Dareshori, Legislative Clerk, Committee on Energy and Commerce, 2125 Rayburn House Office 

Building, Washington, DC 20515 and e-mailed in Word format to zack.dareshori@mail.house.gov. 

Thank you again for your time and effort preparing and delivering testimony before the 

Subcommittee. 

cc: The Honorable Gene Green, Ranking Member, Subcommittee on Health 

Attachment 
250 


29991.179

Answer to questions from Representative Eshoo. 

1. To my knowledge, there is no formal, enforceable requirement by the FDA to 

disclose to patients that a compounded product is being used. The American 

Academy of Ophthalmology (AAO) recommends that ophthalmologists 

inform their patients about the risks, benefits and alternatives of all available 

treatment options and discuss the implications of compounded products. 

2. As noted above, the AAO recommends that patients be informed of the risks 

of all treatments including compounded drugs 

3. In my personal practice, I follow the above recommendations to fully inform 

patients about the risks, benefits and alternatives to treatment with 

compounded drugs. This process involves both verbal and written 

disclosure using an informed consent following the recommendations of the 

Ophthalmic Mutual Insurance Company. I have attached these 

recommendations. 

See OMlC attachment 
251 


29991.180

OMIC '"!''H~":~'"( ~~b~~~ fiCJIR;;J~[! iilM~""~ 

--==---=------=~...=--- ~ --------~~ ~- ~~---=-=--===--~-=---===-=--==-----

lntravitreal Anti-VEGF Treatment for Adults Patients: 

Risk Management Recommendations 

OMIC is grateful to the ophthalmologists on our Board for their expertise. This specific 

document reflects the input of the following Board and staff members: Anne M. Menke, 

RN, PhD; George Williams, MD, Trexler M. Topping, MD; Pauline Merrill, MD, Denise 

Chamblee, MD, Paul Weber, JD, Hans Bruhn, MHS, and Michelle Pineda, MBA. 

Vascular endothelial growth factor, or VEGF, is a protein that stimulates the growth of 

new blood vessels. Ophthalmologists administer intravitreal anti-VEFG agents for a 

variety of indications. Sometimes the indication has been approved by the Food and 

Drug Administration (FDA), other times it is off-label, or the medication itself may never 

have been approved for any eye indication. This risk management document presents 

suggestions to increase patient safety and decrease the likelihood of lawsuits related to 

these drugs. It also provides information about our revised sample consent documents 

for anti-VEGF agents. 

A. Approved indications for anti-VEGF drugs 

The Food and Drug Administration (FDA) has approved a few drugs for the treatment of 

ophthalmic VEGF-mediated diseases. For ease of reading, the first reference to a drug 

will give its trade and generic name; thereafter, only the trade name will be given. Three 

other drugs that are not anti-VEGF agents are approved for some of the same 

indications. 
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• Age-related macular degeneration (AMD): 

o Macugen TM (pegaptanib), LucentisTM (ranibizumab), and Eylea TM (aflibercept) 

are all anti-VEGF agents approved to treat AMD. VisudyneTM (verteporfin) is 

also approved to treat AMD. 

• Diabetic macular edema (DME): 

o Lucentis and Eylea are approved to treat DME. OzurdexTM (dexamethasone) 

and lluvien® (fluocinolone acetonide) are also approved to treat DME. 

• Diabetic retinopathy (DR): 

o Lucentis and Eylea are approved to treat DR in patients with diabetic macular 

edema. 

• Retinal vein occlusion (RVO): 

o Lucentis and Eylea are approved to treat macular edema following retinal vein 

occlusion (RVO); Ozurdex is also approved for this. 

Explaining to patients how these drugs work 

The indications on the labels for these drugs state the conditions they are designed to 

treat. We have learned from field testing our revised forms that patients may have a 

difficult time understanding the names of these diseases, or get confused about which 

one they have. To make our consent forms easier to understand, we incorporated "plain 

language" principles. The goal is simple, short explanations. Here is how we describe 

the indications in our new sample forms: 

• Eye surgeons treat some types of eye problems with a medication called [name 

of drug]. [Name of drug] can help prevent vision loss due to 2 types of eye 

problems: 

1) the growth of harmful blood vessels in your eyes 

2) swelling in the back of the eye (macular edema). 

OMIC-insured ophthalmologists are not required to use our consent forms, and are 

encouraged to adapt them as needed. Sample forms can be found at 

www.omic.com/avastin/, www.omic.com/lucentis/, and www.omic.com/eylea/. 

B. Off-label use of drugs 

Off-label use of an approved medication is a common and legal part of the practice of 

medicine. OMIC believes that the treating ophthalmologist is in the best position to 

determine what a particular patient needs, and leaves this decision up to the physician's 

judgment. 

• Ophthalmologists use the FDA-approved medications just discussed to treat other 

eye conditions. All such use is off-label. 

• Eye surgeons use Avastin TM (bevacizumab), which has not been approved for 

intravitreal use or for eye conditions. All ophthalmic use of Avastin is off-label. 

• Use of any anti-VEGF drug in the pediatric population is off-label. 

OMIC recommends that you obtain consent for off-label use of anti-VEGF drugs. The 

OMIC website has sample consent forms for these medications, as well as risk 

management recommendations and a sample consent form for the use of anti-VEGF 

drugs to treat ROP. The Avastin consent form already addresses this off-label use. Here 

is sample language that can be added if Lucentis or Eylea are used off-label: 

2 
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• The Food and Drug Administration (FDA) approved [name of drug] for treating some 

eye diseases. These diseases may cause the growth of harmful blood vessels in 

your eye and swelling (macular edema). Eye surgeons also use [name of drug] to 

treat other diseases that cause similar problems. This is called off-label use. 

C. Preparation of Avastin 

The medication comes in preservative-free vials intended for intravenous use at a much 

higher concentration on a single cancer patient. Avastin needs to be repackaged for 

intravitreal use. This repackaging must be done in compliance with the Drug Quality and 

Security Act (DQSA), which was passed on November 27, 2013. Under this law, 

repackaging must be done either by a compounding pharmacy or a federally-registered 

outsourcing facility. 

Compounding pharmacies (CFs) operate under Section 503A of the law and are 

governed by their state board of pharmacy. They must be in compliance with USP 

(United States Pharmacopeia) Chapter 797, which regulates the compounding, 

transportation, and storage of compounded sterile products (CSP). CFs require a 

patient-specific prescription. 

Section 503B of the DQSA created outsourcing facilities (OFs), which must register with 

the FDA, which governs them. OFs must comply with current good manufacturing 

practices as well as USP 797. OFs do not require a patient-specific prescription, so 

ophthalmologists may order in bulk from them. 

"Credential" the compounding pharmacy or outsourcing facility: 

• Ask the compounding pharmacy for: 

o Evidence of licensure in the state in which it is dispensing 

o Assurance that it maintains strict compliance with USP chapter 797 mandates 

• Verify with the outsourcing facility that: 

o It has registered with the FDA 

o It maintains strict compliance with current good manufacturing practices 

The pharmacy or outsourcing facility should provide prepare the medication for 

ophthalmic use, confirm the dose and sterility, identify a syringe suitable for this protein, 

provide storage and "beyond-use-date" instructions, and the lot number of the vial. The 

FDA is still determining the "beyond-use-date" requirements for repackaged Avastin. 

D. Preventing endophthalmitis 

The prescribing information for the anti-VEGF agents contain statements about actions 

ophthalmologists should take to prevent and manage known complications. These 

statements tend to reflect protocols in place during clinical trials for these drugs. 

Aspects of the protocols may not be necessary in clinical practice outside of the 

research setting. And guidelines published since the drug was approved make different 

recommendations, especially in relation to infection prophylaxis. Physicians should use 

their clinical judgment to determine what recommendations to follow. 

3 
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FDA-approved labels for both Lucentis and Eylea state that the "intravitreal injection 

should be administered under controlled aseptic conditions, which include the use of 

sterile gloves, a sterile drape, and a sterile eye speculum (or equivalent). Adequate 

anesthesia and a broad-spectrum microbicide should be given prior to the injection." An 

expert panel reviewed published studies of intravitreal injection technique and 

monitoring and released guidelines in 2014. 1 The panel reached different conclusions 

about gloves, drapes, speculum, and antibiotics than the recommendations included in 

the label for Lucentis and Eylea. 

Lack of evidence to support some labeling instructions 

• The experts concluded that "there is insufficient evidence to support the routine use 

of pre-, peri-, or postoperative antibiotics to reduce the rate of endophthalmitis."1 

• Sterile or non-sterile gloves may be used even though they have not been shown to 

reduce the risk of endophthalmitis. 

• There is no evidence to support the routine use of a drape. 

Recommendations to reduce the risk of endophthalmitis 

The experts did make recommendations. Here are some key guidelines. Please see the 

article for full details. 

• External infections 

o Postpone injection until active external infections, including blepharitis, have 

been treated and cleared, unless the benefits of injection clearly outweigh the 

risk of endophthalmitis. 

• Povidone-iodine 

o Ensure that povidone-iodine (5-10%) is the last agent applied to the intended 

injection site before injection. 

• If a gel anesthetic is used, apply povidone-iodine both before and after 

application of the gel. 

o Povidone-iodine may also be applied to the eyelids, including the eyelid 

margins and eyelashes. 

• Avoid eyelid scrubbing or expressing material from the meibomian 

glands. 

o Prevent contact of the eyelashes and eyelid margins with both the injection 

site and the injection needle after final application of povidone-iodine and 

especially during the actual injection. 

• Use either a speculum or other technique, such as manual lid 

retraction. 

• Aerosolized droplets 

o Reduce the spread of aerosolized droplets during the injection preparation 

and procedure. 

o Use a surgical mask or minimize speaking by the physician, assistants, and 

patients. 

• Bilateral injections on the same day 

1 Avery RL et al. lntravitreallnjection Technique and Monitoring. Updated Guidelines of an Expert Panel. Retina. 

2014: 34, number 12, S1-S18. 

4 
255 


29991.184

o Exercise caution when performing bilateral injections on the same day. 

o Consider the injection for each eye as a separate procedure. 

o Use separate site preparation, individual syringes, needles, etc. 

o Use a different medication batch if using a compounded medication such as 

Avastin. 

