U.S. GOVERNMENT PRINTING OFFICE

WASHINGTON : 

For sale by the Superintendent of Documents, U.S. Government Printing Office

Internet: bookstore.gpo.gov Phone: toll free (866) 512–1800; DC area (202) 512–1800

Fax: (202) 512–2104 Mail: Stop IDCC, Washington, DC 20402–0001

85–438 2014

EXAMINING DRUG COMPOUNDING 

HEARING 

BEFORE THE

SUBCOMMITTEE ON HEALTH 

OF THE

COMMITTEE ON ENERGY AND 

COMMERCE 

HOUSE OF REPRESENTATIVES 

ONE HUNDRED THIRTEENTH CONGRESS 

FIRST SESSION 

MAY 23, 2013 

Serial No. 113–48 

( 

Printed for the use of the Committee on Energy and Commerce 

energycommerce.house.gov 

(II) 

COMMITTEE ON ENERGY AND COMMERCE 

FRED UPTON, Michigan 

Chairman 

RALPH M. HALL, Texas 

JOE BARTON, Texas 

Chairman Emeritus 

ED WHITFIELD, Kentucky 

JOHN SHIMKUS, Illinois 

JOSEPH R. PITTS, Pennsylvania 

GREG WALDEN, Oregon 

LEE TERRY, Nebraska 

MIKE ROGERS, Michigan 

TIM MURPHY, Pennsylvania 

MICHAEL C. BURGESS, Texas 

MARSHA BLACKBURN, Tennessee 

Vice Chairman 

PHIL GINGREY, Georgia 

STEVE SCALISE, Louisiana 

ROBERT E. LATTA, Ohio 

CATHY MCMORRIS RODGERS, Washington 

GREGG HARPER, Mississippi 

LEONARD LANCE, New Jersey 

BILL CASSIDY, Louisiana 

BRETT GUTHRIE, Kentucky 

PETE OLSON, Texas 

DAVID B. MCKINLEY, West Virginia 

CORY GARDNER, Colorado 

MIKE POMPEO, Kansas 

ADAM KINZINGER, Illinois 

H. MORGAN GRIFFITH, Virginia 

GUS M. BILIRAKIS, Florida 

BILL JOHNSON, Missouri 

BILLY LONG, Missouri 

RENEE L. ELLMERS, North Carolina 

HENRY A. WAXMAN, California 

Ranking Member 

JOHN D. DINGELL, Michigan 

Chairman Emeritus 

EDWARD J. MARKEY, Massachusetts 

FRANK PALLONE, JR., New Jersey 

BOBBY L. RUSH, Illinois 

ANNA G. ESHOO, California 

ELIOT L. ENGEL, New York 

GENE GREEN, Texas 

DIANA DEGETTE, Colorado 

LOIS CAPPS, California 

MICHAEL F. DOYLE, Pennsylvania 

JANICE D. SCHAKOWSKY, Illinois 

JIM MATHESON, Utah 

G.K. BUTTERFIELD, North Carolina 

JOHN BARROW, Georgia 

DORIS O. MATSUI, California 

DONNA M. CHRISTENSEN, Virgin Islands 

KATHY CASTOR, Florida 

JOHN P. SARBANES, Maryland 

JERRY MCNERNEY, California 

BRUCE L. BRALEY, Iowa 

PETER WELCH, Vermont 

BEN RAY LUJAN, New Mexico 

PAUL TONKO, New York 

(III) 

SUBCOMMITTEE ON HEALTH

JOSEPH R. PITTS, Pennsylvania 

Chairman 

MICHAEL C. BURGESS, Texas 

Vice Chairman 

ED WHITFIELD, Kentucky 

JOHN SHIMKUS, Illinois 

MIKE ROGERS, Michigan 

TIM MURPHY, Pennsylvania 

MARSHA BLACKBURN, Tennessee 

PHIL GINGREY, Georgia 

CATHY MCMORRIS RODGERS, Washington 

LEONARD LANCE, New Jersey 

BILL CASSIDY, Louisiana 

BRETT GUTHRIE, Kentucky 

H. MORGAN GRIFFITH, Virginia 

GUS M. BILIRAKIS, Florida 

RENEE L. ELLMERS, North Carolina 

JOE BARTON, Texas 

FRED UPTON, Michigan (ex officio) 

FRANK PALLONE, JR., New Jersey 

Ranking Member 

JOHN D. DINGELL, Michigan 

ELIOT L. ENGEL, New York 

LOIS CAPPS, California 

JANICE D. SCHAKOWSKY, Illinois 

JIM MATHESON, Utah 

GENE GREEN, Texas 

G.K. BUTTERFIELD, North Carolina 

JOHN BARROW, Georgia 

DONNA M. CHRISTENSEN, Virgin Islands 

KATHY CASTOR, Florida 

JOHN P. SARBANES, Maryland 

HENRY A. WAXMAN, California (ex officio) 

(V) 

C O N T E N T S 

Page 

Hon. Joseph R. Pitts, a Representative in Congress from the Commonwealth 

of Pennsylvania, opening statement ................................................................... 1 

Prepared statement .......................................................................................... 3 

Hon. Joe Barton, a Representative in Congress from the State of Texas, 

prepared statement .............................................................................................. 4 

Hon. Frank Pallone, Jr., a Representative in Congress from the State of 

New Jersey, opening statement .......................................................................... 4 

Hon. Michael C. Burgess, a Representative in Congress from the State of 

Texas, opening statement .................................................................................... 6 

WITNESSES

Janet Woodcock, M.D., Director, Center for Drug Evaluation and Research, 

Food and Drug Administration ........................................................................... 8 

Prepared statement .......................................................................................... 11 

Answers to submitted questions ...................................................................... 136 

Scott Gottlieb, M.D., Resident Fellow, American Enterprise Institute ............... 52 

Prepared statement .......................................................................................... 55 

Joseph H. Harmison, Owner, Harmison Pharmacies, on Behalf of National 

Community Pharmacist Association ................................................................... 70 

Prepared statement .......................................................................................... 72 

Elizabeth Scott (Scotti) Russell, Government Affairs Manager, National Association of Boards of Pharmacy ............................................................................ 78 

Prepared statement .......................................................................................... 80 

Gabrielle Cosel, Manager, Drug Safety, The Pew Charitable Trust ................... 84 

Prepared statement .......................................................................................... 86 

Gerry Migliaccio, Quality Systems Consultant, Migliaccio Consulting ............... 93 

Prepared statement .......................................................................................... 95 

SUBMITTED MATERIAL

Letter of October 9, 2012, from Mr. Dingell to United States Food and 

Drug Administration ............................................................................................ 110 

FDA response dated April 26, 2013 ................................................................ 113 

Letter of October 16, 2012, from Mr. Dingell to U.S. FDA .................................. 125 

FDA response dated April 26, 2013 ................................................................ 127 

Statement of the National Association of Chain Drug Stores, submitted by 

Mr. Pitts ................................................................................................................ 129 

Statement of Central Admixture Pharmacy Services, Inc., submitted by Mr. 

Pitts ....................................................................................................................... 133 

(1) 

EXAMINING DRUG COMPOUNDING 

THURSDAY, MAY 23, 2013 

HOUSE OF REPRESENTATIVES, SUBCOMMITTEE ON HEALTH, COMMITTEE ON ENERGY AND COMMERCE, Washington, DC. 

The subcommittee met, pursuant to call, at 9:58 a.m., in room 

2322, Rayburn, Hon. Joseph R. Pitts (chairman of the subcommittee) presiding. 

Present: Representatives Pitts, Burgess, Shimkus, Murphy, 

Gingrey, Lance, Guthrie, Griffith, Bilirakis, Ellmers, Barton, 

Pallone, Dingell, Engel, Capps, Matheson, Green, Butterfield, Barrow, Christensen, Castor, and Waxman (ex officio). 

Staff Present: Clay Alspach, Chief Counsel, Health; Mike 

Bloomquist, General Counsel; Karen Christian, Chief Counsel, 

Oversight; Paul Edattel, Professional Staff Member, Health; Brad 

Grantz, Policy Coordinator, O&I; Sydne Harwick, Legislative Clerk; 

Nick Magallanes, Policy Coordinator, CMT; Carly McWilliams, Professional Staff Member, Health; Andrew Powaleny, Deputy Press 

Secretary; Krista Rosenthall, Counsel to Chairman Emeritus; Chris 

Sarley, Policy Coordinator, Environment & Economy; Heidi Stirrup, Health Policy Coordinator; John Stone, Counsel, Oversight; 

Brian Cohen, Minority Staff Director, Oversight & Investigations, 

Senior Policy Advisory; Alli Corr, Minority Policy Analyst; Eric 

Flamm, Minority FDA Detailee; Ruth Katz, Minority Chief Public 

Health Counsel; Elizabeth Letter, Minority Assistant Press Secretary; Karen Nelson, Minority Deputy Committee Staff Director 

for Health; Stephen Salsbury, Minority Special Assistant; Rachel 

Sher, Minority Senior Counsel; and Ryan Skukowski, Minority 

Staff Assistant. 

OPENING STATEMENT OF HON. JOSEPH R. PITTS, A REPRESENTATIVE IN CONGRESS FROM THE COMMONWEALTH 

OF PENNSYLVANIA 

Mr. PITTS. The subcommittee will come to order. The Chair will 

recognize himself for an opening statement. 

The purpose of today’s hearing is to hear from FDA and 

healthcare experts regarding the history and importance of drug 

compounding to patients and the current regulation of 

compounding on the Federal and State levels. As we are all aware, 

in the summer and fall of 2012 a Massachusetts company, the New 

England Compounding Center, NECC, shipped over 17,000 vials of 

an injectable steroid solution from 3 contaminated lots to 

healthcare facilities across the country. 

2 

After receiving injections of NECC’s contaminated steroid, over 

50 people died from complications associated with fungal meningitis; further, almost 700 others were stricken with meningitis or 

other persistent fungal infections. The outbreak ranks as one of the 

worst public health crises associated with contaminated drugs in 

the history of the United States. 

This committee began an investigation into the matter, and on 

October 9th a bipartisan committee letter was sent to FDA requesting details surrounding the outbreak and the prevention of future 

outbreaks. On October 17, the committee sent a letter to FDA asking for all documents related to the outbreak, including internal 

memoranda and communications with NECC. The Oversight and 

Investigations Subcommittee held a hearing on November 14, 2012, 

where Dr. Margaret Hamburg testified examining whether the 

meningitis outbreak could have been prevented. Two days later, on 

November 16th, the committee sent yet another letter to FDA stating that the agency had not provided any of the internal communications or memoranda in response to the October 17th letter. 

It was not until March 21st, 2013, over 5 months after the original request, and after being threatened with the possibility of a 

subpoena, that FDA fully complied with the committee’s document 

request. It should be noted that the Massachusetts Department of 

Public Health had fully complied with the committee’s document 

request, turning over thousands of pages of documents related to 

its interactions with NECC before the November hearing took 

place. 

On April 16, 2013, the O&I Subcommittee held another hearing 

entitled, ‘‘A Continuing Investigation Into the Fungal Meningitis 

Outbreak: Could It Have Been Prevented?’’ and released a 43-page 

report on its investigation into the NECC tragedy. The report stated that FDA had been aware of potential problems at NECC since 

2002. During her testimony at the November hearing, Dr. Hamburg repeatedly expressed uncertainty about FDA’s authority over 

compounding pharmacies, partially due to conflicting opinions on 

the matter issued by two different circuit courts of appeals in 2009. 

This uncertainty, however, has not stopped FDA from engaging 

in multiple enforcement activities against compounding pharmacies 

engaged in practices similar to those of NECC since the outbreak 

took place. This year alone, FDA has announced recalls from 

compounding pharmacies in Augusta, Georgia, and Lake Mary, 

Florida, and St. Petersburg, Florida. In addition, the FDA in October of 2012 was prepared to issue new guidance related to 

compounding enforcement under its authority under Section 503. 

Since the outbreak, however, the FDA has called for new authority that creates a new category of compounding manufacturers. 

From what I understand, there are concerns that creating this new 

category could undermine drug safety by lowering standards and 

also weaken intellectual property protection. 

I would like to thank Dr. Woodcock for appearing before us today 

to explain her understanding of FDA’s authority over compounding 

pharmacies and what actions the agency is taking to ensure that 

future outbreaks can be prevented. And I would also like to thank 

all of our other witnesses for sharing their expertise on 

compounding and its importance to patients. 

3 

Thank you. And I will yield the balance of my time to Congressman Barton. 

[The prepared statement of Mr. Pitts follows:] 

PREPARED STATEMENT OF HON. JOSEPH R. PITTS

The Subcommittee will come to order. 

The Chair will recognize himself for an opening statement.The purpose of today’s 

hearing is to hear from FDA and health care experts regarding the history and importance of drug compounding to patients and the current regulation of 

compounding on the federal and state levels. 

As we are all aware, in the summer and fall of 2012, a Massachusetts company, 

the New England Compounding Center (NECC), shipped over 17,000 vials of an 

injectable steroid solution from three contaminated lots to health care facilities 

across the country. 

After receiving injections of NECC’s contaminated steroid, over 50 people died 

from complications associated with fungal meningitis. Further, almost 700 others 

were stricken with meningitis or other persistent fungal infections. 

The outbreak ranks as one of the worst public health crises associated with contaminated drugs in the history of the United States. 

This Committee began an investigation into the matter, and on October 9th, a bipartisan Committee letter was sent to FDA, requesting details surrounding the outbreak and the prevention of future outbreaks. 

On October 17th, the Committee sent a letter to FDA asking for all documents 

related to the outbreak, including internal memoranda and communications with 

NECC. 

The Oversight and Investigations (O&I) Subcommittee held a hearing on November 14, 2012, where Dr. Margaret Hamburg testified, examining whether the meningitis outbreak could have been prevented. 

Two days later, on November 16th, the Committee sent yet another letter to FDA 

stating that the agency had not provided any of the internal communications or 

memoranda in response to the October 17th letter. 

It was not until March 21, 2013—over five months after the original request and 

after being threatened with the possibility of a subpoena—that FDA fully complied 

with the Committee’s document request. 

It should be noted that the Massachusetts Department of Public Health (MDPH) 

had fully complied with the Committee’s document request—turning over thousands 

of pages of documents related to its interactions with NECC—before the November 

hearing took place. 

On April 16, 2013, the O&I Subcommittee held another hearing entitled ‘‘A Continuing Investigation into the Fungal Meningitis Outbreak: Could It Have Been Prevented?’’ and released a 43-page report on its investigation into the NECC tragedy. 

The report stated that FDA had been aware of potential problems at NECC since 

2002. 

During her testimony at the November hearing, Dr. Hamburg repeatedly expressed uncertainty about FDA’s authority over compounding pharmacies, partially 

due to conflicting opinions on the matter issued by two different Circuit Courts of 

Appeals in 2009. 

This uncertainty, however, has not stopped FDA from engaging in multiple enforcement activities against compounding pharmacies engaged in practices similar 

to those of NECC’s since the outbreak took place. 

This year alone, FDA has announced recalls from compounding pharmacies in Augusta, GA, and Lake Mary and St. Petersburg, FL. 

In addition, the FDA in October 2012 was prepared to issue new guidance related 

to compounding enforcement under its authority under Section 503. Since the outbreak, however, the FDA has called for new authority that creates a new category 

of compounding manufacturers. 

From what I understand, there are concerns that creating this new category could 

undermine drug safety by lowering standards and also weaken intellectual property 

protection. 

I would like to thank Dr. Woodcock for appearing before us today to explain her 

understanding of FDA’s authority over compounding pharmacies and what actions 

the agency is taking to ensure that future outbreaks can be prevented. 

I would also thank our other witnesses for sharing their expertise on 

compounding and its importance to patients. 

Thank you, and I yield the balance of my time to Rep. 

——————————————————. 

4 

Mr. BARTON. Thank you, Mr. Chairman. I am glad to be here 

today. We are glad to have Dr. Woodcock. She is a longtime witness before the committee, and we have great respect for her. We 

look forward to hearing what you have to say. 

I think it is pretty obvious to neutral observers that the facts do 

indicate that the FDA had authority that it refused or chose not 

to use in the situation that we are investigating. I am sure Dr. 

Woodcock will elaborate on that and may have a counter point of 

view. 

Mr. Chairman, on the second panel I have a good friend and 

former constituent, Mr. Joe Harmison, who is in the audience. He 

is the past president of the Texas Pharmacy Association, the past 

president of the National Community Pharmacists Association. He 

is that rare breed, he still owns and operates his own pharmacy. 

The only thing I can find negative about him is that he graduated 

from the University of Oklahoma School of Pharmacy back in 1970. 

Other than that, he is a great guy and a good friend, and I am sure 

he will be very helpful in his testimony on the second panel. 

I might also take personal privilege just to say that Mr. 

Shimkus, to my right, threw out a runner at third base today in 

our intersquad game, as we get ready to battle the Democrats who 

have beat us the last 4 years in the congressional baseball game. 

So Shimkus is getting in game for that. With that, I yield back. 

[The prepared statement of Mr. Barton follows:] 

PREPARED STATEMENT OF HON. JOE BARTON

Thank you, Chairman Pitts for holding this hearing. I applaud the Committee’s 

oversight and investigative work on the recent meningitis outbreak. The facts indicate that the Food and Drug Administration did not use its full authority and act 

quickly against the company compounding and distributing the tainted medication. 

I look forward to hearing from our witnesses today in the Health Subcommittee to 

determine what if anything needs to be done legislatively to prevent further harm 

to innocent Americans. 

In particular, I would like to welcome a fellow Texan to the hearing, Mr. Joe 

Harmison, testifying today on behalf of the National Community Pharmacists Association. I have known Mr. Harmison for twenty years or so and the Committee could 

not have asked a more respected and experienced pharmacist to come to DC to 

share the community pharmacy perspective regarding issues relating to drug 

compounding. I hope he can explain the vital role community pharmacies play in 

compounding drugs for their patients and the difference between his operation and 

those of his association versus what was happening at the companies compounding 

the drugs that caused the recent outbreak. 

With that Mr. Chairman, I welcome the witnesses, look forward to the hearing, 

and yield back. 

Mr. PITTS. Chair thanks the gentleman. 

Now recognize the ranking member of the subcommittee, Mr. 

Pallone, 5 minutes for an opening statement. 

OPENING STATEMENT OF HON. FRANK PALLONE JR, A REPRESENTATIVE IN CONGRESS FROM THE STATE OF NEW JERSEY 

Mr. PALLONE. Thank you, Chairman Pitts. I am pleased that the 

Health Subcommittee is finally having a hearing to examine drug 

compounding. But, unfortunately, we are months behind. While we 

are having our first hearing today to gather information on this 

topic, our colleagues in the Senate have already worked together to 

5 

produce and mark up bipartisan legislation in the Health Committee. And so I think this delay is regrettable here. 

Access to compounding drugs is crucial for patients who have 

unique medical needs. We know that the New England 

Compounding Center that distributed the contaminated compounded product last year, resulting in the meningitis outbreak 

that claimed over 50 lives and infected over 700 patients, was 

clearly a bad actor. However, NECC will not be the last bad actor. 

Similar tragedies will undoubtedly occur again unless we address 

the significant gaps that exist in the current regulation and oversight system of compounded products. If patients are to have confidence in the safety and quality of these drugs, we must ensure 

that compounders meet safety and quality standards. 

While traditional compounders who mix medications to fill a prescription for a specific person are regulated at the State level, and 

drug manufacturers are regulated by the Federal Government, 

there are a growing number of companies that do not fall into either of these categories. Many companies are compounding drugs 

without prescriptions and shipping large quantities of the products 

across State lines; in essence, acting more like manufacturers than 

the traditional compounders. In the absence of clear lines of authority, these companies experience very little State or Federal 

oversight. 

So as we begin to examine drug compounding, I urge my colleagues to use this as an opportunity to move forward to determine 

what changes are needed rather than looking back and casting 

blame. We must stop questioning whether the FDA needs new authority. In fact, the past few months of examination by our Oversight Committee and the Senate Health Committee it has become 

abundantly clear that conflicting court opinions and ambiguous 

language in the law show that the FDA does not have adequate authority to oversee compounders. And that is why I support efforts 

to help identify a new category of companies to be subject to Federal regulation and oversight and provide FDA the tools and resources it needs to properly regulate them. 

So, Mr. Chairman, I hope today can be the start to this committee coming together in a bipartisan manner to address this 

issue and create greater clarity in the law so the tragedies like the 

one involving NECC do not happen again. The American people 

should know that the drugs that they receive are safe and effective. 

So I thank all our witnesses. I know we have a second panel. I 

look forward to hearing about how Congress can best address the 

gaps in regulation and oversight that were unfortunately highlighted by the NECC meningitis outbreak and how all stakeholders 

can work together to protect the public health. 

I don’t know if anybody wants any of my 2 minutes on my side. 

You would, Mr. Dingell? I yield to Mr. Dingell. 

Mr. DINGELL. I thank the gentleman for yielding. I thank you for 

having this hearing. I welcome our first panel member today. Good 

to see her back before the committee. 

This committee has a great opportunity. We can quibble all we 

want about whether we have the authority, whether it is needed 

or not. Simple fact of the matter is people are dying, people are 

being made sick. And many people in this compounding industry, 

6 

if that is what you want to say it is, have been studying ways to 

get around food and drug regulation and to continue, for all intents 

and purposes, becoming manufacturers. 

The question is, do we want to persist on that while we engage 

in a monstrous quibble, or do we want to get down and cut the corners that come from courts and judges trying to resolve a question 

that is probably well beyond their competency. 

Having said these things, I would urge us to move forward on 

legislation, effective legislation. This committee has a remarkable 

history in this Congress, which is noteworthy for having done very 

little, to have in fact moved forward with a number of important 

pieces of legislation in a bipartisan fashion. I see no reason why we 

should not continue that kind of effort with all the blessings to the 

public that that obtains. 

So I would urge us to move forward. Let’s put these rascals in 

the compounding industry into a place where they have law to 

obey, where everyone understands what it is, and where we can 

make our people safe. My State of Michigan suffered huge losses 

to people in sickness and death stemming from wrongdoers who 

were deliberately skating around the law. And unsafe pharmaceuticals well beyond the reach of Food and Drug were in fact poisoning and killing our people. 

This is a wonderful opportunity. I commend you for making it 

possible. I look forward to working with you. I commend my colleague Mr. Pallone for his wise counsel and leadership. And I look 

forward to working on this matter in an effective way where we do 

go forward together to solve a major problem for our people. Thank 

you. 

Mr. PITTS. Chair thanks the gentleman. 

Now recognize the vice chairman of the subcommittee, Dr. Burgess, 5 minutes for an opening statement. 

OPENING STATEMENT OF HON. MICHAEL C. BURGESS, A 

REPRESENTATIVE IN CONGRESS FROM THE STATE OF TEXAS 

Mr. BURGESS. Thank the chairman for the recognition. And I do 

support the efforts to examine the role that traditional 

compounding pharmacists play in the healthcare system. I know 

the value that they provide, having used them in my practice for 

a number of years. 

But we are also going to hear this morning how this incident necessitates broad new authorities. Recently the Food and Drug Administration has inspected over 50 compounding facilities. You 

have to ask yourself, by what authority did these 50 inspections 

occur? If the FDA has the authority today, they had it 6 months 

ago. The fact is one of the following statements must be true: The 

agency is acting without authority and risking litigation or they 

have the authority and have always had the authority and have 

simply failed to use it. 

Documents obtained by the Oversight and Investigations Subcommittee are deeply troubling, and I believe show FDA negligence. New England Compounding Center was making upwards 

of 30,000 vials of product without prescriptions and yet the Food 

and Drug Administration questioned whether they had authority 

under the Food, Drug, and Cosmetic Act over manufacturing? 

7 

The Food and Drug Administration was aware that this 

compounding facility was making poor products for years. They 

never followed up on warning letters. Frustrated FDA staff could 

not even warn the State of Massachusetts. Whistleblowers, doctors 

providing dozens of adverse event reports and law firms dealing 

with substandard conditions came forward and the FDA did nothing. They didn’t even pick up the phone. 

This is an example of circling the wagons after the crisis, and 

this member is having none of it. The bureaucracy held up the 

guidance for years. Testimony that is as provided through our 

Oversight and Investigations Subcommittee—the testimony that 

has been provided to both the Oversight and Investigations Subcommittee and this subcommittee today has been carefully crafted 

to avoid asking who failed America and who allowed NECC to introduce contaminated product in its supply line. 

I cannot in good conscience entertain discussion of legislation 

when not one person has been fired, reprimanded, or held culpable 

at the Food and Drug Administration. In fact, legislating transfers 

the blood of those dead and harmed from the agency responsible to 

us, the subcommittee and to Congress. 

Massachusetts fired people because they should have known, and 

yet the Food and Drug Administration, who did know, now wants 

new authority. To what end is new authority going to provide protection to the public if the Food and Drug Administration, by its 

own admission and track record, refuses to pick up and use the 

tools they had at their disposal. The Food and Drug Administration 

refused to go after those operating so far outside the bounds of legality in traditional compounding. Why in the world would we trust 

them to regulate a legitimate compounder? 

Until the agency admits where it failed the American public, I 

for one am not going to be a party to letting them get away with 

this dereliction of responsibility. To do otherwise invites further incompetence from one of the most important agencies under our jurisdiction and sets a dangerous precedent for other agencies under 

our purview. 

I would like to yield the balance of the time to the gentleman 

from Virginia, Mr. Griffith. 

Mr. GRIFFITH. Thank you, Dr. Burgess. 

Last fall’s fungal meningitis outbreak was a true public health 

crisis for our Nation. In Virginia’s Ninth Congressional District, 

which I represent, there were two deaths and 50 confirmed cases 

of fungal meningitis associated with the sterile compounded injections from NECC. Approximately 1,400 patients in southwest Virginia were notified they could have been exposed to fungal meningitis because they received tainted steroid injections. 

I clearly believe that FDA had the authority they needed to prevent the fungal meningitis outbreak. NECC was a manufacturer. 

The committee’s thorough investigation has demonstrated the 

agency failed in their oversight and did not pursue regulatory action against NECC and Ameridose, who were acting illegally as 

manufacturers, not as compounding pharmacies, in violation of the 

Food, Drug, and Cosmetic Act. 

With well over 130 community pharmacists provided invaluable 

access to health care in rural and remote communities in the 

8 

mountains of southwest Virginia, I do not support giving FDA 

broad new authority over the practice of pharmacy, which is the jurisdiction of our States. The type of compounding that goes on in 

our local pharmacies involves making special medications subject 

to the needs of the individuals based on a patient-specific prescription from their physician. 

The real problem is large-scale operations like NECC who are 

acting illegally as drug manufacturers by making large batches of 

drugs, some of which are just copies of FDA-approved drugs, and 

then selling and shipping them all over the country. 

In her testimony, Dr. Woodcock acknowledges that FDA was in 

the final stages of publishing new guidance differentiating pharmacy compounding from drug manufacturing. Three years later, 

FDA finally had all of its ducks in a row and was ready to go forward, but they did not do so in their draft guidance document. I 

believe there are some areas that need clarification. So we have 

been doing our due diligence to understand this issue and develop 

legislation that will make it clear how we define what a 

compounding pharmacy is, which is and should be regulated by the 

States, and what a drug manufacturer is, which should be regulated by the FDA. 

Yield back. 

Mr. PITTS. The chair thanks the gentleman. 

That concludes our opening statements. We have two panels 

today. Our first panel today we have Dr. Janet Woodcock, Director 

of the Center for Drug Evaluation and Research, U.S. Food and 

Drug Administration. 

Thank you for coming, Dr. Woodcock. You will have 5 minutes 

to summarize your testimony. Your entire written testimony will be 

placed in the record. You are welcome and recognized for 5 minutes. 

STATEMENT OF JANET WOODCOCK, M.D., DIRECTOR, CENTER 

FOR DRUG EVALUATION AND RESEARCH, FOOD AND DRUG 

ADMINISTRATION 

Dr. WOODCOCK. Thank you, Mr. Chairman, Vice Chairman, 

Ranking Member, and members of the committee. Thank you for 

the opportunity to testify. 

This has really been an appalling tragedy of a kind not seen really since the early 1900s, where American citizens were harmed by 

grossly contaminated drug. But this is just the worst of a long series of outbreaks over the past 2 decades that have involved 

compounding pharmacies, and these have included multiple deaths, 

blindness, hospitalizations, and other types of harm. So this was 

just the worst of a continuing series of outbreaks. 

As the Commissioner testified, we should have been more aggressive in applying our existing authorities to this industry, despite 

the ambiguities in the statute and despite challenges by industry. 

We are being more aggressive now, and we are inspecting the pharmacies that we know about that present the highest risk. And we 

are seeing really serious systemic quality issues, particularly 

around sterility practices. 

In light of recent events, though, even with the tragedy that has 

occurred, some of these firms challenge our authority when we try 

9 

to go in and inspect them, and they delay or deny full access to our 

records. We have twice had to get administrative warrants from 

the court and have U.S. marshals accompany our inspectors. And 

we have had to threaten warrants in other cases to get cooperation 

to inspect these compounding pharmacies. And because we are inspecting and moving aggressively doesn’t mean we are going to prevail in court. 

Make no mistake, if the approach to this isn’t changed, and I 

think legislation is probably the best approach, we will see more 

of these tragedies. We are already, since the outbreak, we have 

seen several episodes involving human harm from compounded 

products. 

Lack of clarity in our statutory authorities really isn’t the only 

concern. The industry has evolved tremendously since the time of 

the corner pharmacist and traditional compounding in response to 

a prescription. And this is still going on, and FDA has always said 

we felt this was appropriate. But another industry has grown up 

that is basically performing outsourcing for hospitals and making 

large amounts of dosage forms, often starting with FDA-approved 

products. And this industry was really never contemplated in the 

kind of authorities that we have. 

So we feel that we need legislation to preserve the benefits of 

traditional compounding, which is in response to a prescription, 

and which we are not proposing that we should have authority 

over, further authority over, while at the same time giving us the 

right tools to regulate high-risk practices and products. We feel we 

need legislation that requires compliance with Federal quality 

standards; requires Federal registration, because right now we 

don’t know who they are, we don’t know where they are, and we 

don’t know what they are making; and requires reporting to FDA 

of adverse events so that we can act before the problems get out 

of hand. Right now there is no requirement to send us reports of 

death or other harm that might occur with these products. 

And for all pharmacy compounding we feel basic protections 

should be in place, including the fact that FDA should have access 

to the records so that we can go in and see whether they are shipping large amounts of product, all right, and what they are doing; 

and also, should there be an outbreak, we are not delayed by having to go to a marshal and have access to the shipping records. 

A prohibition on compounding the most complex and highest-risk 

products. Our drug manufacturers, as you know, have problems 

manufacturing certain products because they are very complex, and 

they put a tremendous amount of science and effort into that. We 

don’t think they should be compounded. That is a small list, but 

we think that list should be maintained. And clear labeling of compounded drugs to allow prescribers and patients to make more informed choices. 

We look forward to working with you to explore funding mechanisms to support this oversight, should it be put in place. Remember, I think it really is a matter of when this is going to occur the 

next time, not if. That is the state that we are observing of the industry when we are inspecting them. We are all on notice, we owe 

it to the public and the victims of this incident and the numerous 

10 

outbreaks over the years to provide better protection in the future. 

I look forward to answering your questions. 

Mr. PITTS. Thank you, Dr. Woodcock. 

[The prepared statement of Dr. Woodcock follows:] 

11 


85438.001

/~ (.s't.. DEPARTMENT OF HEALTH AND HUMAN SERVICES 

STATEMENT 

OF 

JANET WOODCOCK, M.D. 

PubliC Health Service 

Food and Drug Administration 

Silver Spring, MD 20993 

DIRECTOR, CENTER FOR DRUG EVALUATION AND RESEARCH 

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 DRUG COMPOUNDING" 

May 23, 2013 

RELEASE ONLY UPON DELlVERY 
12 


85438.002

INTRODUCTION 

Mr. Chairman and Members ofthe Subcommittee, I am Dr. Janet Woodcock, Director of the 

Center for Drug Evaluation and Research 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 be here today to discuss important issues related to pharmacy compounding. 

We are at a critical point where we must work together to improve the safety of drugs produced 

by compounding pharmacies. As the compounding industry has grown and changed, we have 

seen too many injuries and deaths over many years caused by unsafe practices. Dr. Margaret 

Hamburg, Commissioner of Food and Drugs, testified in front of the Oversight and 

Investigations Subcommittee on April 16, 2013, regarding the emergence of a tragic fungal 

meningitis outbreak associated with compounded methylprednisolone acetate (MPA), a steroid 

injectable product distributed by the New England Compounding Center (NECC). To date, that 

outbreak has been associated with 55 deaths and over 740 people sickened in 20 States. Sadly, 

NECC was not an isolated incident. Indeed, over the past 20 years we have seen multiple 

situations where compounded products have caused deaths and serious injuries. For example: 

• In 1997, two patients were hospitalized with serious infections after administration of 

contaminated riboflavin injection prepared by a Colorado pharmacy. 

• In 2001,13 patients in California were hospitalized and 22 received medical care 

following injections from contaminated vials ofa steroid solution. Three patients died 

as a result. 

2 
13 


85438.003

• In 2002, five patients in North Carolina suffered from fungal meningitis resulting from 

contaminated methylprednisolone acetate made by a South Carolina pharmacy. One 

person died. 

• In 2005, contaminated cardioplegia solution, made by a finn located in Maryland, 

resulted in five cases of severe system inflammatory infections; three of these patients 

died. 

• In 2007, three people died from mUltiple organ failure after a Texas compounder sold 

superpotent colchicine that was as much as 640 percent the labeled strength. 

• In 2010, FDA investigated a cluster of Streptococcus endophthalmitis bacterial eye 

infections in patients who received injections of A vastin repackaged by a phannacy in 

Tennessee. 

• In 2011, there were 19 cases of Serratia marcescens bacterial infections, including 

nine deaths, associated with contaminated total parenteral nutrition products. 

• In 2012, 43 patients developed fungal eye infections from contaminated sterile 

ophthalmic drug products. At least 29 of these patients suffered vision loss. 

• Recently, in 2013, FDA investigated reports of five cases of eye infections in patients 

who received Avastin repackaged by a phannacy in Georgia. The Avastin was 

contaminated with bacteria. 

These incidents are emblematic oflong-standing issues associated with the practice of 

compounding and the public health concerns that can result from unsafe practices in 

compounding phannacies. 

Since the NECC outbreak, ten additional finns have conducted voluntary recalls overseen by 

FDA of sterile compounded or repackaged drug products as of May 16, 2013. In one recent 

3 
14 


85438.004

incident, the presence of floating particles, later identified to be a fungus, was reported in five 

bags of magnesium sulfate intravenous solution, resulting in a nationwide recall of all sterile 

drug products produced by the pharmacy (over 100 products). Fortunately, we have not received 

reports of patient injury from these products. In another recent recall, all sterile drug products 

(approximately 60 products) from a second pharmacy were recalled as a result of reports that 

five patients were diagnosed with serious eye infections associated with the use of repackaged 

A vastin. Moreover, we believe that presently, there are hundreds of other firms operating as 

compounding pharmacies, producing what should be sterile products and shipping across State 

lines in advance of or without a prescription. However, the current legal framework does not 

provide FDA with the tools needed to identify and appropriately regulate these pharmacies to 

prevent product contamination. 

The history of this issue shows that there is a need for appropriate and effective oversight of this 

evolving industry. It is clear that the industry and the health care system have evolved and 

outgrown the law, and FDA's ability to take action against compounding that exceeds the bounds 

of traditional pharmacy compounding and poses risks to patients has been hampered by 

limitations and ambiguities in the law, which have led to legal challenges to FDA's authority to 

inspect pharmacies and take appropriate enforcement actions. 

The fungal meningitis outbreak has caused the Agency to review our past practices with regard 

to our oversight of compounding pharmacies, and has led to some preliminary conclusions. 

In my view, even in the face of litigation and continuous challenges by industry to our 

authorities, we can nonetheless be more aggressive in pursuing enforcement actions against 

compounding pharmacies within our current authority. I can assure you that we are being more 

aggressive now. We have established an Agency-wide steering committee to oversee and 

4 
15 


85438.005

coordinate our efforts, and we have taken several important steps to identifY and inspect highrisk pharmacies that are known to have engaged in production of sterile drug products. 

Using a risk-based model, we identified 29 firms for priority inspections focused on their sterile 

processing practices. During these 29 inspections, in two instances, FDA identified secondary 

firms associated with the priority inspections, for a total of31 firms. We have taken 

investigators who would normally be doing inspections of conventional drug manufacturers and 

assigned them to conduct inspections of those pharmacies whose history suggests a greater risk 

of potential quality issues with their compounded products. We have coordinated our 

inspections with State officials, who have accompanied our investigators in most cases. At the 

same time, we have also continued to conduct for-cause inspections, often at the request of our 

State counterparts who invited us to accompany them on the inspections. Since the faU, FDA has 

completed 26 for-cause inspections in addition to the 31 described above, as of May 16; 2013. 

When we identified problems during any of the inspections, at the close of the inspection, we 

issued an FDA Form 483 1 listing our inspection observations. We have issued an FDA-483 at 

the close of 47 of the 57 inspections we have conducted since last fall. We have seen some 

serious issues, including quality concerns that have led to product recalls. Observations have 

included: lack of appropriate air filtration systems, insufficient microbiological testing, and other 

practices that create risk of contamination. 

Notably, even in light of recent events, and even though we are often working with the State 

inspectors, our investigators' efforts are being delayed because they are denied full access to 

records at some of the facilities they are inspecting. Just during the recent inspections, several 

I A form FDA-483 is issued when investigators observe any significant objectionable conditions. It does not 

constitute a final Agency determination of whether any condition is in violation of the Federal Food, Drug, and 

Cosmetic Act (FD&C Act) or any of our relevant regulations, but the observations often serve as evidence of a 

violation of the FD&C Act and its implementing regulations. 

5 
16 


85438.006

phannacies delayed or refused FDA access to records, and FDA had to seek administrative 

warrants in two cases. And although we have been able to eventually conduct the inspections 

and collect the records that we have sought, our ability to take effective regulatory action to 

obtain lasting corrective action with regard to substandard sterility practices remains to be seen. 

As we have noted in the past, our ability to take action against inappropriate compounding 

practices has been hampered by ambiguities regarding FDA's enforcement authority, legal 

challenges, and adverse court decisions, and we have learned that the law is not well-suited to 

effectively regulate this evolving industry. For example, hospitals have come to rely on 

compounding pharmacies that function as "outsourcers" producing sterile drngs previously made 

by hospital in-house phannacies. If FDA brings charges against a phannacy, alleging that it is 

manufacturing a "new drug" that cannot be marketed without an approved application, the 

phannacy will have to either obtain individual patient-specific prescriptions for all of its products 

or stop distributing the products until it obtains approved new drug applications for them, 

something most outsourcers are unlikely to do. Several of the phannacies FDA inspected are 

some of the largest outsourcers in the country. These phannacies supply large numbers of sterile 

drugs produced in relatively large quantities to hospitals nationwide, and a shut-down at these 

firms is likely to cause disruptions in the supply of drugs to hospitals and other health care 

providers. FDA should have more tailored authorities appropriate for this type of compounding 

pharmacy. 

In the Commissioner's appearances before the Committee on Energy and Commerce in 

November 2012 and April 2013, she presented a framework that could serve as a basis for the 

development of a risk-based program to better protect the public health, improve accountability, 

and provide more appropriate and stronger tools for overseeing this evolving industry. Since 

6 
17 


85438.007

November, we have met with over 50 stakeholder groups, including pharmacy, medical, hospital, 

payer, and consumer groups, and State regulators, to help further our understanding and inform 

our framework. Today, I will first provide background on FDA's current legal authority over 

compounded drugs, then review that framework, and suggest specific actions that Congress can 

take to help us better do our job and prevent future tragedies like this one. 

FDA's Legal Authority over Compounded Drugs 

FDA regards traditional pharmacy compounding as the combining or altering of ingredients by a 

licensed pharmacist, in response to a licensed practitioner's prescription for an individual patient, 

which produces a medication tailored to that patient's special medical needs. In its simplest 

form, traditional compounding may involve reformulating a drug, for example, by removing a 

dye or preservative in response to a patient allergy. It may also involve making an alternative 

dosage form such as a suspension or suppository for a child or elderly patient who has difficulty 

swallowing a tablet. FDA believes that pharmacists engaging in traditional compounding 

provide a valuable medical service that is an important component of our health care system. 