• Patient education and monitoring 

o Monitor patients for symptoms suggestive of endophthalmitis. 

o Instruct patients to contact you immediately if the eye becomes red, sensitive 

to light, painful, or develops a change in vision. Consider giving these 

instructions in writing. 

E. Informed consent and documentation 

lntravitreal injections carry many of the same risks as other intraocular procedures (i.e., 

infection, lOP changes, etc). There are a few risks specific to these drugs that raise 

questions for ophthalmologists. 

Arterial thromboembolic events CATEs) 

Anti-VEGF agents have been safely administered to hundreds of thousands of patients. 

Clinical trials of Lucentis, Avastin, and Eylea have shown a low incidence of ATEs, 

defined as nonfatal stroke, nonfatal myocardial infarction, or vascular death, including 

deaths of unknown cause. The relationship between administration of anti-VEGF agents 

and these events is unclear, as patients receiving these drugs have co-morbidities 

associated with ATEs. 

Nonetheless, the labels for Lucentis and Eylea indicate that anti-VEGF drugs have a 

potential risk of ATEs. ATEs are also included in the warnings on the label for 

intravenous Avastin. The Lucentis label indicates that the risk for ATEs may be higher in 

patients with diabetes. Further research is needed to confirm this. We recommend 

warning all patients with diabetes who receive anti-VEGF drugs of this possible 

increased risk. OMIC recommends that you discuss the risk of ATEs with patients. We 

have addressed this risk in our sample consent forms for these drugs. 

In addition to ATEs, the prescribing information for intravenous Avastin contains 

warnings about gastrointestinal perforations/wound healing complications, hemorrhage, 

hypertension, proteinuria, and congestive heart failure. These complications have not 

been related to intravitreal use, so OMIC has removed any discussion of them from our 

sample Avastin consent form. 

Potential harm to the fetus 

The FDA changed the safety labeling for intravenous Avastin, adding a section on 

embryo-fetal toxicity in June, 2015. The warning states that "Avastin may cause fetal 

harm based on the drug's mechanism of action and findings from animal studies."2 

Pregnant rabbits were given Avastin IV 10 mg/kg or more every three days, and 

congenital abnormalities were noted. It went on to say that "animal models link 

angiogenesis and VEGF ... to critical aspects of female reproduction, embryo-fetal 

2 http://www.fda.gov/safety/medwatch/safetyinformation/ucm28761D.htm 

5 
256 


29991.185

development, and postnatal development." The FDA instructs physicians to "advise 

females of reproductive potential to use effective contraception during treatment with 

and for 6 months after the last dose of Avastin." 

The FDA does not know if intravenous Avastin causes harm to the human fetus. The 

FDA warning did not address intravitreal Avastin, as this use is off-label. The risk for 

intravitreal use is even less clear, however, as the intravitreal dose of Avastin is a 

fraction of this, and is only administered monthly. If the effect on the fetus is inherent to 

anti-VEGF agents, then Lucentis and Eylea may pose a similar risk. In any event, the 

warning would only apply to the small number of women who are pre-menopausal. 

The warning was only issued for Avastin. Nonetheless, to reduce the potential liability 

for ophthalmologists using anti-VEGF drugs, we feel it is prudent to discuss the FDA 

warning with pre-menopausal women. 

• Explain that the warning was issued for IV use, not for use in the eye. 

• Explain that the FDA does not know if IV Avastin causes harm to the human fetus. 

• Explain that the FDA does not know if intravitreal anti-VEGF drugs pose a risk for 

the human fetus. 

• Advise the woman to talk to her regular doctor about whether to use birth control 

while she is getting Avastin, Eylea, or Lucentis, and for six months after the last 

dose. 

• Ask the woman to sign a document discussing this possible risk, which is available 

at www.omic.com/avastin risk to fetus/, www.omic.com/lucentis risk to fetus/, and 

www.omic.com/eylea risk to fetus/. 

Treatment of both eyes on the same day 

• Document your decision-making process in the medical record. 

• Inform the patient of the possibility of vision-threatening complications in both eyes. 

• Explain the measures you will take to reduce the risk of infection (i.e., you will use a 

new syringe, needle, etc.). 

• Ensure that the patient has a ride home before administering the injections. 

Consent for ongoing treatment 

In general, informed consent is considered valid until1) the patient revokes the consent 

or 2) the patient's medical or ocular condition change so as to materially affect the 

nature of the procedure or the risk/benefit ratio. This means that unless either of these 

situations materialize, you need only obtain the patient's informed consent once as long 

as you document that the consent is for ongoing treatment, and the consent form states 

the same. 

• Obtain consent for each eye. 

• Obtain and document informed consent again if the patient's medical or ocular 

condition changes to the point that the risk/benefit ratio is affected. 

• Review the risks and benefits on a regular basis, such as yearly. 

Documentation 

• Document the decision-making process that led to choosing the particular drug as 

6 
257 


29991.186

the treatment for the patient. Note results of earlier attempts at treatment and the 

results of diagnostic tests. 

• Evaluate and document the continued need, effectiveness, and safety of the 

medication prior to each injection. 

• Note the dose, lot number of the vial, any reactions to the injection and how they 

were handled, and the discharge and follow-up instructions. 

RISK MANAGEMENT ASSISTANCE 

OMIC policyholders may obtain confidential risk management help by contacting 

OMIC's Risk Management Hotline at 800.562-6642, option 4, or by emailing us at 

riskmanagement@omic.com. 

7 
258 


29991.187

GREG WALDEN, OREGON 

CHAIRMAN 

Dr. Bruce Brod 

ONE HUNDRED FIFTEENTH CONGRESS 

FRANK PALLONE, JR., NEW JERSEY 

RANKING MEMBER 

C!Congtt55 of tbe Wntteb ~tate5 

~ouse of l\epresentntibes 

COMMITTEE ON ENERGY AND COMMERCE 

2125 RAYBURN HousE OFFICE BuiLDING 

WASHINGTON, DC 20515-6115 Majority (202)225-2927 

Minority (<'0<')22:5-J641 

February 16,2018 

Chair, Congressional Policy Committee 

American Academy of Dermatology 

1445 New York Avenue, N.W.; Suite 800 

Washington, DC 20005 

Dear Dr. Brod: 

Thank you for appearing before the Subcommittee on Health on January 30, 2018, to testify at the 

hearing entitled "Examining Implementation of the Compounding Quality Act." 

Pursuant to the Rules of the Committee on Energy and Commerce, the hearing record remains 

open for ten business days to permit Members to submit additional questions for the record, which are 

attached. To facilitate the printing of the hearing record, please respond to these questions with a 

transmittal letter by the close of business on Morch 3, 2018. Your responses should be mailed to Zack 

Dareshori, Legislative Clerk, Committee on Energy and Commerce, 2125 Rayburn House Office 

Building, Washington, DC 20515 and e-mailed in Word format to zack.dareshori@mail.house.gov. 

Thank you again for your time and effort preparing and delivering testimony before the 

Subcommittee. 

t;j tlr!J 

1rman 

I C. B gess, M.D. U ~ 

Subcommittee on Health 

cc: The Honorable Gene Green, Ranking Member, Subcommittee on Health 

Attachment 
259 


29991.188

February 23, 2018 

The Honorable Michael Burgess, MD (R-TX) 

Chairman 

House Energy & Commerce 

Subcommittee on Health 

2125 Rayburn HOB 

Washington, D.C. 20515 

The Honorable Gene Green (D-TX) 

Ranking Member 

House Energy & Commerce 

Subcommittee on Health 

2125 Rayburn HOB 

Washington, D.C. 20515 

Dear Chairman Burgess and Ranking Member Green: 

Thank you for forwarding Congresswoman Anna Eshoo's questions from the "Examining 

Implementation of the Compounding Quality Act" hearing. I sincerely appreciated the opportunity to 

testify before your subcommittee, and share the experiences dermatologists and their patients have 

been facing since implementation of the Drug Quality & Security Act. I am happy to answer any 

questions you and Subcommittee members may have. 

Dermatologists diagnose and treat more than 3,000 skin diseases, including skin cancer, 

eczema, infections, psoriasis, immunologic diseases, and many genetic disorders. Dermatologists 

rely heavily on compounded pharmaceutical products and especially topical compounded 

pharmaceutical products obtained via traditional compounding pharmacies to treat many of these 

skin diseases. As physicians dedicated to the safety and wellbeing of our patients, the Academy 

believes that a regulatory structure with appropriate safeguards is paramount to ensuring both the 

safety and continued access to compounded products from traditional compounders and 

pharmaceutical manufacturers. 

The use of these types of compounded medications is an integral part of most dermatology 

practices and is extremely vital in providing the best patient care. A dermatology patient should have 

access to treatment with a compounded product in a timely manner. Over the years, dermatologists 

have been able to safely deliver treatments to meet individual patient needs, including patients with 

orphan diseases that do not have an FDA approved drug for treatment. Prescribing and/or directly 

administering compounded products allows us as dermatologists to tailor treatments to the unique 

needs of our patients, resulting in better outcomes. 

1. Are you currently required, either by the American Academy of Dermatology or the FDA, 

to disclose to dermatology patients that they are receiving a compounded product? 

There is no requirement by the FDA or the AAD to disclose to dermatology patients that they are 

receiving a compounded medication. Likewise, there is no requirement to distinguish between 

generic, branded, and specialty drugs. 

Sunnn- Olbrlcht, MD, FAAD 

Prerident 

Georg.J. Hi'UD, MD, MBA, FAAO l'n-1ident..fJoet 

Theodore Aoson, MD, FAAD 

Vice President 

Jane M. G~nt·Kels, MD, FMO ViuPrnident-El-ct 

Bilrb.ua M. Math ... MD, FAAD 

Sec!'8!3ry-TMa!tM<Or 

Marta J. Van Beak, MD, MPH, FMD 

Aui•tan1St(!'8tary-TrHsur<~r 

Ela!neWefu 

hKuti...,Dir<~ctorandCEO 
260 


29991.189

2. Should dennatology patients be made aware of the risks associated with using 

compounded products? 

There are risks associated with all pharmaceutical medications whether they be compounded, 

generic, branded, or specialty if not manufactured, stored, administered, or used properly. When 

prescribing a drug that has significant, incremental, or more risk than the patient may expect, the 

dennatologist will counsel the patient on expectations with the treatment and mitigating risk. In 

addition, the dermatologist takes into consideration the patient's ability to comprehend and adhere 

to the treatment plan prior to determining what drug to prescribe. 

As I indicated in my testimony, some compounded drugs can produce adverse reactions if they are 

not applied as intended; therefore, a health care provider in the clinical office setting should 

administer them. If the compounded medication is one that may be appropriately administered 

outside the clinical setting, the dermatologist will also instruct the patient to speak to the phannacist 

upon pickup at the phannacy. 

3. In your personal dennatology practice, do you disclose to patients when you are using a 

compounded product? 

As noted above, I counsel my patients on the risks and alternatives involved in the entire spectrum 

of treatment options, including compounded, generic, specialty, and compounded medications. 

Thank you for again for the opportunity to answer these questions. Should you have any 

additional questions or concerns, please feel free to contact Christine O'Connor, Associate Director, 

Congressional Policy at coconnor@aad.org or (202) 609-6330. 

Sincerely, 

Bruce A. Brad, M.D. 

Immediate-Past Chair, Congressional Policy Committee 

American Academy of Dennatology Association 
261 


29991.190

GREG WALDEN, OREGON 

CHAIRMAN 

ONE HUNOREO FIFTEENTH CONGRESS 

FRANK PALLONE, JR., NEW JERSEY 

RANKING MEMBER 

(!Congress of tbe Wntteb ,i)tates 

jl}ouse ot latprtstntatibts 

COMMITTEE ON ENERGY AND COMMERCE 

2125 RAYBURN HousE OFFICE BuiLDING 

WASHINGTON, DC 20515--6115 

Ms. J enn Adams 

President 

PharMEDium Services 

I SO North Field Drive; Suite 350 

Lake Forest, IL 60054 

Dear Ms. Adams: 

Majority (202)225--2927 

Minoriry (202)225-3641 

February 16,2018 

Thank you for appearing before the Subcommittee on Health on January 30,2018, to testilY at the 

hearing entitled "Examining Implementation of the Compounding Quality Act." 

Pursuant to the Rules of the Committee on Energy and Commerce, the heating record remains 

open for ten business days to permit Members to submit additional questions for the record~ which are 

attached. To facilitate the printing of the hearing record, please respond to these questions with a 

transmittal letter by the close of business on March 3, 2018. Your responses should be mailed to Zack 

Dareshori, Legislative Clerk, Committee on Energy and Commerce, 2125 Rayburn House Office 

Building, Washington, DC 20515 and e-m ailed in Word format to zack.dareshori@mail.house.gov. 

Thank you again for your time and effort preparing and delivering testimony before the 

Subcommittee. 

cc: The Honorable Gene Green, Ranking Member, Subcommittee on Health 

Attachment 
262 


29991.191

'})] PharMEDium· 

February 26, 2018 

The Honorable Michael C. Burgess, M.D. 

Chairman, Subcommittee on Health 

Conunittee on Energy and Commerce 

U.S. House ofRepresentatives 

2125 Rayburn House Office Building 

Washington, D.C. 20515-6115 

Dear Chairman Burgess, 

AmerlsourcaBergen 

150 North Field DriYe 

Suite 350 

Lak:e Forest, !l 60045 

Phone; 800.523.7749 

Thank you for inviting me to appear before your Subcommittee on January 30, 2018. I 

appreciated the opportunity to testifY on the important matter of the Drug Quality and Security 

Act (DQSA), as well as the opportunity to respond to additional questions for the hearing record 

from you and the distinguished Ranking Member of the full Committee, Representative Frank 

Pallone, Jr. 

Please find enclosed my responses to your questions. Should you have any questions, please do 

not hesitate to reach out at any time. 

Sincerely, 

tJvr:~ JennAdarns 

President, PharMEDium Services 

Enclosure. 

Cc: Greg Walden, Chairman, Committee on Energy and Commerce 

Cc: Frank Pallone, Jr., Ranking Member, Committee on Energy and Commerce 

Cc: The Honorable Gene Green, Ranking Member, Subcommittee on Health 
263 


29991.192

Responses to Questions from Chairman Burgess 

Ql: FDA recently announced plans to issue future draft guidance to "ensure that outsourcing 

facilities do not compound using a bulk drug substance when an FDA-approved drug can be 

used to meet patient medical needs. ''Does this seem like an appropriate response to the 

concerns that have been raised about your competitors copying FDA-approved drugs by using 

bulk substances? What additional steps do you believe are needed to clarify the law and ensure 

industry's compliance? 

A: Yes. PharMEDium remains hopeful that FDA's forthcoming guidance regarding restrictions 

on the use of bulk drug substances will make clear that outsourcing facilities must compound 

using FDA-approved drugs unless one of the narrow statutory exceptions to start from bulk 

active pharmaceutical ingredients (APis) applies. The DQSA is clear that unless a drug is in 

shortage, compounders must use FDA-approved drugs unless there is a valid clinical need that is 

unmet by use of the approved version of the drug. As Commissioner Gottlieb testified before 

your Subcommittee, the DQSA requires that, "if there was an FDA-approved product available 

that you can compound from, you have to compound from that product." 

PharMEDium remains disappointed that FDA's final guidance defining what is "essentially a 

copy" of an FDA-approved drug failed to clearly differentiate between drugs compounded from 

FDA-approved finished drugs and from bulk API, as required by the statute. Although we urge 

the agency to clarify this guidance, we believe that FDA can help resolve any confusion 

regarding the prerequisites to use bulk API in the forthcoming, separate guidance. Additionally, 

the agency will need to clearly communicate its policy to compounders, customers, regulators 

and the public, and most importantly, must strictly enforce the rules against compounders who 

circumvent these restrictions. 

Q2. Given your testimony that FDA's interim policy on bulks allows compounders to use 

approximately I 00 bulk drug substances that are the active ingredient of an FDA approved drug, 

do you support Commissioner Gottlieb's stated intention to re-evaluate and remove those bulk 

substances from the list? Or how do you recommend FDA resolve concerns over the inclusion of 

FDA-approved products on the bulks list? 

A: Yes. As noted, of the nearly 200 substances on the Category !list of bulk drug substances for 

which FDA has announced it plans not to take enforcement action for the time being, more than 

100 of them are the main active ingredient of an FDA-approved drug. Based on publicly 

available information, it appears that many of these substances were nominated without 

identifying the comparable FDA-approved drug or specifying a clinical need not served by that 

approved drug that would justify the need to use the bulk substance. Commissioner Gottlieb 

explained that the list is not necessarily based on the legitimacy of the need as much as a desire 

to "freeze" the number of bulks used in compounding. He stated that the agency plans to remove 

substances from the Category 1 list. Given the additional dimensions of risk that nonsterile bulk 

substances introduce into the compounding process, PharMEDium supports FDA's efforts to 

remove substances from the list that were nominated without adequate evidence of a distinct 

clinical need. However, it is also important to emphasize that the presence of a substance on the 

Category 1 list does not justify its use in any particular situation; rather, the use of a bulk 

substance must still be supported by establishing a clinical difference compared with the 
264 


29991.193

approved drug. In particular, if an outsourcing facility compounds from a bulk drug substance on 

the Category 1 list that is the active ingredient of an FDA-approved drug, they should be 

required to obtain documentation of a prescriber's determination that the bulk-compounded drug 

produces a clinical difference for an individual patient. Thus, FDA's efforts to revise the 

Category I list should further specify the additional restrictions on using these substances. 

Q3. Does PharMEDium support the FDA's plans to create what some are calling a "503B Lite" 

option for facilities to register with FDA but be held to more lenient standards that will/ower 

their cost of compliance? Although the details have not yet been announced, do you have any 

concerns with what has been articulated about this forthcoming policy or are there 

circumstances under which you think this approach would not be appropriate? 

A: PharMEDium supports efforts to broaden participation in the 503B category to ensure it is 

competitive and robust enough to meet legitimate demand for non-patient specific compounding 

of sterile drugs. As Commissioner Gottlieb explained at the hearing, "the [good manufacturing 

practices] GMP standard is not a fixed standard; it's a risk-based standard." We recognize that 

cGMPs must be appropriately tailored to meet the specific risks that various products, processes, 

and operations present. However, the size and scale of an operation are not significant factors in 

the relative risk level of the sterile products that a compounder prepares, and therefore should not 

be a deciding factor in determining which aspects of cGMP to apply. As the Commissioner 

explained, the applicable controls should be based on the risks that products present, such as 

biologics, rather than the size of the operation alone. Ultimately, the goal of the DQSA to have 

robust quality standards for all 503B products to ensure patient safety must not be undermined 

by efforts, however well-intentioned, to make the outsourcing facility category more accessible. 

Q4. The Subcommittee heard testimony that many physician offices and other health care 

settings have unmet need for "office use" compounded products that cannot be served by 503B 

outsourcing facilities? Are these the types of products that PharMEDium makes and do you 

believe that other outsourcing facilities would have difficulties in meeting these needs? 

A: PharMEDium is sympathetic to all concerns of patients lacking access to needed treatments, 

as all patients should have access to safe compounded drugs when FDA-approved drugs cannot 

meet their individual clinical needs. PharMEDium does not have a finite catalog of products that 

we make. Instead, we prepare products based on the specific formulations that customers order. 

Other witnesses described the need for highly standardized preparations that are "widely used" 

across many physician practices, such as buffered lidocaine. Thus, it may be feasible for these 

needs to be met by currently registered outsourcing facilities, and prepared under section 503B 

cGMP standards. Outsourcing facilities are not currently making everything that physician 

offices need, and thus there should be more collaboration between providers, suppliers and 

regulators to provide accurate information, identify gaps, and address opportunities to meet this 

gap. It would be ill-advised to try to resolve a current shortfall in the supply of compounded 

drugs by creating a workaround to section 503B that eliminates the incentive to register with 

FDA. As the Subcommittee's hearing memo explained, the prescription requirement of section 

503A is that incentive. From PharMEDium's perspective, allowing non-patient specific 

compounding to be performed by entities that are not registered with FDA and do not follow 

cGMPs poses an unjustified risk to patient safety. 