However, by the early 1990s, some pharmacies had begun producing drugs beyond what had 

historically been done within traditional compounding. 

After receiving reports of adverse events associated with compounded medications! FDA became 

concerned about the lack of a policy statement on what constituted appropriate pharmacy 

compounding. In March 1992, the Agency issued a Compliance Policy Ouide (CPO), section 

7132.16 (later renumbered as 460.200) to delineate FDA's enforcement policy on pharmacy 

compounding. It described certain factors that the Agency would consider in its regulatory 

approach to pharmacies that were producing drugs. 

7 
18 


85438.008

The compounding industry objected to this approach and several bills were introduced, some 

with significant support, to limit the Agency's oversight of compounding. 2 In November 1997, 

S. 830, the Food and Drug Administration Modernization Act of 1997 (FDAMA), was signed 

into law as Public Law 105-115.3 FDAMA added Section 503A to the FD&C Act, to address 

FDA's authority over compounded drugs. 4 Section S03A exempts compounded drugs from 

three critical provisions of the FD&C Act: the pre market approval requirement for "new drugs"; 

the requirement that a drug be made in compliance with current good manufacturing 

practice (cGMP) standards; and the requirement that the drug bear adequate directions for use, 

provided certain conditions are met. These provisions were the subject of subsequent court 

challenges, which have produced conflicting case law and amplified the perceived limitations 

and ambiguity associated with FDA's enforcement authority over compounding pharmacies. In 

2002, immediately after a Supreme Court ruling that invalidated the advertising provisions of 

Section 503A, FDA issued a revised compliance policy guide on compounding human drugs. 

Several additional legal challenges and court decisions then followed. More recently, FDA made 

significant progress toward issuing another CPG. In fact, FDA was on track to publish a revised 

draft CPG in the fall of2012, but the fungal meningitis outbreak intervened and we are now 

reevaluating the draft. It is important to note, however, that a CPG is not binding on industry 

and updating the CPG would not alleviate all issues with Section S03A. 

A look at FDA's attempts to address compounding over the last 20 years shows numerous 

approaches that were derailed by constant challenges to the law. As a result, presently, it is 

unclear where in the country Section 503A is in effect, and Section S03A itself includes several 

2 H.R. 5256, Phannacy Compounding Preservation Act of 1994, introduced Oct. 7, 1994, 1 co-sponsor; H.R. 598, 

Phannacy Compounding Preservation Act of 1994, introduced Jan. 20, 1995, 141 co-sponsors; H .R. 3199, Drug and 

Biological Products Reform Act of 1996, introduced March 29, 1996,205 co-sponsors; H.R. 1060, Pharmacy 

Compounding Act, introduced March 13, 1997, 152 co-sponsors; H.R. 1411, Drug and Biological Products 

Modernization Act of 1997, introduced April 23, 1997, 16 co-sponsors 

3 Public Law lOS-lIS, FDAMA, III Stat. 2296 (Nov. 21,1997), available at hltp:/lwww.gpo.govlfdsyslpkglPLAWJ05pub1115IpdflPLAW-J05pubI115.pdf 

8 
19 


85438.009

provisions that have impeded FDA's ability to effectively regulate pharmacy compounding 

practices including those relating to prescription orders, medical need, and copying FDAapproved products. 

Apart from Section 503A, there are additional provisions in the statute that have impeded 

effective pharmacy compounding regulation. For example, if certain criteria are met, the FD&C 

Act exempts compounding pharmacies from registration and the obligation to permit access to 

records during an inspection. As a result, FDA has limited knowledge of pharmacy 

compounders and compounding practices and limited ability to oversee their activities. 

Looking Ahead 

The Administration is committed to working with Congress to address the threat to public health 

from limitations in authorities for effective oversight of certain compounding practices. To that 

end, FDA has developed a framework that could serve as the basis for the development of a riskbased program to protect the public health. 

Risk-based Framework 

Recognizing the history of compounding practice, FDA supports the long-standing policy that all 

compounding should be performed in a licensed pharmacy by a licensed pharmacist (or a 

licensed physician), and that there must be a medical need for the compounded drug. 

Further, we believe there should be a distinction between two categories of compounding: 

traditional and non-traditional. Traditional compounding would include the combining, mixing, 

'Id. 

9 
20 


85438.010

or altering of ingredients to create a customized medication for an individual patient with an 

individualized medical need for the compounded product, in response to a valid patient-specific 

prescription or order from a licensed practitioner documenting such medical need. Traditional 

compounding, while posing some risk, plays an important role in the health care system, and 

should remain the subject of State regulation of the practice of pharmacy. 

Non-traditional compounding would include certain types of compounding for which there is a 

medical need, but that pose higher risks. FDA proposes working with Congress to define nontraditional compounding based on factors that make the product higher risk such as any sterile 

compounding in advance of or without receiving a prescription, where the drug is distributed out 

of the state in which it was produced. Non-traditional compounding would be subject to Federal 

standards adequate to ensure that the compounding could be performed without putting patients 

at undue risk, and FDA would inspect against and enforce these Federal standards. Such a 

definition focuses on the highest risk activities and offers a uniform degree of protection across 

alISO States, for highest-risk compounding activities. 

Non-traditional compounding should, because of the higher risk presented, be subject to a greater 

degree of oversight. Sterile products produced in advance of or without a prescription and 

shipped interstate should be subject to the highest level of controls, established by FDA and 

appropriate to the activity, similar to cGMP standards applicable to conventional drug 

manufacturers. 

In addition, FDA believes that with noted exceptions, certain products are not appropriate for 

compounding under any circumstances. These products would include: I) what are essentially 

copies of FDA-approved drugs, absent a shortage justification based on the drug appearing on 

10 
21 


85438.011

FDA's shortage list; and 2) complex dosage forms such as extended release products; 

transdermal patches; Iiposomal products; most biologics; and other products as designated by 

FDA. Producing complex dosage forms would require an approved application and compliance 

with cGMP standards, along with other requirements applicable to manufactured drug products. 

FDA believes that there are other authorities that would be important to support this new 

regulatory paradigm. For example, FDA should have clear ability to collect and test samples of 

compounded drugs and to examine and collect records in a compounding pharmacy, just as the 

Agency does when inspecting other manufacturers. FDA should also have clear ability to 

examine records such as records of prescriptions received, products shipped, volume of 

operations, and operational records such as batch records, product quality test results, and 

stability testing results. Such inspections are necessary to determine when a pharmacy exceeds 

the bounds of traditional compounding, to respond to public health threats, and to enforce 

Federal standards. 

FDA also believes that an accurate inventory of pharmacies engaged in non-traditional 

compounding would facilitate appropriate oversight and coordination with State regulators. In 

addition, FDA looks forward to working with the Congress on potential improvements that may 

include label statements and adverse event reporting that have proven useful in other areas. A 

user-fee-funded regulatory program may be appropriate to support the inspections and other 

oversight activities outlined in this framework. We look forward to working with Congress to 

explore the appropriate funding mechanisms to support this work, which could include 

registration or other fees, as Congress has authorized and FDA has successfully implemented in 

other settings. 

11 
22 


85438.012

CONCLUSION 

Given our experiences over the past 20 years and the recent fungal meningitis outbreak, we must 

do everything we can to clarify and strengthen FDA's authority in this area. 

I am happy to answer any questions you may have. 

12 
23 

Mr. PITTS. I will begin the questioning and recognize myself for 

5 minutes for that purpose. 

Dr. Woodcock, since the outbreak, the FDA has executed dozens 

of inspections and at least 11 companies were ordered to stop producing some or all drugs. Have any of the companies you inspected 

challenged the FDA authority? If so, how many? 

Dr. WOODCOCK. Certainly, as I said, we have had several challenge our authority to even go in the firm and look at their records. 

Others have challenged and then yielded when we got the lawyers 

talking to one another. Now, as far as whether there will be court 

challenges, that is something I really can’t speak to. But that certainly has been the history in the past. 

Mr. PITTS. Can you provide a list to the committee of the companies who you have inspected and who have challenged your authority? 

Dr. WOODCOCK. We will be happy to do so. 

Mr. PITTS. According to the Senate HELP report, I quote, ‘‘As a 

result of increased oversight from both State and Federal regulators, at least 48 compounding companies have been found to be 

producing and selling drugs that are contaminated or were created 

in unsafe conditions or otherwise violate State licensing requirements. Ten companies have issued nationwide recalls of drugs compounded at their facilities. In at least four cases, the recall was 

issued in response to documentation of actual contamination. Further, 11 compounding pharmacies have been ordered to cease and 

desist operations, including two of those that had issued nationwide recalls.’’ 

Now, as you said, some of these companies challenged the FDA’s 

authority. Can you explain how State and Federal regulators executed this increased oversight? 

Dr. WOODCOCK. Well, we identified firms that we knew about basically from adverse event reports, from reports in the paper, from 

advertisements they had on a Web page and so forth, and we did 

a risk-based approach to inspecting what we felt were the highestrisk firms, based on what we knew. We don’t know the whole universe of firms that are out there. 

We also continue to do for-cause inspections. For example, if we 

get a report from a health department about a cluster of cases of 

an outbreak of one sort or another, we will immediately go into 

that pharmacy and inspect them. In all of those for-cause cases, we 

have gone in with the State authority. So we have gone in together, 

all right. And in most of the other inspections that we did that we 

planned, the 31 inspections, we have gone in with the State authorities as well. 

Mr. PITTS. What were the biggest challenges that you faced during that period? 

Dr. WOODCOCK. Well, the challenges mainly were getting access 

in some cases to be allowed to inspect, all right, particularly some 

of their records. But the real thing that we have found is that the 

aseptic processing practices, which means how you try to make a 

drug to ensure that it is sterile, are not anywhere near the quality 

that is necessary to mass produce sterile drugs. There is a tremendous deficit of quality in their practices that almost assure that 

these drugs will at some point be contaminated. 

24 

Mr. PITTS. What are some of the lessons the agency has learned 

during the period of this outbreak? 

Dr. WOODCOCK. Well, I think we have learned that there are pervasive practices that are unsafe that are going on across the portion of this industry that we have investigated. Primarily, we are 

targeting those sterile manufacturers because that is the highest 

risk when you are actually injecting drugs into the body. So that 

is one thing we have learned, is the pervasive nature of unsafe 

practices across the section of industry that we have inspected. 

Mr. PITTS. In your testimony you reference nine separate incidents where compounded products caused deaths and serious injuries. Explain briefly the actions the FDA took following each of 

these incidents. 

Dr. WOODCOCK. Well, over the years, our actions have been primarily reactive. OK. So when we have learned of an outbreak, as 

I said, we have gone in. Often we go in with the State. The State, 

because they hold the pharmacy license, they are able to shut down 

the firm right away. Like that is how those 11 firms you referred 

to were shut down. OK. 

We have to call for and we often do talk to the firm and say we 

are going to go to the press if you don’t do a recall, because we 

don’t have the authority—they don’t hold a license with us, so we 

can’t just shut them down. We would have to then go court if they 

still refused to shut down their operations. 

Mr. PITTS. My time has expired. Chair recognize the ranking 

member 5 minutes for questions. 

Mr. PALLONE. Thank you. Dr. Woodcock, your testimony mentions the various court challenges that the compounding industry 

has brought over the years regarding FDA’s authority over 

compounding pharmacies. But I would like to learn more about 

that litigation and the impact it has had on FDA’s ability to oversee the industry. 

Those cases center around Section 503A of the act, which was enacted as part of the 1997 FDA Modernization Act. And that law attempted to delineate when compounded drugs were new drugs and 

therefore subject to FDA regulation. Section 503A also restricted 

compounding pharmacies’ right to advertise. 

So I am going to put a map of the U.S. up on the monitors here. 

It is up there. This map was not prepared by me or my staff, it 

was actually prepared by the International Association of 

Compounding Pharmacies, the main compounding industry lobbying group. On this map, the red States and blue States do not 

represent States that voted Democrat or Republican. They represent the different rules under which compounding pharmacies operate. 

So let’s look at the red States. Those represent the Ninth Circuit 

Court, whose jurisdiction includes the Western States. And as 

IACP notes on this chart, in 2001, the Ninth Circuit Court ruled 

that the advertising component of Section 503A was unconstitutional and that the rest of 503A was void because it was inextricably tied to the advertising component, or that it was not severable, as we say. Is that correct? 

Dr. WOODCOCK. Yes. 

25 

Mr. PALLONE. OK. Then in 2002, the Supreme Court agreed with 

the Ninth Circuit that the advertising ban was not constitutional, 

but the Court did not address the question of whether that ban 

could be severed from the rest of Section 503A. The result of that 

decision then was that the advertising ban was unconstitutional 

throughout the country, and the entirety of Section 503A remained 

invalid in those red States on the map. The Supreme Court decision also meant that whether the remaining parts of Section 503A 

was effective in the rest of the country was an open question. Is 

that your understanding? 

Dr. WOODCOCK. That is my understanding. 

Mr. PALLONE. So let’s look now at the blue States on the map, 

Texas, Louisiana, and Mississippi. Those States represent the Fifth 

Circuit. 2008, the Fifth Circuit Court of Appeals held that the unconstitutionality advertising restrictions did not affect the standing 

of the rest of Section 503A. So that means that in Texas, Louisiana, and Mississippi, Section 503A is in effect. Am I correct on 

that? 

Dr. WOODCOCK. That is my understanding. 

Mr. PALLONE. And am I correct that the gray States on the map 

then represent the rest of the country, where we just don’t know 

how courts would rule on whether Section 503A, apart from the advertising restriction, is or is not in effect? 

Can you tell us what the impact of this 503A patchwork has been 

on FDA’s ability to oversee the compounding industry? Have 

compounding pharmacies been able to take advantage of this confusion over the law to block FDA’s ability to aggressively enforce the 

court authority it does have over compounders? 

Dr. WOODCOCK. Yes, I think that definitely contributed to the inability of FDA to have an effective regulatory program. All right. 

We have different circuits with different meanings of the statute 

that was passed by Congress in 1997. In some areas, the statute 

is thrown out; in other areas, it is partially operational; in other 

areas, we don’t know if we went to court what type of decision we 

would get. 

Mr. PALLONE. So this seems to me to be all that we as Members 

of Congress need to see to understand the dire need for clarifying 

the FDA’s authorities here. What I don’t understand is I am hearing from the GOP here on the committee that they don’t seem to 

want to give the FDA additional authority even though the Senate 

passed a bill on a bipartisan basis that does. And yet I don’t see 

any alternative. 

In 1997, for better or worse, Congress spelled FDA’s authorities 

over compounding pharmacies. I think that law is out of date and 

should be updated. But putting that aside, courts have invalidated 

that statute, our statute, in a major swathe of the country. I think 

it is irresponsible for us to stand by and expect FDA to cobble together a piecemeal approach to regulating the practice of 

compounding pharmacy, a practice that, as evidenced by the 

NECC, bears great risk for patients all over the country. 

I don’t quite understand why my colleagues on the other side, at 

least here in the House, not in the Senate, don’t want to step in 

and clarify the rules of the road. I think we have to do that, otherwise we are going to continue to have these problems with 

26 

compounding pharmacies. And I hate to say anything positive 

about the Senate, but they are moving in that direction and we 

need to do the same. 

Thank you. 

Mr. PITTS. We are presently voting on the floor. We have two 

votes. We will recess until the second vote is over and then reconvene. We will have another series of vote around noon. So if you 

can stay, Dr. Woodcock, we will recess at this time for floor votes 

and be back as soon as the members finish their second vote. 

[Recess.] 

Mr. PITTS. Time of our recess having expired, we will reconvene 

and continue our Q&A session. Chair recognize the vice chair of the 

subcommittee, Dr. Burgess, 5 minutes for questions. 

Mr. BURGESS. I thank the chairman. 

And thank you, Dr. Woodcock, again for being here. 

So between 2002 and 2012, according to our investigation on 

Oversight and Investigations Subcommittee, the New England 

Compounding Center was the subject of at least 52 adverse event 

reports. Numerous offenses documented throughout the investigation that was undertaken by both FDA and State regulators. 

So, you know, the big question is, why not do something? Why 

not take action? And to tell you the truth, it was a little hard to 

read through some of the emails that we finally got. Your folks 

were literally pulling their hair out about we can’t just send another warning letter, we have already sent one to which it took us 

2 years to respond and we will have to do something. And it was 

like they got right up to the point of having to do something and 

then no one wanted to do it. Is that an unfair assessment. 

Dr. WOODCOCK. Well, I am unable to comment specifically on 

NECC because of the ongoing criminal investigation. However, generally, I would say we should have been more aggressive overall in 

this industry. There was a pattern for many firms that we were 

looking at of adverse events. And, as I said, there were a series of 

outbreaks. Every year, practically, we would have an outbreak due 

to contaminated compounded product, and we should have been 

more aggressive in going after this industry. 

Mr. BURGESS. Well, again, I just don’t understand some of your 

folks. They just had to be losing their minds over this stuff. Samia 

Nasr, a name kept coming up in the emails that were provided to 

us. Does she still work at the agency? 

Dr. WOODCOCK. Yes. 

Mr. BURGESS. I know you can’t comment on employment. But, I 

mean, I think she did the right thing to bring all these things to 

people’s attention, but it must have driven her crazy that the people just above her wouldn’t do something. 

Dr. WOODCOCK. As I said, overall, we should have been more aggressive as this industry continued to be responsible for outbreaks. 

We investigated outbreaks, we investigated reports, and we did respond reactively to problems. But we did not proactively do everything we could. 

Mr. BURGESS. And as a consequence you had 50 deaths and 500 

people who are living with long-term disability as a consequence of 

the Exserohilum in the betamethasone. 

27 

Dr. WOODCOCK. Well, we have more people who have died than 

that. We have people blinded. We have people with disabilities as 

a result of these outbreaks over the last 12 years. And I would say, 

frankly, if you want my opinion, that we could have done more—— 

Mr. BURGESS. I do. 

Dr. WOODCOCK [continuing]. The States should have done more, 

and Congress could have intervened when these statutes were 

struck down. 

Mr. BURGESS. You know, and the ranking member had a nice 

map up there. He made a nice little comment about red and blue 

States. But, honestly, the 503A limitation doesn’t affect Massachusetts at all. I mean, we are talking about Texas and California, 

Fifth Circuit, Ninth Circuit, but Massachusetts is outside that. So 

what prevented you in Massachusetts? 

Dr. WOODCOCK. As I said, I can’t specifically discuss this particular case because of the ongoing investigation. 

Mr. BURGESS. OK. 

Let me ask you this: How difficult is it to get an injunction from 

a judge? You go a judge and say, we have got a problem here. How 

difficult is it to get an injunction? 

Dr. WOODCOCK. We, as I understand it, I am not one of the agency lawyers, I am a physician, as you know, but we make a recommendation to the Justice Department, who then proceeds to do 

the legal activities. And just because we initiate legal action doesn’t 

necessarily mean we will prevail in court. 

Mr. BURGESS. How many times have you not prevailed? 

Dr. WOODCOCK. I don’t know. We can get back to you. 

Mr. BURGESS. Would you get us that information? 

Dr. WOODCOCK. Absolutely. 

Mr. BURGESS. Out of all of the challenges that you have submitted to companies, how many have actually stood up to you and 

said, we don’t want to do it? 

Dr. WOODCOCK. I think there are—we do bring our cases that 

have the best facts, all right, as we sort through the cases we put 

forth those that have the best facts that we would be most likely 

to win. 

Mr. BURGESS. Well, again, it is just so frustrating to think that 

the guidance that supposedly was going to come out, that was 

going to solve this problem, just really seemed to be enmeshed in 

the bureaucracy for 3 years. Is that a fair time length? 

Dr. WOODCOCK. I think that is fair. However, that was trying to 

make the best of a bad situation. We do not have the tools that fit 

this industry, right? 

Mr. BURGESS. You know what? I disagree. Because do you not 

have power under the Food, Drug, and Cosmetic Act to regulate 

manufacturers? 

Dr. WOODCOCK. Yes. 

Mr. BURGESS. You define manufacturers. Someone is making 

30,000 vials of stuff a month, is that a manufacturer? 

Dr. WOODCOCK. Well, say, if I am Janet the pharmacist, all right, 

and I have a pharmacy that is licensed in a State, right, and I am 

compounding drugs, right, and then I decide, well, I want to broaden my activities, and my State allows the anticipatory 

compounding and my State allows office stock, right, so I can comVerDate Nov 24 2008 11:31 Mar 13, 2014 Jkt 037690 PO 00000 Frm 00033 Fmt 6633 Sfmt 6633 F:\MY DOCS\HEARINGS 113\113-48 CHRIS
28 

pound those in advance of or without a prescription and send them. 

And there is no—— 

Mr. BURGESS. 30,000 vials a month? 

Dr. WOODCOCK. There is no—what is the number? That is the 

thing we have been struggling with for 12 years. Is it 10 vials? Is 

it 1,000 vials? 

Mr. BURGESS. Well, let me ask you this question. 

Dr. WOODCOCK. There is no volume limit in the statute. Excuse 

me for interrupting you. 

Mr. BURGESS. Well, Massachusetts Board of Pharmacy fired people. Is the Food and Drug Administration going to let anyone go? 

Dr. WOODCOCK. No. 

Mr. BURGESS. No? 

Dr. WOODCOCK. No. 

Mr. BURGESS. I yield back, Mr. Chairman. 

Mr. PITTS. Chair thanks the gentleman. 

Now recognize the gentlelady from Florida, Ms. Castor, 5 minutes for questions. 

Ms. CASTOR. Thank you very much. 

I wanted to get just to that point. Where do we draw the line? 

Because I think as legislation is developed, and your testimony is 

that you do not want and it is not appropriate to capture the community pharmacists who are compounding—— 

Dr. WOODCOCK. That is correct. 

Ms. CASTOR [continuing]. And that is not the source of problems. 

So where do you recommend the dividing line should be? What is 

the criteria in law? Has the Senate addressed this in their bill? 

Where do they carve out so that the community pharmacists that 

are compounding are protected and others that have exceeded that 

and are really the large-scale manufacturers, how do we develop 

that criteria? 

Dr. WOODCOCK. Well, the Senate is attempting to set forth a 

framework, and we feel they are going in the right direction. But 

those clear lines between who is a drug manufacturer, who is a traditional compounder, and who is the new category of compounding 

manufacturing, we still feel are not clear enough. So that we could 

have people masquerading—and some of the other witnesses I 

think are going to talk about this, by my reading of their testimony, OK—that we could have people masquerading as traditional 

compounders or as compounding manufacturers who really were 

competing with the generic drug industry or the innovator drug industry and actually should have sent us applications and paid a 

user fee and gone through the established process that we have 

had in the United States since 1962. And so that is really the 

issue, is how do you draw those boundaries. 

Ms. CASTOR. And what are your recommendations then? 

Dr. WOODCOCK. Well, what we had proposed is that we pick off 

the highest risk category, which is those sterile products that are 

shipped interstate. All right. So they are shipped around the country. That is probably the highest risk, because the longer you store 

the sterile product the more likely, if they are contaminated, that 

there will growths that can grow up. And obviously sterile products 

are a high risk. And interstate is one sort of marker for volume. 

29 

And this industry that has grown up, the outsourcing industry 

is valuable to hospitals. We have heard from the hospitals. They 

feel they can’t do without these folk. And they generally take FDAapproved products and they mix them or they put into convenience 

dosage forms. If you have gone to a clinic in an office building and 

you have had a procedure, you may have received products from 

one of these firms that put you to sleep or whatever. And they 

package them, say, in syringes and so forth and send them to these 

various clinics and also to hospitals. 

We feel that type of industry, they produce in pretty high volume 

that is the highest risk. And they should have full aseptic processing controls, just like the regular drug industry does. So we 

agree with carving them out and having certain requirements for 

them, but not submitting a new drug application, having to pay a 

user fee, and going through that entire process. 

Ms. CASTOR. So highest risk, crossing State lines. 

Dr. WOODCOCK. State lines. 

Ms. CASTOR. Sterile products. 

Dr. WOODCOCK. Right. 

Ms. CASTOR. You recommend. And then to clarify your last part 

regarding—what if it is a compounding that is going to hospitals 

within a State. 

Dr. WOODCOCK. Well, what we propose is that would be regulated by the States. The States could decide whether they have capacity to do that. I think you may hear from some of the other witnesses that in fact that type of compounding, especially at volume, 

because it is the mass production that really increases the risk, 

both the risk of contamination and the consequences of contamination once it occurs, because it goes to so many people, right, and 

the risk is there for intrastate, but the States we feel could decide 

whether they would regulate those type of activities or not permit 

them, right. 

And then the traditional compounding is really where a doctor— 

and I have done this too, all right—a doctor writes a prescription 

to a pharmacy and asks them to, for an individual patient who has 

a specific need, to make a dosage form that isn’t available commercially because they have a very specific medical need for that. We 

feel that should be preserved, but a box should be put around it 

and there shouldn’t be competition with established generic products. Because there is always more risk than for a regular product 

for any of these compounded products. 

Ms. CASTOR. Thank you very much. 

Mr. PITTS. Chair thanks the gentlelady. 

Now recognize the chair emeritus of the full committee, Mr. Barton, for 5 minutes for questions. 

Mr. BARTON. Thank you, Chairman Pitts. 

I have very troubled, Dr. Woodcock, by your opening statement. 

I do give you credit for integrity and honesty and forthrightness. 

But you ended up saying that it is not if this is going to happen 

again, it is when it is going to happen. That is pretty strong. You 

are talking about people dying. 

And I have attended, not in their entirety, but I have attended 

every hearing that we have done on this issue with NECC. And it 

is not that Republicans are not willing to regulate, it is not that 

30 

we are not concerned. It is that we do think there is a true StateFederal partnership, and we do think that State regulatory authority is as good as Federal if it is within the State. And we don’t see 

a reason to preempt the States unless the States either can’t do it 

or won’t do it. 

And what struck me in the answers to Dr. Burgess’ questions 

was at some point in the process anybody at the FDA could have 

picked up the phone and called the State regulatory authority and 

apparently never did. 

Now, I don’t understand that. If you really believe that what you 

said is true, that it is not if it is going to happen again, it is when 

it is going to happen again, if you have a list of compounders that 

you think are problematic or in danger of actually endangering 

human life, if you really think the FDA doesn’t have the authority 

to shut those people down or make them clean up their act, you 

have an obligation, or somebody that is designated by you, to call 

the State regulatory authority to inform them of the problem and 

to take whatever steps are necessary to make sure that the State 

does. 

Now, why haven’t you done that? Or why haven’t people at your 

agency done that? That is what I don’t understand. 

Dr. WOODCOCK. We have done that more recently. And we have, 

as I said, we have worked hand in glove with the State authorities. 

We have done joint inspections with them. They have taken the 

steps to close down many of these pharmacies after the inspection. 

And we are sending them our findings, we send them letters. We 

post our 483s, which are our findings of the inspection, so they that 

are available to the public. And we work very closely with the State 

authorities. 

However, there are 23,000 compounding pharmacies in the 

United States, according to the industry. They don’t have to tell us 

who they are and they don’t have to report to us if they have problems. So we are—— 

Mr. BARTON. Well, but they can’t operate if they don’t tell you 

or don’t tell the State. You are not telling me there are 23,000 

compounding pharmacists that are operating out in the ether and 

that are not subject or not licensed by somebody. 

Dr. WOODCOCK. They are licensed by States. They are licensed 

pharmacies. And I read a report by some of the members who 

looked at what amount of control and tracking the States have over 

the different pharmacies, and many States do not have a lot of understanding of what activities those pharmacies are engaged in, 

particularly whether they are shipping to other States and so forth. 

Different patterns in different States, but not all States really have 

close control over what those pharmacies are doing as far as 

compounding. 

Mr. BARTON. Well, the witness that is in my district, Mr. 

Harmison, I have been in his pharmacy. I mean, he is the true 

small independent businessman. He has got a compounding room, 

I think one or two rooms, and has two or three pharmacists, including himself. 

Now, I have also been in other compounding pharmacist situations in Texas where they have 10 or 15. And it is much more of 

a mass production-type situation. So there is a difference. But the 

31 

FDA, in conjunction with the States, should be able to determine 

who has jurisdiction and what needs to be done. 

I don’t think Mr. Pitts or Mr. Upton or any of the Republicans 

are unwilling to sit down and help clarify, to use your term, what 

needs to be done. If there truly is a gap and it truly is best to regulate at the Federal level, I would say that the Republicans are open 

to it. But if it is simply a question of communication between the 

Federal Government and the State regulatory authority, I would 

encourage you to facilitate that communication, because I don’t 

want ‘‘if’’ to become ‘‘when.’’ 

Dr. WOODCOCK. Right. Well, we had a 50–State meeting. We 

have been in close contact with the Association of National Boards 

of Pharmacy. So we are talking to them twice a week. We are talking to all the State boards in the States where we go in and have 

these inspections. And, as I said, we do the inspections with them. 

We have heard from many States that they would prefer Federal 

regulation of these larger-scale facilities. But the real question here 

is and has always been the question is where to draw the line. All 

right. So you have the traditional pharmacist, they are 

compounding in response to a prescription. I, as a physician, I have 

written prescriptions for compounded products that were very valuable to my patients. That is one. All right. And you mentioned, OK, 

then there is somebody, if they have five rooms—— 

Mr. BARTON. My time has expired, and the chairman has been 

very gracious. We can work on helping define and helping to clarify. I think there is a bipartisan trust on this committee and this 

subcommittee that can do that, if you and the stakeholders will 

begin to communicate with each other. I think this is a solvable 

problem. But it is not necessarily the answer it is going to be more 

Federal regulation. It may be, but it is not automatic that it will 

be. 

With that, Mr. Chairman, thanks your time, and I yield back. 

Mr. PITTS. Chair thanks the gentleman. 

And now recognize the ranking member emeritus of the full committee, Mr. Dingell, 5 minutes for questions. 

Mr. DINGELL. You are most courteous. Thank you, Mr. Chairman. I ask unanimous consent to insert 2 letters which I wrote to 

FDA in the record—— 

Mr. PITTS. Without objection, so ordered. 

Mr. DINGELL [continuing]. As well as responses from FDA. And 

I thank you, Mr. Chairman. 

[The information appears at the conclusion of the hearing.] 

Mr. DINGELL. Now, these questions will be mostly yes or no. Does 

FDA have the authority to require all compounding pharmacies to 

register with the agency? 

Dr. WOODCOCK. No. 

Mr. DINGELL. Yes or no? 

Dr. WOODCOCK. No. 

Mr. DINGELL. Please submit for the record the new authority 

that you need. 

Next question: Does FDA have the authority to require all 

compounding pharmacies to report adverse events? 

Dr. WOODCOCK. No. 

32 

Mr. DINGELL. What authority is needed? Submit for the record, 

please. 

Does FDA have the authority to require all compounding pharmacies to follow good manufacturing practices? Yes or no? 

Dr. WOODCOCK. No. 

Mr. DINGELL. What authority is needed? Submit it for the record. 

Question four: Does FDA believe nontraditional compounders 

should be subject to appropriate good manufacturing practices the 

way manufacturers are? Yes or no? 

Dr. WOODCOCK. Yes, as appropriate. 

Mr. DINGELL. What is the authority which is needed? Submit for 

the record. 

Does FDA believe risk-based inspection schedules are appropriate for nontraditional compounders? Yes or no? 

Dr. WOODCOCK. Yes. 

Mr. DINGELL. What authorities do you need to achieve that end? 

Submit for the record. 

Does FDA have full authority to see all records when inspecting 

a compounding pharmacy? Yes or no? 

Dr. WOODCOCK. I think that is being contested, as you know. 

Mr. DINGELL. Yes, you have that problem between the different 

circuits. 

Dr. WOODCOCK. Yes. 

Mr. DINGELL. Plus submit to us what authority is needed. 

Does FDA need additional authorities in these areas to ensure 

that outbreaks of the kind we have seen does not happen again? 

Yes or no? 

Dr. WOODCOCK. Yes. 

Mr. DINGELL. Yesterday, my colleagues in the Senate advanced 

bipartisan legislation giving FDA more authority over compounding 

pharmacies. It is my hope we in the House will do the same thing. 

I have long believed that we must provide agencies like FDA with 

clear authorities and necessary responses to properly help and to 

carry forward their mission. U.S. FDA has a fee system for the approval of pharmaceuticals and medical devices, amongst others. 

Please inform us whether you need that kind of authority, for purposes of the record. 

Now, if we gave FDA the authority in this area, and I believe we 

should, I believe we also should have a strong user fee program. 

Would you submit for the record some information justifying such 

thing if you believe that is appropriate, Doctor. 

Dr. WOODCOCK. Yes. 

Mr. DINGELL. Now, would the user fee contained in the Senate 

bill provide the FDA with the necessary resources to carry out 

these new authorities? Yes or no? 

Dr. WOODCOCK. Partially, 50 percent. 

Mr. DINGELL. OK. Now, I have got just a little bit of time left. 

I am reminded of the situation we have here. We have got people 

being killed because we have unclear authorities. We have a responsibility to see to it that we clarify that as a part of our oversight responsibilities. 

There is a great joke that they tell about a fellow who got a letter from an undertaker saying that his mother, or his mother-inlaw, had just had a stroke and passed on. And he asked for instrucVerDate Nov 24 2008 11:31 Mar 13, 2014 Jkt 037690 PO 00000 Frm 00038 Fmt 6633 Sfmt 6633 F:\MY DOCS\HEARINGS 113\113-48 CHRIS
33 

tions. He said should we cremate, should we bury, or should we 

embalm. And the guy thought for only a second and he sent back 

a telegram saying, do all three, take no chances. 

Now, I think here we have got a problem where people are being 

killed by a dichotomy in the industry. And, Doctor, I want you to 

tell me, you have roughly three classes of compounders. Right? You 

have got essentially the manufacturing compounders who ship all 

over the country, huge volumes. Right? 

Dr. WOODCOCK. Correct. 

Mr. DINGELL. You don’t have very clear authority over them, do 

you? 

Dr. WOODCOCK. No. 

Mr. DINGELL. And the States don’t have the resources to do it, 

do they? 

Dr. WOODCOCK. That has been documented. 

Mr. DINGELL. OK. Now, having said that, you also have the ordinary pharmacies. We are not particularly after them. And they are 

supposed to be regulated by the States. They are licensed by the 

States. And they are identified by State regulations to the States. 

Right? 

Dr. WOODCOCK. Yes. We believe the traditional practice of pharmacy compounding should be preserved and regulated by the 

States. 

Mr. DINGELL. OK. Now, then we have the additional situation 

where you have the hospitals. And they have either in-house or 

they have people who contract with them to compound them to 

meet the specific needs of patients in the hospitals. Right? 

Dr. WOODCOCK. Correct. 

Mr. DINGELL. What authorities do you need there? 

Dr. WOODCOCK. Well, we believe that the hospitals could operate 

under the regular rules of pharmacy. These are hospital pharmacies that are licensed by the State and also regulated by other 

authorities. We believe that outsourced contractors should be regulated under the compounding manufacturing. 

Mr. DINGELL. So here now you have a muddled situation where 

the courts are getting in and assisting us to confuse an already obfuscated situation, and we need to do something to clarify it. And 

since the great events in Michigan, where a bunch of my constituents and others were killed, we have seen that the compounders 

have continued their same merry practices of disregarding the law 

and proceeding to send noxious compounds around that are compounded in unsafe atmospheres and climates. Is that right? 

Dr. WOODCOCK. We have seen since the outbreak—— 

Mr. DINGELL. Yes or no? 

Dr. WOODCOCK. Yes. Yes. 

Mr. DINGELL. Mr. Chairman, I have used 44 seconds too many. 

Thank you. 

Mr. PITTS. Chair thanks the gentleman. 

Now recognize the gentleman from Virginia, Mr. Griffith, 5 minutes for questions. Mr. Griffith, you are recognized for 5 minutes. 

Mr. GRIFFITH. Thank you, Mr. Chairman. 

Thank you, Dr. Woodcock. 

I am looking at your draft, not for implementation report on 

pharmacy compounding that was done in August of this year, and 

34 

I want to clarify this court issue. Disagree with me and tell me yes 

or no, I will ask you at the end of each part of this. But it appears 

that in April of 2002, based on this report, and I believe it to be 

correct, that the U.S. Supreme Court affirmed the Ninth Court’s 

decision related to advertising and solicitation, but did not take up 

the severability as to whether or not the rest of the act would be 

in place after that date. Is that correct? 

Dr. WOODCOCK. My understanding, yes. 

Mr. GRIFFITH. And is it also correct that the Fifth Circuit found 

it was severable, and that decision came out in 2008? 

Dr. WOODCOCK. Correct. 

Mr. GRIFFITH. The FDA took no action—am I correct the FDA 

took no action to clarify the law between 2002 and 2008 when the 

Fifth Circuit came out with their opinion, isn’t that correct? Yes or 

no. 

Dr. WOODCOCK. Yes. 

Mr. GRIFFITH. And it would also be correct that from 2008 until 

the incident with the fungal meningitis, the FDA never came to 

Congress and said we need clarification, isn’t that true? Yes or no. 

Dr. WOODCOCK. Yes. 

Mr. GRIFFITH. And isn’t it true that you were working on these 

draft guidelines because you believe there was a way to figure out 

around the court decision issue and regulate to the best of your 

ability with the Ninth Circuit being a little more difficult but that 

is why you worked on these guidelines for over 3 years; isn’t that 

correct? 

Dr. WOODCOCK. As I said, we were trying to make the best of a 

bad situation. 

Mr. GRIFFITH. Wouldn’t the right thing to have done to have 

come for clarification on the severability and just reenact the old 

law and take the advertising section out, the only part that any 

court said actually violated the Constitution and the whole issue 

was severability; wouldn’t that have been the better thing to do 

from 2002 until 2012? 

Dr. WOODCOCK. Yes, I think in retrospect that would have been 

better. I think there was a fear getting a worse—— 

Mr. GRIFFITH. Was there a fear of coming to Congress and asking 

for help when you needed it? 

Dr. WOODCOCK. Well, you know, the late Senator Kennedy did 

develop a bill and asked around about it with some other Senators 

and there was so much opposition that they never introduced that. 

And I think that was—— 

Mr. GRIFFITH. Did the bill do anything other than clarify that the 

bill could be severed and that the only parts that weren’t in place 

or should be in place were the advertising restrictions? 

Dr. WOODCOCK. I am not familiar with what exactly it is. 

Mr. GRIFFITH. Because I don’t know what was in that bill and 

I suspect there was something other than clarifying the law was 

in there. 

Dr. WOODCOCK. Oh, yes. 

Mr. GRIFFITH. And I would have to say in the draft guidance that 

you all were about to propose the FDA defined a new framework 

for compounded drugs that would be administered in a health care 

setting and basically what you proposed was was that you could 

35 

compound for more than one patient in the hospital setting or in 

a medical practice setting as long as there was a prescription that 

followed if you knew you were going to use it in like in an ophthalmological setting or in a hospital setting as long as you could tie 

that later to a direct patient, isn’t that correct? 

Dr. WOODCOCK. That is my understanding. 

Mr. GRIFFITH. And so under that reading of that, other than 

clarifying that the advertising section is no longer the law, you 

really didn’t need any new authority to do that, did you? 

Dr. WOODCOCK. To make that interpretation? 

Mr. GRIFFITH. Yes or no? To make the interpretation. 

Dr. WOODCOCK. I don’t understand your question. 

Mr. GRIFFITH. It is in your guidance request so I assume that is 

correct. Is that correct? 

Dr. WOODCOCK. That is correct. 

Mr. GRIFFITH. And I appreciate that. And I am looking up to see 

how much time I have left. 

We also have this business about talking to the States. There is 

nothing that prohibited you in the law from talking to the States 

when you got complaints from say Colorado or Ohio, which actually 

happened in the NECC case, nothing prevented you from calling 

Massachusetts, did it? 

Dr. WOODCOCK. No. 

Mr. GRIFFITH. And, in fact, in the guidelines you are setting up 

a new way to make that work so it is efficient, isn’t that correct? 

Dr. WOODCOCK. The guidelines—— 

Mr. GRIFFITH. The guidelines of sharing information between the 

States and making sure that everybody is keeping an eye on these 

folks. 

Dr. WOODCOCK. The guidance, hmm, yes. 

Mr. GRIFFITH. So you didn’t need any new authority to do that, 

did you? 

Dr. WOODCOCK. We don’t need authority to talk to the States. We 

do that all the time in many different areas of regulation. 