2 
265 


29991.194

Responses to Questions from Ranking Member Pallone 

In your written testimony you noted that compounded drugs should only be used when 

FDA-approved drugs do not meet a patient's clinical needs. I agree that this was a .fundamental 

premise of the law, and I believe it is one that should be held in the forefront of our minds as we 

work on successful implementation, and as the agency considers its enforcement of the law. One 

of the requirements of outsourcing facilities under section 503B is the responsibility to comply 

with current good manufacturing practices. These quality requirements are critical to ensuring 

the sterility and safety of compounded drug products. 

Ql. Will you describe further the cGMP requirements that outsourcing facilities are held to and 

how they help to ensure the safety of compounded drug products? 

A: As you know, outsourcing facilities are not exempt from section 501 (a)(2)(B) of the FDCA, 

meaning that unlike traditional pharmacy compounders, we are required to comply with current 

good manufacturing practices ( cGMPs). This means that like traditional drug manufacturers, 

outsourcing facilities must prepare compounded drugs under robust but flexible requirements 

designed to assure the quality of the finished sterile drug products. Producing sterile drugs 

products, particularly through aseptic processing, requires the awareness of, control over and 

monitoring of many process variables, each of which could cause an error that could ultimately 

lead to distribution of contaminated or otherwise substandard product. According to cGMPs, 

outsourcing facilities must understand the importance of a robust monitoring program that 

provides a high degree of assurance as to the level of microbial control of the sterile drug 

processing environment and compounding personnel, maintain facilities and equipment 

specifically tailored for use in the processing of sterile drugs, employ broad cleaning, sanitization 

and disinfection procedures- validating their efficacy, enforce strict aseptic processing controls 

at all times during sterile manipulations, as well as fully test all batches of drug products with 

scientifically sound laboratory testing and control methods. These controls are just a few of the 

important measures required under cGMPs to mitigate the myriad of variables that can impact 

the quality, integrity or sterility of a compounded sterile preparation. 

Q2. Recently FDA announced that the agency will be issuing revised guidance on cGMPs that 

will propose jlexibilities based on the size and scope of an outsourcing facility's operations. My 

understanding is the intent of this proposal is to encourage additional pharmacies that are 

currently operating under section 503A to register as outsourcing facilities under section 503B. 

Will you discuss your perspective on additional flexibility related to cGMPs and whether this is 

an approach that you would support as an outsourcing facility? 

A: In general, PharMEDium supports efforts to broaden participation in the 503B category to 

ensure it is equipped to meet demands for legitimate non-patient specific compounding of sterile 

drugs. But access must not come at the expense of patient safety, and thus FDA must ensure that 

appropriate manufacturing standards govern outsourcing, especially the preparation of high-risk 

products such as sterile drugs. 

Based on our experience operating under cGMP conditions, we believe that regulatory flexibility 

exists for FDA to appropriately oversee outsourcing. cGMPs are designed to be tailored to meet 

the specific risks that various products, processes, and operations present. Importantly, the size or 

3 
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scale of an operation has little to do with the inherent risk of the activities perfonned during the 

manufacturing process, and therefore does not factor into the existing cGMP framework. cGMP 

exemptions could compromise product integrity, and should not be made for small batch size or 

limited distribution, and certainly not for high-risk products such as injectable drugs made from 

nonsterile API powders. 

Q3. What important guardrails do you think the agency should consider in revising this guidance 

to ensure we are maintaining high standards for safety and quality of products compounded by 

outsourcing facilities? 

A: We understand that FDA is preparing new guidance and ultimately new regulations, to help 

outsourcing facilities better understand how the obligations under 21 CFR Parts 210 and 211 

apply to this industry, as those regulations originally contemplated large-scale, conventional drug 

manufacturing of few, large, unifonn batches. As Commissioner Gottlieb emphasized during his 

appearance before the Subcommittee, the cGMP framework is inherently flexible and designed 

to empower manufacturers to design processes to proactively account for the risks they identify. 

Appropriate guardrails should include heightened obligations for high-risk drug products, such as 

manipulated biologics, and robust qualification of high-risk components, such as nonsterile bulk 

API. Bulk API introduces considerable risk into the compounding process, which cannot always 

be fully accounted for under anything short of the full regulatory cGMPs, and thus is considered 

the riskiest fonn of compounding by USP and other experts. Accordingly, specific guardrails 

should be in place to ensure that only suitable sterile grades of bulk API are utilized, that 

incoming bulk materials are appropriately characterized, tested and that their manufacturers are 

qualified according to a define supplier quality management program, and additional 

investigations on requisite bulk substance manufacturing controls is undertaken. 

Appropriate accommodations could be made for lower-risk components, such as FDA-approved 

or FDA-cleared starting materials that have themselves been manufactured under cGMP 

conditions, as well as for lower-risk products, such as nonsterile topical agents. Accommodations 

should not be made for high-risk products simply because they will be prepared in relatively 

small batches or distributed to a limited geographic area. These characteristics do not mitigate 

the risk of contamination, impurity, degradation, or other quality assurance aspects that cGMPs 

are designed to control. 

One of the common complaints we have heard from 503A pharmacies is that registered 503B 

outsourcing facilities are unable to meet the needs of physicians and patients, and fUrther it is 

difficult to identify outsourcing facilities that can meet their needs. On the second panel we heard 

from Dr. Brad, chair of the American Academy of Dermatology Association, that "FDA's website 

lists only the facilities that are registered, but with no contact iriformation no real-time product 

availability iriformation, and no price list. "He argues this results in physicians undertaking a 

scavenger hunt to identify 503B outsourcing facilities that can fit their needs. 

Q4. Does PharMEDium work with 503A pharmacies to provide products for purposes of "office 

use stock"? lfso, will you discussforther the process by which a 503Apharmacy could request 

products for these needs? lfno, what considerations does PharMEDium take into account when 

making a decision of whether or not to supply products for purposes of "office use stock"? 

4 
267 


29991.196

A: All of the products PharMEDium prepares are for "office stock" in that they are provided for 

use in hospitals and other health care settings by providers who are anticipating their need for 

ready-to-administer compounded sterile preparations (CSPs). PharMEDium receives orders from 

health care provider entities for CSPs and fills those orders to the customers' specifications. We 

do not receive prescriptions or other information about the patient. Most of our customers are 

hospital or health system pharmacies that operate pursuant to section 503A for their own 

compounding activities. Section 503B prohibits outsourcing facilities from engaging in 

wholesaling activities, meaning that we only supply CSPs to the end users that will 

dispense/administer them to the patient. We are not permitted to sell to independent pharmacies 

that in turn transfer the product to an end user. PharMEDium believes this obligation to sell 

directly to the end user is an important feature of section 503B which prevents outsourcing 

facilities from operating like conventional drug manufacturers and which also preserves the 

integrity of the supply chain of outsourced products. 

We agree with other witnesses that FDA could provide additional information on its website to 

disseminate more useful information about outsourcing facilities, including their contact 

information and a link to their website. Displaying or otherwise disseminating this type of 

information is consistent with the statute, and would help to mitigate the "scavenger hunt" that 

was described. 

Q5. One of the requirements of outsourcing facilities under section 503B is the submission of 

product lists to the FDA semiannually. FDA has noted that not all outsourcing facilities have 

been complying with this requirement, resulting in the posting of incomplete product lists. What 

steps, if any, is FDA taking to ensure compliance with this requirement? 

A: PharMEDium recognizes that product reporting is a central obligation of section 503B, and 

we therefore support efforts to ensure all registrants come into alignment with statutory 

obligations. However, we cannot speak to what steps FDA is taking to address underreporting of 

compounded products by other outsourcing facilities. Efforts by FDA to ensure more accurate 

and complete reporting could assist in making sure the patient and provider communities are 

aware of the full range of products available through outsourcing facilities, as well as their 

processes and source materials. 

5 
268 


29991.197

GREG WALDEN, OREGON 

CHAIRMAN 

FRANK PALLONE, JR., NEW JERSEY 

RANKING MEMBER 

ONE HUNDRED FIFTEENTH CONGRESS 

Ms. Molly Ventrelli 

C!Congregg of tbt llnittb ~tatts 

;!}ouse of l\epresentatibes 

COMMITTEE ON ENERGY AND COMMERCE 

2125 RAYBURN HousE OFFICE BuiLDING 

WASHINGTON, DC 20515-6115 Majority (202} 226-2927 

Minority (202} 225-3641 

February 16,2018 

Vice President, Regulatory Affairs 

Fresenius Kabi 

3 Corporate Drive 

Lake Zurich, IL 6004 7 

Dear Ms. Ventrelli: 

Thank you for appearing before the Subcommittee on Health on January 30, 2018, to testify at the 

hearing entitled "Examining Implementation of the Compounding Quality Act." 

Pursuant to the Rules of the Committee on Energy and Commerce, the hearing record remains 

open for ten business days to permit Members to submit additional questions for the record, which are 

attached. To facilitate the printing of the hearing record, please respond to these questions with a 

transmittal letter by the close of business on March 3, 2018. Your responses should be mailed to Zack 

Dareshori, Legislative Clerk, Committee on Energy and Commerce, 2125 Rayburn House Office 

Building, Washington, DC 20515 and e-mailed in Word format to zack.dareshori@mail.house.gov. 

Thank you again for your time and effort preparing and delivering testimony before the 

Subcommittee. 

cc: The Honorable Gene Green, Ranking Member, Subcommittee on Health 

Attachment 
269 


29991.198

2. Will you describe how the quality standards that compounding pharmacies are required 

to comply with under sections 503A and 503B differ from those of regulated drug 

manufacturers? 

Manufacturers of FDA-approved drugs must comply with requirements known as current good 

manufacturing practices (CGMP). These standards are described in FDA's regulations at 21 

CFR Parts 210 and 211. The regulations contain stringent requirements for personnel 

qualifications, facility design, production and process controls, environmental monitoring, 

laboratory controls, including required sterility and stability testing, and quality assurance and 

quality control, among other requirements. 

Manufacturers must register with FDA and list the drugs that they produce or intend to produce, 

and FDA regularly inspects manufacturing facilities to determine whether they are in compliance 

with CGMP requirements. Before an Abbreviated New Drug Application (ANDA) is approved, 

FDA will look at the inspection history ofthe manufacturing facilities listed in the ANDA to 

determine whether they have been inspected and found to be in compliance with CGMP 

requirements, and will conduct pre-approval inspections when necessary. 

In contrast to manufacturers of FDA-approved drugs, pharmacies that compound drugs in 

accordance with the conditions in section 503A are exempt from CGMP requirements. They do 

not register with FDA. As a result, FDA does not have an inventory of pharmacies compounding 

under section 503A, and FDA will not normally inspect such pharmacies unless an inspection is 

triggered by a request from a state, or FDA becomes aware of an adverse event or product 

quality problem that is traceable to the pharmacy. Additionally, the FDA may inspect these 

facilities when it is determined to be compounding large quantities without patient prescriptions. 

Because these compounding pharmacies are primarily regulated by the states, individual states 

determine what standards the pharmacies will be held to, how often they will be inspected by the 

state, and what action will be taken if the pharmacies are in non-compliance with the state 

requirements. The standards applicable to pharmacies operating under section 503A are much 

less rigorous than the CGMP requirements applicable to conventional manufacturers. In fact, 

these standards, set by United States Pharmacopeia, are not required by all states to meet full 

compliance standards. 

Pharmacies that register with FDA as outsourcing facilities and compound drugs in accordance 

with the conditions of section 503B are required to follow CGMP requirements, but FDA has 

indicated that it intends to develop specific CGMP regulations applicable to outsourcing facilities 

that will be more suitable for compounding than those applicable to conventional manufacturers. 

It is particularly important to note that 503B facilities are not inspected by the FDA prior to 

launching a new product. In June 2014, FDA issued a draft guidance, Current Good 

Manufacturing Practice- Interim Guidance for Human Drug Compounding Outsourcing 

Facilities Under Section 503B of the FD&C Act 

(https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatorylnformation/Guidances/ 

UCM403496.pdf). The draft guidance describes FDA's expectations regarding outsourcing 

facilities' compliance with the CGMP requirements in 21 CFR parts 210 and 211 during the 

interim period while FDA is developing the regulations. The guidance states: 
270 


29991.199

This interim guidance reflects FDA's intent to recognize the differences between 

compounding outsourcing facilities and conventional drug manufacturers, and to tailor 

CGMP requirements to the nature of the specific compounding operations conducted by 

outsourcing facilities while maintaining the minimum standards necessary to protect 

patients from the risks of contaminated or otherwise substandard compounded drug 

products. (Draft Guidance at 2). 

In its recently issued 2018 Compounding Policy Priorities Plan 

(https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryinformation!PharmacyCompoundin 

g/ucm592795.htm ), FDA indicated it is revising the draft guidance "to describe a new flexible, 

risk-based approach to CGMP requirements for outsourcing facilities." FDA has indicated that 

its goal is "for more compounders to register as outsourcing facilities with the understanding that 

they can still meet the FDA's core requirements for drug quality, based on the size and scope of 

their compounding operations." How FDA will do so remains to be seen, and it will be 

important to ensure that FDA does not relax the CGMP requirements applicable to outsourcing 

facilities in a way that creates additional risk to patients who take a compounded product instead 

of an FDA-approved drug or create disincentives to the submission ofNDAs or AND As by 

conventional drug manufacturers who must follow the stringent standards in Parts 21 0 and 211. 

3. You noted in your testimony that outsourcing facilities, a category of compounding 

pharmacies created under DQSA to address the large-scale compounding needs of 

hospitals or health systems are required to comply with good manufacturing practices. 

What implications would there be for manufacturers if the cGMPs that 503B pharmacies 

are held to are weakened to allow for typically traditional pharmacies to enter into bulk 

compounding space? 

If the CGMPs that 503B pharmacies are held to are weakened to allow pharmacies that currently 

compound under the conditions of 503A to register as outsourcing facilities and compound drugs 

without prescriptions for hospitals or health systems, patients could be put at significant risk of 

receiving substandard drugs. Submission ofNDAs and AND As and compliance with CGMP 

requirements are costly, but the approval process and CGMP requirements significantly reduce 

the risk to patients of receiving poor quality products. If FDA establishes weak CGMP 

requirements for outsourcing facilities, hospitals and health systems may tum to those lower cost 

unapproved compounded products even when an approved product will fulfill the patient's 

needs, placing patients at risk, putting conventional drug manufacturers that hold NDAs and 

AND As at a competitive disadvantage, and reducing the incentives for companies to seek 

approval ofNDAs and AND As. Drawing a regulatory line between these two facilities will be 

challenging at best. A consistent standard needs to be found so as to not reduce regulatory 

oversight to a level of individual interpretation. 

4. One key difference between the requirements an outsourcing facility is held to and 

traditional drug manufacturers is that the compounded drug products compounded by an 

outsourcing facility are not subject to any premarket approval. How can FDA ensure that 

the traditional drug approval process is not undermined by the expansion of the 

outsourcing facility market? 

2 
271 


29991.200

In addition to continuing to require outsourcing facilities to comply with stringent CGMP 

requirements such as those applicable to conventional manufacturers, FDA must enforce the 

provisions of section 503B that limit the bulk drug substances that can be used by outsourcing 

facilities to compound, prohibit outsourcing facilities from copying commercially available drug 

products that are not on FDA's drug shortage list, and strictly enforce the limitations on 

compounding drugs on the drug shortage list, a practice that is permissible only while the drug 

remains on the drug shortage list. These provisions were included in the law to prevent 

outsourcing facilities from undermining the traditional drug approval process. 

Section 503B(a)(2) states that outsourcing facilities can only compound using bulk drug 

substances that appear on a list established by FDA identifying bulk drug substances for which 

there is a clinical need. If a compounded medication can be made from an approved drug, then it 

should not be compounded from a bulk drug substance. If there is no clinical need for a product 

compounded from a bulk drug substance, then FDA should ensure that outsourcing facilities do 

not compound with that substance, and if a bulk drug substance is on the list and allowed to be 

used to compound, FDA should ensure that only patients with the clinical need for the 

compounded product are prescribed that product in place of the FDA-approved drug. 

Section 503B(a)(5) states that outsourcing facilities cannot compound drugs that are essentially 

copies of one or more approved drugs. FDA recently issued a final guidance that describes how 

it intends to apply this prohibition to outsourcing facilities (Compounded Drug Products That 

Are Essentially Copies of Approved Drug Products Under Section 503B of the Federal Food, 

Drug, and Cosmetic Act, 

https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryinformation/Guidances/ 

UCM510153.pdf). It is critical that FDA make it a priority to take enforcement action against 

outsourcing facilities that violate the statutory prohibition against copying approved products. 

FDA must prevent outsourcing facilities from making small changes, such as different container 

systems or simple labeled dilutions, to approved products that are not clinically meaningful and 

then marketing them as appropriate substitutes for approved drugs. FDA must exercise similar 

oversight over pharmacies seeking to operate under section 503A and copying FDA-approved 

drugs, despite the differences between the statutory prohibitions against copying in sections 

503A and 503B. 

The definition of "essentially a copy of an approved drug" in section 503B( d)(2) specifies that a 

drug that is on the FDA's drug shortage list at the time of compounding, distribution, and 

dispensing is not considered to be "essentially a copy of an approved drug". To prevent 

outsourcing facilities from continuing to compound drugs long after they have been removed 

from the drug shortage list, FDA should strictly enforce the language ofthe statute. 

3 
272 


29991.201

Without strict oversight of compounding under both 503A and 503B, FDA's approval process 

for NDAs and ANDAs that is considered to be the gold standard domestically and globally could 

be undermined, placing patients at risk. Additionally, any bulk substance compounding should 

only be performed in CGMP conditions due to the high risk. Particularly when the final product 

is sterile injectable. Patients may be given unapproved compounded drugs that are not made 

under the rigorous CGMP standards applicable to manufacturers of approved drugs when there is 

no clinical need for them to get a compounded product. Lowering the bar so that compounding 

outsourcing facilities can make drugs on a large scale and distribute them without prescriptions 

and without complying with strict quality standards would place manufacturers of approved 

drugs at a competitive disadvantage. It would create disincentives for companies to submit 

NDAs and AND As, invest in state of the art manufacturing facilities and manufacture drugs in 

compliance with CGMP requirements. Congress enacted protections in section 503B to prevent 

this from happening, and FDA must enforce those provisions to ensure that Congress's intent is 

fulfilled. 

5. You noted in your testimony that Fresenilis Kabi will be launching a 503B compounding 

center. What consideration did you take into account when considering entering the 503B 

space? 

Currently most Fresenius Kabi products in the U.S. serve hospital customers and we will 

continue to do the same with our compounding business. We replied to a request for proposal 

from a large health care delivery system in Massachusetts for outsourced compounding services 

and will be begin producing for this customer in Q2 of this year. Our longer-term plan is to look 

at similar provider networks to offer this service. 

4 
273 


29991.202

GREG WALDEN, OREGON 

CHAIRMAN 

FRANK PALLONE, JR., NEW JERSEY 

RANKING MEMBER 

ONE HUNDRED FIFTEENTH CONGRESS 

<!Congre£)£) of tbe llniteb ~tate£) 

1!,louse of l\epresentatibes 

COMMITTEE ON ENERGY AND COMMERCE 

2125 RAYBURN HousE OFFICE BuiLDING 

WASHINGTON, DC 20515--6115 

Ms. Elizabeth Jungman 

Director, Public Health 

The Pew Charitable Trusts 

901 E Street, N.W, 

Washington, DC 20004 

Dear Ms. Jungman: 

Majority (202) 225-2927 

Minority {202)225-3641 

February 16, 2018 

Thank you for appearing before the Subcommittee on Health on January 30, 2018, to testify at the 

hearing entitled "Examining Implementation ofthe Compounding Quality Act." 