Mr. GRIFFITH. But you failed to do that in the NECC matter, and 

I guess my concern is, is that while I too have learned to respect 

your veracity and think you are a great witness, much better than 

that other lady that came in here, we couldn’t get anything 

straight out of her, so I do appreciate it—but I would have to say 

that one of my concerns is that the FDA had all these tools available to it, if it had chosen to do so and I understand people make 

mistakes, things happen, I understand that, I am not being critical, 

but instead of asking for new authority shouldn’t we just clarify the 

fact that the advertising restrictions aren’t the law, and that if 

there are areas that need to be clarified, not giving new authority 

but just clarifying some things, that we could follow your guidance 

proposal from August of last year and come up with a pretty good 

proposal, isn’t that true? Yes or no. 

Dr. WOODCOCK. No. I don’t think so. 

Mr. GRIFFITH. So that was a bad proposal that you all were putting guidelines out on? 

Dr. WOODCOCK. The guidance—— 

Mr. GRIFFITH. Yes or no. Were those guidance proposals bad? 

36 

Dr. WOODCOCK. They were based on the 503, which is not really 

that workable for the current industry that we have. I am sorry I 

can’t give you just a ‘‘no’’ answer. I don’t think we have a good—— 

Mr. GRIFFITH. All right. I am out of time so if you could submit 

your recommendations I would greatly appreciate it. 

Mr. Chairman, I yield back. 

Mr. PITTS. The chair thanks the gentleman, and now recognize 

the gentleman from Texas, Mr. Green, 5 minutes for questions. 

Mr. GREEN. Thank you, Mr. Chairman. 

Dr. Woodcock, thank you for being here today, and I am concerned that the majority side has looked at this issue and said the 

FDA has the necessary authority to properly regulate. As Commissioner Hamburg explained at the last meeting, the current level of 

scrutiny being applied by the FDA is a result of the outbreak. The 

court case may be strengthened, but a favorable ruling on the authority over compounding manufacturers and non-traditional manufacturers is far from certain. 

As a result, I think we must pass limited legislation that allows 

the FDA to regulate compounding manufacturers across State 

lines. The draft currently being debated in the Senate is a good 

first step, but I think there are some changes we could made to 

strengthen the bill. 

In her testimony before the committee, and I won’t judge on 

Commissioner Hamburg’s testimony, asserted the agency needs 

greater authority over large compounding pharmacies that are essentially manufacturers. The Senate legislation would create a new 

category of compounding manufacturers that would be under FDA 

regulatory authority. 

Commissioner Hamburg also told us that the FDA agrees that 

the regulation of a traditional pharmacy compounding should be 

left to the State legislators and State boards of pharmacy. We have 

laws in my home State of Texas that allow when medically necessary and in very limited circumstances a compounding of medications before the receipt of a patient specific prescription for administration in the office of the prescribing physician. Those are called 

office use compounding. It is my understanding a majority of States 

have these similar laws. 

Dr. Woodcock, what do you recommend that Congress craft or 

how do you recommend that Congress craft language to give the 

FDA the necessary authority to regulate large, interstate 

compounding manufacturers while still preserving the ability of 

States to regulate the traditional compounders? 

Dr. WOODCOCK. It is a complicated question. We want to make 

sure that the traditional compounders can flourish because they 

provide a valuable service but not that they don’t go to 20 rooms 

or 50 rooms, right, and start making large scale. So there have to 

be boundaries there. 

Traditional manufacturers, obviously, have to submit applications to FDA, pay user fees and then undergo review and frequent 

inspections for GNPs. The hospitals have told us, the hospitals in 

your district and all around the country have told us that they rely 

on this industry now for the compounding manufacturing industry, 

if you wish to call it that, for certain services that used to be done 

in the hospitals but are now outsourced. However, these operations 

37 

are proceeding under the rubric compounding right now but they 

are doing something quite different and in a larger scale. And so 

if Congress would see fit, what we are saying is not we want more 

regulation, we want regulation that would fit this new activity, 

right, and would be appropriate for that and allow them to flourish. 

Mr. GREEN. I only have a couple minutes. For example, if a hospital in Houston wants to contract with a company in Massachusetts, that still should be under FDA authority. 

Dr. WOODCOCK. For sterile products is what we are proposing, so 

if they want to get injectables from a New Jersey firm, they want 

to buy injectables and use it in their hospital or in their clinic, we 

think that should be under FDA authority if those are sterile products. 

Mr. GREEN. OK. Do you agree that legislation should clarify the 

current law in the area and protect the ability of States and boards 

to decide what is the appropriate scope of practice for traditional 

pharmacies? 

Dr. WOODCOCK. Absolutely. 

Mr. GREEN. Including the areas of anticipatory and office use 

compounding? 

Dr. WOODCOCK. Well, we have to make sure that it draws the 

line and doesn’t allow them to produce, say, and how do you do 

that, is 17,000 vials, is that anticipatory compounding? You have 

to have some clarity on that. 

Mr. GREEN. It seems like it would be. What is the FDA’s position 

on office use compounding pursuant to State law where it occurs? 

Under the current Federal law, FDCA, and under the legislation 

being considered in the Senate? 

Dr. WOODCOCK. Well, right now, under current Federal law it is 

blurry, all right, as far as how much you could make? You all are 

saying to me that you think you can tell what a manufacturer is 

but there is no bright line in the statute that says when you cross 

that line and become a manufacturer. 

Mr. GREEN. And that is our job to define that. 

Dr. WOODCOCK. That would be very useful. 

Mr. GREEN. The other thing I am concerned about is traditional 

compounder in an area that is close to State boundaries. Again in 

Massachusetts with New England there is maybe a different problem whereas in Texas it is not that big a problem except along our 

border with other States. 

How do we keep those traditional compounders from being classified if they work across State lines, geographically fairly close, from 

being classified as a compounding manufacturer? 

Dr. WOODCOCK. Well, we think there are some Federal standards 

that ought to be in place, OK, that distinguish even a traditional 

compounder so that there are certain things that they are held to 

do and then they remain traditional compounders. 

Mr. GREEN. Thank you, Mr. Chairman. I appreciate it and look 

forward to working on the legislation. 

Mr. PITTS. The chair thanks the gentleman. I now recognizes the 

gentleman from Pennsylvania, Dr. Murphy, 5 minutes for questions. 

Mr. MURPHY. Thank you for being here, Dr. Woodcock, I have the 

highest respect for you and I appreciate your candid conversations. 

38 

I want to cut to the chase here because I don’t want this to be 

a political discussion and I think it is being mislabeled as that. 

I held hearings in my Subcommittee on Oversight and Investigation and it was my impression we weren’t getting clear answers 

about missteps within the FDA. And I just want to make sure that 

I know that the FDA is saying we have learned from our problems 

and here is how we change. 

So let me run through a series of questions with you and help 

get that on the record. 

First of all, the FDA has repeatedly cited the fact that the Fifth 

and Ninth Circuit Courts of Appeals have issued conflicting decisions on whether section 503A of the Food, Drug and Cosmetic Act 

remains valid, and in a written statement on November 14th of 

last year oversight committee hearing Commissioner Hamburg 

cited the Circuit Court’s split as having ‘‘amplified the perceived 

gaps and ambiguity associated with FDA’s authority over 

compounding pharmacies.’’ 

Now the Fifth Circuit Court decision was July 2008, is that correct? 

Dr. WOODCOCK. Right. 

Mr. MURPHY. In May 2009, just prior to Commissioner Hamburg 

being confirmed, a briefing was provided to Acting Commissioner 

Joshua Sharfstein proposing several paths forward in light of the 

Fifth Circuit’s decision upholding 503A. 

Do you recall participating in that briefing? Yes or no. 

Dr. WOODCOCK. No. 

Mr. MURPHY. The FDA produced to the committee an email 

chain from the Office of the Chief Counsel from July 2009. A copy 

of this document I think is now in front of you. The top email is 

from Michael Landa, FDA’s Acting Chief Counsel at the time, and 

notes the plan is to enforce section 503A nationwide except in the 

Ninth Circuit and that, quote, Josh is on board, unquote. 

Mr. Landa then notes that Dr. Sharfstein, quote, would touch 

base with Peggy but did not think she would have any objection, 

unquote. Do you know whether or not Commissioner Hamburg was 

consulted in the decision to proceed with enforcement of section 

503A? 

Dr. WOODCOCK. I do not know affirmatively, no. 

Mr. MURPHY. Do you suspect that she did or—— 

Dr. WOODCOCK. I would suspect that she was. 

Mr. MURPHY. Thank you. And if you turn to the second page of 

that email chain, the leader of the compounding team in FDA’s 

drug center, your center, notes that Dr. Sharfstein and Deb Otter 

asked to chart the timeframe for each step we plan to do to implement the new plan. 

Dr. Woodcock, this plan had yet to be implemented when the outbreak began in September, 2012, am I correct? 

Dr. WOODCOCK. That is correct. 

Mr. MURPHY. And yes or no, prior to announcing the new plan 

FDA felt as though it needed to draft a new guidance document detailing the approach it would be taking as well as various regulations that 503 required? Yes or no. 

Dr. WOODCOCK. That is my understanding. 

39 

Mr. MURPHY. Thank you. And yes or no, during this time period 

inspections and enforcement actions came to a standstill. 

Dr. WOODCOCK. My understanding is that it is not true, that we 

did certainly went for cause inspections. 

Mr. MURPHY. Certainly with NECC. 

Dr. WOODCOCK. I can’t comment specifically on NECC. I am 

sorry. 

Mr. MURPHY. Is that—— 

Dr. WOODCOCK. Due to the ongoing criminal investigation. 

Mr. MURPHY. I understand. By August 2012 your center signed 

off on another draft guidance document that was going through 

final clearance, yes or no. 

Dr. WOODCOCK. Yes, my understanding. 

Mr. MURPHY. Thank and a briefing has been had, in fact been 

scheduled to discuss the new guidance documents with Commissioner Hamburg back in September 2012, is that correct. 

Dr. WOODCOCK. That is correct. 

Mr. MURPHY. And yes or no, Commissioner Hamburg testified before O&I that she was really not that aware of issues related to 

drug compounding until after the meningitis outbreak; therefore, 

would any additional changes to this draft document guidance have 

been made based on Commissioner Hamburg’s input. 

Dr. WOODCOCK. I don’t know. That would be speculation. 

Mr. MURPHY. OK. The point is the agency had a solution here 

that would have allowed it to conduct inspections was my understanding. But so the FDA failed to even acknowledge the existence 

of this guidance document until it produced it to this committee in 

March of 2013, well after the FDA promoted an entirely new regulatory paradigm. 

Here is where I want you to help clarify this for all of us. My 

question is what does FDA now know about the compounding industry that it did not incorporate in this guidance document and 

is provided as a learning experience to make some changes? You 

may respond. 

Dr. WOODCOCK. What we have seen as we have done inspections 

of this industry, we have focused on the highest risk areas and we 

have seen violations of aseptic processing, that basically mean that 

there is no insurance of sterility of the products coming out of these 

compounding pharmacies. 

And this means that this outbreak that we have seen will happen again. Since the outbreak, we have had an instance of fungal 

bodies being observed in an IV bag ready to be given to a cancer 

patient, all right, that came from a compounding pharmacy. We 

have also had other instances of patients having eye infections and 

other instances of non-sterility of products. So we have had harm 

as well as the nonsterile practices that lead to the harm. 

Mr. MURPHY. With regard to the way that FDA approaches these 

things and I understand you are looking for more authority to handle some things but what we really need to know is within the 

realm of the authority you already had—and I am not asking you 

to hang anybody out right now, that is not the purpose of this hearing—but are there internal lessons that the FDA has learned they 

could have handled some things differently that could have possibly 

40 

led to different results other than dealing with the lawyers’ issues 

here. 

Dr. WOODCOCK. Well, I think we should have been more aggressive. There was great concern about our, the limitations of our authority and that we would lose and then have even less ability to 

influence this industry. But in retrospect I think it would have 

been more important to simply go forward and see how it turned 

out in the courts, aggressively exert our current authority, which 

is primarily new drug authority. 

Mr. MURPHY. Thank you. That is why I like hearing from a physician instead of a lawyer. I will need to submit these e-mails for 

the record if that is all right, Mr. Chairman. 

Mr. PITTS. Without objection, so ordered. 

Mr. MURPHY. Subject to redactions by staff. 

Mr. PITTS. The chair thanks the gentleman and now recognizes 

the gentlelady from California, Mrs. Capps, for 5 minutes for questions. 

Mrs. CAPPS. I believe—am I before Mr. Engel? 

Mr. PITTS. Yes. 

Mrs. CAPPS. Oh. 

Mr. PITTS. We are going in order of appearance. 

Mrs. CAPPS. OK, all right. I thank you. I just want to thank you 

for your testimony today, Dr. Woodcock, and I want to thank Mr. 

Pallone for holding this necessary hearing. This is an important 

issue and I believe needs to be revisited. 

Under current statute, a great deal of uncertainty and variation 

exists between regulations. And this uncertainty creates gaps that 

can lead to compromised patient safety, as we have seen most recently with the meningitis outbreak. We cannot wait for another 

public health crisis to act, and what we have right now isn’t working. 

Dr. WOODCOCK. Right. 

Mrs. CAPPS. I believe you would agree. Families don’t have the 

peace of mind they are receiving effective drugs that they can trust 

and compounding pharmacies across the States are not on a level 

playing field. Many States are inadequately inspecting facilities. 

After a similar incident in my State of California almost a decade 

ago, regulations were enhanced and sterile compounding pharmacies now require an inspection or accreditation through a national agency. You know, this isn’t good enough because many hospitals and clinics in California buy drugs from out of state, 

compounding pharmacies in other States, including the Massachusetts pharmacy. So hospitals and States don’t exist in isolation. 

Hospitals have a great need to be able to buy large quantities of 

compounded drugs. 

Mr. Migliaccio suggests in his written testimony that there 

should be no special regulatory program for these large scale drug 

compounders. Instead he implies that they should be treated like 

conventional drug manufacturers and should have to go through 

the new drug application process to manufacture and distribute 

any drugs. 

My question now, Dr. Woodcock, could you explain to us why you 

believe requiring new drug applications for all drugs would not be 

41 

warranted and what the consequences would be particularly for 

hospitals if FDA were to take such an approach? 

Dr. WOODCOCK. Well, that approach would be our current authorities. It is not that we don’t have current authorities. Our current authorities require submission of applications, payment of a 

user fee, thanks to the user fee bill you all passed for generics recently, and we have had the new drug one for a while, and review 

of all the information, a large package submitted to the agency, 

and then we inspect those facilities frequently, including a 

preapproval inspection to make sure everything is OK before the 

product gets out on the market. So that is our current authorities. 

Now many of these outsourcers, what they are actually doing is 

taking FDA approved products and putting them into convenience 

forms or putting them into, combining them, say for hyper alimentation or something like that, and then shipping them around the 

country based on patient need. 

The industry has basically told us that they can’t make all these 

different very patient specific forms and convenience forms. And 

there are questions of efficacy that are related because these are 

already FDA approved products. The key is, and this used to be 

done by the hospital pharmacy, by the clinic they would do this. 

I did this when I was an intern, all right, when the interns were 

able, had to be kind of worker bees. So we made up the chemotherapy, we put things into bags and the nursing staff would do 

this as well or the hospital pharmacy. 

Now, with the very large scale of medicine they want to buy 

these, and many of the clinics are in office buildings, they don’t 

have a pharmacy or clean room there. So they need to order these 

products, right. 

Mrs. CAPPS. I want to get to another question. 

Dr. WOODCOCK. I am sorry. It is so complicated. Let me finish 

then. So there isn’t good regulatory fit right now. It isn’t where we 

say we have to have all these broad new authorities, no, there is 

no fit for this industry that has grown up. 

Mrs. CAPPS. All right. I want to make sure that I am able to 

enter a statement from the American Society of Health System 

Pharmacists which addresses this issue as well. Their statement 

details the many ways in which hospitals have come to rely on 

compounded medications from outside compounding pharmacies 

which you are alluding to. 

And I want to ask that this statement that I am holding up be 

entered into the record. 

Dr. Woodcock, if there is a time for you to address this, would 

a two-tiered regulation system that clarifies a uniform set of rules 

for compounding manufacturers while preserving the State’s role in 

traditional pharmacy compounding be a practical thing? 

I will just let you comment on that. 

Dr. WOODCOCK. Yes. We have proposed something like that as 

something that would be practical but it would require a new regulatory scheme for this new industry that has evolved to make sure 

they are making the product safely. It is no good to have convenience products if they are contaminated or they are super potent 

or there are other things wrong with them. However, of course that 

is up to Congress whether they want this industry to persist beVerDate Nov 24 2008 11:31 Mar 13, 2014 Jkt 037690 PO 00000 Frm 00047 Fmt 6633 Sfmt 6633 F:\MY DOCS\HEARINGS 113\113-48 CHRIS
42 

cause our current regulatory authorities require submission of application. 

Mrs. CAPPS. I see. OK, thank you. I yield back. 

Mr. PITTS. And did you want to submit that for the record? 

Mrs. CAPPS. Yes, I would like to. 

Mr. PITTS. Without objection so ordered. 

The chair recognizes the gentlelady from North Carolina, Mrs. 

Ellmers, 5 minutes for questions. 

Mrs. ELLMERS. Thank you, Mr. Chairman, and thank you, Dr. 

Woodcock, for being here today. I just want to clarify a few terms 

because we are putting terms out and I want to make sure I am 

understanding them. When we are talking about traditional 

compounders, who are we talking about? 

Dr. WOODCOCK. We are talking about pharmacies, licensed pharmacies who react to a prescription for a specific individual patient 

and make a specialized dosage. 

Mrs. ELLMERS. And right now that is under the authority of the 

State, not under FDA, correct? 

Dr. WOODCOCK. Correct. 

Mrs. ELLMERS. And when we are talking about the compounding 

manufacturers, how is that different from the term drug manufacturers. 

Dr. WOODCOCK. Compounding manufacturers is a new term that 

is contained in the Senate bill, OK—— 

Mrs. ELLMERS. Right, so this is Senate language. 

Dr. WOODCOCK [continuing]. To reflect this large scale industry. 

They are not usually reacting to a prescription. They are making 

things that hospitals need and order frequently so they make them 

at large scale like a drug manufacturer. But often they are not— 

a drug manufacturer starts from scratch. They start from what we 

call the active pharmaceutical ingredient, which often someone will 

buy from India or China, bring it in, test it and then make the 

product. 

Mrs. ELLMERS. So sometimes it may be in a different form but 

is it not the same product, and you are saying that because products might be coming from somewhere else that that is the essential difference? 

Dr. WOODCOCK. No, there are two different activities that are 

lumped under this compounding manufacturing. One is what we 

call the outsourcers, OK, they get generally outsource from a hospital or clinic, something the clinic or hospital pharmacy used to 

do, all right, and that is putting things in syringes, little IV bags, 

diluting chemotherapy, getting everything all right so they can just 

hang it on the patient rather than having to do that—— 

Mrs. ELLMERS. Rather than having to actually do it in house. 

Now—— 

Dr. WOODCOCK. That is one. And then the other is people who 

are doing larger scale compounding. 

Mrs. ELLMERS. Larger scale. And that would currently fall under 

the jurisdiction of the FDA. 

Dr. WOODCOCK. That is what kind of is under dispute. 

Mrs. ELLMERS. And that is what we are trying to get to is when 

do we make that distinction between compounding pharmacy and 

compounding manufacturer. 

43 

Dr. WOODCOCK. And also a manufacturer who is already a pharmaceutical company has to submit an application to FDA and be 

under that regime. 

Mrs. ELLMERS. Now, currently, so basically the compounders 

have the same regulations and requirements as the drug manufacturers? Yes or no? 

Dr. WOODCOCK. No. 

Mrs. ELLMERS. And I am not just talking about numbers but I 

am just talking about regulations again, is this State versus Federal, is that the main difference that we are talking about? 

Dr. WOODCOCK. The States regulate pharmacies. They license 

pharmacies and these activities right now occur all in licensed 

pharmacies. 

Mrs. ELLMERS. OK. What are the changes to compounding you 

propose making in order to prevent the meningitis outbreak last 

year to ensure compounded products are safe? If you can just 

quickly give us an idea of what you would like to see. 

Dr. WOODCOCK. Well, limit the traditional compounding to more 

or less reaction to a prescription, OK, and compounding something 

for a specific patient, that is traditional compounding. And don’t 

allow compounding of really complicated dosage forms that even 

the traditional manufacturers have trouble making. Then we are 

saying establish a new group, the compounding manufacturers is 

what the Senate called them. They don’t get prescriptions, but they 

have to register and list with FDA. Tell us who they are, what they 

are making and where they are located, right, and then they have 

to submit adverse events to us. And they would be subject to proper GMP requirements to make sure they make safe products, OK, 

but they wouldn’t have to submit applications to us. 

Mrs. ELLMERS. But you did mention application process a moment ago. Can you repeat that? 

Dr. WOODCOCK. Sure. Some of the members are talking we have 

current authorities, yes, we do have authorities. Our authorities 

are you are a new drug manufacturer or a generic drug manufacturer, you must submit an application to us. You must a pay user 

fee or you should not be producing drugs in the United States. 

Mrs. ELLMERS. So once that application process is fulfilled, that, 

it is just so that you know that that particular facility exists and 

what their plan of action is? 

Dr. WOODCOCK. I am sorry, it is really hard to do this. That is 

our current authorities. That is how we regulate generic drugs and 

new drugs in the United States, all right, through that process. 

That is not what compounding is. 

Mrs. ELLMERS. OK. Now let me ask this question. The number 

and how much a parmacy is making seems to be the issue of where 

it falls, what jurisdiction. In your own words, where do you, where 

would you see that line of action? What do you see, how much 

product can a compounder make without being designated a manufacturer? 

Dr. WOODCOCK. That is what we have been struggling with since 

the 503 was passed, OK, there is no line in there in the statute. 

And so what is an inordinate quantity? We don’t know. Is it 10 

units? Is it 1,000 units? Is it 17,000 units? So we have endeavored 

44 

to use other criteria to say, OK, when you would be subject to Federal jurisdiction. 

Mrs. ELLMERS. Well, my time is expired but obviously that is the 

main question here. So thank you. 

Dr. WOODCOCK. We would be happy to work with you. 

Mr. PITTS. The chair thanks the gentlelady and now recognizes 

the gentleman from New York, Mr. Engel, 5 minutes for questions. 

Mr. ENGEL. Thank you, Mr. Chairman. 

Dr. Woodcock, thank you for the good work that you do. We appreciate it very much. 

Dr. WOODCOCK. Thank you. 

Mr. ENGEL. I want to first ask a New York question. New York, 

it is my understanding that New York has no licensing requirements specific to compounding pharmacies and according to the 

National Conference of State Legislatures there is no requirement 

that New York pharmacies comply with the U.S. Pharmacopeia 

chapter 795 or 797 compounding standards and according to the 

Pharmacy Compounding Accreditation Board, which accreditation 

is entirely voluntary, they say there are only 10 pharmacies in all 

of New York accredited for pharmacy compounding. 

So that being said, I am pleased that no New York pharmacies 

were included as part of the FDA’s most recent risk-based priority 

inspections of 31 sterile compounding pharmacies. So what I want 

to ask New York specific is, does the FDA know which pharmacies 

in New York are compounding medications? 

Dr. WOODCOCK. We have no way of nothing in any State, OK, we 

have been told by the industry that there are 23,000 pharmacies 

that may engage in some form of compounding across the country, 

but we don’t know who they are, where they are or what they are 

making, because they don’t have to tell us. 

Mr. ENGEL. So I assume then that the answer would be ‘‘no’’ to 

this, does the FDA currently have the authority to collect and test 

samples or examine the records of a compounding pharmacy in 

New York? And can you elaborate on why this information is critical for public health and safety? 

Dr. WOODCOCK. Well, we do believe we have the authority to go 

in and get samples and look at records but it has been contested. 

Mr. ENGEL. OK. Thank you. I am intrigued by the part of your 

written testimony which lays out a proposed risk-based framework 

for a new legislative approach to compounding to ensure patient 

safety and health. 

First, you proposed dividing the world of compounding into nontraditional compounders which would be subject to FDA’s jurisdiction and traditional compounders who would remain under State 

oversight. 

Is there a concern that non-traditional compounders may create 

a category of pseudo drug manufacturers? And if so, how do you 

protect against that? 

Dr. WOODCOCK. Well, there is a concern that traditional manufacturers could actually be drug manufacturers in disguise and that 

non-traditional manufacturers could be. And for traditional we 

really feel that prescription requirement and the statement of medical need for the patient is important, for non-traditional we have 

proposed a series of things, including that they would register and 

45 

list with us so we would not who they are and also not make copies 

of commercially available drugs. 

Mr. ENGEL. You mentioned the need for sort of do not compound 

list as part of this framework. Can you explain why this is necessary and why you cannot do this using your current authority? 

Dr. WOODCOCK. Yes. Well, we feel that products say we have 

withdrawn from the market for reasons of safety should not be allowed to be then compounded and U.S. citizens would then be exposed to them again. And we are seeing this now as you know in 

dietary supplements, we have to go after them because they sneak 

in drugs that have been pulled off the market, all right. So that 

is one category. 

Another category might be very difficult to manufacture dosage 

forms where the pharmaceutical industry that has a lot of science 

available to them and a lot of engineers and scientists still have 

trouble making them reliably, some of the patches, some of the inhalers and so forth. 

Mr. ENGEL. You sort of touched on this, but can you elaborate 

further on what steps the FDA is taking now utilizing the authority that you believe the that FDA has to conduct improved oversight over compounding pharmacies? 

Dr. WOODCOCK. Well, it is more oversight on whether it has improved because we are having to go to the ones we read about or 

we know about or we have had prior actions and we are doing a 

risk-based approach and going to those pharmacies as well as going 

to pharmacies where you have had reports of problems recently, all 

right, and for cause type of inspections. 

And as I said, we are going in with the States, the State board 

of pharmacy, their investigators, we often do an inspection together 

and we are taking very aggressive action. But we do not, for example, have recall authority, we cannot, we don’t have the authority, 

we don’t have recall authority for any drugs, right, and we do not 

have the authority to shut these pharmacies down, they are licensed by the State, but we have shared full information with the 

States, and they have shut 11 pharmacies down as a result of the 

findings in these inspections. 

So that is improved oversight, but we will see about if we go to 

court like what kind of response we get from the courts as far as 

our authority. 

Mr. ENGEL. Well, again thank you for the good work that you do. 

And I especially appreciate your testimony here this morning. It is 

concise, it is to the point. When we ask a question you respond 

very pointedly and it is very much appreciated. Thank you. 

Dr. WOODCOCK. Thank you. 

Mr. PITTS. The chair thanks the gentleman. The chair now recognizes the gentleman from New Jersey, Mr. Lance, 5 minutes for 

questions. 

Mr. LANCE. Thank you, Mr. Chairman. And good morning to you, 

Doctor. You stated to Dr. Murphy that if you had it to do over, you 

might move more aggressively regarding the situation that, unfortunately, occurred, is that accurate? 

Dr. WOODCOCK. Well, I think we would have moved aggressively 

as we are now against all pharmacies. There was no way to predict 

at any time which of these pharmacies will cause this problem. 

46 

And as I said, it will happen again because the conditions under 

which these sterile products are manufactured are not acceptable 

and the products are contaminated. 

I have learned, what I have learned from this is the resilience 

of the human body to microbial invasion because we have cultured 

many samples from these pharmacies and we have grown organisms. And we haven’t had outbreaks and that is because both the 

human body can repel them and because some of them aren’t 

human pathogens. 

Mr. LANCE. Thank you. This is a very complicated subject and 

certainly I think answers require more than ‘‘yes’’ or ‘‘no.’’ 

Dr. WOODCOCK. I am sorry. 

Mr. LANCE. And you don’t have to be sorry at all, I think that 

this is extremely complicated. 

One of the difficulties as I read the background information is 

the split in the circuits. 

Are you advised by attorneys at the Department of Justice on 

these matters or do you have attorneys at your own agency regarding the significant split between the Fifth and the Ninth Circuit 

and the Supreme Court decision? 

Dr. WOODCOCK. We have our staff attorneys that belong to the 

Office of General Counsel at HHS and they are the FDA branch of 

that, and then they work with the Justice Department as well. 

Mr. LANCE. Perhaps you are not the appropriate person to ask, 

but it seems to me, speaking as an attorney, that there needs to 

be much greater clarification so that there can be one standard 

across the Nation and not a split between the circuits, with the Supreme Court decision that did not answer the question fully. 

Would that be your understanding? 

Dr. WOODCOCK. That is my understanding. I am not a lawyer, 

but I appreciate clarity when I try to perform regulations. 

Mr. LANCE. And I would hope moving forward in our responsibilities to protect the health of the Nation in conjunction with your 

responsibilities that we could work together to clarify the situation. 

I have 2–1/2 minutes, and I defer to Dr. Burgess. 

Mr. BURGESS. I thank the gentleman for that. Well, Dr. 

Woodcock, what is it about the Exserohilum fungus that rendered 

it such a bad actor? You said sometimes the human body actually 

can resist these things, sometimes they don’t even register. But 

Exserohilum was a bad one. 

Dr. WOODCOCK. Let me talk in general so I am not talking about 

NECC, but clearly it is the amount of bioburden of the contamination and that is why shipping these—bioburden means how many 

organisms are in there, OK, for the nonclinicians in the room—and 

so shipping something around unrefrigerated, which is happening 

a lot, OK, if you happen to get something in there, it gets a long 

chance to grow, all right. If you put it in a part of the body that 

is sort of protected from the immune system a little bit or is particularly vulnerable, if you inject with a steroid, we have had multiple outbreaks where there is an injection with a steroid and of 

course steroids suppress the immune system so then that weakens 

that part of the body and even systematically weakens the body’s 

ability to respond to infectious attack because of the actual mediVerDate Nov 24 2008 11:31 Mar 13, 2014 Jkt 037690 PO 00000 Frm 00052 Fmt 6633 Sfmt 6633 F:\MY DOCS\HEARINGS 113\113-48 CHRIS
47 

cine that has been given. But we have had sepsis from IV products. 

Nine people died in 2011. 

Mr. BURGESS. Let me just stop you there because we could obviously could go on. But that is significant because you have a steroid which inhibits fighting infection, you have a space in the epidural space that is relatively protected from white blood cells and 

things that normally fight infection, it is preservative-free because 

it is going into the epidural space if you had preservatives that 

would be bad for nerves so. 

Dr. WOODCOCK. High risk. 

Dr. BURGESS. So it is the confluence of bad events. So you know 

this stuff is high risk. 

On the issue of manufacturing, I just have to tell you looking at 

the notes compiled by the other subcommittee, Oversight and Investigations, going back to May 10, 2012, when the Colorado Board 

of Pharmacy issued to NECC a cease and desist order and the 

same day FDA’s Denver office informed New England the cease 

and desist order, New England compliance officer responsible for 

NECC spoke to an optometrist with the U.S. Department of Veterans Affairs inquiring about whether or not they could use NECC 

to repackage Avastin. This communication is significant because 

once again it confirms that FDA understood that NECC was acting 

like a manufacturer not a traditional compounding pharmacy. An 

email response ‘‘I did not think they could use firms if profiles were 

unacceptable. NECC Framingham is profiled as a manufacturer because we determined that they are a manufacturer and not a 

compounding pharmacy,’’ an email from the compliance officer for 

the New England district to FDA May 11, 2011. 

Dr. WOODCOCK. Well, I am not going to argue with you about 

this particular case because I can’t talk about the case. But clearly 

the decision about whether a firm is making, is making product legally under 503A would be for the courts ultimately, all right, that 

is just how it was set up. 

Mr. BURGESS. But under the Food, Drug and Cosmetic Act, if I 

may, you have the regulatory authority over manufacturers and 

your own compliance officers identified NECC is a manufacturer, 

acts like a manufacturer, walks like a manufacturer, they are a 

manufacturer. 

Mr. Chairman, I will yield back. 

Mr. PITTS. The chair thanks the gentleman and I now recognize 

the gentleman, Mr. Butterfield, for 5 minutes for questions. 

Mr. BUTTERFIELD. Thank you, Mr. Chairman. And thank you, 

Dr. Woodcock, for your testimony today. 

I will be brief. The hour is certainly getting late. But in studying 

this issue, Mr. Chairman, it seems that the FDA lacks clear direction and clear authority over what can be done once a compounding 

pharmacy is found to have failed to meet the standards. 

And so, Dr. Woodcock, after the meningitis outbreak at the New 

England Compounding Center about a year ago, FDA increased its 

inspection of compounding pharmacies. I think that is true. The 

findings by Federal investigators have been alarming. And hopefully there will be more aggressive investigations. 

I want to take you to the subject of sequestration. FDA is understaffed, underfunded and stretched very thin, at least that is what 

48 

we have been told. How are the cuts from sequestration hindering 

the FDA and your inspectors from conducting the thorough oversight that is critical to patient health? 

Dr. WOODCOCK. Well, don’t forget, the Energy and Commerce 

Committee overall have been very concerned that we haven’t been 

to manufacturers overseas, traditional drug manufacturers, and 

that has been partly due to our resource limitations. Now we do 

have the user fee, the Generic Drug User Fee Act, and that will 

allow us to increase our inspectors who go overseas but my point 

is even the traditional industry we have difficulty covering that 

adequately. Now there are over 20,000 compounding pharmacies, 

and we don’t know who is who. And so—— 

Mr. BUTTERFIELD. Can some of your lack of resources be attributable to sequestration? 

Dr. WOODCOCK. Oh, yes, absolutely. Well, sequestration took another bite out of what was already a stressed agency, particularly 

as far as inspectional coverage and now, to give you perspective the 

whole drug industry has about 5,600 establishments, all right, and 

so we try to inspect those on a regular basis. To say now that there 

are 20,000, 26,000, 28,000 compounding pharmacies the question 

how do we get there, and then sequestration has reduced our funding, our user fee funding as well as our base appropriation funding. 

Mr. BUTTERFIELD. And is that really having a negative impact on 

your work? 

Dr. WOODCOCK. Absolutely. 

Mr. BUTTERFIELD. Now does your agency fully understand that 

sequestration is not a 1 year process, it is a 10-year process so unless it is repealed or modified it is going to continue for some years 

to come. 

Dr. WOODCOCK. We have grave concerns about our continued 

ability to operate our programs under the various financial stresses 

that we have and these new activities that we need to take on. 

Mr. BUTTERFIELD. What is an FDA Form 483? 

Dr. WOODCOCK. That is a form with the investigators’ observations that is left with the firm at the end of the inspection. 

Mr. BUTTERFIELD. Are these posted on the Web site? 

Dr. WOODCOCK. Yes. They are public. 

Mr. BUTTERFIELD. OK. And from what we can gather, some 48 

form 483s that have been conducted are posted on the Web site? 

Dr. WOODCOCK. Yes. We are posting them publicly to make sure 

that people understand what our findings are. 

Mr. BUTTERFIELD. What are some of the worst conditions that 

have been observed by some of your inspectors? 

Dr. WOODCOCK. Well, primarily, it relates to not keeping, not 

having practices that would assure the product would be sterile. 

Don’t forget, these are going to be injected in people’s bodies, into 

their eyes, around their spinal cord into their veins and the practices would allow fungal spores, mold, contamination from the body 

of a person so that would be bacteria, to actually get into the products and then multiply. 

Mr. BUTTERFIELD. Finally, are there any tools other than money, 

of course, that Congress can provide to the FDA so the American 

people can feel more assured that the compounded drug they are 

taking is prepared in a safe and secure way? 

49 

Dr. WOODCOCK. We need clear lines of authority. We need to 

know what the States regulate, what the Feds regulate and what 

our authorities are. If we regulate part of the industry, I would like 

to know who they are, where they are located and what they are 

making so that then we can then prioritize where to go because we 

are not going to get to thousands and thousands of sites in the next 

several months. 

Mr. BUTTERFIELD. Thank you. You have been very kind. I yield 

back. 

Mr. PITTS. The chair thanks the gentleman. I now recognize the 

gentleman from Utah, Mr. Matheson, 5 minutes for questioning. 

Mr. MATHESON. Thank you, Mr. Chairman. Dr. Woodcock, it is 

always good to have you before the committee. I have always appreciated my conversations with you and I appreciate your trying 

to highlight an issue where I think it is all important we take a 

hard look at this and figure out a better way to go forward. If I 

want to oversimplify this hearing, that is kind of where we are. 

I fear my questions may be a bit repetitive for what you may 

have already covered that is the reality of being the last people 

asking questions. 

But I was interested as I understand it when you were discussing, when the FDA discussed some informant actions back in 

2006, after—can you tell me at that point what actions—can you 

elaborate what actions were discussed by the agency 7 years ago? 

Are you familiar with that discussion that took place? That is before your time. Maybe you can’t answer that. 

Dr. WOODCOCK. No. No. I wasn’t. I wasn’t head of Center for 

Drugs at that time either. 

Mr. MATHESON. You present several policy options in your testimony, and it is going to provide FDA some different authorities for 

certain compounders. Can you describe how those options, how 

they might have played out, allowed the 2012 outbreak to play out 

differently than it did if you had those options at that time? 

Dr. WOODCOCK. If we have clear Federal authority and a clear 

idea of what is traditional compounding and what is not traditional 

compounding because don’t forget this industry maintained they 

are working within the scope of State pharmacy practice. That is 

what they have maintained all along, all right, and so we need a 

clear understanding of what is the scope of traditional pharmacy 

compounding practice which FDA has already supported as appropriate in providing individualized therapy for people, and what is 

beyond that and requires Federal oversight, and to make sure that 

is delineated. And I think you will hear from the other witnesses, 

that is delineated from people masquerading as one of these buckets who are actually drug manufacturers. So we need clarity in 

whatever. 

And if Congress decides not to allow compounding manufacturing 

at all, all right, then we have heard from the hospitals and the 

clinics that that would be a tremendous burden on them because 

they would have to take back all this that they had outsourced. 

Mr. MATHESON. Mr. Chairman, that is all I am going to ask now. 

I will yield back. 

50 

Mr. PITTS. The chair thanks the gentleman. I now recognize the 

ranking member of the full committee, Mr. Waxman, 5 minutes for 

questions. 

Mr. WAXMAN. Thank you very much, Mr. Chairman. 

Dr. Woodcock, your testimony states that the current legal 

framework does not provide FDA with the tools it needs to appropriately regulate the compounding industry in its current state. 

You explained that you are referring both to section 503A and 

other parts of the Federal Food, Drug, and Cosmetic Act. 

I would like to start with section 503A. Obviously as you explained to Mr. Pallone, there are major questions about whether it 

would even remain in effect if challenged in most of the country 

apart from the Fifth Circuit. With regard to the circuit split, Representatives Barton and Griffith have asked why you could not fix 

this with guidance. 

Can you explain what a guidance could or could not do to address the circuit split? 

Dr. WOODCOCK. Certainly. A guidance says on every page that it 

is not binding either on FDA or the industry. That is what it says 

on every page. It is more or less an explanation of our thinking. 

It doesn’t add new requirements or cannot solve differences in 

court opinions. 

Mr. WAXMAN. But putting that aside you say that section 503A 

actually contains provisions that have impeded FDA’s ability to effectively regulate pharmacy compounding. 

Can you elaborate on what those provisions are and how they 

have impacted FDA’s oversight of compounding pharmacies? 

Dr. WOODCOCK. Yes, well, I think there are provisions in there 

that are vague, and so we need clarity about what is the line. So, 

for example, it says you shouldn’t compound without a prescription 

in inordinate amounts. What is ‘‘inordinate?’’ That is in the eye of 

the beholder. The industry has maintained that all of their activities, regardless of their scale, are within the scope of traditional 

pharmacy compounding. 

Mr. WAXMAN. The Oversight and Investigations Subcommittee of 

Energy and Commerce conducted a detailed investigation involving 

thousands of pages of FDA documents. 

One thing we found in that investigation is that for years, going 

back to the Bush administration, key FDA decision makers have in 

numerous internal meetings and memoranda indicated that section 

503A is inadequate and that new legislation is necessary. 

Are you familiar with any of these documents or any of these internal discussions? 

Dr. WOODCOCK. Well, I was present in the early 2000s when the 

court cases came down, all right. We had been preparing to try and 

implement 503A and making the preparations for that when the 

Circuit Court and then the Supreme Court ruled. So I am familiar 

with that set of discussions. 

Mr. WAXMAN. Well, is it fair to say that the agency leaders going 

back to the Bush administration understood that they needed new 

legislation because of fundamental weaknesses in section 503A? 

Dr. WOODCOCK. Yes, it was very difficult to implement in any 

reasonable manner. 

51 

Mr. WAXMAN. Mr. Chairman, the notion that FDA is asking for 

legislation simply to cover for past mistakes or in some sort of 

power grab is not correct. For years through two different administrations, agency leaders have known that there were problems with 

the underlying law. 

Let’s turn to the other provisions in the act apart from section 

503A. 

Dr. Woodcock, your testimony indicated that you are encountering difficulty when you attempt to inspect compounding pharmacies now using your current authorities. You mentioned that you 

actually had to seek a warrant in two cases after the pharmacies 

delayed or refused your access to records. 

Can you describe in more detail exactly what has happened during those inspections and describe which current statutory provisions are contributing to the difficulties you have faced when attempting to conduct inspections? 

Dr. WOODCOCK. Well, I probably can’t speak to statutory provisions. I am sorry. But what has happened is we have gone in there 

and, as I said, the industry has long maintained that we do not 

have authority over these licensed pharmacies that are in States, 

right, and so we go in and we ask to either inspect or to inspect 

records. And they say under some of the court cases that have occurred we don’t have to turn over records to you. 

Mr. WAXMAN. So some might argue that there is no problem here 

since you were eventually able to conduct the inspections and obtain the records you were seeking. But can you—— 

Dr. WOODCOCK. Certainly. 

Mr. WAXMAN [continuing]. Speak to that assertion? 

Dr. WOODCOCK. The real problem is what is clarity? What is a 

compounding pharmacy? What is a traditional compounding pharmacy? What about the status of these large scale and how do you 

define a large scale operation? You might say, well, I know it when 

I see it. OK, but how do you—— 

Mr. WAXMAN. Well, I was amazed to hear during your responses 

to earlier questions that in order for FDA to begin conducting the 

more recent inspections, you had to actually look in the newspapers 

and at the television ads and Web sites to even know where the 

compounding pharmacies were. 

Obviously, we don’t ask you to search the Internet or watch TV 

to figure out where drug manufacturers are. 

What is the difference here and do you need new authority to 

remedy the situation? 

And before you answer that, not only are we uncertain as to the 

continued validity of FDA’s authorizing statutes with respect to 

compounding pharmacies, but that statute itself is plagued by 

problems. And so I think we need to clarify the situation. 

But why should you have to go on TV and the Internet to be able 

to do inspections? 

Dr. WOODCOCK. Because they don’t have to tell us who they are, 

where they are operating, and what they are making. They don’t 

have to submit anything to us. They are operating under State law. 

And they don’t have to send us adverse events if they occur, even 

deaths, and we would read about them in the paper, hear about 

52 

them from the CDC or State health department, or a consumer or 

doctor will call us. 

And that is how we learn about this. And we don’t know of all 

this universe of 28,000 firms. We don’t know what they are doing. 

And so you might say, well, you should know about this. But when 

it happens, most of our actions have been reactive to things that 

we have heard about. 

Mr. WAXMAN. Thank you very much. Thank you for your indulgence, Mr. Chairman. 

Mr. PITTS. The chair thanks the gentleman. 

We are voting now on the floor so we will again recess until the 

floor votes are concluded, and then we will come back and reconvene with the second panel. 

I think all of the members have asked their questions. There 

may be some follow-up questions and we will ask you to please respond when we send you those. 

Dr. WOODCOCK. Certainly. 

Mr. PITTS. So at this point we will recess until conclusion of floor 

votes. 

[Recess.] 

Mr. PITTS. The time of our recess having expired, we will reconvene our hearing. At this time, I would like to request unanimous 

consent to enter a statement from the National Association of 

Chain Drug Stores into the record. Without objection, so ordered. 

[The information appears at the conclusion of the hearing.] 

Mr. PITTS. At this point, I will introduce our second panel. Today 

on our second panel we have Dr. Scott Gottlieb, resident fellow, 

American Enterprise Institute. Mr. Joseph Harmison, owner, 

Harmison Pharmacies, on behalf of the National Community Pharmacist Association. Ms. Elizabeth Scott Russell, Government Affairs Manager of the National Association of Boards of Pharmacy. 

Ms. Gabrielle Cosel, Manager, Drug Safety Project, Pew Health 

Group at the Pew Charitable Trust. And Mr. Gerry Migliaccio, 

Quality Systems Consultant, Migliaccio Consulting. 

Thank you all for coming. You each will have 5 minutes to summarize your testimony. Your entire written statement will be entered into the record. 

So, Dr. Gottlieb, we will begin with you. You are recognized for 

5 minutes for an opening statement. 

STATEMENTS OF SCOTT GOTTLIEB, M.D., RESIDENT FELLOW, 

AMERICAN ENTERPRISE INSTITUTE; JOSEPH H. HARMISON, 

OWNER, HARMISON PHARMACIES, ON BEHALF OF NATIONAL 

COMMUNITY PHARMACIST ASSOCIATION; GERRY 

MIGLIACCIO, QUALITY SYSTEMS CONSULTANT, MIGLIACCIO 

CONSULTING; ELIZABETH SCOTT (SCOTTI) RUSSELL, GOVERNMENT AFFAIRS MANAGER, NATIONAL ASSOCIATION OF 

BOARDS OF PHARMACY; GABRIELLE COSEL, MANAGER, 

DRUG SAFETY, THE PEW CHARITABLE TRUSTS 

STATEMENT OF SCOTT GOTTLIEB 

Dr. GOTTLIEB. Thanks a lot, Mr. Chairman Pitts, Mr. Ranking 

Member Pallone, and members of the committee. Thanks for the 

opportunity to testify today. I have a longer statement for the 

53 

record. I would like to summarize a few key points for you this 

morning. 

The tragic deaths of 55 Americans and the sickening of more 

than 740 resulting from contaminated steroid injections that were 

shipped by a disreputable firm have rightly focused public attention on a largely unfamiliar but prominent part of the drug supply 

chain, the practice of pharmacy compounding. 

Before this Congress are proposals to tighten Federal regulatory 

oversight of these compounding pharmacies and the practice of 

pharmacy more generally. Observers are calling on Congress to 

give the FDA more oversight of these firms. New laws merit consideration. We should articulate clear and bright lines between a 

legitimate practice of pharmacy compounding and those firms operating illegally as large-scale manufacturers under the guise of a 

pharmacy license. Some key considerations should, in my opinion, 

guide this work. 

First, there exists a practice of pharmacy. It was never intended 

that all compounding would create a new drug and be subject to 

FDA regulation but for the enforcement discretion or for the willingness of Congress to provide explicit exemption to certain pharmacists and certain activities that pharmacists undertake. 

Second, FDA has authority to target compounders that cross the 

line between the practice of pharmacy and engage in drug manufacturing under the guise of a pharmacy license. What FDA largely 

lacks is ease of administering this authority. FDA is generally not 

able to force firms to submit advance information to the agency before the firm is suspected of any wrongdoing, and so that the agency is more efficiently able to identify firms engaged in wrongdoing 

and target its oversight. 

Third, FDA generally lacks tools and resources to regulate a new 

class of firms that the agency has dubbed nontraditional 

compounders. I would argue that the firms in question here are not 

compounders, and calling them such confuses different issues. 

Rather, they are engaging in the bulk, large-scale repacking and 

manufacturing of sterile preparations of FDA-approved drugs, typically in advance of and often not in response to prescriptions for 

individual patients. 

To the degree that these large-scale operations prepare sterile 

volumes of drugs in a bulk form and ship these units widely, they 

present some novel risks and they have the potential for what I 

would call distributed risks. The public health could benefit from 

applying additional oversight to these firms, especially requirements that they adhere to good manufacturing practices. 

Fourth, as we address issues of supply, we must also address the 

policy decisions that have increased demand for products from 

some disreputable firms, from large-scale compounders who are 

breaking existing law and violating existing regulations. For example, the recent crackdown on manufacturing of generic drugs have 

shifted a lot of the demand for generic preparations to 

compounders. Likewise, decisions by FDA to suspend enforcement 

against compounders in certain select situations where the agency 

and policymakers had concerns about the high cost of FDA-approved drugs relative to the low costs of compounded versions has 

54 

also given greater license to certain compounders to bend, if not 

break existing law. 

Consistent enforcement is going to be especially important if we 

create a new class of compounders that FDA has dubbed the nontraditional compounding. If FDA doesn’t exercise its enforcement 

evenly and consistently, which means not allowing firms to compound identical versions of FDA-approved products, then the agency will give more incentive for drug makers to remask themselves 

as nontraditional compounders to skirt FDA’s new drug requirements. 

Finally, the market for compounding drugs is evolving very 

quickly. It is consolidating as other entities like distributors could 

well start buying out the large compounders. As this process 

unfolds, it will leave behind a much different compounding industry. This should serve as a cautionary tale to all of us. We should 

be mindful that the rules that we might write today would no 

longer be applicable to the market that we see tomorrow. 

Thank you for the opportunity to testify this morning. I look forward to your questions. 

Mr. PITTS. Thank you, Dr. Gottlieb. 

[The prepared statement of Dr. Gottlieb follows:] 

55 


85438.013

Examining Drug Compounding 

Testimony before the House Energy & Commerce Committee 

Subcommittee on Health 

Key Points: 

Thursday May 23, 2013 

By Scott Gottlieb, MD 

Resident Fellow 

The American Enterprise Institute 

1. There exists a practice of pharmacy. It was never intended that all compounding 

would create a new drug and be subject to Food and Drug Administration regulation 

but for the enforcement discretion of the FDA or for the willingness of Congress to 

provide explicit exemption to certain pharmacists and certain activities. 

2. FDA has authority to target compounders that cross the line between the practice 

of pharmacy and engage in drug manufacturing under the guise of a pharmacy 

license. While legal precedents cited by other witnesses have created some 

ambiguity, what the FDA largely lacks is ease of administering its authority. FDA is 

generally not able to force firms to submit advance information to FDA (before the 

firm is suspected of any wrongdoing) so that the agency is able to more efficiently 

identify firms engaged in wrongdoing and target its oversight In some cases, FDA 

doesn't know about these firms until a problem arises. In other instances, FDA is 

forced to make an affirmative case that a compounding pharmacy is violating the 

law before the agency is able to compel an inspection or take other measures. 

3. FDA generally lacks tools and/or resources to regulate a new class of firms that 

the agency has dubbed "non traditional compounders". I would argue that the finns 

in question here are not compounders, and calling them such confuses different 

issues. These are firms that repackage sterile FDA approved products into new 

dosage forms to improve their administration and enable the drugs to be tailored to 

therapy - for example, breaking chemotherapy into pediatric volumes, mixing 

hyperalimentation, preparing IV fluids, and breaking hospital-volume anesthetics 

like propofol for use in appropriately supervised outpatient settings. These firms fall 

into a gray area right now where they are treated as compounders but are not 

engaging in traditional forms of compounding. Rather they are engaging in the bulk 

repacking and manufacturing sterile preparations of FDA approved drugs, in 

advance of (and often not in response to) prescriptions for individual patients. To 

the degree that these large-scale operations prepare sterile volumes of drugs in a 

bulk form and ship these units widely, they present some novel risks. 

1 
56 


85438.014

4. As we address issues of supply, we also must address the policy decisions that 

have increased demand for compounded products from large scale "non traditional" 

compounders. At times, FDA has exercised its authority unevenly, which has given 

more incentive to compounders to skirt the law. Also FDA's actions against generic 

firms have driven the market for many drugs to compounders. In law and 

regulation, we need to take a risk-based approach that encourages sourcing of drugs 

from the most competent parts of the market, not its least competent elements. 

5. This is going to be especially important if we create a new class of compounders 

that FDA has dubbed "non traditional compounding". If FDA doesn't exercise its 

authority evenly, which means not allowing firms to compound identical versions of 

FDA approved products, then FDA will give incentive for drug makers to re-mask 

themselves as "non traditional compounders" to skirt the new drug requirements. 

6. Part of the reason why FDA's oversight has been, at times, inconsistent is that the 

agency often had a product orientation -- not a facility-based orientation - to its 

enforcement activity. That needs to change. FDA often targeted products they 

believed were being inappropriately marketed for inappropriate uses, rather than 

firms that were not operating under sound conditions. Enforcement was often 

reactive as a result. The agency's enforcement needs to take on both considerations. 

7. Finally, the market for compounded drugs is evolving qUickly. It's consolidating, 

and other entities (distributors, generic manufacturers) could well start buying out 

the large compounders. To these ends, what we do today may be irrelevant to the 

market we see in the near future. It may pay to wait and see how things shake out, 

and also to see how FDA's recent enforcement activity impacts these markets. 

The views expressed in this testimony are those of the author alone and do not 

necessarily represent those of the American Enterprise Institute. 

Introduction 

Mr. Chairman Pitts, Mr. Ranking Member Pallone, and members of the House Energy 

and Commerce Committee, Subcommittee on Health: 

Thank you for the opportunity to testify today before this Committee. 

The tragic deaths of 55 Americans and Sickening of more than 7401, resulting from 

contaminated steroid injections (methylprednisolone acetate) that were shipped by 

a disreputable "compounding pharmacy" located in Massachusetts, have rightly 

focused public attention and the work of this Committee on a largely unfamiliar, but 

prominent part of our drug supply chain - the practice of pharmacy compounding. 

1 CDC Statistics: http://www.cdc.gov/hai/outbreaks/meningitis.html 

2 
57 


85438.015

Before this House Committee, as well as the Senate, are proposals to tighten federal 

regulatory oversight of these compounding pharmacies, and of the practice of 

pharmacy more generally. Observers are calling on Congress to give the Food and 

Drug Administration (FDA) expanded oversight of these establishments. 

New laws merit consideration. We should articulate clear and bright lines between 

the legitimate practice of pharmacy compounding, and those firms operating 

illegally as large-scale drug manufacturers under the guise of a pharmacy license. 

I don't believe that it should be left to FDA's discretion to establish these boundaries 

as the agency goes about its work, or allow a fuzzy standard to persist. I believe that 

this would only add to uncertainty in the marketplace and create an undue burden 

on FDA to interpret vague authority. Ultimately it would result in uneven 

enforcement that would risk repeating some of the past mistakes. 

Nor do I believe any pharmacy practice where drugs are compounded necessarily 

creates a new drug. There is such a thing as the practice of pharmacy that was, in my 

view, a sphere of medical practice that was never intended to be subject to FDA 

oversight There are pharmacies that clearly practice within the scope of their 

profession, and are subject to state and professional regulation. And there are 

pharmacy compounders that are clearly crossing the line between the practices of 

pharmacy and taking on all the characteristics of a drug manufacturers and, as such, 

already fall squarely within FDA's existing oversight and authority. 

But it seems illogical, inconsistent with prior statute, and administratively 

burdensome to declare that all pharmacy compounding - even done locally, for 

individual patients, and in response to valid prescriptions - creates a new drug and 

could be subject to FDA oversight but for Congress' willingness to exempt certain 

activity from new drug requirements, or FDA's exercise of enforcement discretion. 

Instead, we should establish a clear boundary and objective tests for when 

pharmacies are engaging in legitimate compounding - and are subject to state 

regulation; and when establishments have crossed the line and are operating as 

drug manufacturers under the facade of a pharmacy license. When these lines are 

crossed, FDA has clear authority to assert - at the least - its Good Manufacturing 

(GMPc) standards to ensure the safety and effectiveness of products. This basic 

principle exists today, and should be part of any further clarification of existing law. 

The merit in considering these issues is made urgent by the tragedy in 

Massachusetts and the apparent malfeasance at the New England Compounding 

Center (NECC). But it's also made necessary by the changing face of this industry. 

These changes in the way compounding pharmacies operate, along with policy 

decisions (some made by FDA) that have increased demand for these compounded 

products, have strained FDA's existing resources and its policies in this area. 

3 
58 


85438.016

These challenges may call for a greater role for both state and federal regulators. 

But we need to be mindful of the reasons why the practice of pharmacy has 

traditionally been left to state regulation. When proper oversight demands that 

regulators examine the relationship between a provider and a patient (as proper 

oversight of the practice of pharmacy entails) then these endeavors are best left to 

state and professional authorities who have more proximity to the actual provision 

of care. Not every regulatory endeavor benefits from federal involvement. 

In addition, we also need to be mindful of the policy decisions that drive more 

widespread - and sometimes inappropriate - use of compounded products. Finally, 

we need to be aware of the authority that FDA currently has that - with proper 

attention and perhaps additional resources - could provide better protections. 

We need to take measure of these things before we enact new laws. 

The recent problems didn't arise from traditional compounding, which is a 

legitimate part of the practice of pharmacy and an important part of medical care. 

The traditional practice of pharmacy compounding is generally regarded as the 

combining or altering of ingredients by a licensed pharmacist, in response to a 

licensed practitioner's prescription for an individual patient. This activity produces 

a medication tailored to a patient's special medical needs. Compounding pharmacies 

mix or alter drug ingredients to adapt a medicine based on a doctor's prescriptionfor example by changing a pill into a formula, changing dosage forms, tailoring 

chemotherapy, or adding cherry flavoring to a child's medicine. 

The practice of pharmacy compounding lets physicians customize drugs to 

individual patients. Traditional pharmacy compounding typically is performed on a 

small scale and is always performed in response to a valid patient prescription. 

The FDA normally doesn't get involved with such practices because it isn't tasked 

with regulating the legitimate practice of pharmacy. Like the practice of medicine, 

pharmacy is largely left to professional and state oversight. But once pharmacies 

begin manufacturing and shipping medicines on a wide scale, and do so in a way 

that isn't in response to a valid prescription, these firms often become "drug 

manufacturers" and fall squarely under the FDA's extensive authority.2 

In recent years, we have seen much more widespread use of compounded pharmacy 

products. Along with this increased use, we have seen the simultaneous expansion 

in the scope of the industry, and the advent of very large compounding pharmacies 

that commercialize and distribute drugs on a wide scale, without a doctors' 

prompting, and outside the boundaries of an individual patient encounter. 

2 A compounding fracture at the FDA. Scott Gottlieb and Sheldon Bradshaw. The 

Wall Street Journal, November 14, 2012. A24. 

4 
59 


85438.017

These mega establishments stretch the traditional definition of what it means to be 

a compounding pharmacy. It's the intersection between the activities ofthese nontraditional establishments and existing state and federal regulation, that I believe 

bears closer scrutiny. With my testimony today I want to do three things: 

First, I want to outline some policy decisions that I believe have increased demand 

and weakened oversight of compounding under FDA's existing authorities. 

I believe these policy decisions merit scrutiny, and perhaps re-examination. The 

compounding industry has evolved significantly in recent years, in many cases 

magnifying old risks and creating new ones. Some of this evolution owes to changes 

in the market for these products. But in other cases, it stems from changes in 

regulation that have shifted the market away from traditional manufactures, and at 

times, emboldened compounders to expand production into gray areas. 

All of these factors bear close scrutiny. Any solution to mitigate existing risks must 

address not only the supply of higher-risk products, but also the factors that create 

the demand for these products to be produced by lower-standard manufactures. 

Moreover, if Congress does seek to give FDA clearer authority to regulate these socalled non-traditional compounders, who I believe already fall outside the 

traditional practice of pharmacy and are subject to FDA oversight today, there is an 

important consideration. This new authority has to go hand-in-hand with vigorous 

enforcement by FDA of rules that prohibit compounders from making copies of 

FDA-approved drugs. Otherwise, creating this third category of "compounding 

manufacturers" where the full brunt of FDA's requirements don't apply will create 

incentive for drug manufacturers to re-cast themselves as non-traditional 

compounders so that they can float into this new, regulatory-light category. 

In recent years, FDA has been reluctant to stop compounders from copying FDAapproved drugs out of economic concerns that it would limit consumers to higher 

priced products. These economic concerns have to be addressed separately. 

If the NDA process imposes costs that end up raising the price of finished goods, that 

has to be separately addressed, perhaps through thoughtful review of how the NDA 

process could be made more efficient when it comes to certain lower risk, better 

understood sterile products. But so long as FDA is going to create a new category of 

compounding manufactures, it needs to prevent traditional FDA approved products 

from mOving into this new category and undermining the safety of products now 

being produced by reputable manufacturers to high standards. We also need to 

make sure that the intellectual property surrounding those NDA products is not 

deliberately undermined by a new category of FDA-sanctioned manufacturers. 

Second, I want to outline where FDA has existing authority to regulate nontraditional pharmacy compounding, and try and give this committee a sense for 

5 
60 


85438.018

how, in my view, that authority has been exercised by FDA and why the agency has 

made certain choices in how it interpreted those rules. Much is made of FDA's 

concern that legal challenges to the existing statute and policies have left FDA's 

current authority muddled. While these complaints have merit, I believe that there 

are other considerations that also shape the strength of FDA's authority. 

For example, FDA often targets specific products rather than troubled facilities. The 

FDA has also, at times, not enforced rules evenly out of concern that knocking 

certain violating products and firms out of the market might impose higher costs on 

consumers. All of these considerations and policy choices have merit But they 

create a regulatory scheme that is at times reactive and can appear arbitrary. 

Third and finally, I want to propose some ideas for how I believe that a clearer 

standard in policy and law could provide for more effective overSight in this area 

and create a clearer boundary between the legitimate practice of pharmacy 

compounding and those firms that are distorting that traditional custom. 

FDA has noted that legal challenges to its existing policies have served to muddle its 

authority. We also need to consider the way that FDA's own actions have 

contributed to this haziness. The FDA's influence on stoking some of the challenges 

it now faces is instructive because as I will explain, it speaks to the need for FDA and 

Congress, to establish a clear line between the activities that fall within the FDA's 

scope and those that are traditional pharmacy left to state authority. 

The Evolution of Large Scale Compounding 

As FDA Commissioner Dr. Peggy Hamburg stated in recent testimony, the practice of 

pharmacy compounding has undergone an evolution in recent decades. We have 

seen the advent of very large scale compounding firms that operate with many of 

the characteristics of traditional drug manufacturers. In recent months, FDA has 

referred to this practice as "non traditional compounding."3 

Part of this growth in compounding has been driven by greater sourcing of these 

products by hospitals. As Dr. Hamburg stated in recent testimony, to save costs, 

hospitals have outsourced compounding that they used to do in house.4 

3 Pharmacy Compounding: Implications of the 2012 Meningitis Outbreak, Statement 

of Margaret A. Hamburg. M.D., Commissioner of Food and Drugs, Food and Drug 

Administration, Department of Health and Human Services, Before the Committee 

on Health, Education, Labor and Pensions United States Senate. November 15, 2012 

4 Statement of Margaret A. Hamburg. MD Commissioner of Food and Drugs, Food 

and Drug Administration, Before the Subcommittee on Oversight and Investigations, 

Committee on Energy and Commerce, U.S. House of Representatives. "A Continuing 

Investigation Into the Fungal Meningitis Outbreak and whether it Could have Been 

Prevented." April 16, 2013. 

6 
61 


85438.019

Let me elaborate on this point. While I agree with the FDA's general analysis, I 

would cast the different pieces of this broader industry into different slices. 

What have evolved are essentially three types of outfits when it comes to the area 

generally referred to as compounding. 

First is traditionally compounding, where a pharmacy works in consultation with a 

physician to tailor a product based on a valid prescription. 

This practice of pharmacy falls within professional and state purview and has not 

been the source of recent concerns. 

Next, there are firms that masquerade as pharmacies, but engage in large scale 

manufacturing. often of unique products or drugs designed to compete with FDA 

approved medicines. These firms develop these drugs in bulk, without valid 

prescriptions or in anticipation of prescriptions, and do not adhere to good, sterile 

manufacturing techniques. These firms seem to be violating current federal law. 

Many are manufacturing new and unapproved drugs. In so doing, they are already 

subject to FDA's current and extensive oversight. 

There is a third category of manufacturers that FDA has dubbed "non traditional 

compounding" but which I would offer is not compounding in its traditionally form, 

but another new and vital manufacturing service that has evolved over time. 

Firms in this third category typically produce sterile products in bulk, usually to 

supply large medical practices and hospitals. In its most common form, these outfits 

will break down large volumes of FDA approved products into smaller units, for 

example taking large units of an anesthetic and breaking it into syringes to be more 

easily administered, taking a large unit chemotherapeutic and breaking it into 

smaller units to be dosed for a pediatric indication, or producing hyperalimentation 

for supplemental nutrition delivered by parental or enteral means. 

These outfits are really sterile repackaging and re-mixing firms - not compounders 

in the traditional, local sense. Hospitals used to do this sort compounding of work in 

house, in their own pharmacies. When it was a hospital-based pharmacist working 

on a small scale under a sterile hood, there was manageable risk and a lower 

likelihood of wide contamination. But to save costs and improve quality and 

efficiency (in part, as a response to the tightening of the hospital industry's 

regulations) the hospitals have outsourced this work to these new,large firms. 

The firms now performing this role are doing it on a wide scale, and are not 

compounders in the traditional sense. FDA confuses the issues by referring to these 

firms as "non traditional compounders", I would call these firms sterile preparation 

manufacturers or sterile prep manufacturers, These firms are a new, and important 

category of drug suppliers. They are now a vital part of the drug supply chain for 

hospitals and large outpatient practices. And their work creates certain risks. 

7 
62 


85438.020

If generic drug firms were engaging in this activity, FDA would require separate 

drug applications for each dosage firm. FDA would require the generic firms to do 

stability studies, container closure studies, and pay separate user fees, among other 

things. This is one of the reasons why the generic drug makers do not supply drugs 

in the full range of dosage forms and packaging - and why the hospitals have to turn 

to these "sterile prep manufacturers" (or non-traditional compounders). 

This begs the question: Should these sterile prep manufacturers be subject to the 

same oversight as a generic drug firm engaging in the same activity? 

It's a relevant question, but I think the answer is no. Because these hospital preps 

and repackaged drugs have a shorter dating period, it might be reasonable to 

subject them to a lighter regulatory touch. 

The firms doing this sort of "non traditional compounding" (to borrow FDA's poorly 

suited lexicon) generally do a good job. But they have been the source of some 

problems, including some fatal contaminations in recent years. A review of FDA's 

recent oversight work has found that these products are not uniformly produced 

under sterile techniques, and in some cases have some significant contaminations. 

To the degree these "sterile" products are being used in hospitalized patients, who 

often have a lot of co-morbid illness, this can create public health risks. 

It is reasonable to consider whether these outfits should be subject to GMP 

requirements to make sure they adhere to sterile techniques. 

I would offer that these firms should be the focus of the present discussion. 

Traditionally compounding should continue to be the domain of state and 

professional oversight. And the compounders like NECC engaged in manufacturing 

new drugs already fall under FDA's current scrutiny. As for the sterile prep 

manufacturers (or "non traditional compounders") since the sterile preps and repackaged goods are often produced and shipped on a wide scale, an inadvertent 

contamination in one lot could have widely distributed risks before a product could 

be recalled by an overlapping patchwork of state and federal authority. 

Policy Choices and the Rising Demand for Compounded Products 

To exam why the industry has grown and evolved in recent years, also requires a 

closer examination of the policy measures that I believe have contributed to these 

circumstances. Some of these recent policy decisions have driven demand away 

from traditional manufacturers like generic drug firms, and to compounders. 

In at least some cases, providers are turning to a small number of unreliable 

compounders because they cannot sources these products elsewhere. 

8 
63 


85438.021

To begin, a recent tightening in FDA's oversight of generic drug firms that made 

nearly identical versions of the same sterile injectable drugs produced by many 

compounders (including NECC) has prompted providers to source more products 

from large scale compounders. This tightening was rooted in some legitimate 

concerns that FDA had about the reliability of the generic manufacturing facilities. 

But it has created a contradictory set of policies that at has had the effect of shifting 

purchases from more reliable sources to firms with more questionable practices. 

A key question is this: Even assuming that the FDA's concerns around the generic 

drug makers were all proven correct, would the continued production of drugs from 

these facilities - under close FDA supervision - been preferable to the alternative 

outcome -- closing these generic facilities and driving some providers to source 

products that were in shortage from compounders. By driving the generic firms to 

close their facilities while they underwent remediation, it left the market to be 

supplied by the only outfits still capable of operating - the compounders. This fueled 

further growth of these compounded products. But one must also ask whether the 

overall risk to the public was increased as a result of the fact that so much of the 

utilization had shifted to these more lightly regulated outfits. 

This question is important is because it gets to the heart of the kinds of 

considerations that a risk-based approach to regulating these products should take 

up, and to how we make sure clinical needs are met with the most reliable products 

available. This same challenge has played out in other contexts where the decisions 

that FDA took may have served to increase demand for compounded drugs. 

For example, Congress intended for FDA's enforcement over compounding to take 

into consideration when drugs were being manufactured by compounders that 

competed directly with FDA approved medicines, and therefore didn't offer any 

unique tailoring or differentiation that was a key clinical characteristic of the 

practice of pharmacy and the traditional role of compounding. 

To these ends, the FDA has historically asserted its authority when compounding 

pharmacies were supplying their own versions of drugs that were also available 

commercially -- as FDA-approved branded and generic products. In these 

circumstances, the FDA held that these compounding firms were guilty of 

distributing unapproved new drugs. Among other things the New England 

Compounding Center, the outfit behind the tainted steroid shots, was cited for this 

sort of activity in that 2006 warning letter that FDA sent to the troubled firm. 

However, a policy change made in recent years curtailed some of the exercise of this 

authority. This policy change gave greater economic incentive and political license 

to compounders to engage in more widespread production of drugs that exist as 

FDA approved products and compete directly with FDA regulated medicines. 

9 
64 


85438.022

In particular, FDA changed a longstanding guidance document that stipulated that 

the agency would clear the market of compounded drugs once a drug went through 

the new drug approval process and earned FDA approval for the same indication. 

The guidance was changed to read that FDA would use its discretion in such cases, 

and only take action to remove the compounded products in cases where it had 

specific public health concerns. While I understand the agency's economic concerns 

around the potential for drug costs to rise when compounders are forced to exit the 

market, these considerations should not factor into the consistency by which the 

agency applies its policy. There are other avenues to address these economic 

concerns. FDA could also give greater consideration to the cost of the NDA process 

and ways to make that more efficient, especially in the case of old, well-understood 

drugs seeking FDA approval to sell approved versions of compounded drugs. 

But the policy of removing the older, unapproved drugs remains controversial, and 

expectations that FDA would enforce it were largely squashed after FDA said it 

would not step in when the company KV Pharma, sought and received FDA's nod for 

Makena, an approved form of a type of progesterone that's widely compounded. 

The FDA decided not to take action out of a well-publicized concern about the high 

cost of Makena relative to the compounded formulations. This political decision 

undermines the incentive for other companies to run registration trials to get FDA 

approval for drugs that are widely compounded. It emboldened compounders. The 

company that got FDA approval for Makena, KV Pharma, went into bankruptcy. 

What kind of incentive does that give to other firms to invest in the development of 

FDA-approved versions of drugs that are being widely compounded? 

The intervention in the KV Pharma case sends a message to would-be violators that 

the pricing of products could factor into how the FDA can enforce its own safety 

rules. The New England Compounding Center was also among the compounding 

firms distributing an unapproved version of the KV Pharma product. Does this 

committee believe that it's a good outcome that the active ingredient in Makena is 

now being widely used in woman who are pregnant, and made by firms like NECC? 

Or would an FDA approved version of that medicine be preferable? 

It's hard to have it both ways when it comes to these matters. That's why it was 

important that FDA layout clear lines and enforces them vigorously and 

consistently to reduce the incentive of firms to skirt the law by operating as new 

drug manufacturers under the guise of a pharmacy license. 

This is especially true if Congress creates a third category of "non traditional 

compounders". If FDA doesn't vigorously and consistently enforce a clear boundary 

between drugs that must be compounded because of the way they are made, and 

those that have gone through the NDA process and exist in the market as FDA 

10 
65 


85438.023

approved new drugs, then the agency will create a clear and improper incentive for 

some drug manufacturers to re-cast themselves as "non traditional compounders" 

to skirt the new drug requirements of the Act. Congress should be aware that there 

are significant, competing tradeoffs as a result of this approach. For example, there's 

the potential for new policies to drive compounders out of certain popular markets. 

The Exercise of FDA's Existing Authorities 

Even while we consider new legislation, we should first look for avenues to help 

FDA make better use of its existing authority to regulate non-traditional pharmacy 

compounding. As FDA has shown with its recent, robust actions, the agency has 

some clear authority in this space and the ability to exert considerable oversight. 

Indeed, by FDA's account, it targeted 29 firms for inspections based on their sterile 

processing practices and took stern actions against some of those firms. In most 

cases FDA was able to exercise its oversight without interference. In a few instances 

FDA needed to seek a court's backing to get access to the records. While this may 

have imposed some brief delays, the agency seems to have fulfilled its mission. 

Much is made of FDA's concern that legal challenges to the existing statute and to 

the agency's policies have left FDA's current authority muddled. 

While these complaints have some merit, I believe there are other considerations 

that also shape the exercise of FDA's authority. Considering these can provide a 

fuller understanding of the challenges that FDA faces, and potential policy solutions. 

In particular, I believe that the FDA has historically taken a product approach to its 

enforcement of its compounding oversight, rather than a facility based approach. 

What I mean by this, more specifically, is that the enforcement actions were often 

taken in response to individual products that the FDA was concerned with - either 

because the products carried inappropriate claims, or were being used for 

circumstances where FDA didn't believe that the benefits justified the risks. 

For example, in 2006 FDA sent a series of warning letters to compounders who 

were formulating topical lidocaine for use as a pre-treatment in electrolysis, to help 

numb peoples' legs before they had the sometimes-painful procedure. 

FDA was rightly concerned that using large amounts of topical lidocaine in this way 

could cause systemic side effects, and was an inappropriate use of the drug. 

I use this example to illustrate a simple point: That the enforcement activity often 

targeted the products rather than the facilities. This often made the agency's 

enforcement a reactive process, rather than a pro-active assessment of risk While 

products being used in inappropriate ways create risks, and deserve regulatory 

scrutiny, the FDA can probably get as much, if not more bang for its public health 

dollar by bringing equal or even greater focus on the facilities that are 

11 
66 


85438.024

inappropriately compounding products in ways that are unsterile and cross the line 

between traditional compounding and the wholesale manufacture of new drugs. 

It's a difference of where the enforcement mindset emanates from - whether it 

flows from the drug reviewers in charge of reviewing products, or facility inspectors 

in charge of overseeing the quality of facilities, or some combination of each. 

In the past, a lot of the enforcement activity emanated from the drug review 

divisions and the drug center's office of compliance. This let to an orientation that 

sometimes targeted products, rather than facilities. FDA would bring enforcement 

actions in cases where FDA found drugs that were being compounded for uses that 

the agency believed created risk, or misled consumers. 

I believe an equal focus should be placed on targeting unsafe, unsanitary facilities 

whose business practices violate existing law. This requires a greater role for the 

FDA field in doing. actual inspectional work that focuses on unsafe facilities as much 

as it requires a focus by drug review staff on the products themselves, and the 

indications they are used for. 

Establishing Bright Regulatory Lines 

Above all else, the inspectional activities must be targeted in a way that creates a 

clear delineation between the protected practice of pharmacy, and those firms that 

are creating new, unapproved drugs, or the sterile prep manufacturers I spoke of. 

FDA has outlined a number of key factors that establish the boundary between 

traditional and "non traditional" compounding pharmacy. So it has historically 

articulated where a boundary could rest. These principles should guide policy. 

It's these factors that have been the basis of FDA's recent vigorous and successful 

oversight efforts in this area. The agency's recent enforcement work demonstrates 

that the agency is able to enforce its supervision when firms fall outside of these 

boundaries. Moreover, some of these factors have already formed the basis of 

CongreSSional statute in section 503(A). These factors should form one basis of 

FDA's enforcement going forward and any re-articulation of that policy. 

It's noteworthy that size, as well as shipping across state lines, alone, are not reliable 

criteria. There are good reasons why some products may be produced on a large 

scale even in response to physician prescriptions. For example, it may not be 

possible to develop a Single dose from a bulk ingredient. 

So a pharmacy producing a drug for a single physician in response to a single 

prescription may be forced to produce extra volumes of the same finished product. 

12 
67 


85438.025

There are equally good reasons why some pharmacies might ship products 

interstate. It could be as simple as a pharmacy that resides close to a state border. 

Proper criteria involve more than just one or several factors, but a multi-part test 

FDA has expressed some of the factors that would be part of a multi-part test in its 

prior guidance documents that addressed its enforcement They include: 

1. Compounding of drugs in anticipation of receiving prescriptions, except in 

very limited quantities that are done in close relation to the amounts of drugs 

that will need to be compounded after receiving valid prescriptions. 

2. Compounding drugs that were already withdrawn by FDA or removed from 

the market for safety reasons. 

3. Compounding finished drugs from bulk active ingredients that are not 

components of FDA approved drugs without an FDA sanctioned 

investigational new drug application (IN D) in accordance with 21 U.S.C. § 

355(i) and 21 CFR 312. 

4. Receiving, storing, or using drug substances (for use in compounding) 

without first obtaining written assurance from the supplier that each lot of 

the drug substance has been made in an FDA-registered facility. 

5. Receiving, storing, or using drug components not guaranteed or otherwise 

determined to meet official compendia requirements. 

6. Using commercial scale manufacturing or testing equipment for 

compounding drug products. 

7. Compounding drugs for third parties who resell to individual patients or 

offering compounded drug products at wholesale to other state licensed 

persons or commercial entities for resale. 

8. Except in certain narrow circumstances, compounding drug products that 

are commercially available in the marketplace or that are essentially copies 

of commercially available FDA-approved drug products. 

9. Failing to operate in conformance with applicable state law regulating the 

practice of pharmacy. 

Conclusion 

FDA has rightly noted that non-traditional compounding should, because of the 

higher risk presented, be subject to a greater degree of oversight The large scale 

compounding we've seen in the marketplace, where firms manufacture large 

volumes of sterile products, and do so in advance of (and sometimes without) a 

proper physician prescription, and then ship these finished products across the 

country, should be subject to a higher level of manufacturing controls. 

"Compounders" operating in this manner are not operating as pharmacies. Let's 

make no mistake. They are making new sterile dosage forms on a mass scale. 

13 
68 


85438.026

Other "compounding pharmacies" operating with these same characteristics, and 

making unapproved new drugs (like NECC) already fall outside the traditional 

practice of pharmacy and make themselves subject to FDA's oversight. 

FDA's main complaint, in my opinion, isn't that these entities aren't subject to the 

agency's regulation under the existing law. The FDA's main complaint, when you 

boil it down, is that the existing legal framework puts too much burden on FDA (in 

the agency's opinion) to have to make the affirmative case that these firms are 

operating in a way that places them under the agency's jurisdiction. That's a valid 

complaint, but it' a different concern than the one commonly reported. 

At its core, the issues we are talking about here aren't issues of whether or not FDA 

has proper authority. They do. The issues are whether or not FDA has the legal and 

regulatory tools to make its role in these regulatory endeavors administratively 

easier, more consistent and anticipatory, and less resource intensive. 

FDA's traditional regulatory posture is to compel the submission of information to 

the agency that allows FDA to target its regulatory oversight. In the case of 

compounding pharmacies, FDA - at the margins - needs to often make the 

affirmative case that certain firms are not acting as pharmacies but as drug 

manufacturers and are therefore subject to the agency's oversight. 

What FDA wants, in my view, is the means to compel the submission of certain 

information that would enable FDA to more easily demonstrate when compounders 

are no longer acting as compounders. But we should be candid about this key fact. 

Legislation could be narrowly tailored to address the real problems here. I believe 

that some of the proposals address issues that are peripheral to the key challenge. 

In closing, I wish to make one final point. The market for compounding is changing 

very rapidly, not only as a result of the tragedy in Massachusetts, but the stepped up 

oversight that FDA has exerted in recent months, as well as the activity on Capitol 

Hill. It's also driven by issues in the marketplace itself, where certain lower margin 

businesses are looking to get into higher margin work in drug manufacturing. 

To these ends, we're seeing compounders consolidate, and get acquired by more 

reputable manufacturers. It's my belief that this industry will undergo an evolution 

in the next few years, where many of the large-scale compounders will either 

consolidate or close because they can't meet the current scrutiny, and reputable 

manufacturers and maybe drug distributors will acquire many others. 

We may also benefit from seeing the culmination of FDA's recent enforcement 

activity, and get a better sense of the contours of FDA's existing influence. 

As this process unfolds, it will leave behind a much different compounding industry. 

This should serve as a cautionary note to all of us. The rules that we might write 

today may no longer be applicable to the market that we see tomorrow. 