Pursuant to the Rules of the Committee on Energy and Commerce, the hearing record remains 

open for ten business days to permit Members to submit additional questions for the record, which are 

attached. To facilitate the printing of the hearing record, please respond to these questions with a 

transmittal letter by the close of business on March 3, 2018. Your responses should be mailed to Zack 

Dareshori, Legislative Clerk, Committee on Energy and Commerce, 2125 Rayburn House Office 

Building, Washington, DC 20515 and e-mailed in Word format to zack.dareshori@mail.house.gov. 

Thank you again for your time and effort preparing and delivering testimony before the 

Subcommittee. 

Subcommittee on Health 

cc: The Honorable Gene Green, Ranking Member, Subcommittee on Health 

Attachment 
274 


29991.203

THE 

PEW 

CHARITABlE TRUSTS 

The Honorable Greg Walden, Chairman 

Committee on Energy & Commerce 

U.S. House of Representatives 

Washington, DC 20515 

The Honorable Michael Burgess, Chairman 

Subcommittee on Health 

Committee on Energy & Commerce 

U.S. House of Representatives 

Washington, DC 20515 

2005 Market Street, Suite 2800 

Pl'liladelpl'lia, PA 19103·7077 

901 E Street NW 

Washington, DC 20004 

www.pewtrusts.org 

215.575.9050 Phon~ 

202.552.2000 Pl\one 

The Honorable Frank Pallone, Ranking Member 

Committee on Energy & Commerce 

U.S. House of Representatives 

Washington, DC 20515 

The Honorable Gene Green, Ranking Member 

Subcommittee on Health 

Committee on Energy & Commerce 

U.S. House of Representatives 

Washington, DC 20515 

Dear Chairman Walden, Ranking Member Pallone, Chairman Burgess, and Ranking Member Green, 

Thank you for the opportunity to testify before the Subcommittee on Health on January 30, 2018 at the hearing 

entitled "Examining Implementation of the Compounding Quality Act." My responses to the questions for the 

record are below. If Pew can be of additional service to the Subcommittee, please contact Sarah Despres at 

sdespres@pewtrusts.org or 202-540-6601. 

The Honorable Mjcbael C. Burgess. M.D. 

In testimony before this committee, allegations were raised regarding potential financial conflicts of 

interest and Pew's role as a voting member on the FDA's Pharmacy Compounding Advisory 

Committee. Would you please respond to these allegations? 

In written testimony before the subcommittee January 30, 2018 the witness representing the 

International Association of Compounding Pharmacists alleged financial conflicts arising from 

Pew'sjoint activities with the pharmaceutical industry in connection with my service as a member 

of the Pharmacy Compounding Advisory Committee. I appreciate the opportunity to state 

unequivocally for the record that neither The Pew Charitable Trusts nor I personally have financial 

conflicts of interest in my work on the committee. The FDA process for choosing advisory 

committee members lays out guidelines for preventing conflicts of interest, and my appointment was 

vetted by FDA in accordance with those guidelines. 

Pew is an independent, nonprofit organization dedicated to serving the public. We have a 

longstanding focus on drug safety. Over the last five years we have advocated for federal and state 

policies to ensure that patients who receive compounded drugs are protected from the risks 

associated with these medications. The benefits these safeguards provide to Americans' health are 

the only driver of our work on this issue. 

The Drug Quality and Security Act mandates the range of expertise required to serve on the 

committee, and includes a representative from a public health advocacy organization. I was invited 
275 


29991.204

to serve on the committee in that role when it was formed in 2014, and have served in that capacity 

since, with the exception of a one-year period during which another Pew employee served as the 

public health advocacy organization representative. 

The Honorable Frank fa!lone. Jr. 

DQSA established the Pharmacy Compounding Advisory Committee to advise on scientific, technical 

and medical issues related to implementation of sections 503A and 503B of the Drug Quality Security 

Act and to make recommendations to the Commissioner. The Committee is required to include 

representatives from the National Association of Boards of Pharmacy, the United States Pharmacopeia, 

pharmacists with current experience and expertise in compounding, physicians with background and 

knowledge in compounding, and patient and public health advocacy organizations. 

1. As a member of the Pharmacy Compounding Advisory Committee can yon describe briefly 

the matters that have come before the Committee for review? 

In accordance with its charter (see Appendix A), the Pharmacy Compounding Advisory Committee 

(PCAC) "provide[s] advice on scientific, technical, and medical issues concerning drug compounding 

under sections 503A and 503B of the Federal Food, Drug, and Cosmetic Act, and, as required, any 

other product for which the Food and Drug Administration has regulatory responsibility, and make[s] 

appropriate recommendations to the Commissioner of Food and Drugs." This role is described in 

sections 503A(c)(l) and 503B(c)(2) of the FDCA. Thus far, the committee has made 

recommendations to FDA regarding: (I) bulk substances that should and should not be made 

available for compounding under Section 503A; (2) products that should be included on FDA's list of 

drugs that have been withdrawn or removed for safety or effectiveness reasons; and (3) products that 

are demonstrably difficult to compound. 

2. There bas been criticism that the current Pharmacy Compounding Advisory Committee 

does not have a voting member that is a practicing compounding pharmacist. What is the 

Committee's current make-up and how are members selected for participation on the 

Advisory Committee? 

The PCAC charter (Appendix A) describes the process for selecting members as follows: 

"The Committee shall consist of a core of 12 voting members including the Chair. Members 

and the Chair are selected by the Commissioner or designee from among authorities 

knowledgeable in the fields of pharmaceutical compounding, pharmaceutical manufacturing, 

pharmacy, medicine, and related specialties. These members will include representatives from 

the National Association of Boards of Pharmacy (NABP), the United States Pharmacopeia 

(USP), pharmacists with current experience and expertise in compounding, physicians with 

background and knowledge in compounding, and patient and public health advocacy 

organizations." 

The specific expertise required of the committee, including the public health advocacy role in which I 

serve, is mandated by statute in 503A(c)(l) and 503B(c)(2). In addition to voting members, the 

charter provides that "the Committee may include one or more non-voting members who are 

identified with industry interests." 

According to the committee roster (attached as Appendix B), the current voting members have 

expertise in a range of areas including pharmacology, pharmaceutical formulation and processing, 

pharmacy compounding, consumer advocacy, clinical pharmacy, dermatology, anesthesiology, 
276 


29991.205

pharmaceutical science, public health advocacy (Pew), and hospital and health system pharmacy. 

There are two nonvoting members: one from a pharmaceutical company, and one from a 

compounding pharmacy. 

3. It is my understanding that some members are not voting members of the committee. Can 

you describe why some members are voting and others non-voting? Further, can you 

discuss how FDA ensures that the membership of this Committee remains free of any 

financial, legal, or other conflicts? 

PCAC's charter describes non-voting members as those "who are identified with industry interests." 

Voting members are subject to a conflict-of-interest screening process prior to each meeting. 

At the beginning of each PCAC meeting, an FDA representative reads a statement regarding the 

status of the committee's compliance with federal conflict of interest laws and regulations, including 

those found at 18 U.S.C., Section 208. In that statement, FDA represents that it has determined that 

the members of the committee (including any temporary members attending that particular meeting) 

are in compliance with the federal ethics and conflict of interest laws. FDA notes at the beginning of 

each meeting that members and temporary voting members of the committee have been screened for 

potential financial conflicts of interest of their own as well as those imputed to them, including those 

of their spouses or minor children and, for the purposes of 18 U.S.C., Section 208, their employers. 

These interests may include investtnents; consulting; expert witness testimony; 

contracts/grants/cooperative research and development agreements; teaching/speaking/writing; 

patents and royalties; and primary employment. 

In my experience, upon appointtnent to the committee, members must complete a general conflicts 

disclosure form (OGE F ann 450). This is the form that executive branch employees who are less 

senior than public filers use to report their financial interests as well as other interests outside the 

Government. The purpose of this report, according to the instructions on the form, is to assist 

employees (PCAC members are "Special Government Employees") and their agencies in avoiding 

conflicts between duties and private financial interests or affiliations. 

In addition, prior to each committee meeting, members are required to disclose financial, legal, and 

ideological conflicts (FDA Form 341 0) directly relevant to the substance being discussed at the 

upcoming meeting. On occasion, committee members are excluded from particular votes because of 

these conflicts rules. 

Section 503A of the law prohibits a pharmacist, pharmacy, or health care provider from distributing 

compounded drug products across state lines that exceed five 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. FDA released a draft MOU in February 

2015 that proposed defining "inordinate amounts" for purposes of interstate distribution to be no 

greater than 30 percent of all products distributed or dispensed. More recently, FDA has indicated they 

will be revising this threshold to increase it to 50 percent. 

4. Under this construct, a pharmacy is severely limited in its ability to ship compounded 

drugs out of state unless the state in which the pharmacy operates has signed a MOU with 

FDA. If there is an MOU in place, then the pharmacy may be able to ship more 

compounded drug out of state. Can you explain why the law contemplates restricting 

interstate shipment of compounded drugs and how that restriction could impact patient 

safety? 
277 


29991.206

The MOU provision in section 503A addresses the circumstance when a compounder ships patientspecific drugs across state lines. When that happens, patients affected by the compounding activity 

are not in the state overseeing it. As an illustration of the potential consequences of failing to 

properly oversee interstate shipment of compounded drugs, during the fungal meningitis outbreak of 

2012, products from one dangerous facility harmed patients in 20 states. No victims lived in 

Massachusetts, where the compounder was located. 

As contemplated by the statute, the MOU gives pharmacies in states that agree to investigate and 

respond to complaints from patients outside of its borders more flexibility to sell products across 

state lines. As such, the MOU helps to ensure adequate oversight for patients who receive a patientspecific compounded drug made in another state. 

FDA has indicated that it will issue a new draft MOU in 2018 that will not restrict distribution of 

high volumes of patient-specific drugs, but instead will identify facilities shipping significant 

quantities of drug interstate to federal authorities. The new MOU will require states to identify 

pharmacies that ship most of their product interstate and flag those pharmacies for FDA. This would 

then allow FDA to prioritize its oversight of 503A facilities- e.g. inspections to ensure compliance 

with federal guidelines on preventing insanitary conditions- on those pharmacies that do the most 

interstate shipment (where, arguably, the federal interest is strongest). The effectiveness of the 

provision, if finalized, will depend on states knowing when compounders dispense products over 

state lines, and regulators having sufficient authority to take action when that activity presents public 

health concerns. 