14 
69 


85438.027

The market forces that are transforming this industry may accomplish many of the 

public health goals that we seek to address through legislation. 

### 

Dr. Scott Gottlieb is a physician and Resident Fellow at the American Enterprise 

Institute. From 2005-2007 he served as the FDA's Deputy Commissioner for Medical 

and Scientific Affairs, and before that as the agency's Director of Medical Policy 

Development and as a Senior Advisor to the FDA Commissioner. Dr. Gottlieb consults 

with and invests in biopharmaceutical companies and serves as a director to several 

life science companies. Scott Gottlieb is a member of the policy boards to the Leukemia 

and Lymphoma'Society and the Society ofHospitalist Medicine. 

Dr. Gottlieb can be reached at ScottGottlieb@gmail.com 

15 
70 

Mr. PITTS. Mr. Harmison, you are recognized for 5 minutes for 

opening statement. 

STATEMENT OF JOSEPH H. HARMISON 

Mr. HARMISON. Thank you, Mr. Chairman. I wish I could speak 

as quickly—— 

Mr. PITTS. Poke the button on that. If you will push the button, 

speak into the mike, please. Thank you. 

Mr. HARMISON. OK. Excuse me. 

Chairman Pitts, Ranking Member Pallone, Vice Chairman Burgess, thank you for the opportunity to be here today. As stated, I 

am Joe Harmison. I am a practicing pharmacist, pharmacy owner, 

and past president of the Texas Pharmacy Association and the National Community Pharmacists Association. NCPA appreciates the 

opportunity to share the community pharmacist’s perspective regarding issues relating to drug compounding. NCPA represents the 

views of community pharmacists, including 23,000 independently 

owned community pharmacies. According to an NCPA member survey, 86 percent of our members do some kind of compounding. This 

can range from flavoring pediatric liquids to changing dosage forms 

to pay for patients that can’t take oral solids to topicals to injections. In my practice, we mainly emphasize pain medications. And 

we are U.S. Pharmacopeial 797 standard compliant. 

Our hearts go out to the families who have suffered from the 

tragic events surrounding New England Compounding Center, and 

NCPA is committed to working with Congress on the issues of 

practice that exceed State-regulated compounding. NCPA commends the committee for taking a closer look at those actions and 

inactions that led to the tragic NECC event. We believe the committee is taking the proper steps to address this tragedy by focusing its investigations on what steps should have been taken and 

oversight that ensures that the proper regulatory bodies are exercising their full authority. 

Compounding is the backbone of pharmacy. It goes back to the 

time of the alchemist. For centuries, pharmacy only did 

compounding, until World War II, then commercially prepared 

medicines became more prevalent, which is still the thing today. 

But it did start dawning on people a couple of decades ago that 

there are people that need something that just isn’t commercially 

available. So compounding came back into being an important part 

of the pharmacy practice. 

Another thing, compounding serves to bridge a gap which we are 

experiencing more and more when commercial products are not 

available. Patients must be assured that they are not forced to go 

without medicines or their treatment because medications are unavailable and compounding for that medication is prohibited or tied 

up in a bureaucracy. It is important to reiterate that pharmacist 

compounding is an integral part of pharmacy profession and meets 

patients’ needs in hospitals, long-term care, home infusion, hospice, 

every community setting I can think of. 

NCPA has always and will continue to advocate that pharmacy 

compounding is best regulated by the State boards of pharmacy 

while manufacturing oversight is the purview of the FDA. Pharmacy compounding medication is an important part of the medical 

71 

care and allows dispensing custom-made medications and should 

continue to be related by State boards of pharmacy, as all other 

medical profession licenses are. 

State boards of pharmacies currently oversee all aspects of pharmacy and in most cases their records are public. So it is not hard 

to obtain who is doing what. If the FDA has concerns about appropriate licensed pharmacy, then the FDA currently has the authority to ask the State board of pharmacy to work with them to address the issues. If it is found that they have an entity that is acting under the guise of a pharmacy and is exceeding its State-regulated authority, then the States board of pharmacy should suspend 

the license of that pharmacy until it complies with the State regulations or meets the FDA regulations to be a manufacturer. 

All parties involved must make certain that the State boards of 

pharmacy are adequately staffed, trained, and funded to effectively 

regulate compounding. NCPA encourages the State boards of pharmacy to acquire uniform compliance with USP 797 standards in 

order to provide more uniform product standards. As such, every 

State will be assured that resident and nonresident pharmacies 

alike are all in compliance with the USP standards. 

In most cases, compound medication must originate from a prescription for a specific patient. There are times that we may do 

things in advance, but we have to be able to prove that we use historically a certain amount in a very short period of time. 

I see I am out of time. Compounding should not be defined by 

nuance, such as types of product, whether it is sterile or nonsterile, 

as risk of complexity of compounding is not solely dependent on the 

product type. Neither is quantity of the product made in a pharmacy of bearing because we can make many different things and 

they are all safe. And interstate commerce should not be—because 

we, was stated earlier, we are a border State to 5 different States, 

and, being rural, there are places that just have to go across State 

lines. But if it is the issuance of a prescription for a specific patient 

for a specific malady, this should be allowed and under the purview 

of the States. 

Thank you for the opportunity to be here. NCPA pledges to work 

with Congress to put this to rest. 

Mr. PITTS. Chair thanks the gentleman. 

[The prepared statement of Mr. Harmison follows:] 

72 


85438.028

United States House of 

Representatives 

Committee on Energy 

and Commerce 

Subcommittee on Health Hearing on 

"Examining Drug Compounding" 

Thursday, May 23, 2013 - 10:00am 

Chairman Pitts, Vice-Chairman Burgess, Ranking Member Pallone and Members 

of the Subcommittee, my name is Joe Harmison and I am a pharmacist, owner of DFW 

Prescriptions and past president of the National Community Pharmacists Association 

(NCPA). NCPA appreciates the opportunity to share the community pharmacy 

perspective regarding issues relating to drug compounding. NCP A represents the 

interests of America's community pharmacists, including the owners of more than 23,000 

independent community pharmacies. According to a NCPA member survey, almost 

86% of independent community pharmacies compound medications. Our members 

perform a wide variety of compounding services including hormone replacement 

medications, making suspensions palatable for pediatric patients, different dosage forms 

for patients suffering from intractable nausea and vomiting, and medications for cystic 

fibrosis patients, to name a few. Specific to my practice, I compound medications 

primarily used in the treatment of pain that help patients and their p'hysicians treat their 

conditions. We are compliant with U.S. Pharmacopeial Convention (USP) <797> 

Pharmaceutical Compounding-Sterile Preparations standards. 
73 


85438.029

Our hearts go out to the families who have suffered from the tragic event 

surrounding the New England Compounding Center (NECC), and NCPA is committed to 

working with Congress on the issue of practices that exceed state regulated 

compounding. NCP A commends the Committee for taking a closer look at what actions 

and inactions led to the tragic NECC event. We believe the Committee is taking the 

proper steps to address this tragedy by focusing on investigations into what steps should 

have been taken and oversight to ensure that the appropriate regulatory bodies are 

exercising their full authority. 

Importance of access to compounded medications 

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 in accordance with a prescription based on the patient's individual needs. 

Compounding services can help bridge the gaps during times of prescription drug 

shortages. Drug shortages have nearly tripled, according to the FDA, and their impact can 

be devastating. Patients must be assured that they are not forced to go without needed 

medications or treatments because their medication is unavailable and compounding of 

that medication is prohibited or tied up in bureaucracy. 

2 
74 


85438.030

It is important to reiterate that pharmacist compounding is an integral part of the 

pharmacy profession and meets patients' needs in hospitals, long-term care and assisted 

living facilities, home infusion settings, and many community settings. 

State Board of Pharmacy oversight of pharmacy compounding is critical 

NCP A 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. These state Boards of Pharmacy currently oversee all aspects of a pharmacy 

from licensure, oversight of pharmacists and technicians, the process of filling 

prescriptions, records, documents, and compliance with the state's laws and regulations. 

If the FDA has a concern about an appropriately-licensed pharmacy, then the FDA 

currently 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 

exceed 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 for manufacturing and registers with the FDA. All 

parties involved must make certain that the state Boards of Pharmacy are adequately 

staffed, trained, and funded to effectively regulate compounding. 

3 
75 


85438.031

NCP A encourages state Boards of Pharmacy to require uniform compliance with 

USP 797 in order to provide more uniform production standards. As such, every state will 

be assured that resident and non-resident pharmacies alike are all in compliance with 

these USP standards. 

Compounds are prepared based on prescriptions or on anticipation of demand 

In most cases, compounded medications must originate from a prescription for a 

specific patient from a health care professional and are made specifically for an 

individual patient's needs. In other instances, pharmacists participate in anticipatory 

compounding where they anticipate a demand that a physician might have for a 

compounded drug based on historical prescribing patterns. In order to preserve access to 

these vital compounded medications, pharmacies should not be hindered in their ability to 

engage in anticipatory compounding as long as it is reasonable and based on a historical 

pattern of prescriptions received by that pharmacy or for specific patients served by that 

pharmacy. 

Compounding should not be defined by the quantity of medications produced or to 

where the medications are shipped. Compounding should be defined as the preparation of 

medications upon receipt of a prescription, or, where in reasonable quantities, in 

anticipation of need for a medication based upon historical patterns. 

4 
76 


85438.032

To the contrary, compounding should not be defined by nuances such as type of 

product (i.e. sterile and non-sterile) as risk and complexity of compounding is not solely 

dependent upon product type; quantity of product made as a pharmacy can produce a 

significant number of compounded medications and not be a manufacturer as long as the 

pharmacy is making these medications based on individual prescriptions or in 

anticipation of need based on historical patterns; or interstate commerce as a pharmacy 

may legitimately ship to more than one state as long as the pharmacy makes the 

medications being shipped based on individual prescriptions or in anticipation of need 

based on historical patterns. 

Clear lines of communication between the FDA and State Boards of Pharmacy are 

needed 

The FDA should share all inspection data in a timely fashion with state Boards of 

Pharmacy. Furthermore, FDA should communicate to state Boards of Pharmacy whether 

the response from the entity inspected addresses all concerns and is sufficient without 

necessary further action or whether further action is needed to address these concerns. 

The FDA should strengthen the communication between its regional offices and the 

states. In addition, FDA should utilize all existing authority and resources in developing 

and sharing data with states. In order to address the failure in communication in the past, 

FDA must utilize, and strengthen if necessary, all existing portals and resources in order 

to produce the needed data sharing to increase communication between the states and 

FDA. 

5 
77 


85438.033

In conclusion 

While discussing what new regulations should be undertaken to prevent this 

tragedy in the future, before expanding federal authority it is imperative that Congress 

look at whether current laws and regulations are being properly enforced. NCP A urges 

the Committee to preserve the authority of state Boards of Pharmacy over compounding 

by defming any new category with FDA oversight in a very limited and narrowly targeted 

manner. In addition, any legislation must not be used to facilitate a broad expansion of 

FDA power over the historically state-regulated practice of pharmaceutical compounding. 

NCP A is committed to working with Members of Congress in order to make 

certain that a tragedy such as the New England Compounding Center does not occur in 

the future while also preserving patients' access to customized and safe compounded 

medications. Thank you for inviting me to testifY and to share the viewpoints of 

independent community pharmacy. 

6 
78 

Mr. PITTS. Ms. Russell, you are recognized for 5 minutes for 

opening statement. 

STATEMENT OF ELIZABETH SCOTT (SCOTTI) RUSSELL 

Ms. RUSSELL. Thank you. Good afternoon, Chairman Pitts, Ranking Member Pallone, and members of the subcommittee. The National Association of Boards of Pharmacy appreciates the opportunity to appear before you today and provide information related 

to pharmacy compounding. I am Elizabeth Scott Russell, government affairs manager for the association. 

As part of a comprehensive action plan that assists States following the meningitis outbreak, NABP partnered with the Iowa 

Board of Pharmacy to begin conducting inspections of all of its approximately 609 resident pharmacies, focusing first on those delivering compounded drugs into Iowa. Our inspections confirmed that 

the activities that occurred with NECC were also occurring in other 

facilities in other States. 

To date, NABP has inspected approximately 165 pharmacies and 

is in discussions about similar inspection programs with other 

States. We are building a system of proactive information exchange 

for all pharmacies that will include verifications of licensure, disciplinary checks, and assurances of a timely and robust inspection 

that meets uniform standards at no cost to boards to assist them 

in making licensure and registration determinations for nonresident pharmacies. 

NABP does believe that Federal legislation is needed to provide 

the needed distinction between compounding and manufacturing to 

address critical concerns and provide a safe and equitable environment for both to occur in the best interest of the patient. NABP 

supports the major concepts of the legislation proposed by the Senate HELP Committee and welcomes the proposed clarifications to 

the regulatory uncertainties that currently exist, uncertainties that 

were a primary factor leading to the recent meningitis tragedy. 

In particular, NABP affirms that the regulation of the practice 

of pharmacy remains the responsibility of the State boards of pharmacy and agrees with the language in the proposed Senate legislation that defines traditional pharmacy compounding as part of the 

practice of pharmacy to be regulated by State boards of pharmacy. 

NABP also supports the establishment in legislation of a new category for the preparation of nonpatient-specific sterile products 

that would be registered and regulated by FDA and a clear distinction between this new category and traditional pharmacy 

compounding. 

Although we understand that some terminology must be employed to describe this new category, we would prefer that the term 

‘‘compounding’’ not be included in the name because of potential 

confusion with traditional pharmacy compounding. 

NABP supports Federal legislation prohibiting entities that fall 

into this new category also being licensed as a pharmacy by the 

State, as this separation is essential to addressing the ambiguous 

authority that currently exists between the States and FDA; that 

is, who is responsible. Our experience affirms the importance of a 

clear separation between manufacturing and compounding and 

clarifying what activities fall under Federal jurisdiction and what 

79 

fall under State jurisdiction. Not having a clear separation could 

also provide a veil for unscrupulous entities to hide their activities. 

NABP does not believe that the interstate distribution of nonpatient-specific sterile products should be a required criteria for 

meeting this definition, this new category, as is in the Senate proposal. We understand the need to establish a delineation point, but 

such differentiation between intrastate and interstate distribution 

could create patient safety concerns by allowing large-scale intrastate entities to avoid Federal regulation. NABP could still support 

proposed legislation that exempts intrastate distributions from the 

definition for this new category provided the situation is monitored 

for any additional future action that may be necessary. 

In conclusion, NABP believes there is a need for Federal legislation that addresses the safe preparation of compounded medications for patients, that distinguishes between compounding and 

manufacturing, defines a new category of manufacturers under 

FDA regulation, balances effective regulation with reality, and 

carefully constructs the scope and activities of this new category to 

meet patient needs while maintaining necessary protections. We 

appreciate this opportunity for input and are available to discuss 

our comments and any legislative solution in greater detail. Thank 

you. 

Mr. PITTS. Chair thanks the gentlelady. 

[The prepared statement of Ms. Russell follows:] 

80 


85438.034

Testimony 

on behalf of the 

National Association of Boards of Pharmacy 

to the 

House Energy and Commerce Committee 

United States House 

May 9, 2013 

presented by: 

Elizabeth Scott Russell, RPh 

Government Affairs Manager 

National Association of Boards of Pharmacy 
81 


85438.035

Good morning Chainnan Pitts, Ranking Member Pallone, and members of the Committee. I am 

Elizabeth Scott Russell, Government Affairs Manager for the National Association of Boards of 

Pharmacy (NABP). NABP appreciates the opportunity to appear before you today and provide 

infonnation related to phannacy compounding. 

NABP is the impartial organization founded in 1904 whose members are the state agencies that 

regulate the practice ofphannacy. NABP supports the state boards of pharmacy by developing, 

implementing, and enforcing unifonn standards for the purpose of protecting the public health. 

NABP also helps state boards of pharmacy to ensure the public's health and safety through its 

pharmacist license transfer, pharmacist competence assessment, and accreditation programs. 

Following the tragic meningitis outbreak caused by contaminated injectable drugs, several states 

implemented compounding phannacy inspections or conducted surveys of pharmacies, focusing 

especially on those engaged in sterile compounding. As part of the NABP Compounding Action 

Plan that was developed in November 2012 and implemented in December 2012, NABP 

partnered with the Iowa Board of Pharmacy and other states to begin conducting inspections of 

all nonresident pharmacies delivering compounded drugs into Iowa. Our initial inspections 

confinned that what occurred at the New England Compounding Center (NECC) was also 

occurring at other facilities in other states. To date, NABP has inspected approximately 165 

phannacies across the states and will continue our inspections until all ofIowa's approximately 

600 nonresident phannacies are inspected. 

NABP is also in discussions about similar inspection programs with a number of other states and 

has plans to establish an e-Profile for each pharmacy in the United States. These e-Profiles will 

include verifications oflicensure, disciplinary checks, and verification that a timely and robust 

inspection has occurred for each pharmacy, including those perfonning sterile and non-sterile 

compounding. The infonnation in the e-Profiles for phannacies will be sent proactively to 

boards for use in making licensure and registration detenninations for nonresident phannacies. 

In the event that a board of phannacy has been unable to perfonn a timely or robust inspection, 

NABP will conduct an inspection on behalf of the states to ensure relevant laws and phannacy 

practice standards are being met. In addition, once an inspection has been completed, NABP 

will make all publicly available documents, including inspection reports and disciplinary actions, 

available at no cost to consumers, boards, and Food and Drug Administration (FDA) through a 

user-friendly and searchable console. 

NABP supports the legislation proposed by the United States Senate Committee on Health, 

Education, Labor, and Pensions (HELP), with some minor modifications. The proposed 

legislation addresses the critical concems identified by the states and validated by NABP through 

its inspections of compounding pharmacies. We welcome the Senate legislation's clarifications 

to the regulatory uncertainties that currently exist - uncertainties that were a primary factor 

leading to the recent meningitis tragedy. Most importantly, the clarifications provide the needed 

distinction between compounding and manufacturing and provide a safe and equitable 

environment for both compounding and manufacturing to occur in the best interest of the patient. 
82 


85438.036

Authority ofthe States 

As provided in the proposed Senate legislation, NABP agrees that the regulation of the practice 

of pharmacy, which includes traditional pharmacy compounding, remains the responsibility of 

the state boards of pharmacy. NABP supports the establishment of the new category of 

"compounding manufacturing" regulated by FDA, and the clear distinction between this new 

category and traditional pharmacy compounding. Although we would prefer that "compounding" 

not be included in the proposed designation because of the inference to traditional compounding 

and the confusion that could result, we understand that some terminology must be employed that 

describes the activity being regulated. 

The separation of compounding from manufacturing is also critical to maintain the present 

authority of the states and address one of the contributing factors to the NECC crisis, 

specifically, the ambiguous authority between the states and FDA. The provision of the 

proposed legislation that specifies a compounding manufacturer cannot be licensed as a 

pharmacy is essential to distinguishing between state-regulated compounding and FDA-regulated 

manufacturing. Our experience, and most recently our inspections of compounding pharmacies, 

affirms the importance of this prohibition in clarifYing what activities fall under federal 

jurisdiction (FDA) and what entities can engage in compounding and operate under state 

jurisdiction (state boards of pharmacy). 

If a compounding manufacturer is allowed to hold dual licensure or registration, it will be more 

difficult to separate the two enterprises and could provide a veil for unscrupulous entities to 

obfuscate their activities. NABP supports FDA receiving authority to access any and all 

documents and records required for the oversight and regulation of compounding manufacturers. 

We are concerned, however, about allowing FDA access to pharmacy records for activities that 

are regulated by the states. If an entity is manufacturing or compound manufacturing, then under 

the proposed legislation and current authority, FDA will have access to all documents and 

records concerning these activities. Authorizing FDA access to pharmacy records could create 

jurisdictional conflicts with the states and impede the states from investigating or prosecuting a 

case because FDA has seized evidence or information needed by the state(s). What is needed in 

lieu of allowing such access is increased communication between the states and FDA. 

Intrastate Exemption from Definition of Compounding Manufacturer 

NABP discussed with the Senate HELP Committee concern with the proposed exemption for 

intrastate distribution ofnon-patient-specific sterile compounded products. We understand the 

logic of establishing a delineation point to more readily identifY and regulate large-scale 

operations that conceivably pose more risk to patients than smaller operations. However, as we 

explained to the Senate HELP Committee, it is our finding that non-patient-specific, sterile 

prepared products distributed within a state bear the same risk levels to patients as products that 

are introduced into interstate commerce. The differentiation between intrastate and interstate 

activities to define a compounding manufacturer could create patient safety concerns by allowing 

large-scale intrastate entities to avoid federal regulation. We indicated to the Senate HELP 
83 


85438.037

Committee that although this is a critical concern for the states, NABP would support the 

proposed legislation absent this revision, if our concern is noted and the situation monitored for 

any additional future action that may be necessary. 

Conclusion 

As stated earlier in our statement, NABP supports the proposed Senate legislation, as it addresses 

the safe preparation of medications and products for patients and aligns well with the approaches 

suggested and recommended by the states. NABP supports legislation that distinguishes 

between compounding and manufacturing, defines a new category of manufacturing that 

balances effective regulation with reality, and carefully constructs allowances and prohibitions 

on the scope and activities of a compounding manufacturer in order to meet patient needs while 

maintaining the necessary protections. NABP appreciates this opportunity for input and is 

available to discuss our comments and any legislative solution in greater detail. 

Thank you. 
84 

Mr. PITTS. Ms. Cosel, you are recognized for 5 minutes for an 

opening statement. 

STATEMENT OF GABRIELLE COSEL 

Ms. COSEL. Thank you. Chairman Pitts, Ranking Member 

Pallone, Vice Chairman Burgess, and members of the subcommittee, thank you for the opportunity to testify on the need for 

Federal legislation to improve the safety of compounded medicines. 

My name is Gabrielle Cosel. I work on pharmaceutical quality and 

safety at the Pew Charitable Trusts, which is an independent research and public policy organization. 

Pharmacists have always compounded medicines. But many of 

the activities we refer to as compounding today are far removed 

from traditional pharmacy practice. In recent months, this committee has stressed the responsibility of FDA to ensure the safety 

of activities that depart from traditional compounding and are 

more akin to manufacturing. Today I will focus on a regulatory 

framework that clarifies the agency’s role, ensures that limited resources are used wisely, and sets clear expectations for the industry. 

First, though, it is important to look over the risks. The fungal 

meningitis epidemic illustrates how patients can be harmed by substandard compounded drugs. But it is far from an isolated incident. 

My written testimony describes 19 additional pharmacy 

compounding errors from the past decade that have caused serious 

injuries and deaths in at least 29 different States. The list includes 

meningitis, blood stream infections, and at least 38 patients who 

suffered partial or complete vision loss. 

Recent history raises further concern. Two months ago, a New 

Jersey compounder recalled all of its products because of mold contamination. When a drug is produced in mass quantities, the potential harms from a quality failure also multiply. There are companies today that compound thousands of packages of vials of 

medicines and ship them to buyers all over the country. These activities have outgrown the State regulatory structures established 

to oversee them. Federal law already regulates some aspects of 

compounding, and today we urge you to make changes to ensure 

clarity and effective oversight. 

First, large-scale compounding should be subject to higher quality standards, specifically applicable good manufacturing practices. 

Second, the FDA is the appropriate agency to oversee GMPs, and 

States should not exercise redundant oversight. And finally, patients must be protected by ensuring that compounders do not undermine gold standard FDA-approved drugs. 

Compounding quality standards are currently set by the States, 

and they are variable. Pew recently joined with the American Hospital Association and the American Society for Health System 

Pharmacists to host a summit on sterile compounding, and experts 

at that meeting emphasized that pharmacy compounding standards 

were never intended and are not suitable for large-scale production. 

Compounding high volumes or repeat batches of medicines involves 

standardized processes and should be subject to applicable GMPs. 

The FDA is best placed to enforce these standards, but resources 

should be focused on activities that pose the highest public health 

85 

risk. Facilities that produce large volumes of sterile products that 

may reach many patients or that carry out particularly high-risk 

compounding, such as creating sterile products from a nonsterile 

bulk ingredient, should be required to register with the FDA. 

FDA should issue regulation clarifying the criteria for registration. As with pharmaceutical manufacturing, FDA should inspect 

compounding facilities on an ongoing basis with a frequency based 

on risk. And facilities should pay fees to ensure FDA is adequately 

resourced to provide this oversight. 

Under this framework, States may continue to require FDA-registered compounding facilities to hold pharmacy licenses, but State 

enforcement of quality standards should be preempted for these facilities. To exercise effective oversight, the FDA must have access 

to the records of facilities it regulates or that it believes fall under 

its jurisdiction. This requires a fix to current law. Even today, 

compounders continue to challenge FDA’s access to records. Key 

safety requirements should also be set at the Federal level, such 

as a ‘‘do not compound list,’’ and this should apply to all 

compounding facilities. 

It is important to state that large-scale compounding cannot be 

addressed simply by requiring these facilities to submit new drug 

applications. Some large compounders fill a niche in our health system, such as for hospitals that don’t have sufficient capacity to mix 

drugs in-house. However, any new regulatory scheme must not undermine the approvals process and encourage compounding at the 

expense of traditional manufacturing. While the goal is to ensure 

the quality of compounded medicines, patients, doctors, and pharmacists should prefer FDA-approved products whenever possible. 

Only the latter go through pre-market review to establish safety, 

efficacy, and bioequivalence, along with pre-approval of manufacturing methods and facilities. Legislation should be clear that a 

compounder may not make a copy or a variation of a marketed 

drug except when that drug is in shortage or to address a specific 

medical need of a specific patient. 

In conclusion, I thank you for your leadership, and I urge you to 

create a clear, workable framework to protect patients. I welcome 

your questions. 

Mr. PITTS. Chair thanks the gentlelady. 

[The prepared statement of Ms. Cosel follows:] 

86 


85438.038

Testimony before the Committee on Energy and Commerce 

Subcommittee on Health 

United States House of Representatives 

May 22,2013 

The Pew Charitable Trusts 

Dear Chainnan Pitts, Ranking Member Pallone and members of the Subcommittee, 

Thank you for the opportunity to testifY on the need for federal legislation to improve the safety of 

compounded medicines. 

My name is Gabrielle Cosel. I work on pharmaceutical quality and safety at the Pew Charitable Trusts, an 

independent, nonpartisan research and public policy organization. 

Pharmacists have always compounded medicines - it is the origin of the profession - but many of the 

activities we refer to as compounding today are far removed from the traditional practice of preparing 

individualized medicines for one patient at a time. Some compounders today produce large volumes of 

drugs and ship them to clinics and hospitals across the country. 

In recent months, this committee has repeatedly stressed the responsibility of FDA to ensure the safety of 

activities that depart from traditional compounding and are more akin to manufacturing. I will focus today 

on a regulatory framework that clarifies the Agency's role, ensures that limited resources are used wisely, 

and sets clear expectations of the industry. First, though, it is important to understand the risks we fuce. 

Examining the risks 

The epidemic caused by the New England Compounding Center highlights the dangers to patients from 

compounded drugs. As of May 6, that outbreak has been associated with 55 deaths and 741 serious 

infections in 20 states. 

But what happened at NECC is not an isolated incident. I have included with my testimony a Pew 

sununary that describes 19 additional pharmacy compounding errors since 200 I. I 

These errors caused serious injuries and deaths in at least 29 different states. The list includes 22 

additional deaths, as well as serious infections - meningitis, bloodstream, and at least 38 patients who 

suffered partial or complete loss of vision. It also includes patients harmed by sub-potent or super-potent 

doses. For example, three people in Oregon and Washington who died after receiving drugs from Texasintravenous injections for back pain that were eight times the labeled strength.2 

Recent inspections of compounders raise further concern: For example, two months ago, the FDA 

announced a recall of all of the products manufactured by a New Jersey compounder because of potential 

mold contamination. The FDA press release referred to "visible particulate contaminants" in what was 

supposed to be a sterile product. 3 Also this year, a Georgia compounder conducted a nationwide recall of 

sterile products after reports of serious eye iufections.4 
87 


85438.039

Compounding errors can cause exponentially greater hanns if the product has been produced in mass 

quantities. There are companies today that compound thousands of packages or vials of medicine and ship 

them to buyers all over the country, going well beyond the traditional practice of a phannacist making a 

single drug in response to a specific prescription for a specific patient. These activities have outgrown the 

state regulatory structures established to oversee them. 

Congress, through section 503(A) of the Food, Drug and Cosmetic Act, already recognizes FDA's 

responsibility to oversee some compounding activities. Today, we urge you to amend certain elements of 

this provision to ensure its effectiveness and provide greater clarity on state and federal roles. We urge the 

following elements: 

1. When appropriate, large-scale compounding should be subject to higher quality 

standards - specifically applicable Good Manufacturing Practices (GMPs), 

2. FDA is the appropriate agency to oversee GMPs, and states should not exercise 

redundant oversight, 

3. Patients must be protected by ensuring that compounders do not undermine "gold 

standard" FDA-approved drugs. 

Today, compounding quality standards are set by states. Some states incorporate United States 

Phannacopeia standards for sterile and non-sterile compounding (USP chapters 797 and 795, 

respectively), but experts at a recent phannacy compounding summit co-hosted by Pew, the American 

Hospital Association (AHA), and the American Society of Health-System Phannacists (ASHP) stressed 

that USP compounding standards were developed for use in phannacies and are not suitable for largerscale production. 

Compounding large volumes of repeated batches of medicines implies standardized processes that should 

be subject to appropriate quality standards such as those outlined in current Good Manufacturing 

Practices (cGMPs) for drug manufacturers. 

For example, cGMP requires manufacturers to validate systems and processes to ensure that medicines 

meet consistent quality and safety standards. Process validation becomes increasingly important as the 

same drug is compounded in repeat batches. In addition, USP 797 does not require the testing of a drug's 

starting ingredients, while cGMP does. And expiration dates are set for a manufactured drug based on 

extensive stability testing. But a beyond-use date for a compounded medicine may in some cases be set by 

referencing publisbed studies of drugs that may not conform exactly to the compounded product.'·· 

GMPs are developed by the FDA, and the agency is best placed to enforce them. 

Facilities that produce large volumes of sterile products, or carry out particularly high-risk compounding, 

such as manufacturing from a non-sterile bulk ingredient, should be required to register with the FDA. 

FDA should issue a regulation clarifying the criteria for registration. As with phannaceutical 

manufacturing, FDA should inspect compounding facilities on an ongoing basis, with a frequency based 

on risk. 
88 


85438.040

To avoid an unfunded mandate, the FDA will need adequate resources to conduct ongoing inspections of 

registered facilities. These resources should be provided through facility fees. 

It is important to state that large-scale compounding cannot be addressed simply by asserting these 

facilities are making unapproved new drugs and requiring them to submit to the New Drug Approval or 

Abbreviated New Drug Approval process. For example, some large compounders have become a source 

of intravenous and epidural therapies for hospitals and health systems that do not have the capacity to 

compound them in-house. Entities that playa role in our health care system should not be left to default or 

ad-hoc application of full requirements of the FDCA. The regulatory oversight system for these entities 

should be clearly defined. However, as addressed below, it is important to ensure that compounding does 

not encourage the sector to produce new drugs that undermine the FDA-approval paradigm. 

Under this framework, states may continue to require FDA-registered compounding facilities to hold state 

pharmacy licenses, but state enforcement of quality standards should be preempted for these facilities. 

The section 704 provision that exempts pharmacies from the requirement to provide records access to 

FDA should be removed for registered facilities. Without this authority the FDA will be challenged when 

it attempts to investigate a facility that should be under its jurisdiction. Such challenges have been well 

documented. In the wake of deadly meningitis outbreak a Congressional investigation clearly showed that 

even when the FDA had access to a facility its ability to access records was challenged. 7 Additionally, in 

March of 20 \3 the FDA reported that compounders denied FDA investigators access to" records in a 

number of recent cases. • 

Key safety requirements should also be set at the federal level, such as a "do not compound" list. 

Congress has already recognized that certain products are not suitable for compounding (frequently cited 

examples include transdermal delivery systems, biologic products and sustained release formulations) and 

has given FDA the authority to establish a "do not compound" list. This authority should be maintained 

and should apply to both FDA-registered and non-registered facilities, as it does now. The section 704 

records exemption should also be removed for purposes of enforcing the do not compound list. 

It is important to emphasize that compounded drugs do not go through the pre-market approval process 

that brand and generic drug companies go through to demonstrate safety, efficacy and bioequivalence, 

along with pre-approval of manufacturing methods and facilities. These are critical systems to protect 

patients. Because they do not apply to compounders, compounded medicines can never be an adequate 

substitute for FDA-approved drugs. 

Any new federal regulatory scheme must not encourage compounding at the expense of conventional 

manufacturing. Legislation should be clear that a compounder may not make a copy or a variation of a 

marketed drug, except when that drug is in shortage or to address specific medical needs of a specific 

patient. Congress should also prohibit the wholesale of compounded drugs. 

Another important safeguard against circumvention of the approvals process is limiting compounding 

from bulk to only well-characterized and already in-use active ingredients, such as those described by a 

USP monograph, or those in an existing drug application. These concepts are not new, but are part of 

current 503A language. 
89 


85438.041

Conclusion 

We thank you for your leadership on this important issue. Congress has long recognized the role of FDA 

in providing oversight of compounding. It is time to update the Food, Drug and Cosmetic Act to remove 

ambiguities and create a clear, workable framework to address patient safety. 

Thank you for the opportunity to testify, and I welcome your questions. 

References 

1 The Pew Charitable Trusts. U.S. Illnesses and Deaths Associated With Compounded Medications (2oo1-Present). 

April 15, 2013. http:Uwww.pewhealth.org/other-resource/us-illnesses-and-deaths-associated-with-compoundedmedications-85899468587 

2 U.S. 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. October 

12,2007.56(40): 1050-1052. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5640a3.htm. Accessed January 

8,2013. 

3 Medprep Consulting Inc. "Medprep Consulting Inc. Announces Voluntary Nationwide Recall Of All Lots Of All 

Compounded Products Due To Potential Mold Contamination." Press Release. March 20, 2013. 

http:Uwww.fda.gov/Safety/Recalls/ucm344787.htm. 

4 U.S. Food and Drug Administration. "FDA alerts health Care providers and patients of the nationwide recall of all 

lots of sterile products distributed by Clinical Specialties Compounding Pharmacy". Press Release. March 21, 2013. 

http:Uwww.fda.gov/NewsEvents!Newsroom/PressAnnouncements/ucm345019.htm 

5 United States Pharmacopoeial Convention. USP-NF General Chapter <797> Pharmaceutical CompoundingSterile Preparations. 

6 21 CFR 211. Current good manufacturing practice for finished pharmaceuticals. 

7 Committee on Energy & Commerce, Majority Memo. "The Fungal Meningitis Outbreak: could it have been 

prevented?" Nov 12, 2012. . 

http:Uenergycommerce.house.gov!sites/republicans.energycommerce.house.gov/files/Hearings/OI/20121114/H 

MTG-112-HHRG-IF02-20121114-SD001.pdf 

8 Hamburg, Margaret A. "FDA Must Have New Authorities to Regulate Pharmacy Compounding." FDA Voice. 

March 22, 2013. http:Ublogs.fda.gov/fdavoice/index.php{2013!03/fda-must-have-new-authorities-to-regulatepharmacy-compoundingl 
90 


85438.042

The Pew Charitable Trusts has identified 20 pharmacy compounding errors associated with 1022 adverse events, including 75 deaths, since 2001. 

Contamination of sterile products was the most common compounding error, though some incidents were the result of pharmacists' and technicians' 

miscalculations and mistakes in filling prescriptions. 

2012 Fl, GA, ID, IL, 733 53 Fungal meningitis and other Contamination; Spinal injections: preservatjve~ 

IN, MD, MI, MN, infections free sterile methylprednisolone 

NC, NH, NJ, NY, acetate 

OH, PA, RI, SC, 

TN, TX, VA 

2012 CA and six other 33 FUngal eye infection; 23 cases of ConlaminatioW' Eye injections: Brilliant 

states partial to severe vision loss Blue-G (BBG) retinal dye and 

triamcinalone 

2011 FL, TN 21 Bacterial eye infection; one case ContaminationS Eye injections: intravitreal 

of meningitis and encephalitis; four bevacizumab (Avastin) 

cases of loss of eyesight; three injections 

patients had eye removals 

2011 CA Blindness Unintended presence Eye injections: intravitreal 

of another medication~ bevadzumab (Avast!n) 

injections 

2011 AL 19 Bacterial bloodstream infecllon Contaminat!on~ Parenteral nutrition solution 

2010 IL Fatal overdose Dose of sodium 60 IV solulion: sodium chloride 

times stronger than 

ordere~ 

2007 WA,OR F ata! overdose Dose of colchicine eight IV solution: colchicine 

times stronger than 

labeled concentration! 

2007 MD,CA Bacterial bloodstream infection Contamination6 IV solution: fentanyl 
91 


85438.043

2004· MI, MO, NY. SD, 80 Bacterial bloodstream infection Contamination9 IV flush syringes: heparinized 

2006 TX.WY saline 

2006 OH Fatal overdose Dose of sodium Chemotherapy infusion 

chloride stronger than 

ordered1O 

2006 NV Fatal overdose Dose of zinc 1,000 Neonatal parenteral nutrition 

times stronger than solution 

orderedll 

2005 Bacterial bloodstream infection Contamination12 IV flush vials: preservative-free 

heparinized saline 

2005 MN and one Bacterial eye infection; all cases Contamination13 Eye solution: trypan blue 

other state had partial or complete loss of 

vision; two patients had eye 

removals 

2005 VA Systemic inflammatory response Contamination14 Heart infusion: cardioplegia 

syndrome 

200S CA, NJ, NC, NY, 18 Bacterial bloodstream infection Contamination15 IV solution: magnesium sulfale 

MA 

2004 CT Bacterial bloodstream infection Contamination'5 IV flush syringes: heparin:-

vancomycin 

2004 MO. NY. TX. MI. 64 Bacterial bloodstream infection Contamination17 IV flush syringes: heparinized 

SO saline 

2002 NC Fungal meningitis and sscroiHitis Contamination!~ Spinal injections: 

methylprednisolone acetate 

2001 CA 11 Five cases of bacterial meningitis; Contaminatlon19 Spinal or Joint injections: 

five cases of epidural abscess; one betamethasone 

patient had an infected hip joint 

2001 Bacterial bloodstream infection Contaminationow IV infusion: ranltidine 
92 


85438.044

References 

1 U.S. Centers for Disease Control and Prevention. Multi· 

state Meningitls OUtbreak Investigation. http://www.cdc. 

govlHAlloutbreaksJmeningitis.html. Accessed January 29, 

2013. 

2 U.S, Centers for Di",ase Contra! and Prevention. 'Notes 

from the fi:eid: Multistale outbreak of postprocedural fungal 

endophthalmitls associated with a single compounding 

pharmacy-United States, Mareh-ApriI2012: Morbidity 

and Mortality Weakly Repott. May 2012. 61(17}, 310-1. 

http://www.cdc,govlmmwr/previawfmmwrhtmUmm6117a5. 

htm.Accessed December21, 2012. 

3 Based on two separate outbreaks: 12 in Florida, nine 

in Tennessee. Respective cites below. 

Goldberg RA, Aynn HW Jr, lsom RF, Mmer 0, Gonzalez 

S. "An outbreak of streptOCOcct.lS endophthalmiJis after 

intravitrea! injection of bevacizumab," American Jountslof 

Ophthalmology. February 2012.153(2). 204-208.e1. 

Frost SA, Kainer MA. ·Safe preparation and admmistra· 

!ion of intravitreal bevaciwmab injections." New England 

Joumal of Medicifl8. December 2011. 385(23)" 22:38. 

• Department of VeteransAffrurs Office of Inspector 

General. "Heathcare Inspeclion Overs'lght Revlew ofOphthalmology Adverse Drug Events VA Greater Los Angeles 

Healthcare System Los Angeles, Caltfomia." Report No. 

12.01515-151 April 12, 2012. htq>}fwww.va.gov/oig/pUbsi 

VAOIG-12.o1515-151.pdf.Accessed January 8. 2013. 

5 Thompson, Cheryl A "Bacteremia outbreak tied to 

Improper flltratJon by ccmpournfing pharmacy: American 

Joumal of HaBlth System Pharmacy. November 2011. 

68(22): 2110-11. http://www.ashp.org/menuiNewsiPharmacyNewslNewsAr1;icle.aspx1id=3$28. Accessed January 

8,2011. 