5. Some have suggested that the MOU is only intended to apply to drugs that are distributed 

without a prescription. Given the public health purpose of the MOU, are there some drugs, 

such as those dispensed directly to patients, which could he excluded consistent with that 

purpose? What impact could exclusions related to the distribution of compounded drug 

products across state lines could have on patient safety? 

It would be difficult to reconcile this position with the language of section 503A. The MOU applies 

to compounding under 503A, and all compounding under 503A assumes a prescription. As such, it 

would not make sense for the MOU provision to exempt the only drugs to which it applies: 

prescription-specific compounded drugs. 

Limiting the MOU to drugs provided to healthcare providers would mean that a facility regulated as 

a traditional compounder could operate at manufacturer scale and dispense an unlimited amount of 

product interstate, without FDA oversight, as long as it had prescriptions. Any error or substandard 

practice would potentially affect many people nationwide; a pharmacy that prepares thousands of 

patient-specific drugs a week has the potential to affect many thousands of patients if their facility 

controls are insufficient to prevent contamination. And there really are facilities that sell very large 

volumes of patient-specific drugs. For example, patients who cannot eat and digest normally require 

intravenous administration of liquid nutrition that is tailored to their individual dietary needs; those 

infusions are often prepared by specialized compounders who may be located across the country 

from the patient. 

The MOU provision addresses the risk of state-regulated traditional compounders engaging in 

manufacturer-scale drug production and distribution across state lines, and helps to ensure that this 

practice only occurs in states that have agreed to appropriately oversee this activity, e.g., by 

responding to complaints from patients in states to which the products are distributed. 
278 


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In August 2016, FDA released guidance intended to help compounding pharmacies address insanitary 

conditions at their facility. This guidance document outlines examples of what the agency considers to 

be insanitary conditions and conditions that inspectors have observed, as well as procedures that 

compounding pharmacies can put in plan to ensure their facilities are sanitary and what actions should 

be taken ifthere are insanitary conditions. 

6. We heard at the hearing from providers that having to meet FDA's insanitary conditions 

guidance will make it more difficult for them to provide patients with certain compounded 

medications. I understand that Pew has concerns with exempting certain groups from those 

standards. What is the potential risk of not requiring doctors to meet the same standards as 

pharmacies? 

The safety of compounded preparations depends on the conditions under which they are made. 

Anyone who compounds drugs - in any setting- should be subject to appropriate quality standards 

and meaningful oversight. 

Quality standards, such as those promulgated by the United States Pharmacopeia (USP), recognize 

that the level of risk posed by a drug is partly determined by when and how it is administered. Even 

if a medication has become contaminated, if it is administered immediately, as often occurs in 

physician offices, there is a lower risk of patient harm than if it sits on the shelf for a while, which 

gives those contaminants a chance to multiply to dangerous levels. As such, the USP's standards 

already strike a balance, to ensure patient access to drugs that have been made in a way that 

mitigates their risks. 

If physicians do not have the equipment or specialized training to adhere to USP's quality standards, 

however, patients are put at risk. Patients should not have to sacrifice quality for access. Public 

health is not served by improving access to drugs that are not made under sanitary conditions, for 

which safety cannot be assured. Patients should have access to safe compounded drugs. 

Your written testimony includes an appendix outlining illnesses and deaths associated with 

compounded or repackaged medications. From 2001 to 2017, Pew identified over 1400 adverse events, 

including 114 deaths, that were the result of an identified 71 reported compounding errors or potential 

errors. 

7. Will you describe briefly some of these adverse events Pew identified and the circumstances 

that lead to these adverse events? 

In 2017, at least 43 people in Texas had contaminated antibiotics injected into their eyes; several 

suffered vision loss. Also in 2017, 41 patients received contaminated injections at a New Jersey 

clinic. They developed joint infections caused by microorganisms that should only be found in our 

mouths. Precautions like aseptic technique and appropriate gowning are designed to prevent these 

types of errors. These cases illustrate the importance of adhering to robust quality standards when 

compounding drugs. 

8. In your review, did you see similar or different quality and safety issues between 503A 

compounding pharmacies and 503B outsourcing facilities? 

We have not formally compared quality and safety issues between 503A compounding pharmacies 

and 503B outsourcing facilities, so it is not really possible for me to speak to any similarities or 

differences between the categories, but we are aware of adverse events linked to drugs from both 

types of facilities. 
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29991.208

9. Pew's review of the adverse events associated with compounded or repackaged medications 

highlighted that because adverse events associated with compounding are underreported, 

your review could constitute an underestimation of the number of compounding errors 

since 2001. What more could Congress or FDA do to improve adverse event reporting by 

compounding pharmacies to ensure that such information is more consistently shared with 

the federal government? 

Outsourcing facilities are required to repon all serious, unexpected adverse experiences to FDA. 

FDA has issued guidance to facilitate compliance with this requirement. 

For traditional compounders, which arc primarily subject to state oversight, states set adverse event 

reponing requirements. Pew published research in 2016 showing that only 30 percent of states (13 

of the 43 that responded) require sterile compounding pharmacies to repon serious adverse events. 

For these primarily state-regulated facilities, FDA may be better positioned than states to identify 

problems with particular drugs; if the same adverse events occur with the use of a product, 

regardless of where it is made, the federal agency might be first to become aware of the problem. 

States would need to keep track of adverse events linked to specific facilities to identify problematic 

compounders, but FDA may be able to offer technical assistance with those effons as well. 

10. The states also play a critical role in ensuring the safety of compounding pharmacies. What 

keeps stat·cs from falling short of annual inspections, a best practice your advisory 

committee Identified? How can FDA better assist states as they continue to align with 

federal law? 

The frequency of inspections for traditional pharmacies located in a given state is not typically 

dictated by that state's laws or regulations, but is instead often based on resources. Pew's new repon 

demonstrates that states may be inspecting traditional pharmacies that do sterile compounding less 

frequently now than in 2015. Then, 26 states and the District of Columbia conducted routine 

inspections at least annually for in-state pharmacies that perform sterile compounding; today, just 22 

states and the District do so. Interviews with state officials underscore the need for more financial 

resources and inspection capacity. 
280 


29991.209

Appendix A 

Pharmacy Compounding Advisory Committee Charter 

Authority 

The Phannacy Compounding Advisory Committee is authorized by section 503A and section 503B of the 

Federal Food, Drug, and Cosmetic Act (21 U.S.C. 353a (c) (I) and 21 U.S.C. 353b (c)(2)), as amended by 

sections 102 and 106 of the Drug Quality and Security Act (Pub. L.113-54. The committee also is authorized by 

15 U.S.C. 1451 et seq.;21 U.S.C. 321, 341, 342, 343, 343-1, 344, 345, 346, 348, 349, 350, 350a, 351, 352, 

353(f), 355, 360b, 360c-j, 371,375,376,378, 379e, 381,393,394, 881(b); 42 U.S.C. 217a, 241,242, 242a, 

262, 264; 21 CFR Part 14, 330.10(a); Pub. L. 92-463 (5 U.S.C. App.), and the Federal Advisory Committee 

Act, which sets forth standards for the fonnation and use of advisory committees. 

Objectives and Scope of Activities 

The Phannacy Compounding Advisory Committee advises the Commissioner or designee in discharging 

responsibilities as they relate to compounding drugs for human use and, as required, any other product for 

which the Food and Drug Administration has regulatory responsibility. 

Description of Duties 

The Committee shall provide advice on scientific, technical, and medical issues concerning drug compounding 

under sections 503A and 503B of the Federal Food, Drug, and Cosmetic Act, and, as required, any other 

product for which the Food and Drug Administration has regulatory responsibility, and make appropriate 

recommendations to the Commissioner of Food and Drugs. 

Agency or Official to Whom the Committee Reports 

The Committee provides advice to the Commissioner of Food and Drugs. 

Support 

Management and support services shall be provided by the Center for Drug Evaluation and Research. 

Estimated Annual Operating Costs and Staff Years 

The estimated annual cost for operating the Committee, including compensation and travel expenses for 

members but excluding staff support, is $125,603. The estimated person years of staff support required is 1.10, 

at an estimated annual cost of $86,898. 

Designated Federal Officer 

FDA will select a full-time or pennanent part-time Federal employee to serve as the Designated Federal Officer 

(DFO) to attend each Committee meeting and ensure that all procedures are within applicable statutory, 

regulatory, and HHS General Administration Manual directives. The DFO will approve and prepare all meeting 

agendas, call all of the Committee and subcommittee meetings, adjourn any meeting when the DFO determines 

adjournment to be in the public interest and chair meetings when directed to do so by the official to whom the 

Committee reports. The DFO shall be present at all meetings of the full committee and subcommittees. 

Estimated Number and Frequency of Meetings 

Meetings shall be held approximately 4 times a year. Meetings shall be open to the public except as detennined 

otherwise by the Commissioner or designee in accordance with the Government in the Sunshine Act (5 U.S.C. 

552b(c)) and the Federal Advisory Committee Act. Notice of all meetings shall be given to the public. 

Duration 

Continuing 
281 


29991.210

Termination 

Unless renewed by appropriate action, the charter for the Pharmacy Compounding Advisory Committee will 

expire two years from the date it is filed. 

Membership and Designation 

The Committee shall consist of a core of 12 voting members including the Chair. Members and the Chair are 

selected by the Commissioner or designee from among authorities knowledgeable in the fields of 

pharmaceutical compounding, pharmaceutical manufacturing, pharmacy, medicine, and related specialties. 

These members will include representatives from the National Association of Boards of Pharmacy (NABP), the 

United States Pharmacopeia (USP), pharmacists with current experience and expertise in compounding, 

physicians with background and knowledge in compounding, and patient and public health advocacy 

organizations. Members will be invited to serve for overlapping terms of up to four years. Almost all nonFederal members of this committee serve as Special Government Employees. The core of voting members may 

include one or more technically qualified members, selected by the Commissioner or designee, who are 

identified with consumer interests and are recommended by either a consortium of consumer-oriented 

organizations or other interested persons. In addition to the voting members, the Committee may include one or 

more non-voting members who are identified with industry interests. 

The Commissioner or designee shall have the authority to select members of other scientific and technical FDA 

advisory committees (normally not to exceed I 0 members) to serve temporarily as voting members and to 

designate consultants to serve temporarily as voting members when: (I) expertise is required that is not 

available among current voting standing members of the Committee (when additional voting members are 

added to the Committee to provide needed expertise, a quorum will be based on the combined total of regular 

and added members), or (2) to comprise a quorum when, because of unforeseen circumstances, a quorum is or 

will be lacking. Because of the size of the Committee and the variety in the types of issues that it will consider, 

FDA may, in connection with a particular committee meeting, specify a quorum that is less than a majority of 

the current voting members. The Agency's regulations (21 CFR § 14.22(d)) authorize a committee charter to 

specify quorum requirements. 

If functioning as a medical device panel, a non-voting representative of consumer interests and a non-voting 

representative of industry interests will be included in addition to the voting members. 

Subcommittee 

Temporary subcommittees consisting of two or more Committee members may be established by the 

Commissioner or designee as needed to address specific issues within their respective areas of expertise. 

Subcommittees make preliminary recommendations regarding specific issues for subsequent action by the full 

Committee. The Department Committee Management Officer shall be notified upon establishment of each 

subcommittee, and shall be provided information on its name, membership, function, and estimated frequency 

of meetings. 

Recordkeeping 

Meetings of the Committee and its subcommittees will be conducted according to the Federal Advisory 

Committee Act, other applicable laws and Departmental policies. Committee and subcommittee records will be 

handled in accordance with General Records Schedule 6.2, Federal Advisory Committee Records or other 

approved agency records disposition schedule. These records will be available for public inspection and 

copying, subject to the Freedom of Information Act, 5 U.S.C. 552. 

Filing Date 

April 25, 2016 
282 


29991.211

Approved 

March 30,2016 

Jill Hartzler Warner, J.D. 

Associate Commissioner for Special Medical Programs 

Charter is available at: 

https:(/www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/PharmacyCompoundingAdvisoryComm 

ittee/ucm381305.htm 
283 


29991.212

AppendixB 

Pharmacy Compounding Advisory Committee Roster 

Chairperson 

Jurgen Venitz, MD, PhD 

Expertise: Pharmacology 

Term: 11113/2014 9/30/2018 

Professor and Vice Chairman 

Virginia Commonwealth University 

SchoolofPharmacy 

Department of Pharmaceutics 

410 N. 12th Street 

R.B. Smith Bldg., Room 450 B, PO Box 980533 

Richmond, Virginia 23298-0533 

Robin H. Bogner, Ph.D. 

Expertise: Pharmaceutical Formulation and 

Processing, Pharmacy Compounding 

Term: 1131/2017-9/30/2020 

Professor 

University of Connecticut 

School of Pharmacy 

Department of Pharmaceutical Sciences 

69 North Eagleville Road, PBB 438 

Storrs, Connecticut, 06269 

*Michael A. Carome, MD, FACP 

Expertise: Consumer Advocacy 

Term: 11/24/2014-9/30/2018 

Director, Health Research Group 

Public Citizen 

1600 20th Street, NW 

Washington, District of Columbia 20009 

Seemal R. Desai, M.D., FAAD 

Expertise: Dermatology 

Term: 10/112017-9/30/2021 

President and Medical Director 

Innovative Dermatology 

5425 W. Spring Creek Parkway, Suite 265 

Plano, Texas 75024 

Designated Federal Officer (DFO) 

Cindy Chee, PharmD 

Division of Advisory Committee and Consultant 

Management 

Office of Executive Programs 

Center for Drug Evaluation and Research 

Food and Drug Administration 

10903 New Hampshire Avenue 

Silver Spring, Maryland 20993-0002 

Phone: (301) 796-9001 

Fax: (301) 847-8533 

E-mail: PCAC@fda.hhs.gov 

**Ned S. Braunstein, MD 

Expertise: Molecular Immunology, Clinical 

Rheumatology 

Term: 11/13/2014 10/3112019 

Senior Vice President and Head of Regulatory 

Affairs 

Regencron Pharmaceuticals, Inc. 

777 Old Saw Mill River Road 

Tarrytown, New York 10591 

Gigi S. Davidson, BSPh, DICVP 

Expertise: Clinical Pharmacy 

Term: 11/13/2014-9/30/2018 

Director, Clinical Pharmacy Services 

North Carolina State University 

College of Veterinary Medicine 

1052 William Moore Drive 

Raleigh, North Carolina 27 607 

Padma Gulur, MD 

Expertise: Anesthesiology 

Term: 11113/2014-9/30/2020 

Vice Chair, Operations and Performance 

Duke University School of Medicine 

Department of Anesthesiology 

Duke University Medical Center Box 3094 

Durham, North Carolina 27710 
284 


29991.213

Stephen W. Hoag, PhD 

Expertise: Pharmaceutical Science 

Term: 11/13/2014~9/30/2020 

Professor 

University of Maryland, Baltimore 

Department of Pharmaceutical Science 

20 North Pine Street 

Baltimore, Maryland 21201 

Elizabeth Jungman, JD 

Expertise: Public Health Advocacy 

Term: 11/14/2017~9/30/2021 

Director, Public Health Programs 

The Pew Charitable Trusts 

90 I E Street, Northwest, I Oth Floor 

Washington, District of Columbia 20004 

Kuldip R, Patel, Pharrn.D. 

Expertise: Hospital and Health System Pharmacy 

Term: 9/21/2017~ 9/30/2020 

Associate Chief Pharmacy Officer 

Duke University Hospital 

2301 Erwin Road 

Durham, North Carolina 27710 

Donna Wall, PharmD 

Expertise: Clinical Pharmacy 

Term: 11/13/2014 ~ 9/30/2018 

Clinical Pharmacist 

Indiana University Hospital 

550 North University Boulevard, AOC 6204 

Indianapolis, Indiana 46202 

• Consumer Representative 

•• Industry Representative 

William A. Humphrey, BSPharm, MBA, MS 

Expertise: Clinical Pharmacy 

Term: 11113/2014 ~ 9/30/2020 

Director, Pharmacy Operations 

St. Jude Children's Research Hospital 

262 Danny Thomas Place 

Memphis, Tennessee 38105 

**William Mixon, RPh, MS, FIACP 

Expertise: Pharmacy Compounding 

Term: 11/24/2014-10/31/2019 

Former Owner 

The Compounding Pharmacy 

750 Fourth Street, Southwest 

Hickory, North Carolina 28602 

Allen J. Vaida, BSc, PbarmD, FASHP 

Expertise: Medication Safety 

Term: 11/13/2014-9/30/2019 

Executive Vice President 

Institute for Safe Medication Practices 

200 Lakeside Drive 

Suite 200 

Horsham, Pennsylvania 19044-2321 

Roster is available at: 

https://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/PharmacyCompoundingAdviso 

ryCommittee/ucm38130 l.htm 
285 


29991.214

GREG WALDEN, OREGON 

CHAIRMAN 

FRANK PALLONE, JR., NEW JERSEY 

RANKING MEMBER 

Ms. Nancy Dargan 

654 3 Barrie Circle 

Brighton, Ml48114 

Dear Ms. Dargan: 

ONE HUNDRED FIFTEENTH CONGRESS 

(!Congre~~ of tbe llnfttb ~tate~ 

j!)ouse of l!epresentatibes 

COMMITTEE ON ENERGY AND COMMERCE 

2125 RAYBURN HousE OFFICE BuiLDING 

WASHINGTON, DC 20515-6115 Majority 1202)225-2927 

Minority (202) 225-3641 

February 16,2018 

Thank you for appearing before the Subcommittee on Health on January 30, 2018, to testifY at the 

hearing entitled "Examining Implementation of the Compounding Quality Act." 

Pursuant to the Rules of the Committee on Energy and Commerce, the hearing record remains 

open for ten business days to permit Members to submit additional questions for the record, which are 

attached. To facilitate the printing of the hearing record, please respond to these questions with a 

transmittal letter by the close of business on March 3, 2018. Your responses should be mailed to Zack 

Dareshori, Legislative Clerk. Committee on Energy and Commerce, 2125 Rayburn House Office 

Building, Washington, DC 20515 and e-mailed in Word format to zack.dareshori@mail.house.gov. 

Thank you again for your time and effort preparing and delivering testimony before the 

Subcommittee. 

cc: The Honorable Gene Green, Ranking Member, Subcommittee on Health 

Attachment 
286 

Æ 


29991.215

1. From your perspective, are there portions of the Drug Quality Safety Act that you think should be 

strengthened, or better enforced, to prevent something like this happening again? 

I would like to thank Congress for passing the Drug Quality and Security Act. As I understand it, this law 

is designed to prevent something like what happened to me- or worse-from happening again to 

someone else. 

I worry that ifthat law is not fully implemented in the way Congress intended, patients will pay the price 

the way I have. Patients have to be assured that the drugs that they are taking, or drugs that are being 

injected into them, are safe. That was what Congress intended to do when it passed the DQSA. 

Congress and FDA need to take whatever steps are necessary to make sure that people who are 

compounding drugs have the training and equipment to do it safely. 

2. What steps can the FDA or Congress take to improve patient awareness and safety when it comes 

to compounded drugs? 

Patients shouldn't have to be aware of compounded drug safety issues. Most patients do not have the 

expertise needed to evaluate compounding safety. I am a well-educated and knowledgeable person 

who was totally blindsided by what happened to me. And it is also important to remember that in 

plenty of cases, patients do not have a choice about whether to take a compounded drug because there 

are many instances in which the compounded drug is the only drug available. 

Patients should be able to assume their drugs are safe. FDA and states can make sure that compounders 

use safe procedures, and Congress can continue to pay attention- as they did by holding this hearingto be sure that FDA is implementing the law.