• Vitello, Barbara. 'Lutheran General to pay $8.25 million 

in baby's death," Daily Herald. AprilS. 2012. htq>.Itwww. 

dalIyherald.comfartlcief2012lJ405/newsl7040598061. 

Accessed January 8, 2012. 

1 U.S. Centers for Disease Control and Prevention. "Deaths 

from Intravenous ColchiCine Resulting from a Compounding PharmaCy Error-Omgon and Washington, 2007," 

Morbidity and Mortality Weekly Report. October 12, 2007. 

56(40): 105Q.l052.Irttp://Www.cdc,govlmmwr/preview/ 

mmwmlmllmm564Da3.htm. Acc:essed January 8, 2013. 

~ Maragakis LL. Romanee C, Srinivasan A, et at "Sphlngomonas paucimobilis bloodstream infections associated 

with contaminated intravenous fentanyl: Emerging Infectious Diseases. January 2009. IS.12-S. http:{!wwwnc.cdc. 

gov/eldiartlcle11S/11Oa.l 054_Intro.htm. Accessed January 

9,2013. 

• Gershman MD, Kennedy OJ, Noble-Wang J, (It al. "Multistate outbreak of Pseudomonas fluorescens bloodstream 

infection after e1qlosure to contaminated heparinized 

saline flush prepared by a compounding pharmacy," 

Chniesllnfectious DiSfl8S8S. December 2008,47(11): 

1372~9. httpJlcid.oxfordjoumals.orglcontentl47111f1312. 

fuH.pdf+html. Accessed January 9, 2013. 

to Institute for Safe Medication Practices. Medication Safety 

Alert. "Failed check system for chemotherapy leads to 

pharmaclst's no contest plea for involuntary manslaugh~ 

ler," April 23, 2009. htq>JIwww.ismp.orgInewsletters/&:lJtecare/articlesl20090423,asp. Accessed January 9, 2013. 

11 Grissinger, MattheW RPh, FASep, 'A Fatal lim: Overdose in a Neonate. ConfuSion Of Micrograms With Milligrams: Pharmacy and Tharapeutics. July 2011; 36(7): 

393-394,409. hltp:flwww.rn:bLnlm.nih.govlpmrJartidesi 

PMC3171817/. Accessed January 9, 2013. 

" Per.::, Joseph E el aI. "Pseudomonas pulida Septicemia in 

a Special Care Nursery Due to Contaminated Flush Solulions Prepared in a Hospital Pharmacy." Jol.lfT!8J of Clinical 

Microbiology. October200S. 43(10): 5316-5318, http:/~cm. 

asm.orglcontentJ43J10!5316Jong.Accessed January 9, 

2013. 

'3 Sunenshine, Rebecca. (It al. 'An Outbreak of Postoperative Gram-Negatlva Sacterial Endophthalmltls Associated 

with ContamInated Trypan Blue Ophthalmic Solution," 

Clinical infectious Diseases. April 2009. 48(11): 158Q-. 

1583. http.//cid.oxfordjoumals.orglcontentl48i11/1580Jull. 

pdf+htm!. Accessed January 9, 2013 . 

" Maryland State Board of Pharmacy. "Order for Summary 

Suspension." In the matter of Central Admixture Pharmacy 

ServiceS, !nc:. hltp:lfwww.dhmh.maryland.govlpharmacy/ 

docslFonnatOTdersIC/C.A.P.S%2011~ 15-0S.pdf. Accessed 

January9,2013. 

'I Sunenshlne, Rebecca H. at at "A Multistata Outbreak of 

Serratia marcescens: Bloodstream !nfection Associated 

with Contaminated Intravenous Magnesium Sulfate from 

a Compounding Pharmacy," Clinical Inf&ctJous Diseas(!s. 

July 2007. 45: 527-33. http://cid.oxfordjoumals.org/contentf45151S21.fuU.pdf. Accessed January 9, 2013. 

•• Held MR, Begier EM, BeardSley OS, at aI. 'life-threatenil1g sepsis caused by Burkholderia cepaciafrom 

contamlOatedintravel1OtJsllm;hsolutionspreparedbya 

compounding pharmacy in another state," Pediatrics. July 

2006. 118:e212-5. http://pedtatrics.aappublk:alionS,orgl 

contantf1161l1a212Jong. Accessed January 9, 2013. 

\]" 8aS&d on two sets of infection$, one immediate and 

one delayed. Immediate Infection cases Included 

nine in Missouri. 121n Haw York, 14 in Teos,. and one 

in Michigan. Delayed infection cases Included 15 in 

Michigan and 13 In South Dakota, Respective cites 

below. 

U.S. Centers for Disease Control and Prevention. 

"Pseudomonas Bloodstream Infections Associated with 

a HeparinlSaline Flusil-Missouri, New York, Texas, and 

M!chigan. 2004-2005,' Morbidity and Mortality Weekly 

Report. Mardl2005. 54(11): 269-2n htq>:/twww.cdc. 

gov/mmwr/preview/mmwrhtmllmm5411a1.htm. Accessed 

Janusry9,2013. 

U.S. Centers for Disease Control and Prevention. 'Update: Delayed Onset Pseudomonas lI00rescens Bloodstream Infections After Exposure to Contaminated Heparin 

F1ush-Mlchigan and South Dakota, 2005-2006: MortJicf. 

ity and Mortality Weekly Report. Septemb&r 2006. 55(35) 

961·963. hltp:/lwww.ctlc.govlmmwrlpreviewlmmwrhtml! 

mm5535a1.htm. Accessed January 9, 2013. 

to U.S, Centers ror Disease Control and Prevention. ~E)(ophiala infection from Contaminated Injectable Steroids 

Prepared by a Compounding Pharmacy-United States, 

July-November 2002,· MorlJidify end Morlality Weekly Report. December 2002. 51(49): 1109-1112, http://www.cdc. 

goVlmmwr/previewfmmwrhtmllmm5149a1.htm. Accessed 

January 9, 2013. 

'9 Civen R. Vugia OJ, Alexander R, at at 'Outbreak of 

Serratia marooscens infections foUowing injection of 

betamethasone compounded et a community phalTTl8c:y," 

Clinicallnfecfious Diseases. All1JU&t 2006. 43: 831-7. 

htlp.:l!cid.oxfordjouma!s.org!contenU43I1f831.fuU.pdf+htmL 

Accessed January 9, 2013. 

«l Selenic, D. et at "Enterobacter cloacae bloodstream jnfeo. 

tions jn pediatric patients tra<:ed to e hospital pharmacy: 

American Journal of Health System Pharmacy. July 2003. 

60{14):1440-6. 
93 

Mr. PITTS. Mr. Migliaccio, you are recognized for 5 minutes for 

opening statement. 

STATEMENT OF GERRY MIGLIACCIO 

Mr. MIGLIACCIO. Thank you, Chairman Pitts and Ranking Member Pallone, for inviting me here to speak today. My name is Gerry 

Migliaccio. I am a consultant in the area of pharmaceutical quality 

systems. In 2012, I retired from Pfizer, Incorporated, after a 33- 

year career in pharmaceutical manufacturing and quality operations. For 11 of those years, I served as the head of the Global 

Quality Organization at Pfizer. So this experience has provided me 

with quite an intimate knowledge of the quality requirements and 

regulatory framework applicable to manufacturing medicines for 

the United States public. 

Patient safety is the highest priority for pharmaceutical manufacturers. Companies comply with the gold standard of quality 

manufacturing as defined by FDA’s current Good Manufacturing 

Practice regulations and the associated guidance documents. These 

regulations apply to all prescription drugs approved for sale in the 

United States, wherever they are made, and extend to all components of a finished drug product, including the active pharmaceutical ingredients. 

FDA’s regulations are based on the fundamental principle that 

you cannot inspect or test quality into a finished product. Quality 

must be designed into the manufacturing process and designed into 

the product. The regulations also drive manufacturers to establish 

a quality systems approach to assure consistent quality. 

In pharmaceutical manufacturing, quality systems and GMP requirements begin at the investigational stage. FDA requires that a 

new drug application describe the quality safeguards for the proposed manufacturer of a new medicine in the Chemistry, Manufacturing, Control section of the application. Part of the evidence required by FDA to demonstrate safety and efficacy is the requirement that a manufacturer provide, and I quote, ‘‘a full description 

of the methods used in and the facilities and controls used for the 

manufacture, processing, and packing of a new drug.’’ 

The manufacture of medicines, whether by NDA holders or largescale compounders, involves similar activities and similar potential 

for risk. Large-scale compounding can involve mixing of active and 

inactive ingredients, as well as other manufacturing steps. Therefore, in order to assure the safety of the American public, the manufacture of medicines, whether by manufacturers or by pharmacies, 

should be regulated in a consistent risk-based manner. Large-scale 

commercial manufacturing of prescription medicines, whether the 

producer is designated as a pharmacy or as a manufacturer, should 

be governed by the same high standards currently in effect for 

pharmaceutical manufacturing and subject to the same inspection 

and enforcement actions by FDA. 

Moreover, large-scale compounders should be required to prove 

that they can manufacture medicines consistently and safely by 

submitting an application to FDA containing a Chemistry, Manufacturing, and Control section, and submitting to both pre-approval 

and routine GMP inspections. 

94 

Let me give you a personal perspective on the importance of 

GMP regulations. During my career, I considered the regulatory 

framework in the United States as the blueprint for assuring safety 

and efficacy. Whether you are a small startup company or a large 

multinational manufacturer, the regulations and guidance documents provided a template for success. From designing quality into 

a manufacturing process to the selection of material suppliers to 

construction of facilities, the selection of equipment, the training of 

employees, all the way to the final approval to distribute the product, the regulations and guidance documents provide for a consistent risk-based approach to assure quality. The regulations have 

also evolved to encourage innovation and continuous improvement 

and to help support the justification of new technology to further 

enhance quality assurance. 

Therefore, it is just very logical to me that any large-scale manufacturer of medicines, including compounders, should comply with 

these same regulations. A manufacturer in full compliance will 

have a high degree of assurance that the medicines they produce 

will be of consistently high quality. A large-scale company making 

thousands of doses of medicine with the name ‘‘Pharmacy’’ on the 

door and another with the name ‘‘Pharmaceutical Company’’ on the 

door should be regulated in a similar manner when they perform 

similar manufacturing steps and present similar risks to patients. 

Thank you for your attention. 

Mr. PITTS. Chair thanks the gentleman. 

[The prepared statement of Mr. Migliaccio follows:] 

95 


85438.045

Oral Statement of Gerry Migliaccio 

Quality Systems Consultant 

Retired Senior Vice President of Global Quality 

Pfizer Inc 

House Energy and Commerce Committee 

Health Subcommittee 

Examining Pharmacy Compounding 

May 23,2013 

I would like to thank Chairman Pitts and Ranking Member Pallone for 

inviting me to speak today. My name is Gerry Migliaccio. I am a consultant 

in the area of pharmaceutical quality systems. In 2012, I retired after a 33-

year career in pharmaceutical manufacturing and quality operations at 

Pfizer. For eleven years I served as the head ofPflZer's Global Quality 

Operations. This experience has provided me with an intimate knowledge of 

the quality requirements and regulatory framework applicable to 

manufacturing medicines for the United States public. 

Patient safety is the highest priority for pharmaceutical manufacturers. 

Companies comply with the "gold standard" of quality manufacturing as 

defined by FDA's current Good Manufacturing Practice (cGMP) regulations 
96 


85438.046

and associated guidance documents. These regulations apply to all 

prescription drugs approved for sale in the United States, wherever they are 

made, and extend to all components of a fmished drug product including 

active pharmaceutical ingredients. FDA's regulations are based on the 

fundamental principle that quality cannot be inspected or tested into a 

fmished product. Quality must be designed into the manufacturing process 

and product. The regulations also drive manufactures to establish a quality 

systems approach to assuring consistent quality. 

In pharmaceutical manufacturing, quality systems and cGMP requirements 

begin at the investigational stage. FDA requires that a new drug application 

(NDA) describe the quality safeguards for the proposed manufacture of a 

new medicine in the Chemistry, Manufacturing, and Controls (CMC) section 

of the application. Part of the evidence required by FDA to demonstrate 

safety and effectiveness is the requirement that a manufacturer provide "a 

full description of the methods used in, and the facilities and controls used 

for, the manufacture, processing, and packing of [a new] drug .... ,,1 

1 See 21 U.S.C. 355(b)(1). 
97 


85438.047

The manufacture of medicines - whether by NDA holders or large-scale 

compounders - involves similar activities and the potential for risk. Largescale compounding can involve mixing of active and inactive ingredients as 

well as other chemical and even biological manufacturing steps. Therefore, 

in order to assure the safety of the American public, the manufacture of 

medicines, whether by manufactures or pharmacies, should be regulated in a 

consistent, risk-based manner. Large-scale commercial manufacturing of 

prescription medicines, whether the producer is designated as a "pharmacy" 

or as a "manufacturer" should be governed by the same high standards as 

biopharmaceutical manufacturing, and subject to the same inspection and 

enforcement actions by FDA. 

Moreover, large-scale compounders should be required to prove that they 

can manufacture medicines consistently and safely by submitting an 

application to FDA containing a CMC section and submitting to both preapproval and routine cGMP inspections. 

Let me give you a personal perspective on the importance ofthe cGMP 

regulations. During my career, I considered the regulatory framework in the 

US as the blueprint for assuring safety and efficacy. Whether you are a 
98 


85438.048

small start-up company or a large multinational manufacturer, the 

regulations and guidance documents provide the template for success. From 

designing quality into a manufacturing process, to the selection of material 

suppliers, the construction of facilities, selection of equipment, training of 

employees and fmal approval to distribute product, the regulations and 

guidelines provide for a consistent risk-based approach to assure quality. 

The regulations have also evolved to encourage innovation and continuous 

improvement and to help support the justification of new technology to 

further enhance quality assurance. 

It is logical to me that any large-scale manufacturer of medicines, including 

compounders, should comply with these same regulations. A manufacturer 

in full compliance will have a high degree of assurance that the medicines 

they product will be of consistent high quality. A large-scale company 

making thousands of doses of medicines with the name "pharmacy" on its 

building and another with the name "pharmaceutical company" should be 

regulated in a similar manner when they perform similar manufacturing 

steps and present similar risks to patients. 
99 


85438.049

Thank you for your attention. 
100 

Mr. PITTS. I will begin the questioning. And I recognize myself 

for 5 minutes for that purpose. 

Dr. Gottlieb, the FDA has proposed creating a new category of, 

quote, ‘‘nontraditional compounders,’’ end quote. Do you believe 

this has the potential to add confusion rather than clarity to regulated industry? 

Dr. GOTTLIEB. I do believe there is this category of companies, 

large companies, that have grown up that basically do the 

outsourced work of the hospitals. And it is not really traditional 

compounding in the sense that we understand that word. What 

they are really doing is sterile preparations of drugs, breaking 

down FDA-approved products into different formulations that make 

it easier to administer to patients, and it is a completely different 

thing than what traditional compounding is. 

I do think it creates the potential that traditional manufacturers 

might have a temptation to recast themselves into this new category if we don’t have very equal enforcement and very aggressive 

enforcement of the existing law because there will be an incentive 

to go into this pathway because it will be sort of a regulatory light 

pathway. 

The reason why Teva Pharmaceuticals doesn’t, you know, manufacture all the formulations of Propofol that doctors might want is 

because if they went about doing that they would have to file an 

ANDA for each one and pay a user fee for each one. So if we create 

this category, it could be an incentive for traditional manufacturers 

to try to move back into this new category, and that wouldn’t serve 

the public interest. 

Mr. PITTS. To follow up, impact on intellectual property rights. 

How would this new category potentially impact intellectual property rights? 

Dr. GOTTLIEB. Well, again, I think it could create an avenue for 

people to try to game around the new drug regulations to create 

products that would fit into this category. And it is not an argument for not trying to think about how we could apply GMP regulations to this emerging, this new category of manufacturers. But 

it is an argument for trying to make sure that we enforce existing 

law against compounders who, for example, compound versions of 

FDA-approved products. 

In recent years, the FDA has backed off enforcement that was 

put into place to crack down on people who are engaging in the 

compounding of drugs that exist in FDA-approved formulations. 

And so that creates an incentive to try to obviate existing intellectual property. 

Mr. PITTS. Mr. Migliaccio, Director Woodcock mentioned on the 

previous panel that the agency could not require compounders to 

register with the FDA. However, the FDA has the full authority to 

require manufacturers operating under the guise of compounders to 

register with the FDA, like NECC. Isn’t that correct? 

Mr. MIGLIACCIO. Yes. Well, every manufacturing establishment 

within a pharmaceutical company has to have an establishment 

registration with the FDA. 

Mr. PITTS. Hasn’t the FDA recently used its manufacturing inspection authority to inspect manufacturers acting under the guise 

of compounding recently? 

101 

Mr. MIGLIACCIO. I believe they have used their inspection authority to attempt to inspect compounding manufacturers. And I understand that they have been turned away in certain cases. 

Mr. PITTS. Please explain the similar scope of risk between NDA 

holders manufacturing drugs and large-scale compounders. 

Mr. MIGLIACCIO. Well, pharmaceutical manufacturers make 

pharmaceutical products at very different scales. I mean, we make 

small volume, we make large volume. Compounders are doing the 

same thing. We are following similar manufacturing steps. We are 

taking active ingredients and inactive ingredients, combining them, 

trying to yield a product that has the potency and purity required 

by the patient. 

Compounding the problem with sterile products is the risk 

around sterility. Sterility is not something that you can test into 

a product. Yes, you do a sterility test, but it is not a reliable measure of sterility. You have to have a very robust system to assure 

sterility. And the GMPs require that we actually prove that to the 

FDA before we can market the product. We have to prove that we 

can assure sterility to a very high degree before we can put a product on the market. That is not the case, the risks are the same for 

compounding pharmacies, but they don’t have to provide that same 

evidence. 

Mr. PITTS. Could legislation that applies different standards adversely affect the quality of drugs made available to patients? 

Mr. MIGLIACCIO. Oh, I believe that compounding pharmacies 

making product at large volume are manufacturers and should be 

regulated according to the manufacturing regulations, the GMPs, 

which have proven to be very successful in protecting the American 

public. 

Mr. PITTS. Let me squeeze one more question in here, Mr. 

Harmison. What safety precautions are you required to comply 

with? 

Mr. HARMISON. I comply with USP 797 and State laws and rules 

and regulations of the State of Texas. 

Mr. PITTS. And can you briefly describe the importance of traditional compounding that occurs in independent pharmacies across 

the country? 

Mr. HARMISON. Mr. Chairman, that is a very broad subject. If we 

are talking about somebody making a cream, there is one thing. If 

I am making a sterile injection, that is quite another thing. I am 

making a capsule for somebody. We still strive, basically, we are 

not going to make anything we wouldn’t give to our children or 

grandchildren. 

Mr. PITTS. Thank you. 

My time has expired. Recognize the ranking member 5 minutes 

for questions. 

Mr. PALLONE. I wanted to start with Ms. Russell. In your testimony, you cite the need for FDA to be given new and better authority over drug compounding. Obviously, your organization is 

made up of State agencies that regulate the practice of pharmacy, 

so you are in a unique position to have insight into whether FDA 

needed new authority in this area. 

So, Ms. Russell, your testimony describes the fact that there 

were regulatory uncertainties that were a major factor leading to 

102 

the NECC meningitis tragedy. Can you elaborate on what those— 

I always hate to say elaborate—but can you tell us what those uncertainties were and how they contributed to the meningitis outbreak? 

Ms. RUSSELL. Sure. I think that there are a number of entities 

in the United States, across the United States, that would tell 

boards of pharmacy that they were distributing nonpatient-specific 

sterile products as an FDA manufacturer. And they may have actually gone on FDA’s Web site and registered as a manufacturer and 

State boards of pharmacy didn’t think they had jurisdiction over 

those particular activities. FDA didn’t necessarily recognize them 

as an approved manufacturer because they hadn’t filed an NDA. So 

there were uncertainties and ambiguities in who had responsibility 

over these particular firms. 

Mr. PALLONE. So you also indicate that NABP is supportive of 

the Senate legislation clarifying the distinction between 

compounding manufacturers and traditional compounders. And you 

further indicate that your recent inspections of compounding pharmacies has underscored the importance of getting this clarity 

through Federal legislation. So can you explain more about what 

you have done in your inspection’s undertaking? I am curious about 

why, if any BP in the States have been able to conduct such widespread inspections recently, that isn’t enough. In other words, what 

would be achieved by FDA through new Federal legislation that 

can’t be accomplished by the State boards of pharmacy? 

Ms. RUSSELL. Maybe I wasn’t clear. We do think traditional 

pharmacy compounding should remain the purview of State boards 

of pharmacy. But we do think that there are these entities that are 

engaged in large-scale activities that more resemble manufacturing 

and that FDA should have jurisdiction to inspect and investigate 

those. 

Our initial inspections that we have been involved in for the 

State of Iowa, part of it has been trying to determine which of 

these large-scale entities are engaged in these more resembling 

manufacturing-type processes, and those are not condoned by the 

Iowa Board of Pharmacy, nor most other States. And we don’t 

think that State boards of pharmacy have the resources to be able 

to adequately inspect basically manufacturing operators that are 

operating under the guise of legitimate pharmacy practice. 

Mr. PALLONE. Thank you. 

Let me ask Ms. Cosel. I would like to ask you a question that 

we heard a little about during the first panel. That has to do with 

hospital use of compounding medications. As we heard, hospitals 

have increasingly come to rely on compounded medicines that they 

obtain from large-scale pharmacies, and Dr. Woodcock talked some 

about how FDA’s authorities to oversees these large-scale facilities 

are not appropriately tailored to the task. So I wanted to ask you, 

do you agree that hospitals do have a legitimate need for drugs 

from these large-scale pharmacies? Can you explain more about 

why they have come to rely on them? And what are your views on 

whether the FDA has the right authorities to handle regulation of 

that type of entity. 

Ms. COSEL. Yes. And I think the question is very astute, because 

it hits on just what is at hand today. There is a question about bad 

103 

actors and if they cross a certain line whether they should be shut 

down. Yes. But there is also a question of entities that do fill a 

niche in our healthcare system, such as the outsources you reference, sir. And it has become clear over the years that hospitals 

have increasingly looked to outsourced operations to provide them 

sterile mixed products, mixed variations of finished FDA drugs. 

And the simple answer can’t just be calling these entities manufacturers and requiring them to submit a new drug approval. We 

need to make absolutely clear that when you are compounding on 

a large scale and filling this niche for the health system you should 

be held to high quality standards, GMPs, as my colleague Mr. 

Migliaccio testified on as well. 

Mr. PALLONE. Mr. Harmison, I have got a little time. Your testimony can be summarized as follows: States always have and always should regulate compounders with no role for the FDA. But 

we know that numerous failure by Massachusetts regulators led to 

the NECC tragedy. In light of this tragedy, is it still your view— 

and I don’t mean—you tell me if I am wrong—is it still your view 

that States are capable of regulating large-scale compounders? 

Mr. HARMISON. Yes, Mr. Pallone. I think if they have the willpower to do it, they have the ability. 

Mr. PALLONE. So you don’t think there is a role for FDA in the 

regulation of large-scale compounders like NECC. 

Mr. HARMISON. I think the rule of the FDA is oversight. If they 

think that there is a problem, they should go talk to the State 

boards of pharmacy, say, come, go with me, let’s inspect this. If it 

is in violation of the State law, then the State should take action 

on them. If they say, we don’t have this, somebody decide if they 

are a manufacturer. If they are a manufacturer, certainly they are 

under the purview of the FDA. 

Mr. PALLONE. I don’t know. It just seems to me that what you 

are proposing sounds nice in theory, but I think much of the testimony seems to indicate it doesn’t work out practically. But whatever, I don’t want to put words in your mouth. Thanks a lot. 

Mr. PITTS. Chair thanks the gentleman. 

Now recognize the vice chair of the committee, Dr. Burgess, for 

5 minutes for questions. 

Mr. BURGESS. Mr. Harmison, let’s continue on that line for a moment, because when another subcommittee of the Energy and Commerce Committee, the Oversight and Investigations Subcommittee 

first started this investigation, we were joined by the brand new 

head of the Massachusetts Board of Pharmacy. And the reason she 

was the brand new head was because the old head had been recently dismissed because of the problems that occurred. 

We have heard from the FDA this morning that, no, we are not 

going to replace anyone in our organization. And looks to me like 

the Massachusetts Board of Pharmacy acted. Although there may 

have been problems leading up to the crisis, their response to the 

crisis and after seems much more reasonable than what I have 

seen under the Federal regulatory agency. Is that a fair assessment 

that I am making? 

Mr. HARMISON. As an employer, if I were in that position, somebody wouldn’t be in my employ anymore. 

104 

Mr. BURGESS. Well, that is, you know, this was so baffling about 

all of this. I mean, again, the poor individual who was the head, 

the brand new head of the Massachusetts Board of Pharmacy had 

to come here and answer some pretty tough questions and some for 

which she no answer, and simply said those people are no longer 

working for us. And you have to wonder if whether or not there are 

civil or even criminal activities are going to follow them for a while. 

I wouldn’t be surprised to learn that. 

But, again, you have a large Federal regulatory agency, and they 

are immobile. And not only are they immobile, after they find out 

that there is a problem, but the months and years leading up to 

this. Well, we are going to have to have guidance, and, well, it is 

bound up in some stuff. 

And I read you the email chain. From 18 months before this crisis hit, they recognized that it was manufacturing, that they were 

required to list these compounds, they were required to submit to 

GMP. The people in the FDA understood that. And for whatever 

reason it didn’t translate to the street level to get it done. In fact, 

I don’t think the people that were working in the agency, again, I 

just—the mental image, they must be tearing their hair because 

they keep coming up to this point waiting for someone to say ‘‘go’’ 

and no one ever said ‘‘go.’’ 

And that is the problem I see if we divested away from the State 

agencies. Bad news at Massachusetts Board of Pharmacy. You 

know, bad news at what happened. But at least they have reacted 

in what I would consider a sensible way. I can’t say the same to 

the FDA. That is painful for me to say that. 

Mr. HARMISON. Well, if I can go back to an old Paul Newman 

movie, it appears what we have is a failure to communicate between regulatory agencies and enforcement agencies. 

Mr. BURGESS. Dr. Gottlieb, let me just ask you because you have 

some experience working within the agency. Is that not correct? 

Dr. GOTTLIEB. Look, I think NECC was breaking existing law. 

They were acting as a large-scale manufacturer under the guise of 

a pharmacy license. They were compounding identical versions of 

FDA-approved products, they were doing it in bulk, they weren’t 

doing it in response to prescriptions. They had had previous GMP 

violations. So they were known bad actor. 

I think the issue isn’t necessarily what is FDA’s authority. FDA 

has extensive authority. I think that the challenge is that they 

don’t have ease of administrating authority because they don’t have 

the ability to compel the submission of certain information. And it 

is not the posture by which they typically regulate. 

In the case of compounding, in many cases FDA is forced to have 

to make an affirmative case before it could go in and start to do 

its work. Typically, the FDA doesn’t regulate that way. Typically, 

the FDA regulates from a posture where they compel submission 

of information to the agency and then they are able to target their 

activities based on that information. You know, under existing law 

they have extensive authority, in my view, but it is authority that 

makes it administratively more burdensome for them in this area 

than others. 

Mr. BURGESS. But, you know, the concept of an affirmative case, 

and for heaven sakes, the system was blinking red for years. For 

105 

years. You had whistleblowers, you had people bringing brochures 

in, you had people showing up saying, this is what we heard at a 

conference. These guys were clearly skating way beyond the edge, 

way beyond the fringe. And, OK, well, it may not be the normal 

FDA posture to take an affirmative case, when the evidence is laid 

in front of you, it shouldn’t take—— 

Dr. GOTTLIEB. Well, this one was obvious. 

Mr. BURGESS [continuing]. It shouldn’t take years to come to the 

conclusion of filing the action that eventually closed the NECC. Is 

that correct? 

Dr. GOTTLIEB. This was a known bad actor over a long period of 

time—including, frankly, the time in which I was at FDA, we sent 

out a warning letter to this firm in 2006. 

Mr. BURGESS. OK. 

Thank you, Mr. Chairman. I will yield back. 

Mr. PITTS. Chair thanks the gentleman. 

And now recognize the ranking member emeritus, Mr. Dingell, 

for 5 minutes for questions. 

Mr. DINGELL. Mr. Chairman, I thank you. 

First question is for Ms. Russell of the National Association of 

Boards of Pharmacy and also Ms. Cosel of the Pew Charitable 

Trusts. 

Ladies, do you believe that there is regulatory uncertainty regarding the FDA’s role in overseeing compounding pharmacies? Yes 

or no? 

Ms. RUSSELL. Yes. 

Ms. COSEL. Yes. 

Mr. DINGELL. Now, these next two questions are for Ms. Russell. 

In your testimony, you mentioned that NABP partnered with the 

Iowa Board of Pharmacy to inspect pharmacies which deliver compounded drugs into Iowa. Is that correct? 

Ms. RUSSELL. Yes. 

Mr. DINGELL. Now, in your testimony also, you also mention that 

your inspections found that what occurred at NECC was happening 

elsewhere. Is that correct? 

Ms. RUSSELL. Yes. 

Mr. DINGELL. Could you briefly describe what you found at some 

of the facilities where you found a repeat of this kind of situation? 

Ms. RUSSELL. We found large-scale operations similar to what 

NECC was doing where they were allegedly compounding or producing bulk quantities of sterile injectable products, some that 

were essentially copies of commercial products. We found issues 

with compliance with standards for sterility compounding and basically that they were shipping nonpatient-specific drugs into the 

State of Iowa in violation of Iowa State law. 

Mr. DINGELL. What did the Iowa agency do about this? 

Ms. RUSSELL. Iowa is in the process of—they have got three attorneys now working on the inspections that we provided. And they 

have issued notices of regulatory hearing for 5 of the first 6 pharmacies that we went in, which were some of the larger-scale operations. Those hearings I believe will be held in June this year, next 

month. 

Mr. DINGELL. They seem to be in great haste. Am I correct? 

Ms. RUSSELL. Pardon? 

106 

Mr. DINGELL. They seem to be in great haste to get around to 

processing this matter. Yes or no? 

Ms. RUSSELL. Yes. 

Mr. DINGELL. I don’t see it that way. 

Would you submit also for the record other details of the events 

that you found, if you please? 

Now, in your testimony you mentioned there has been 19 significant compounding errors since 2001. Is that correct? 

Ms. COSEL. Yes, 20, including NECC. 

Mr. DINGELL. OK. Would you for the record submit the details 

of those events, please, to us? 

Ms. COSEL. Yes, sir. 

Mr. DINGELL. Now, how many people died as a result of these incidents? 

Ms. COSEL. Not including NECC, there were 22 deaths associated with these incidents, and including NECC there were 77. 

Mr. DINGELL. Could you submit for the record the details on 

these things, if you please? 

Ms. COSEL. Yes, sir. 

Mr. DINGELL. Now, as far as you know, have there been further 

problems with compounding pharmacies after the NECC outbreak? 

Yes or no? 

Ms. COSEL. Yes. We have seen a number of recalls related to 

quality problems with compounded drugs this year. 

Mr. DINGELL. Could you submit again for the record what you 

found in those matters? 

Ms. COSEL. Certainly. 

Mr. DINGELL. Could you give us a brief perhaps picture of what 

you found done in these instances and whether this was the responsibility of the State agencies or the Feds? 

Ms. COSEL. Well, I can give one example. There was a recall by 

a Georgia compounder this year, I believe in March, of all sterile 

products, because there were serious eye infections in at least 5 patients associated with a contaminated eye injection. In this case, 

this was a nationwide recall. So if we are—if Congress is considering a new regulatory system that is clear that large-scale 

compounding of high-risk sterile products would be explicitly under 

FDA oversight, I think we would have had a much better chance 

of ensuring the safety of those processes. 

Mr. DINGELL. Particularly since they are shipping all across the 

United States and this is touching many agencies, many States, 

and people in many States and agencies. Is that right? 

Ms. COSEL. Yes. 

Mr. DINGELL. And, by the way, thank you for your patience. It 

lets me get a lot more questions in. 

Would you for the record please submit the information that you 

have on these instances? 

Ms. COSEL. Yes. 

Mr. DINGELL. Now, in your opinion, is the outbreak at NECC an 

exception to the rule or do you believe that it is but one example 

of a larger problem? 

Ms. COSEL. It is certainly an extremely horrific example, but it 

is just one of the larger issues we face. We acutely need greater 

clarity on oversight structures for large-scale compounding. 

107 

Mr. DINGELL. And one of the things we have do is to clarify it 

so that everybody knows who is supposed to and who can do what. 

Is that right? 

Ms. COSEL. Yes. 

Mr. DINGELL. Because we have the court cases that have screwed 

up the interpretation by both State and Federal agencies on this 

matter. Is that right? 

Ms. COSEL. Legal uncertainty is one problem, as is changes with 

the industry and the emergence of the large-scale sector. 

Mr. DINGELL. I have used more than my time. Thank you, Mr. 

Chairman. 

Mr. PITTS. Chair thanks the gentleman. 

Now recognize the gentleman from Virginia, Mr. Griffith, 5 minutes for questions. 

Mr. GRIFFITH. Thank you, Mr. Chairman. 

I have to tell you all, and I appreciate all of you being here, that 

I think part of the problem is, is that we have a clash of two 

worlds, the legal world and the medical world. Because when I look 

at the authority granted to the FDA under the code, with the exception of the advertising overreach, which was stricken down, 

there is plenty of authority already there to get to every problem 

that you all have raised today. And that is my concern. 

And I asked the doctor earlier, and she was very kind, you know, 

this happened, the Supreme Court case came down that dealt with 

the Ninth Circuit in 2002. Where was the request to Congress to 

clarify? Because the only clarification is that the rest of the authority granted, with the exception of the advertising provision, should 

have been reenacted by Congress. 

Now, can we tweak it a little bit and make it a little bit better? 

I am sure we can. And I am certain that we will work on that, because none of us want to see this problem happen again. But I 

heard one of the witnesses, and I don’t remember which one now, 

say that they understood that there had been problems, you know, 

getting the records and getting into things. And, in fact, I think because the medical world—and I was a courtroom attorney, and so 

maybe it is a little different, not attorneys, but courtroom attorneys, they see things differently. 

So I asked legal counsel who was here at a previous hearing, for 

the FDA, do you have any trouble getting warrants? And I expressed that my opinion always was as a defense attorney, criminal 

defense attorney, that the government didn’t have too much trouble 

getting warrants. He said, that wasn’t my experience. And I asked 

him to get me information. Yesterday, we received that information. 

And, sure enough, FDA cannot point to a single example of 

where they requested a warrant where they were denied that warrant. So while the common belief is they have a hard time getting 

this information, the data would indicate otherwise. 

I also asked, how long does it take you to get the warrant? And 

they said, in the most recent administrative warrant we sought for 

a pharmacy, 10 days passed between when the refusal was encountered and when the warrant was signed by the magistrate judge. 

I have got to believe that if, as somebody said earlier, the blinking light, the red light warning, warning had been going off for 

108 

years, that if instead of being timid and being afraid of the law, 

the medical folks had burst in, as often police officers have to do— 

if they think somebody has a DUI, they may not win the case in 

the end, but they get that person off the road, at least temporarily, 

to see what is going on—that is what should have happened in this 

situation. 

Would you agree with that, Mr. Harmison, that that is probably 

what should have happened, instead of coming in, trying to rewrite 

the law. 

Mr. HARMISON. Yes, sir. If there is public safety at risk, the State 

board of pharmacy absolutely has the power to come in and say, 

wait a minute, you are shut down. 

Mr. GRIFFITH. Yes. And I think that the guidelines that were 

worked on, never fully finalized, but that were worked on in the 

draft guidelines of August of last year that we didn’t learn about 

until March of this year, make that clear as well. Because it goes 

through and when it talks about distinguishing between, as you all 

have called them different names, large-scale producers or production of compounded drugs, large-scale manufacturers, I think they 

are manufacturers. And I said in one of the earlier hearings, you 

know, I can call myself the Duke of Earl if I want to, but that 

doesn’t mean I am getting diplomatic immunity. 

And that is where I think we run into this problem. But when 

they did that draft, they said, when you are looking at whether or 

not somebody is doing a compounded drug product that qualifies 

for the exemptions, they came up with 10 guidelines. And they are 

all significant and important, but I noted with interest two of 

those. Number 8 says the licensed pharmacist or licensed physician 

does not compound regularly or in inordinate amounts any drug 

products. Number 10 says that you should have a memorandum of 

understanding with the States so that you can work out these 

areas that aren’t clarified or in a State where they have not entered into a memorandum of understanding the pharmacists 

shouldn’t be sending to another State more than 5 percent of the 

total prescription orders dispensed or distributed by such pharmacy 

or physician. 

These seem to me to be reasonable restrictions, and it makes the 

definition that I think each one of the witnesses here today is looking for, distinguishing between the traditional pharmacy that is 

doing some things for their patients and their customers and these 

large-scale manufacturers who are, in fact, in my opinion, they are 

not compounders in the traditional pharmacy sense, but they are, 

in fact, manufacturers. 

I look forward to trying to make sure that we clarify some of that 

because I do think that part of the problem is, is not having some 

street lawyers at the FDA who know that sometimes you have got 

to go in and kick the courthouse door down and say here is what 

we are doing. And when the judge sees the risk to the public he 

will say, OK, I will sign the warrant, OK, we will shut them down 

at least until we can find out whether or not they are a risk to the 

public. I think the authority already exists for that. I just think 

there has been some timidity in the legal department at the FDA. 

And when you talk about registration, when you look at the rules 

in section 510 of the act, I think it is pretty clear that unless you 

109 

are a small town pharmacist you are supposed to be registering 

anyway. Does anybody disagree with that? 

Dr. Gottlieb, do you disagree with that? 

Dr. GOTTLIEB. No, 510 has a requirement for registration. And 

I think 503A actually lays out some criteria to try to distinguish, 

you know, these illegitimate compounders from the legitimate ones. 

So the language does exist and this could—even 503A could be better interpreted in regulation. But I think the compliance policy 

guide which you just quoted is a very good start for that. 

Mr. GRIFFITH. I think they did a nice job in that guidance. I am 

not going to say I would agree with every word of it, but most of 

it is pretty good stuff and it indicates the FDA had the authority 

to move forward even under the rules that they now say they don’t 

have the authority to do. 

With that, I see my time is up and I yield back. But I do appreciate all of you all staying through two vote series on a long day. 

Thank you. 

Mr. PITTS. The chair thanks the gentleman. 

And with that, we again thank the witnesses for your patience. 

That concludes the questions of the members who are present. 

There are other questions I am sure that other members who are 

not here will also like to submit to you and we will ask that you 

please respond promptly once you receive those questions. 

And I will remind members that they have 10 business days to 

submit questions for the record, and Members should submit those 

questions by the close of business on Thursday, June the 6th. 

Very informative and important hearing. Thank you very much 

for your attendance. 

Without objection, the subcommittee is adjourned. 

[Whereupon, at 1:50 p.m., the subcommittee was adjourned.] 

[Material submitted for inclusion in the record follows:] 

110 


85438.050

WASHINGTON OfFICE: 

ROOM 232B 

JOHN D. DINGELL 

15TH DISTRICT, MICHIGAN 

COMMITTEE ON 

ENERGY AND COMMERCE 

CO·CHA1R 

HOUSE GREAT LAKES 

TASK FORCE 

MEMBER 

MIGRATORY B!RD 

CONSERVATION COMMISSION 

RAYBURN HOUSE OFFICE aUILDING 

WASHINGTON, DC 20515-21'15 

(202) 225-4071 [ongff55 of the ilnited ~tate5 

llouse of lReprescntatinc.s 

fllashington, ]E)~ 20515-2215 

DISTRICT OFFICES: 

19855 WEST OUTER DRiVE 

SUITE 10J.-E 

DEARBORN, MI4B124 

(313) 276-2936 

23 EAST FRONT STREET 

SUITE 103 

MONROE, MI48161 

(734) 243-1849 

The Honorable Margaret Hamburg 

Commissioner 

u.s. Food and Drug Administration 

5600 Fishers Lane 

Rockville, MD 20857 

Dear Commissioner Hamburg; 

October 9,.2012 

301 WEST MICHIGAN AVENUE 

SUITE 305 

YPSILANTI, MI4S197 

(734) 481-1 100 

I write to you regarding the recent fungal meningitis outbreak thought to be related to 

epidural steroid injections. 

As you know, this is not the first case of fungal infection as a result of contaminated 

methylprednisolone acetate produced by a compounding pharmacy, nor is this the first case of 

contamination and adverse events resulting from compounded sterile injectable products. In this 

more recent case, it is my understanding that an investigation into the source of the outbreak is 

still ongoing; however, the New England Compounding Center (NECC) in Framingham, 

Massachusetts, has voluntarily recalled preservative-free methylprednisolone acetate products 

produced and distributed from this facility. I am aware of the fact that U.S. Food and Drug 

Administration (FDA) have recommended that none of the facility's compounded products be 

used, and further, NECC has voluntarily shut down. 

While these actions may help to prevent a larger outbreak from OCCUlTing, I am deeply 

concemed that this outbreak may be due to a contaminated pharmaceutical produced by a 

company that has not been properly regulated by federal or state authorities. Therefore, I 

respectfully request the answers to the following questions. 

1. Although the investigation is still ongoing, FDA has discovered fungal 

contamination of sealed vials of methylprednisolone acetate collected at 

NECC. How many vials of this steroid has NECC produced? How many vials of 

this steroid produced by NECC have been distributed? How many facilities have 

received vials of this steroid produced by NECC? Where are these facilities 

located? When were the vials linked to the outbreak distributed? How many 

patients have received injections of this steroid produced by NECC thus far? 

2. Who first discovered the contamination of vials of methylprednisolone acetate? 

When was the contamination first discovered? Where was the contamination first 

discovered? How was contamination discovered? When was the contamination 

first reported to FDA? How did this contamination occur? 

THIS MAILING WAS PREPARED, PUBLISHED, AND MAILED AT TAXPAYER EXPENSE 

nus STATIONERY PRINTED ON PAPER MADE OF RECYCLED FIBERS 

~" 
111 


85438.051

3. NECC has issued a vohmtary recall of the methylprenisolone acetate products and 

has voluntarily shut down. When was the voluntary recall first initiated? How 

many lots have been recalled? How many doses were included in the recall? 

When did NECC shut down its facility? 

4. Are any vials of methylprednisolone acetate from NECC stiU available on the 

market? If yes, how many vials remain on the market? 

5. What alerts regarding methylprednisolone acetate has FDA issued to health 

professionals? What alerts regarding methylprenisolone acetate has FDA issued 

to consumers? How have these alerts been transmitted to these parties? 

6. With what federal and state agencies has the FDA been working on this 

investigation? 

7. It has been reported that Massachusetts's Board of Registration in Pharmacy has 

had at least four previous complaints about the sterility ofNECC's productsin 2002, 2003, 2011, and one complaint is currently being investigated. Were 

these complaints shared with the FDA? If yes, when were these complaints 

shared? 

8. What has been the inspection history of the NECC facility? When was the NECC 

facility in Framingham last inspected? What were the results of tPat inspection? 

9. Does FDA have the authority to inspect compounding pharmacies? If yes, when 

was the last time FDA officials have inspected NECC's facility? What were the 

results of that inspection? 

10. It has been reported that more than 17,000 vials compounded byNECChave been 

recalled thus far. What does FDA consider to be legitimate forms of pharmacy 

compounding? What volume does FDA consider to be legitimate uses of 

pharmacy compounding? 

11. Do compounding pharmacies, like NECC, register with FDA? If yes, how many 

compounding pharmacies are currently in operation? 

12. Do compounding pharmacies list their products with FDA? If yes, how many 

products produced by compounding pharmacies are currently on the market? 

13. Does FDA approve drug products produced through compounding 

pharmacies? Are drug products made through pharmacy compounding required 

to meet the safety and efficacy standard set by FDA? 

14. Does FDA have sufficient authority to oversee compounding pharmacies, such as 

NECC, now? If so, please explain why. If no, please explain why. 
112 


85438.052

15. Does FDA need additional authority to oversee compounding pharmacies? If yes, 

please explain why and list the authorities needed. If no, please explain why. 

While I recognize that compounding serves an important purpose and provides 

pharmaceuticals for individual patients with unique needs, I am concerned that NECC was 

operating at such a volume to be outside of what may be considered traditional pharmacy 

compounding. Further, I am concerned that a facility with a long history of sterility complaints 

was allowed to operate at such margins and endanger the lives of thousands of patients. I urge 

FDA to use its enforcement authority to the fullest extent possible to ensure that NECC cannot 

again distribute contaminated compounded drug products and to swiftly identifY what other 

authorities are needed to ensure such an incident cannot occur again. I will be sending you 

further inquiry as to what FDA can do with existing regulatory authority and what additional 

statutory authority is needed by FDA. 

Given the serious nature ofthls outbreak; I respectfully request that a response be sent to 

my office no later than October 22, 2012. Should you or your staff have any questions, please do 

not hesitate to contact me or Kimberlee Trzeciak of my staff at (202) 225-4071. 

With every good wish, 
113 


85438.053

The Honorable John D. 

House of Representatives 

Washington, D.C. 20515-2215 

Dear Mr. Dingell: 

APR 26 

Thank you for your letter of October 9, 2012, concerning the fungal outbreak 

associated with methylprednisolone acetate, a steroid injectable product distributed by the New 

England Compounding Center (NECq. This outbreak has had devastating effects on 

individuals and families across the country. 

The Food and Drug Administration (FDA or the Agency) believes that pharmacists engaging in 

traditional compounding provide a valuable medical service that is an important component of 

our health care system. The history of this issue shows that there is a need for appropriate and 

effective oversight of this evolving industry. It is clear that the industry and the health care 

system have evolved and outgrown the law, and FDA's ability to take action against 

compounding that exceeds the bounds of traditional pharmacy compounding and poses risks to 

patients has been hampered by gaps and ambiguities in the law, which have led to legal 

challenges to FDA's authority to inspect pharmacies and take appropriate enforcement actions. 

The fungal meningitis outbreak has caused the Agency to review our past with regard 

to our oversight of compounding pharmacies. We have established an Agency-wide steering 

committee to oversee and coordinate our efforts, and we have taken several important steps to 

identify and inspect high-risk phanllacies that are known to have engaged in production of sterile 

drug products. 

The Administration is committed to working with Congress to address the threat to public health 

from gaps in authorities for effective oversight of certain compounding practices. To that end, 

FDA has developed a framework, discussed below, that could serve as the basis for the 

development of a risk-based program to protect the public health. 

We have restated your questions below in bold, followed by our responses. 

1. Although the investigation is still ongoing. FDA has discovered fungal coutamination of 

sealed vials of methylprednisolone acetate collected at NECC. How mallY vials of this 

steroid has NECC produced? How many vials of this steroid produced by NECC have 

been distributed? How many facilities have vials ofthis steroid produced by 

NECC? Where are these facilities located? were the vials linked to the outhreak 

distributed? How many patients have received injections of this steroid produced by 

NECC thus fa,,? 
114 


85438.054

Page 2 - The Honorable John D. Dingell 

As part of the public health investigation into the outbreak, FDA has learned that, among the 

three suspect lots of methylprednisolone acetate (MP A) produced by NECC, there are 17,676 

total vials. These lots were distributed to facilities in 23 states (California, Connecticut, 

Florida, Georgia, Idaho, Illinois, Indiana, Maryland, Michigan, Minnesota, North Carolina, 

New Hampshire, New Jersey, Nevada, New York, Ohio, Pennsylvania, Rhode Island, South 

Carolina, Tennessee, Texas, Virginia, West Virginia), between the date of preparation of the 

first lot (May 21, 2012) and the date on which the suspect lots were recalled (September 26, 

2012). After the recall ofNECC steroid medications on September 26, state and local health 

departmentS identified almost 14,000 people in 23 states who were potentially exposed to the 

implicated MPA; of these, an estimated 11,000 individuals received spinal or paraspinal 

injections. 

2. Who first discovered the contamination of vials of methylprednisolone acetate? When 

was the contamination first discovered? Where was the contamination first 

discovered? How was contamination discovered? When was the contamination first 

reported to FDA? How did this contamination occur? 

As part of the public health investigation into the outbreak, FDA has learned that, on 

September 21,2012, the Centers for Disease Control and Prevention (CDC) was notified by 

the Tennessee Department of Health of a patient with the onset of meningitis approximately 

19 days following epidural steroid injection at a Tennessee ambulatory surgical center. On 

September 25, 2012, CDC notified FDA that it was working with the Tennessee Department 

of Health to investigate a cluster of meningitis cases at a single clinic, which might be 

associated with product contamination. On October 18,2012, FDA and CDC announced that 

"CDC and FDA have confirmed the presence of a fungus known as ExserohilufI! rostratufI! in 

unopened medication vials of preservative-free methylprednisolone acetate (80mglml) from 

one of the three implicated lots from NECC (Lot #08102012@51,BUD2/6/2013). The 

laboratory confirmation further liilks steroid injections from these lots from NECC to the 

multistate outbreak of fungal meningitis and joint infections." 

Due to the ongoing criminal investigation, FDA cannot comment further. 

3. NECC has issued a voluntrary recall of the methylprenisolone acetate products and has 

voluntarily shut down. When was the voluntary recall first initiated? How many lots 

have been recalled? How many doses were included in the recall? When did NECC 

shut down its facility? 

As part of the public health investigation into the outbreak, FDA worked with NECC to 

initiate a voluntary recall of the suspect lots ofMPA on September 26, 2012. At the time, 

three lots (17,676 vials) were included in the recall; however, since that time, the recall was 

expanded to include all products made by NECC. FDA was notified that NECC ceased 

production on October 3, 2012, and has not recommenced production. 

4. Are any vials of methylprednisolone acetate from NECC still available on the market? 

If yes, how many vials remain on the market? 
115 


85438.055

Page 3 - The Honorable John D. Dingell 

As of October 6, 2012, all products compounded and distributed byNECC were recalled by 

the firm. NECC posted notice of the recall on their website, www.neccrx.com. As of January 

30,2013, as part of the public health investigation into the outbreak, FDA had completed 

1,155 audit checks with customers who received NECC products. FDA found no unexpired 

product remaining for use with any of the customers, and all customers had knowledge of the 

recall either through NECC, CDC, state health departments, the media, or other sources. 

5. What alerts regarding methylprednisolone acetate has FDA issued to health 

professionals? What alerts regarding methylpredinsolone acetate has FDA issued to 

consumers? How have these alerts been transmitted to these parties? 

As part of the public health investigation into the o~tbreak, FDA issued two MedWatch 

alerts in October 2012 (with updates through November 2012), advising health care 

professionals and consumers of the risks associated with drug products produced by NECC, 

including MPA acetate, and providing updates as FDA's investigation progressed. Links to 

the MedWatch alerts on FDA's website are provided below. 

FDA issued an alert on October 5, 2012 (updated on October 6, 2012), advising that FDA 

had observed fungal contamination in a sealed vial of methylprednisolone collected from 

NECC, and recommending that health care professionals and consumers not use any product 

produced by NECC. The alert indicated that although the investigation into the source of the 

outbreak was ongoing, it was possibly associated with preservative-free MPA acetate 

produced and distributed by NECC. This alert is available at 

http://wwwjda.govISajetyIMedWatchiSajetylnjormationiSajetyAlertsforHumanMedicalProdu 

ctslucm322849.htm. 

FDA issued another MedWatch alert on October 15, 2012, which was updated multiple 

times. The initial alert dated October 15, 2012, advised of a patient with possible meningitis 

associated with triamcinolone acetonide, and two transplant patients (revised on October 16, 

2012, to one transplant patient) with Aspergillus fumigatus infections following 

administration of cardioplegic solution made by NECC. The alert was updated on October 

18,2012, noting that CDC and FDA confirmed the presence of Exserohilum rostratum in 

unopened vials of preservative-free MPA acetate made by NECC. Further updates, dated 

October 22, 2012, informed that FDA was making available lists of customers who received 

products shipped on or after May 21, 2012, from NECC, and dated October 24,2012, was to 

provide an updated list of customers. The final update, dated November 1,2012, advised 

that two additional products recalled by NECC, preservative-free betamethasone and 

cardioplegia solution, tested positive for bacterial contamination. This alert is available at 

http://wwwjda.gov/Safety/MedWatchiSajetylnformationiSafetyAlertsjorHumanMedicalProdu 

ctslucm323946. htm. 

FDA communicated throughout its investigation with the media, Congress, state health 

officials, health care professionals, and the public to keep them apprised of important 

findings and developments as our investigation proceeded. FDA's website was updated on a 

frequent basis to provide broad access to any new public information. This information was 

further disseminated through the Agency's electronic listservs and through Twitter and 
116 


85438.056

Pl\ge 4 - The Honorable JOM D. DingeU 

Facebook. Along with CDC, FDA provided health care professionals with infonnation they 

needed on an ongoing basis, and as new infonnation came to light, to advise and treat 

patients affected by this situation. 

Targeted alerts were sent to 150 health care professional organizations, including the national 

specialty-specific societies that work with spinal injections, such as the American Society of 

Anesthesiologists, the American Academy of Physical Medicine and Rehabilitation, and the 

North American Spine Society, and also to all state medical, pharmacist, nursing, and 

physicians' assistant societies, as well as all state boards ofphannacy. Regular phone 

updates were provided to state health departments, in collaboration with CDC, and written 

updates were also distributed to national phannacy and ophthalmology professional 

~organizations. FDA also contacted patient and health care professional groups and consumer 

groups and worked with the American Hospital Association as part of our response. 

FDA pharmacists fielded calls from the public and extended their hours of availability for 

several weeks to help respond to the public's concerns. We also continued to respond to 

calls and e-mails from health care professionals, hospitals and clinics, and others with 

questions about the NECC and Ameridose recalls. 

6. With what federal and state agencies has the FDA been working on this investigation? 

FDA cannot comment at this time. 

7. It has been reported that Massachusetts Board of Registration in Pharmacy has had at 

least four previous complaints about the sterility of NECC's products- in 2002, 2003, 

2011, and one complaint is currently being investigated. Were these complaints shared 

with the FDA? If yes, when were these complaints shared? 

FDA received three adverse event reports in 2002 suggesting sterility concerns associated 

with MP A acetate compounded by NECC. These reports came directly to FDA via the 

MedWatch reporting system from the hospital that treated the patients. The Agency is not 

aware that the Massachusetts Board of Registration in Phannacy (MBRP) provided any 

report of these adverse events to FDA. FDA's investigations of these reports were, however, 

communicated to the Massachusetts' Board of Registration in Pharmacy (MBRP)' The 

inspection beginning in 2002 regarding the adverse event reports associated with 

methylprednisolone was conducted jointly by FDA with MBRP. 

FDA does not have a record of having received from MBRP reports of any complaints or 

adverse events in 2002, 2003, or 2011, regarding sterility ofNECC's products. 

8. What has been the inspection history of the NECC facility? When was the NECC 

facility in Framingham last inspected? What were the results of that inspection? 

See enclosed document entitled "Timeline of FDA Interactions with NECC and Ameridose" 

that was provided to the House Energy and Commerce Committee on January 4, 2013. 
117 


85438.057

Page 5 - The Honorable John D. Dingell 

9. Does FDA have the authority to inspect compounding pharmacies? If yes, when was 

the last time FDA officials have inspected NECC's facility? What were the results of 

that inspection? 

Under FDA's current inspection authority in section 704 of the Federal Food, Drug, and 

Cosmetic Act (FD&C Act), FDA's authority to inspect records at a pharmacy depends upon 

knowing certain facts about the pharmacy's operations that oftentimes can only be 

determined through inspection of records. The first of three criteria for being exempt from 

having records inspected is whether the pharmacy is operating in conformity with state law, a 

determination most readily made by a state and, in any case, likely dependent upon 

examining certain records. The second criterion is whether the pharmacy is dispensing 

prescription drugs without a prescription, but in many cases, FDA must be able to inspect 

records to determine that fact. Similarly, the third criterion is whether the pharmacy is 

compounding drugs for sale other than in the regular course of its retail business, which is 

also something that would be difficult to determine without a full inspection of the facility, 

including an inspection of appropriate records. So the authority is circular, and compounding 

pharmacies have cited this language in opposing FDA's efforts to inspect. 

In addition, the records exemption for pharmacies can present an obstacle to FDA in 

determining the source of a complaint or outbreak associated with a compounded drug that 

may be adulterated or misbranded under the FD&C Act. FDA's ability to inspect in a timely 

manner any firm producing drugs is critical for effective oversight and regulation. Therefore, 

FDA strongly recommends that the provision in section 704 of the FD&C Act that limits the 

Agency's ability to inspect a pharmacy's records be removed. It is critical that FDA have 

clear authority to inspect pharmacies to determine the scope and nature of their operations to 

determine whether they are operating as compounding pharmacies or conventional drug 

manufacturers. The determination of whether a compounding pharmacy is engaging in 

conventional drug manufacturing is fact-specific, and FDA must be able to fully inspect 

pharmacies, and review their records, to gather the facts to make this determination. 

Therefore, FDA should have clear ability to examine records such as records of prescriptions 

received, products shipped, volume of operations, and operational records such as batch 

records, product quality test results, and stability testing results. Such inspections are 

necessary to determine when a pharmacy exceeds the bounds of traditional compounding, 

respond to public health threats, and enforce federal standards. 

See enclosed document entitled "Timeline of FDA Interactions with NECC and Ameridose," 

which was provided to the House Energy and Commerce Committee on January 4, 2013, for 

additional information. 

10. It has been reported that more than 17,000 vials compounded by NECC have been 

recaned thus far. What does FDA consider to be legitimate forms of pharmacy 

compounding? What volume does FDA consider to be legitimate uses of pharmacy 

compounding? 

Due to the ongoing criminal investigation, FDA cannot comment on NECC specifically. 
118 


85438.058

Page 6 - The Honorable John D. DingeU 

With regard to compounding generally, FDA issued a Compliance Policy Guide (CPG) in 

2002 (CPG Sec. 460.200) that describes the factors FDA considers in determining whether to 

take enforcement action against a compounding pharmacy. The CPG recognizes that 

pharmacists traditionally have extemporaneously compounded and manipulated reasonable 

quantities of human drugs upon receipt of a valid prescription for an individually identified 

patient from a licensed practitioner, and states that this traditional activity is not the subject 

of the CPG. In its simplest form, this compounding may involve reformulating a drug, for 

example, by removing a dye or preservative in response to a patient allergy. Or it may 

involve making a suspension or suppository dosage form for a child or elderly patient who 

has difficulty swallowing a tablet. FDA believes that pharmacists engaging in traditional 

compounding provide a valuable medical service that is an important component of our 

health care system. 

Section S03A of the FD&C Act, added to the law in 1997, also attempts to draw a line 

between pharmacy compounding and conventional manufacturing using different but similar 

factors to draw the line. That statute was challenged in court and the compounded product, 

consistent with the factors set forth in section S03A, is exempt from three key provisions of 

the FD&C Act: the requirement of premarket review for safety and effectiveness, the 

requirement to provide adequate directions for use, and the requirement that the drug meets 

Current Good Manufacturing Practice standards. The statute contains some ambiguous 

provisions that make it difficult to draw a clear line between compounded drugs that are 

subject to exemptions from the above proviSions of the Act and those compounded drugs 

which are not. 

Further, regulating certain types of compounding pharmacies as conventional manufacturers 

is not a good fit for the evolving category of outsourcer pharmacy, which provides drugs for 

hospitals and other health care entities. The Administration is committed to working with 

Congress to address the threat to public health from gaps in authorities for effective oversight 

of certain compounding practices. To that end, FDA has developed a framework that could 

serve as the basis for the development of a risk-based program to protect the public health. 

FDA has suggested that legislation be enacted to create a new framework for regulating 

compounding. FDA suggests Congress create a new category of non-traditional 

compounding, subject to appropriate federal standards, which may be based on certain 

Current Good Manufacturing Practice (CGMP) requirements in 21 Code of Federal 

Regulations (CFR) Parts 210 and 211, and oversight to ensure consistent product quality 

standards are applied to sterile compounding done in advance of or' without a pharmacy 

receiving a prescription where the compounded product is then shipped across state lines. 

FDA believes that there are other authorities that would be important to support this new 

regulatory paradigm. For example, FDA should be given clear, full authority to collect and 

test samples of compounded drugs and to examine and collect records in a compounding 

pharmacy, just as the Agency does when inspecting other manufacturers. FDA should have 

clear statutory authority to examine records, such as records of prescriptions received, 

products shipped, volume of operations, and operational records such as batch records, 

product quality test results, and stability testing results. Such inspections are necessary to 
119 


85438.059

Page 7 - The Honorable John D. Dingell 

determine when a pharmacy exceeds the bounds of traditional compounding to respond to 

public health threats and to enforce federal standards. 

11. Do compounding pharmacies, like NECC, register with FDA? If yes, how many 

compounding pharmacies are currently in operation? 

Generally, pharmacies are exempt from registration under section 510 of the FD&C Act, 

provided they meet certain conditions (S10(g) ofthe Act). Such conditions include 

operating under applicable local laws regulating the practice of pharmacy and medicine, 

regularly dispensing drugs upon a valid prescription, and not compounding drugs other than 

in the regular course of dispensing drugs at retail. As a result, FDA does not know all of the 

compounding pharmacies in the United States, and FDA does not conduct regular 

surveillance inspections of pharmacies as it does with typical drug manufacturers. 

According to the International Academy of Compounding Pharmacists (IACP), there are an 

estimated 28,000 pharmacies that compound, including 7,500 pharmacies that specialize in 

compounding. About 3,000 of these pharmacies compound sterile products. 

An accurate inventory of pharmacies engaged in non-traditional compounding would 

facilitate appropriate oversight and coordination with state regulators. Under FDA's 

proposed framework, certain sterile compounding facilities should be subject to federal 

oversight to ensure that the compounding of sterile drug products at those facilities can be 

done without putting patients at undue risk. These requirements would include federal 

registration of the compounding facilities that will be subject to federal quality standards, so 

that FDA knows where they are and what drug products they are making. 

12. Do compounding pharmacies list their products with FDA? If yes, how many 

products produced by compounding pharmacies are currently on the market? 

Because pharmacies that meet certain criteria generally are not required to register or list, 

FDA does not have a list or count of marketed compounded products. 

An accurate inventory of pharmacies engaged in non-traditional compounding would 

facilitate appropriate oversight and coordination with state regulators. Under FDA's 

proposed framework, requirements would include federal registration of the compounding 

facilities that will be subject to federal quality standards, so that FDA knows where they are 

and what drug products they are making, 

13. Does FDA approve products produced through compounding pharmacies? Are drug 

products made through pharmacy compounding required to meet the safety and 

efficacy standard set by FDA? 

Under section 503A of the FD&C Act, compounded drugs that meet certain criteria are 

provided an exemption from three key provisions ofthe Act, including the drug approval 

requirements of section 505. The CPG on pharmacy compounding, CPG Sec. 460.200 

Pharmacy Compounding, sets forth factors that FDA considers in determining whether to 
120 


85438.060

Page 8 - The Honorable John D. Dingell 

exercise enforcement discretion in applying the drug approval requirements of section 505 of 

the FD&C Act. Thus, under either section S03A or the CPG, compounded drugs are not 

approved by FDA and lack an FDA finding of safety and efficacy. 

14. Does FDA have sufficient authority to oversee compounding pharmacies, such as 

NECC, now? Uso, please explain why. Uno please explain why. 

With regard to compounding generally, FDA is working with Congress, states, industry, and 

other interested stakeholders to develop a basic framework to help the Agency effectively 

oversee firms engaged in widespread distribution of sterile compounded drug products in 

advance of or without receiving a prescription. In the proposed framework, FDA believes 

that certain sterile compounding facilities should be subject to federal oversight to ensure that 

the compounding of sterile drug products at those facilities can be done without putting 

patients at undue risk, including requiring: 

• Compliance with federal quality standards that are appropriate for the compounding of 

riskier products and exposure of larger numbers of patients 

• Federal registration of the compounding facilities that will be subject to federal quality 

standards, so that FDA knows where they are and what drug products they are making; 

and 

• These higher-risk compounding pharmacies to report to FDA serious adverse reactions to 

their drugs, of which they become aware, so that we can act quickly on potential 

problems that may be associated with compounded drugs. 

And for all pharmacy compounding, FDA believes certain basic protections should be in 

place. These include: 

• Clear authority to examine a pharmacy's records to more quickly locate the cause of an 

outbreak or other violations of the law 

• Requirements for clear label statements that identifY the nature and source of 

compounded products, providing prescribers and consumers with valuable information 

about the products they are using, so that they can make informed judgments about their 

use; and 

• Prohibiting co~pounding of the most complex and highest-risk products-drugs and 

biologics that should only be made for patients by an FDA-registered drug manufacturer 

under an approved new drug application in which the manufacturer has demonstrated that 

the product is safe and effective and that it can be safely made according to the highestquality standards. 

This proposed framework requires legislative action. We look forward to continuing to work 

with Congress to enact an oversight framework to protect the public health before an 

outbreak. 

15. Does FDA need additional authority to oversee compounding pharmacies? U yes, 

please explain why and list the authorities needed. If no, explain why. 
121 


85438.061

Page 9 - The Honorable John D. Dingell 

There is a need for appropriate and effective oversight of this evolving industry. It is clear 

that the industry and the health care system have evolved and outgrown the law, and FDA's 

ability to take action against compounding that exceeds the bounds of traditional pharmacy 

compounding and poses risks to patients has been hampered by ambiguities in the law, which 

have led to legal challenges to FDA's authority to inspect pharmacies and take appropriate 

enforceIp.ent actions. The Administration is committed to working with Congress to address 

the threat to public health from limitations in authorities for effective oversight of certain 

compounding practices. To that end, FDA has developed a framework that could serve as 

the basis for the development of a risk-based program to protect the public health. 

Recognizing the history of compounding practice, FDA supports the long-standing policy 

that all compounding should be performed in a licensed pharmacy by a licensed pharmacist 

(or a licensed physician) and that there must be a medical need for the compounded drug. 

Further, there should be a distinction between two categories of compounding: traditional 

and non-traditional. Traditional compounding would include the combining, mixing, or 

altering of ingredients to create a customized medication for an individual patient with an 

individualized medical need for the compounded product, in response to a valid patientspecific prescription or order from a licensed practitioner documenting such medical need. 

Traditional compounding, while posing some risk, plays an important role in the health care 

system, and should remain the subject of state regulation of the practice of pharmacy. 

Non-traditional compounding would include certain types of compounding for which there is 

a medical need, but that pose higher risks. FDA proposes working with Congress to define 

non-traditional compounding based on factors that make the product higher risk such as any 

sterile compounding in advance of or without receiving a prescription, where the drug is 

distributed out of the state in which it was produced. Non-traditional compounding would be 

subject to federal standards adequate to ensure that the compounding could be performed 

without putting patients at undue risk, and FDA would inspect against and enforce these 

federal standards. Such a definition focuses on the highest-risk activities and offers a 

uniform degree of protection across all 50 states, for highest-risk compounding activities. 

Non-traditional compounding should, because of the higher risk presented, be subject to a 

greater degree of oversight. Sterile products produced in advance of or without a 

prescription and shipped interstate should be subject to the highest level of controls, 

established by FDA and appropriate to the activity, similar to CGMP standards applicable to 

conventional drug manufacturers. 

In addition, with noted exceptions, certain products are not appropriate for compounding 

under any circumstances. These products would include: I) what are essentially copies of 

FDA-approved drugs, absent a shortage justification based on the drug appearing on FDA's 

shortage list; and 2) complex dosage forms, such as extended release products; transdermal 

patches; liposomal products; most biologics; and other products as designated by FDA. 

Producing complex dosage forms would require an approved application and compliance 

with CGMP standards, along with other requirements applicable to drug products made by 

conventional manufacturers. 
122 


85438.062

Page 10 - The Honorable John D. DingeU 

There are other authorities that would be important to support this new regulatory paradigm. 

For example, FDA should have clear ability to collect and test samples of compounded drugs 

and to examine and collect records in a compounding pharmacy, just as the Agency does 

when inspecting other manufacturers. FDA should also have clear ability to examine 

records, such as records of prescriptions received, products shipped, volume of operations, 

and operational records such as batch records, product quality test results, and stability 

testing results. Such inspections are necessary to determine when a pharmacy exceeds the 

bounds of traditional compounding to respond to public health threats and to enforce federal 

standards. 

An accurate inventory of pharmacies engaged in non-traditional compounding would 

facilitate appropriate oversight and coordination with state regulators. In addition, FDA 

looks forward to working with Congress on potential improvements that may include label 

statements and adverse event reporting that have proven useful in other areas. 

Thank you, again, for contacting us concerning this important matter. If you have further 

questions please let us know. 

Enclosure 

Sincerely, 

Michele Milal 

Acting Associate Commissioner 

for Legislation 
123 


85438.063

Timeline of FDA InklJlcttons with. NEtt and Ameridose 

Background 

Please find below an overview of certain facts related to the Food and Drug Administration's (FDA, 

or tbe Agency) past interactions with the New England Compounding Company (NECC) and 

Ameridose. No Information related to FDA's ongoing investigations or these companies is 

Included. The information in these tlmelines is representative of our current understanding. 

based upon the records and Information we have been able to review to date. We continue to 

collect information related to our history with these companies. We would be pleased to provide 

additional Information If and when it becomes available. 

Tim.line for NECC 

• According to the records FDA bas reviewed to date, our earliest record of contact with 

NECC was an April 2002 inspection to follow-up on two adverse event reports submitted to 

FDA associated with betamethasone compounded by NECC. On April 16, 2002, FDA Issued 

a Form FDA 483, which included three observations voicing concerns regarding NECC's 

process for producing sterile drugs. 

• From October 24, 2002, until February 10, 2003, FDA and the Massachusetts Board of 

Pharmacy (MABP) conducted a jointly coordinated Inspection to follow-up on adverse 

event reports received in July and August 2002 ofbactenal meningitis associated with 

methylprednisolone compounded by NECC. 

• In a meeting held on February 5, 2003, toward the end of the 2002·2003 inspection, FDA 

and MABP jointly decided that MABP would take the lead in enforcement and inspections 

ofNBCC's compounding operations since NECC was functioning as a compounding 

pharmacy. On February 10, 2003, FDA Issued a 483 closing out its inspection. The firm 

responded on February 26, 2003, and supplemented its response an May 20, 2003, 

describing the corrective steps the firm was taking in response to the 483. 

• FDA inspected NECC from September 23,2004, until January 19, 2005, in a focused 

inspection related to a competitor's complaint that NECC had compounded a drug using 

bulk active ingredients that were not a component of an FDA-approved drug. FDA 

subsequently approved another firm's appllcation to market the drug. and FDA issued a 

Warning Letter in December 2006 to NECC stating the firm was compounding copies of 

commerCially available products; compounding standardized anesthetic drug products, 

which was outside the scope of traditional pharmacy compounding; and repackaging 

Avastin. The Warning letter charged that the copies of the FDA approved drugs and the 

anesthetic cream were misbranded and that the repackaged Avastin was an unapproved 

new drug. The Warning Letter did not pertain to sterility failures at NBCC. During the 

2004-05 inspection, FDA reviewed NECC's procedures in light of the February 10, 2003483 

and concluded that corrective actions had been implemented. 

• In January 2006, NECC entered Into a consent agreement with the Commonwealth of 

Massachusetts related to inadequacies in the firm's sterile and non-sterile compounding 
124 


85438.064

practices. The consent agreement required NECC to hire a consultant and take corrective 

actions. which would be verified by tbe consultant. In June 2006. MABP notified NECC that 

the firm had fulfilled the terms of the consent decree. 

• In January 2007, NECC responded to the 2006 Warning Letter. 

• FDA responded to NECC's Warning Letter response In October 2008. 

Tlmellne for AmerJdose 

• Ameridose first registered with FDA in September 2006, but never listed any drugs. 

• FDA and MABP conducted a jointly coordinated Inspection of Amendose in December 2007 

to follow-up on a complaint related to the company making IV solutions without receipt of 

patient-spedfic prescriptions and to gather facts since the firm had recently registered 

with FDA. FDA advised the firm to validate and verify its aseptic processes since it was 

making sterile products. 

• FDA performed a second Inspection of Ameridose seven months later Ouly-Aug. 2008). 

This was an inspection to review the firm's "good manufacturIng practices." The agency 

issued the firm a 483 on August 6, 2008, dting several observations, such as not confirming 

the sterility of products before distribution. Ameridose responded in August 2008 stating 

that it would take corrective actions to address FDA's observations in the 483. 

• During the 2008 inspection, FDA also collected samples of Fentanyl (a strong pain 

medication), which was found to be super-potent, leading to a Class I recall in September 

2008. 

• (n September 200B and November 2008, FDA returned to the firm to review shipping 

records specific to the super-potent Fentanyl, to review the firm's corrective and 

preventative actions since the September 2008 recall, and to follow-up on questions 

discussed during the prior inspection. 

• In June 2010, FDA received a commercial complaint related to the compounded product 

nicardipine and conducted at the same time as MABP a limited inspection in response. In 

January 2011, FDA was Informed that the complainant and Ameridose reached amicable 

resolution. Massachusetts oflidally dismissed the complaint In June 2011. 
125 


85438.065

JOHN D. DING ELL 

151'H DlSTiUCT, MICHIGAN 

WASHINGTON OFFICE: 

!lOOM 2329 

COMMImEON ENERGY AND COMMERCE 

CO..cHAIR 

HOUSe GREAT lAKES 

TASK FORCE 

MEMSER 

MIGRATORY BIRD CONSERVATION COMMISSiON 

~ngrtSs of tht tlnittd ~mtrs 

"!I\OUSt of 'Rtprtstntatiuts 

'ltJl)ashington, J!)1.t 20515-11}5 

RAV8UAN HOUSE OfFfCf 8UllDlNG 

WASHiNGTON. DC 2061s-.22t5 

(202) 22Hl111 

DISTRlCT OFFICES: 

19855 WEST OUTEll DRIVE 

SU.ITE 103-E 

OEAABORN. MI 48124 

(313) 278-2936 

23 EAST .RONT STREET 

SUITE 1113 

MONROE. MI48161 

(7341243--1849 

The Honorable Margaret Hamburg 

Commissioner 

U.S. Food and Drug Administration 

5600 Fishers Lane 

Rockville, MD 20857 

Dear Commissioner Hamburg: 

October 16,2012 at)1 WEST MICHIGAN AVENUe 

SUrrE.305 

VPSl1.ANT1, M! 48197 

(7341481-1100 

I write to you in regards to the most recent update on the U.s. Food and Drug 

Administration's (FDA) investigation of the contaminated products at the New England 

Compounding Center (NECC). 

On Monday, FDA noted that additional products produced at NECC may have sterility 

issues. This includes a patient with possible meningitis that was injected with triamcinolone 

acetonide and two transplant patients who received cardioplegic solution during surgery who 

now have Aspergillus jumigatus infection. FDA has also cautioned against the use of any 

ophthalmic drugs that are injectable or used in conjunction with eye surgery. While I understand 

that FDA's investigation is still ongoing, I am greatly concemed that additional contaminated 

NECC products may still remain on the market and could cause harm to thousands more 

Americans. 

Given this latest update, I respectfully request the answers to the following questions: 

1. Please provide a complete list of the products produced at NECC, including the 

proprietary name, the nonproprietary name or common name, the quantity of 

doses produced, dosage forms, strengths, route of administration, and proposed 

indication for each of the products. How many of these products were prepared 

based on a prescription for a specific patient? 

2. How many facilities, in how many states, have received NECC products? 

3. Please provide an estimate of how many patients are at risk from infection or 

meningitis from the use ofNECC products. How does FDA intend to notify 

patients that may have been treated with NECC products? 

THIS MAIUNG WAS PREPARED. PUBltSHED, AND MA!l.ED AT TAXPAYER EXPENSE 

,THIS $TAl1O"IlRYP~INTED DN PAPER MAOE OF RECYCLED FlBIi" 

....... 
126 


85438.066

4. Do any ofNECC's products remain on the market? If so, which products remain 

on the market? Of those that remain on the market, how many doses remain on 

the market? 

AB the meningitis outbreak continues to grow and now newer fungal infections are 

reported, I remain concemed that FDA and state regulators have not collected full and accurate 

information about the activities ofNECC. It is clear that NECC willfully disregarded state 

regulations and did not properly address the concerns laid out by FDA in previous warning 

letters. This company's actions have shown that new authority and further oversight over 

compounding pharmacies is needed. I will be sending you further inquiry as to what authority, 

personnel, and funding is needed by FDA to better oversee compounding pharmacies. 

Given the serious nature of this outbreak, I respectfully request that a response be sent to 

my office no later than October 30, 2012. Should you or your staffhave any questions, please do 

not hesitate to contact me or have a member of your staff contact Kimberlee Trzeciak in my 

office at (202) 225-4071. 

With every good wish, 
127 


85438.067

The Honorable John D. Dingell 

House of Representatives 

Washington, D.C. 20515-2215 

Dear Mr. Dingell: 

APR 262013 

Thank you for your letter of October 16, 2012, concerning the fungal meningitis outbreak 

associated 1i'>ith methylprednisolone acetate, a steroid injectable product distributed by the New 

England Compounding Center (NECC). 

We have restated your questions below in bold, followed by our responses. 

1. Please provide a complete list of the products produced at NECC, including the 

proprietary name, the nonproprietary name or common name, the quantity of doses 

produced, dosage forms, strengths, route of administration, and proposed indication for 

each of the products. How many of these products were prepared based on a 

prescription for a specific patient? 

The list of products subject to NECC's voluntary recall is available on NECC's website. 

www.neccrx.com. Due to the ongoing criminal investigation, we are not able to provide 

additional infomlation at this time. 

2. How many facilities, in how many states, have received NECC products? 

A list that includes this information as received by FDA is available on FDA's website at 

htlpj':wwwjda.gov'downloadv'Dl'lIgs/DrugSa!etyiFungaIMeningitis(UCM325-166.pdj 

3. Please provide an estimate of how many patients are at risk from infection or 

meningitis from the use of NECC products. How does FDA intend to notify patients 

that may have been treated with NECC products? 

As part of the public health investigation, FDA has learned that approximately 14,000 

patients have been exposed to methylprednisolone acetate from the suspect lots of 

product. CDC and the departments of health in the affected states have been working 

together to notify those patients who were treated with the suspect product after May 

21,2012. A notice from the Centers for Disease Control and Prevention (CDC), 

"Notice to Clinicians: Continued Vigilance Urged for Fungal Infections among Patients 

Who Received Contaminated Steroid Injections," is available on CDC's website at 

http://emergency.cdc.govlHAN/han00342.asp. Through active notification by clinics Mth 

assistance from states and CDC in early October, nearly all of these exposed persons were 

contacted at least once and informed of their risk for fungal infection as a result of receiving 
128 


85438.068

Page 2 - The Honorable John D. Dingell 

injections with contaminated medication. FDA has also advised health care professionals 

to follow up with patients who have been treated with NECC injectable products 

shipped after May 21, 2012. 

4. Do any of NECC's products remain on the market? If so, which products remain on 

the market? Of those that remain on the market, how many doses remain on the 

market? 

As of October 6, 2012, all products compounded and distributed by NECC were recalled by 

the firm. NECC posted notice ofthe recall on their website, www.neccrx.com. As of January 

30,2013, as part of the public health investigation into the outbreak, FDA had completed 

Ll55 audit checks with customers who received NECC products. FDA found no unexpired 

product remaining for use at any of the customers and all customers had knowledge of the 

recall either through NECC, CDC, state health departments, the media, or other sources. 

Thank you, again, for contacting us concerning this important matter. If you have further 

questions, please let us know. 

Sincerely, 

Michele Mital 

Acting Associate Commissioner 

for Legislation 
129 


85438.069

Statement 

Of 

The National Association of Chain Drug Stores 

For 

U.S. House of Representatives 

Subcommittee on Health 

Hearing on: 

"Examining Drug Compounding" 

May 23, 2013 

10:00 a.m. 

2322 Rayburn House Office Building 

National Association of Chain Drug Stores (NACDS) 

1776 Wilson Blvd Suite 200 

Arlington, V A 22209 

703-549-3001 

\-vww.nacds.org 
130 


85438.070

U.S. House Energy and Commerce Health Subcommittee 

May 23. 2013 

Page 2 of4 

The National Association of Chain Drug Stores (NACDS) thanks Chairman Pitts, Ranking 

Member Pallone, and Members ofthe Subcommittee on Health for consideration of our 

statement for the hearing "Examining Drug Compounding." We look forward to our continued 

work with you on ensuring that Americans receive safe and effective compounded prescription 

drugs. 

NACDS commends the Committee for your efforts to better understand issues related to the 

compounding of prescription drugs. NACDS represents traditional drug stores, supermarkets, 

and mass merchants with pharmacies - from regional chains with four stores to national 

companies. Chains operate more than 41,000 pharmacies and employ more than 3.8 million 

employees, including 132,000 pharmacists. They fill over 2.7 billion prescriptions annually, 

which is more than 72 percent of annual prescriptions in the United States. The total economic 

impact of all retail stores with pharmacies transcends their over $1 trillion in annual sales. 

Every $1 spent in these stores creates a ripple effect of $1.81 in other industries, for a total 

economic impact of$I.81 trillion, equal to 12 percent ofGDP. For more information about 

NACDS, visit www.NACDS.org. 

Introduction 

NACDS supports the mission and work of FDA in ensuring that Americans receive only safe 

and effective prescription drugs. Safeguarding the health and welfare of our patients remains 

our highest priority. Pharmacist compounding services are the only source of critical 

medications for millions of patients who each have their own unique health care needs. For 

these patients, there are no commercially-manufactured preparations available. Accordingly, 

we agree with FDA that prescription drug compounding services are a valuable and important 

part of our nation's healthcare system. 
131 


85438.071

U.S. House Energy and Commerce Health Subcommittee 

May 23, 2013 

Page 3 of4 

Background on Compounding 

Prescription drug compounding has been a traditional function of the practice of pharmacy ever 

since the beginning of the profession. Compounding is an important component of patient care 

because many patients need prescription products that are not made commercially by drug 

manufacturers. Compounding by pharmacists is the only way to meet these patients' needs. 

Traditional prescription drug compounding is based on individual prescription orders for 

individual patients for products that are not commercially available. Because of these patient 

needs compounding continues to be an integral function of pharmacy practice. 

Pharmacists are trained to prepare compounded medications and are tested on this competency. 

State boards of pharmacy license pharmacies after ensuring, among other things, that they have 

the proper tools and equipment to compound prescription drug medications. 

The definition of what constitutes "compounding" is consistent from state to state. Generally, it 

involves the mixing of two or more drug substances together to deliver to the patient a product 

that is not commercially available. Most retail pharmacies engage in the compounding of skin 

creams, lotions, ointments, liquids, or suppositories. For example, chain pharmacists helped to 

meet the need for liquid Tamiflu during the 2009 HINI flu outbreak through their ability to 

compound the liquid product from Tamiflu capsules - and at the request of FDA. In other 

cases, a pharmacist may be called on to compound a liquid form of a medication for a patient 

battling cancer, when that patient is not able to swallow the pill form of the medication. 

Some chain pharmacies may have a local or regional central compounding facility that they use 

to compound frequently-ordered products that are not commercially available, which are then 

distributed to individual retail stores in the chain. These compounded products are made in 

anticipation of prescriptions for these products based on the prescribing patterns of physicians. 
132 


85438.072

U.S. House Energy and Commerce Health Subcommittee 

May 23, 2013 

Page 4 of4 

Preserving State Board Authority 

NACDS believes that state boards of pharmacy should retain sole jurisdiction over traditional 

prescription drug compounding. This is a proper role for state pharmacy boards. Prescription 

drug compounding has been an integral function of the practice of pharmacy since the early 

days of the profession. State boards of pharmacy have the experience and expertise to continue 

to regulate this integral function. We urge the Committee to continue to maintain this policy. 

We believe that state boards of pharmacy should continue to regulate functions that are the 

practice of pharmacy, while FDA should regulate the manufacturing of prescription drugs. 

FDA should not be granted authority over traditional pharmacy functions. FDA would not have 

the resources, ability or expertise to regulate pharmacies and the practice of pharmacy. 

Moreover, concurrent state and federal jurisdiction over pharmacies would cause unnecessary 

confusion for FDA, state boards of pharmacy, and pharmacies. All would be unsure as to where 

federal authority ends and state authority begins. 

State and Federal Collaboration 

We support efforts among FDA and the state boards of pharmacy to work together to 

investigate any questionable practices so that prescription drug compounding is regulated in the 

best interests of patients. To prevent future tragedies, there must be a close collaboration 

among FDA and the boards of pharmacy. Despite best efforts, there still may be entities that 

seek to circumvent patient safety measures as well as federal and state regulation. We support 

state and federal joint efforts to root out rogue entities that seek to use a state pharmacy license 

as a shield from federal oversight. 

Conclusion 

NACDS thanks the Committee for consideration of our comments. We look forward to 

working with policy makers and stakeholders on these important issues. 
133 


85438.073

CAP S' 

d~JI~il1!J $#lutiOM~ 

May 21, 2013 

Central Admixture Pharmacy Services. Inc. 

2530 Meridian Parkway. SuHe 200 

Research Triangle Park, NC 27713 

Telephone:(919) 806-4448 

Fax: (484) 821-9420 

The Honorable Joe Pitts 

House Committee on Energy and Commerce 

Heal1h Subcommittee 

420 Cannon House Office Building 

Washington, DC 20515 

Re: "Examining Drug Compounding" 

Dear Chairman Pitts, 

On behalf of Central Admixture Pharmacy Services, Inc. (CAPS), I am writing to provide comments and 

insights that are relevant to current discussions regarding pharmacy compounding. CAPS appreciates the 

opportunity to work with the House Committee on Energy and Commerce to ensure that compounding 

pharmacies produce safe compounded sterile preparations. 

Compounding pharmacy has a storied history in the provision of pharmaceutical care, from a time when 

essentially all prescriptions were compounded (estimated at 80% in the 1920's) to a period in which only 

a very small percentage are compounded (estimated at <1 % in the 1970's). Today, the definition of 

pharmacy compounding is unclear and encompasses a host of practices ranging from adding simple 

flavorings to commercially available oral pharmaceuticals to the preparation of sterile injectables from 

approved pharmaceutical ingredient (API) powders. 

In recent years pharmaceutical compounding has grown rapidly in the acute care setting. The hospital 

segment of the health care industry is facing extraordinary pressure to provide better patient care, 

improved patient outcomes and cost reductions. Hospital pharmacies have adapted their practices to be 

hannonized with these priorities end in doing so have appropriately focused on the provision of 

pharmaceutical care models to optimize outcomes. One such strategy is to contract sterile injectable 

compounding to outsourcing partoers thus allowing scarce pharmacy resources to be focused on direct 

patient care activities. Over the last several years severe drug shortages have forced physicians and 

hospitals to seek compounded alternatives to otherwise commercially available products. The pharmacy 

compounding community continues to adapt their practices to meet the growing demands and needs of 

the market. 

CAPS was founded in 1991 with seven original pharmacies to serve as an intravenous (IV) outsourcing 

partoer to hospital and health system pharmacies. We work closely with our clients to identifY 

compounded sterile preparations (CSPs) and services that add value to their pharmaceutical care model. 

Our activities and the CSPs we provide are an extension of the activities routinely performed onsite at the 

host hospital pharmacy. Centralization of these compounding activities allows CAPS to focus on 

associated quality systems, compounding processes, facilities, enviromnental controls, qualification 

practices and validation activities not commonly associated with traditional pharmacy practice. 
134 


85438.074

The Honorable Joe Pitts 

House Committee on Energy and Commerce 

Health Subcommittee 

May 21, 2013 

• Today we have grown into a network of 25 pharmacies serving more than 1500 hospital 

pharmacies with clients and patients in all 50 states. 

• In 1994 CAPS voluntarily registered all of our pharmacies with the FDA. 

• Today our pharmacies that perform compounding activities beyond fulfilling patient specific 

prescriptions remain registered with FDA. 

• Our business model focuses on both acute care and out patient care market segments. 

• Our core business is comprised of patient specific parenteral nutrition formulations for those 

patients unable to meet nutritional needs orally. 

• Other business components consist of non-patient specific compounded CSPs prepared in 

anticipation of a prescription in limited quantities based on historic ordering patterns. These 

formulations range from complex multi-ingredient admixtures such as cardioplegic solutions to 

single component admixtures such as standard antibiotic doses. 

Recent discussions within the pharmacy community have sought to better define pharmacy compounding, 

clarifY regulatory authority over the variations in practice, identifY the appropriate rules and regulations to 

govern the practice, and establish minimum standards for all stakeholders who wish to engage in the 

practice. CAPS is of the belief that there are several key concepts that should be adopted when 

considering governance of compounding manufacturing. 

• Language in the Federal Food, Drug, and Cosmetic Act should be revised to remove loopholes 

that permits pharmacies to "manufacture" under the guise of "Anticipatory Compounding": 

o Define traditional pharmacy compounding as a compounding activity resulting in a CSP 

specifically made for an identified individual patient and dispensed only upon receipt of 

said patient specific prescription. Defining the practice in this way does not prohibit 

compounding in anticipation of a prescription in limited quantities and based on historic 

ordering patterns. It does however impose a requirement that all CSPs be dispensed only 

upon receipt ofthe patient specific prescription. 

• State Boards of Pharmacy should be responsible for governing the practice of traditional 

pharmacy compounding. 

• Define compounding manufacturing as a compounding activity resulting in CSPs that are sold 

and distributed to identifiable clients without patient specificity. Such activities should be 

construed as compounding manufacturing regardless of distribution in interstate or intrastate 

commerce. Third party distribution or reselling should not be permissible. 

• The FDA should be responsible for governing the practice of compounding manufacturing and 

has such authority within the existing framework. 

• The FDA should be required to clearly define the applicable standards on which compounding 

manufacturers will be evaluated for compliance. 

• An exemption for hospital pharmacies should be considered that will allow them to compound 

and distribute CSPs within their institution without patient specificity, at the time of distribution, 

to meet the needs of the patients within their institution. 

• Such hospital pharmacy exemption should not extend beyond the care of patients within that 

specific institution. If a hospital or health system wishes to distribute non-patient specific CSPs 

to other entities under common ownership or otherwise, they should be required to register and 

meet the requirements of a compounding manufacturer. 
135 


85438.075

The Honorable Joe Pitts 

House Committee on Energy and Commerce 

Health Subcommittee 

May 21, 2013 

• To this end, compounding manufacturers should be pennitted to hold a phannacy pennit in 

addition to registration with FDA. Such hybrid practices should meet all requirements for a 

compounding manufacturer and the standards set for phannacies within the states in which they 

are registered. The FDA and Boards of Phannacy have demonstrated the ability to conduct joint 

inspections and focus on the component of business within their respective enforcement areas. 

• Any CSP designated for office use that is compounded and distributed in advance of a patient 

specific prescription should be considered compounding manufacturing and the phannacy 

engaged in such a practice held to that standard. 

• A provision for intracompany transfer of compounded sterile preparations produced by a 

compounding manufacturer and designed to be used as components of finished doses (e.g. 

parenteral nutrition electrolytes) should be a pennissible act. This is especially true during this 

period of significant drug shortages. 

CAPS appreciates the opportunity to comment on this issue that is a vitally important to public health 

today. We look forward to supporting your efforts and are most willing to be available and serve as a 

resource to you during this process. 

Sincerely, 

Thomas Wilverding 

President 

Central Admixture Phannacy Services, Inc 
136 


85438.076

rRED UPTON, MICHIGAN 

CHAIRMAN 

HENRY A. WAXMAN, CALIFORNIA 

RANKING MEMBER 

ONE HUNDRED THIRTEENTH CONGRESS 

Dr. Janet Woodcock 

Director 

<!ongrC1l1l of tuc 1ltlniteb ~tatt1l 

j!,OU5C of l'cprcscntaW.1l':5 

COMMITTEE ON ENERGY AND COMMERCE 

2125 R/WBURN HOUSE OFHCE BUILDIN(, 

WASHINGTON, DC 20515-6115 Mdj(Hity 

Mn()l\ty 'i",) "'*'Je"; 

June 13,2013 

Center for Drug Evaluation and Research 

U.S. Food and Drug Administration 

10903 New Hampshire Avenue 

Silver Spring, MD 20993 

Dear Dr. Woodcock: 

Thank you for appearing before the Subcommittee 011 Health on Thursday. May 23. 2013. to 

testii)' at the hearing entitled "Examining Drug Compoullding.~ 

Pursuant to the Rules orlhe 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 fonnat of your responses to these questions should be as f(1I1ows: (I) the name of the 

Member whose question you arc addressing, (2) the complete text of the question you are addressing in 

bold, and (3) your answer to that question in plain text. 

Also attached are Member requests made during the hearing. The format of your responses to 

these requests should follow the same fornlut as your responses to the additional questions for the record, 

To facilitate the printing of the hearing record, please respond to these questions and requests by 

the close of business 011 Thursday, June 27, 2013, Your responses should be mailed to Sydnc Harwick, 

Legislative Clerk, Committee on Energy and Commerce, 2125 Rayburn Ilousc Office Building, 

Washington, D.C. 20515 and e-mailed in Word format to Sydne.Harwick(ulmail.huuse.gov. 

Thank you again for your time and effort preparing and delivering testimony before the 

Subcommittee. 

S~:~ . _ ~ .. _~~ ~ "JJ:r: I). TtMo 

cc: TIle Honorable Frank Pallone, Jr., Ranking Member, Subcommittee on Health 

Attachments 
137 


85438.077

DEPARTMENT OF HEALTH &. HeMAN SERVICES 

The Honorable Joseph R. Pitts 

Chairman 

Subcommittee on Health 

Committee on Energy and Commerce 

House of Representativcs 

Washington, D.C. 20515-6115 

Dear Mr. Chairman: 

Food and Drug Administration 

Silver Spring, MD 20993 

MAR 072014 

Thank you for providing the Food and Drug Administration (FDA or the Agency) with the 

opportunity to testify at the May 23, 2013, hearing before the Subcommittee on Health, 

Committee on Energy and Commerce, entitled "Examining Drug Compounding." This letter 

is a response for the record to questions posed by certain Members of the Committee, which we 

received on June 13,2013. We are also responding to questions posed at the hearing by you 

and other Members. 

If you have further questions, please let us know. 

Si~~~J~ly. / ",f ._S-<---<:-~~( Sally Iewafcf 

Deputy Commissioner 

Policy, Planning, and Legislation 
138 


85438.078

Page 2 - The Honorable Joseph R. Pitts 

We have restated each Member's questions below in bold, followed by our responses. 

The Honorable Joseph R. Pitts 

1. In your testimony, you reference nine separate incidents where compounded 

products caused deaths and serious injuries. Please explain the actions that the 

FDA took foDowing each incident. What happened to the pharmacies where these 

contaminated products originated? 

Below are descriptions of the actions that FDA took in response to the nine incidents 

described in Dr. Woodcock's testimony. We note that most, but not all, of these 

adverse events were associated with product contamination: 

• "In 1997, two patients were hospitalized with serious infections after administration 

of contaminated riboflal'jn injection prepared by a Colorado pharmacy. '.' 

In 1997, Riboflavin Injection made by College Pharmacy in Colorado Springs, 

Colorado, was administered intravenously to two patients who subsequently developed 

septicemia. FDA laboratory analysis of an intact vial of this drug product confmned 

the presence of Pseudomonas aeruginosa gram-negative bacteria and a bacterial 

endotoxin level greater than 1,250 Endotoxin Units per milligram of riboflavin. 

In April 1999, FDA issued a Warning Letter to College Pharmacy that addressed these 

findings and included adulteration [§§ 501 (a)(1) and 501(b)] and misbranding [§§ 

502(a) and 5020)] violations of the Federal Food, Drug, and Cosmetic Act (FD&C 

Act). 

FDA's Office of Criminal Investigations (OCI) later initiated a criminal investigation 

into the owner and operator of College Pharmacy, Thomas Bader, and referred its case 

to the Justice Department. In January 2010, Bader was convicted on 31 counts related 

to the distribution of human growth hormone (HGH) that was smuggJed into the 

United States from China, and tbe distribution of an anabolic steroid to customers with 

no legitimate relationship to physicians. He was found gnilty on two counts of 

conspiracy, including conspiracy to facilitate the sale of misbranded and unapproved 

Chinese-made HGH, and conspiracy to manufacture, distribute, dispense, and possess 

with intent to distribute anabolic steroids; 27 counts of distribution ofHGH; one count 

of facilitating the sale of smuggled HGH; and one count of possessing with intent to 

distribute HGH. In June 2010, Bader was sentenced to serve 40 months in Federal 

prison and was ordered to forfeit $4.8 million and the pharmacy building. College 

Pharmacy remains in operation, but under different ownership. 
139 


85438.079

Page 3 - The Honorable Joseph R. Pitts 

• "In 2001, 13 patients in California were hospitalized and 22 received medical care 

following il'!;ecrions.from contaminated vials of a steroid solution. Three patients died 

as a result. " 

In May 2001, FDA was notified that Doc's Pharmacy of Walnut Creek, California, 

shipped vials ofbetamethasone injection that were contaminated with Serratia 

marcescens to six health care facilities in California. Thirty-eight patients received the 

contaminated steroid; 13 patients were hospitalized, 22 received follow-up medical 

care, and three patients died. FDA needed to obtain an Administrative Warrant to 

complete an inspection of Doc's Pharmacy and documented several deficiencies in the 

firm's processes for the production of sterile drugs. In July 2001, an administrative 

law judge ordered the pharmacy to halt all compounding operations. The owner 

violated the Order, and the California Board of Pharmacy suspended his Pharmacist 

License in November 200 I. The owner surrendered his license in March 2002, and 

Doc's Pharmacy was sold. 

• "In 2002,flve patients in North Carolina s14feredfromfungal meningitis resulting 

from contaminated methylprednisolone acetate made by a South Carolina pharmacy. 

One person died ., 

This incident refers to five cases of fungal infections, including one death, resulting 

from methylprednisolone acetate contaminated by Urgent Care Pharmacy in 

Spartanburg, South Carolina. FDA and the South Carolina Board of Pharmacy (SC 

BOP) conducted a joint inspection, and the SC BOP imposed a Cease and Desist 

Order. FDA recommended an immediate recall of all injectable drug products made 

by this facility, and although the firm initially refused to comply with this 

recommendation, it ultimately agreed to voluntarily recall all methylprednisolone 

acetate sterile injectables. FDA issued an alert warning the public about Urgent Care's 

injectable drugs, and the pharmacy subsequently closed permanently. 

• "in 2005, contaminated cardioplegia solution. made by aflrm located in Maryland, 

resulted injive cases of severe systemic inflammatory irifeclions; three of these 

patients died. " 

Five patients were hospitalized with severe systemic inflammatory infections and three 

of these patients died after receiving cardioplegia solution during open heart surgery 

that was made by Central Admixture Pharmacy Services (CAPS) in Lanham, 

Maryland. After FDA laboratories identified gram-negative rods in two lots of the 

firm's cardioplegia solution, CAPS recalled all injectable drug products made at this 

facility, and FDA posted a Medical Products Safety Alert on its website notifYing 

health care professionals about the product recall. FDA also inspected the CAPS' 

facility in Lanham, Maryland, and several other CAPS facilities, and then met with 

CAPS' management to discuss the Agency's concerns regarding CAPS' compounding 

activities. In 2006, FDA issued a Warning Letter to CAPS' parent company, B. Braun, 

which addressed this incident and other deficiencies in the firm's processes for the 
140 


85438.080

Page 4 - The Honorable Joseph R. Pitts 

production of sterile drugs that FDA identified during inspections of several CAPS' 

sites. CAPS subsequently hired a consultant to improve its processes . 

• "In 2007, three people diedfi'om multiple organ/ailure after a Texas compounder 

sold superpotent colchicine that was as much as 640 percent the labeled strength. .. 

In 2007, Apothc!Cure, Inc. in Dallas, Texas, prepared and dispensed 72 vials of 

injectable colchicine, some of which were 640 percent superpotent, resulting in the 

deaths of three patients. FDA obtained an Administrative Warrant to complete an 

inspection of the fum and identified several deficiencies in the firm's processes for the 

production of sterile drugs. FDA's OCI investigated the incident and referred the case 

to the Department of Justice for criminal prosecution. In April 2012, Apothc!Cure and 

its owner pleaded guilty to two misdemeanor counts of introducing a misbranded drug 

into interstate commerce. In addition, the Texas Attorney General's Office brought a 

civil case against Apothc!Cure, asking for a permanent injunction and civil penalties 

related to the firm's compounding activities, which include misbranded, adulterated, 

and unapproved drug products; misbranded foods; and false advertising of drugs and 

dietary supplements under Texas law. Before trial in November 2012, ApothCCure's 

owner signed a Consent Decree with the state of Texas, enjoining his firm from 

distributing adulterated or misbranded drugs. 

In April 2013, FDA inspected and issued an FDA Form 483 1 list of inspectional 

observations to ApothCCure and its related company, NuVision, reflecting deficiencies 

in the finns' processes for the production of sterile drugs. On April 15, 2013, 

Apothc!Cure recalled all lots of sterile products compounded, repackaged, and 

distributed due to sterility assurance concerns, and on April 17, 2013, ApotheCure 

indicated in its response to the FDA-483 that it decided not to continue doing business, 

effective May 31, 2013. NuVision recalled all compounded lyophilized products due 

to sterility assurance concerns on April 15,2013, and FDA issued a press release on 

May 18, 2013, alerting health care pro"iders about lack of sterility assurance of all 

sterile drug products from this facility . 

• "In 2010, FDA investigated a cluster o/Streptococcus endophthalmitis bacterial eye 

infections inpatients who received infections 0/ Avastin repackaged by a pharmacy in 

Tennessee . . , 

FDA attempted an inspection of Health and Wellness Compounding Pharmacy in 

Nashville, Tennessee, after learning of a cluster of Streptococcus endophthalmitis 

bacterial eye infections in patients who received injections of Avastin repackaged by 

this pharmacy. FDA needed to obtain an Administrative Warrant after the pharmacy's 

owner refused to allow FDA to inspect. Based on fmdings from the inspection, FDA 

determined that the firm was, at that time, operating as a pharmacy, and therefore, 

referred the incident to the Tennessee Board of Pharmacy. 

I An FDA Form 483 is issued when investigators observe any significant objectionable conditions. II does not constitute a 

final Agency detennination ofwhe!her any condition is in violation of the FD&C Act or any of our rei ""anI regulations, 

but the observations often scrve as evidence of a violation ofthe FD&C Act and its implementing regulations. 
141 


85438.081

Page 5 - The Honorable Joseph R. Pitts 

• "In 2011, there were 19 cases o/Serratia marcescens bacterial irifections, including 

nine deaths, associated with contaminated total parenteral nutrition products . .. 

In 2011, Advanced Specialty Pharmacy dba Meds IV (Meds IV), located in Bessemer, 

Alabama, prepared and dispensed total parenteral nutrition (TPN) drug products 

contaminated with Serratia marcescens, which resulted in 19 infections, including nine 

deaths. After learning of this incident, FDA, the state, and the Centers for Disease 

Control and Prevention (CDC) inspected, and the firm recalled, all intravenous drug 

products that it produced in 2011. FDA issued a Warning Letter to Meds IV, including 

adulteration [§ 501 (a)(2)(A)] and misbranding [§§ 502(a) and 5020)] violations of the 

FD&C Act. Meds IV subsequently surrendered its pharmacy license to the Alabama 

Board of Pharmacy. 

• "In 2012, 43 patients developed/ungal eye inftctionsfrom contaminated sterile 

ophthalmic drug products. At least 29 of these patients s!iffered vision loss ... 

FDA and the Florida Department of Health conducted a joint inspection of Franck's 

Lab in Ocala, Florida, after receiving reports of fungal endophthalmitis in patients who 

were administered ophthalmic injections of Brilliant Blue G and triamcinolone made 

by this fum. Franck's Lab subsequently ceased sterile compounding operations and 

after FDA' s environmental sampling of the firm's clean room revealed the presence of 

microorganisms and fungal growth, the fum announced a recall of all sterile human 

and veterinary prescriptions distributed from November 21, 2011, to May 21, 2012. 

FDA issued MedWatch statements warning health care providers of the infections and 

alerting them to the recalls. FDA issued a Warning Letter to the firm. including 

adulteration [§§ 501(a)(2)(A) and 501(c)] and misbranding [§ 502(a)] violations of the 

FD&C Act. The owner of Franck's Lab sold the facility to Wells Pharmacy Network, 

but he still owns an infusion pharmacy, Trinity Healthcare. in Ocala, Florida. 

• "Recently, in 2013, FDA investigated reports a/five cases of eye irifections in 

patients who received Avastin repackoged by a pharmacy in Georgia. The Avastin 

was contaminated with bacteria. " 

After learning of eye infections in patients who received A vastin repackaged by 

Clinical Specialties Compounding Pharmacy in Augusta, Georgia, FDA inspected and 

issued to the firm an FDA-483 list of inspectional observations reflecting deficiencies 

in the firm's processes for the production of sterile drugs. Clinical Specialties 

voluntarily recalled all lots of sterile drug products repackaged and distributed by the 

firm between October 19,2012, and March 19,2013, due to lack of sterility assurance. 

In its response to the FDA-483, Clinical Specialties indicated that it was permanently 

discontinuing the production of sterile drug products at its facility. effective March 8, 

2013, and that it did not intend to prepare or sell sterile products in the future. 

2. More likely the FDA has gone through extensive self-evaluation to fully 

comprehend every single regulation related to compounding. You are likely more 
142 


85438.082

Page 6 - The Honorable Joseph R. Pitts 

knowledgeable now about the current compounding regulations than you were six 

months ago. It would be invaluable for this subcommittee to know exactly what 

the FDA can do before we determine what you cannot do. So, please explain the 

tools you currently have. 

Under the law as it existed as of the date of the hearing, section S03A of the FD&C 

Act provided FDA some authority to regulate what drugs can be compounded. For 

example, under section S03A, FDA could, through rulemaking, establish a list of drugs 

that may not be compounded because the drugs or their ingredients have been 

withdrawn or removed from the market because the drugs or their ingredients "have 

been found to be unsafe or not effective." FDA could also establish a list of drugs that 

present "demonstrable difficulties for compounding that reasonably demonstrate an 

adverse effect on the safety or effectiveness" of the drug and, therefore, may not be 

compounded. However, due to legal challenges regarding constitutionality of the law, 

under the law as it existed as of the date of the hearing, section S03A did not apply 

nationwide. Furthermore, FDA's authority to regulate compounded drugs is more 

limited than our authority over conventional manufacturers. For example, under 

section 510 of the FD&C Act, if certain criteria are met, compounding pharmacies are 

not required to register with FDA or report adverse events. As a result, FDA has 

limited knowledge of pharmacy compounders and limited ability to oversee their 

activities. 

In 2002, the U.S. Supreme Court had held the advertising, solicitation, and promotion 

provisions in section S03A unconstitutional, and, at the time of the hearing, there were 

conflicting court decisions on whether the unconstitutional provisions could be severed 

from the remainder of the statute. 

On November 27,2013, the President signed Public Law 113-54, the Drug Quality and 

Security Act (DQSA), which removes certain provisions from section 503A of the 

FD&C Act that were found to be unconstitutional by the U.S. Supreme Court in 2002. 

The new law removes uncertainty regarding the validity of section 503A, which will 

be applicable to compounders nationwide. The DQSA also creates a new section 5036 

in the FD&C Act. Under section 503B, a compounder can become an "outsourcing 

facility." Outsourcing facilities Vl-ill register under section 503B; however, the 

legislation did not change the exemptions from registration for pharmacies under 

section 510 of the FD&C Act. 

3. Between 2002 and 2012, NECC was the subject of a least 52 adverse event 

reports. Numerous offenses were documented throughout investigations at NECC 

undertaken by both the FDA and state regulators. Why did the Agency not shut 

down NECC after these inspections? Did NECC chaUenge the FDA's authority to 

inspect'! 

FDA is uuable to comment specifically on NECC due to the ongoing investigations. 
143 


85438.083

Page 7 - The Honorable Joseph R. Pitts 

The Honorable Marsha Blackburn 

1. I am concerned about the growing incidence of skin cancer in the United States 

and the significant delay in proving the latest sunscreen technology to help 

address this risk from exposure to the sun's harmful rays. According to the Skin 

Cancer Foundation, Americans are diagnosed with more than 3.5 million cases of 

skin cancer each year and 1 American dies every hour from Melanoma, the most 

deadly form of skin cancer. 

I understand that the FDA created the Time and Extent Application (TEA) 

process in 2002 to streamline applications for over-the-counter applications, such 

as sunscreens, however FDA has not made a fmal decision on any product 

through the TEA process. In fact, eight new sunscreen ingredients have been 

waiting for FDA review, some for over 10 years. The TEA process is clearly 

broken and needs to be reformed. 

a) In light ofthe public health epidemic regarding skin cancer, please 

explain significant delay in making a fmal decision on any of the 8 

pending sunscreen applications. 

b) Please also explain why taking fmal action on the 8 pending sunscreen 

applications has been on the FDA's Unified Agenda as a priority since 

2008, however no action has been taken. 

In the 19705, sunscreens were used primarily on a seasonal basis to prevent sunburn 

among consumers with the fairest skin coloration, and sunscreen active ingredients 

were not thought to penetrate beyond the skin surface. Today, sunscreens are used 

routinely by a large percentage of the population and in large amounts covering a 

much greater body surface area, with the result that the extent and duration of 

consumers' exposure to sunscreen ingredients is orders of magnitude greater than it 

was in the 19708. There is also increasing evidence that some sunscreen ingredients 

can be absorbed through the skin, leading to systemic exposures to these agents that 

were not previously anticipated or evaluated. These shifts in sunscreen usage, together 

with advances in scientific understanding and safety evaluation methods, have given 

rise to new questions about what information is needed and available to support 

general recognition of safety and effectiveness for both currently marketed sunscreens 

and ingredients seeking inclusion in the monograph via the Time and Extent 

Applications (TEA) process. 

Within FDA, there has been an active examination of these important scientific 

questions, one result of which was significant new rulemaking in 2011 that focused 

primarily on updated efficacy testing and related labeling issues. We also are engaged 

in an ongoing internal evaluation of current sunscreen safety issues and evidentiary 

standards, which is directly informing our evaluation of all sunscreen active 

ingredients, including the eight TEA ingredients. 
144 


85438.084

Page 8 - The Honorable Joseph R. Pitts 

The TEAs ask FDA to include eight new sunscreen active ingredients in the Over-theCounter (OTC) Drug Review, also known as the OTC drug monograph system. In 

brief, TEA reviews are regulatory proceedings that are inherently complex and must 

compete for resources and priority with other OTe monograph reviews and 

proceedings, among other FDA activities. As noted above, FDA is currently 

evaluating important scientific questions relating to OTe sunscreen ingredients. 

Because of the public health importance ofOTe sunscreens, FDA is actively working 

to complete our review of these TEA ingredients and expects to take action on them in 

the near future. We are committed to finding ways to facilitate the marketing of 

additional OTe sunscreen products, but we must ensure their safety, effectiveness, and 

overall risk-benefit profile. 

To elaborate, the pace of FDA's ongoing review of the sunscreen TEAs is best 

understood in the context of the overall OTe drug monograph system, of which the 

TEA process is a part. In brief, the FD&e Act requires FDA review and approval of a 

new drug application (NDA) for all new drugs before they may be marketed in the 

United States. To avoid "new drug" status, as defined in the FD&C Act, a drug must 

be generally recognized as safe and effective (the GRASIE standard), and must also 

have been marketed to a material extent and for a material time under the conditions 

described in its labeling (the material time-and-extent standard). The OTC Drug 

Review is a multi-step notice-and-comment rulemaking procedure that was established 

in 1972 to review the safety and effectiveness of OTe drugs then or previously 

marketed in the United States (which were presumed to satisfy the material time-andextent standard) and provide a regulatory mechanism (the OTe monograph system) 

allowing OTC drug products that were found to be GRASIE to be marketed under an 

applicable OTC monograph rather than product-specific NDAs. OTe drug 

monographs are FDA regulations that describe conditions, including specified active 

ingredients, for marketing various categories of OTe drugs (such as sunscreens). 

The TEA process (21 CFR § 330.14) was established in 2002 to provide a pathway to 

OTe monograph status for additional active ingredients and other conditions not 

marketed in the United States for OTe use prior to the establishment of the OTe Drug 

Review, by enabling sponsors to establish that a condition satisfies the material timeand-extent requirement based on historic marketing data other than the date of U.S. 

market entry. This is done by submitting a TEA containing the required marketing 

data, which is reviewed by FDA to determine whether or not the condition is eligible 

to be considered for inclusion in an OTe monograph (eligibility detennination). 

TEA ingredients and other conditions must satisfy the same GRASIE standard and 

evidentiary requirements that apply to other active ingredients and conditions under 

the general OTe monograph process. And, consistent with the general monograph 

process, ingredients found eligible for review under TEA applications are subject to 

multi-step notice-and-comment rulemaking procedures before they may be included in 

a tinal OTe drug monograph. FDA has issued eligibility determinations for all TEAs 

submitted to date, and all eight sunscreen TEAs were found eligible to continue to the 

next stage of the TEA process, the GRASIE determination, which is now ongoing. 
145 


85438.085

Page 9 - The Honorable Joseph R. Pitts 

c) WiUyou commit to work with Congress and stakeholders to enact 

reforms to the TEA process that will ensure that sunscreen products 

receive a transparent review and a predictable timeline for 

consideration? 

FDA is willing to work with Congress and stakeholders on this issue. 

2. As you may know, on January 1, 2013, CMS made a technical change to its billing 

methodology for compounding pharmacies providing drugs used in implanted 

pain pumps. This change requires pharmacies to sell these compounded 

medications to physicians who then re-sell then to the patient and bill Medicare. 

Prior to January lst, pharmacies were not required to sell drugs to the physician 

and instead could bill Medicare directly. To further complicate the matter, the 

Tennessee Board of Pharmacy does not allow pharmacies to sell these 

compounded medications to physicians for resale to patients. This practice is also 

illegal in Mississippi, and other state Boards of Pharmacy are assessing the 

impact ofCMS' change on pharmacy practice. I am concerned that this technical 

change has jeopardized access to necessary pain medications for some of 

Medicare's most vulnerable beneficiaries. Even more, this change - prohibiting 

pharmacies from billing Medicare directly - eliminates an important 

accreditation requirement designed to protect patient safety. Pharmacies billing 

Medicare directly for these drugs must comply with Medicare supplier standards 

and federal regulations, such as U.S. Pharmacopeia 797. These standards provide 

an additional layer of quality promotion and patient safety for pharmacies 

compounding and dispensing sterile products for use in implanted pain pumps. 

Saying all of this, do you find it concerning the CMS - in the wake of the tragic 

out break, in spite of state pharmacy law, and in spite of stakeholder oppositionis encouraging pharmacies to seD drugs directly to physicians as opposed to 

billing Medicare directly and complying with quality accreditation standards? 

For at least 20 years to 2013, pharmacies had billed Medicare directly for these 

patient specific compounded medications, and the National Home Infused 

Association supports legislation sponsored by Congressman Harper (HR 232) 

which would restore access to these therapies for beneficiaries. Saying all of this, 

do you find it concerning that CMS - in the wake of a tragic outbreak, in spite of 

state pharmacy law, and in spite of stakeholder opposition - is encouraging 

pharmacies to seD drugs directly to physicians as opposed to billing Medicare 

directly and complying with quality accreditation standards? 

As these questions relate to eMS' reimbursement policies, we recommend contacting 

CMS with these questions. 

3. As you mayor may not know, the State of Tennessee recently passed legislation 

that allows pharmacies to compound products for use in a practitioner's office for 
146 


85438.086

Page 10 - The Honorable Joseph R. Pitts 

administration to that prescribing practitioner's patients - a practice known as 

"office use" compounding. It is my understanding that 43 other states also anow 

for office use compounding. 

a) What is the Agency's position regarding traditional compounding taking 

place in an office setting? 

b) Should this be regulated by the FD A or State Board of Pharmacies? 

Please explain. 

In light of recent outbreaks associated with sterile drugs produced by pharmacies, the 

Agency has taken a critical look at our surveillance and enforcement approach to 

pharmacies that produce compounded drugs. Over the past year, FDA has conducted 

numerous for-cause and proactive inspections of firms that produce compounded 

drugs. The Agency continues to evaluate the information obtained during the 

inspections. 

Since the hearing, the President signed the DQSA. Under the DQSA, hospitals and 

health care professionals can purchase compounded drugs ",ithout a prescription from 

a compounder that is registered as an outsourcing facility under section 503B. Section 

503A requires, among other things, that, to qualifY for the exemptions under section 

503A, there be a prescription for an identified individual patient. The Agency intends 

to exercise its authority, as appropriate to protect the public health. against 

compounded drugs that do not qualifY for the exemptions in section 503A or section 

503B, and drugs that are adulterated or misbranded or otherwise violate Federal laws. 

The Honorable Renee Enmen 

1. Are compounders making the same products that drug-manufacturers make? 

know it may be in a different form, but is it the same product? 

Compounders sometimes take FDA-approved products and dilute them to achieve a 

different strength, or they may make a liquid or suppository. They may also mak:e 

drugs from bulk active ingredients. This may be done, for example, to make a product 

without an allergen, such as peanut oil, that some patients cannot tolerate. Many 

compounders do make products that appear to be only slightly different from those 

made by traditional drug manufacturers. For example, they might make an 8 mL vial 

of a product when the FDA-approved product is available in 10 mL vials. Although 

these products may appear to be similar to FDA-approved drug products, it is 

important to remember that compounded drugs do not undergo the same premarket 

review as FDA-approved drugs and thus lack an FDA finding of safety and efficacy, as 

well as manufacturing quality. The active ingredients may come from sources that 

have not been reviewed by FDA, and the methods by which they are made have not 

been reviewed to detenlllle whether they are adequate to produce a safe, pure, and 

potent product. 
147 


85438.087

Page 11 - The Honorable Joseph R. Pitts 

2. Currently, do compounders have the same regulations and requirements that 

drug manufacturers have? Why or why not? 

Under current Federal law, when certain conditions are met, compounding pharmacies 

are not subject to the same requirements as drug manufacturers. For example, 

compounding pharmacies, but not drug manufacturers, are exempt from certain 

requirements under the FD&C Act, as described below. 

These disparate requirements derive from the FD&C Act. Section 503A, added to the 

FD&C Act in 1997 as part of the Food and Drug Administration Modernization Act of 

1997 (FDAMA), describes the conditions under which certain compounded human 

drug products are entitled to exemptions from three sections of the FD&C Act 

requiring: 

• Compliance with CGMP requirements (section 501(a)(2)(B»; 

• Labeling with adequate directions for use (section 502(f)(1 »; and 

• FDA approval prior to marketing (section 505). 

Drugs produced by compounders must meet the conditions of section 503A to qualify 

for the exemptions specified in that section. All other applicable provisions of the 

FD&C Act remain in effect for compounded drugs, even if the conditions in section 

503A are met. For example, a compounded drug cannot be contaminated or made 

under insanitary conditions (see sections 501(a)(I) and 501 (a)(2)(A». And if a 

compounded drug does not qualifY for the exemptions under section 503A of the 

FD&C Act, the compounded drug would be subject to all of the requirements of the 

Act that are applicable to drugs made by conventional manufacturers, including the 

new drug approval, CGMP, and adequate directions for use. 

However, at the time of the hearing, the validity of section S03A of the FD&C Act was 

uncertain. Section 503A FD&C Act had been challenged in court, and there were 

conflicting court rulings regarding the validity of this section. Since the hearing, 

President Obama signed the DQSA, which removes certain provisions from the FD&C 

Act that the U.S. Supreme Court held unconstitutional. By removing the 

unconstitutional provisions, the new law removes uncertainty regarding the validity of 

section S03A, which will be applicable to compounders nationwide. 

3. What are the changes to compounding you propose making in order to prevent 

the meningitis outbreak last year and ensure compounded products are safe? 

On April 16, 2013, FDA Commissioner Margaret Hamburg outlined the Agency's 

proposed framework for improving oversight of compounding in testimony before this 

Committee. Please see attached document (April 16, 2013, Statement of Dr. Margaret 

Hambw'g Before the Subcommittee on Health, Committee on Energy and Commerce). 

4. Is there a limit to how much product a compounder can make? 
148 


85438.088

Page 12 - The Honorable Joseph R. Pitts 

Under current Federal law, there is no limit to how much product a compounding 

pharmacy can make. Section 503A of the FD&C Act places a limit on the volume of 

drugs that may be shipped interstate. Under that provision, a pharmacy may only 

distribute interstate compounded drugs in quantities that do not exceed 5 percent of the 

total prescription orders dispensed or distributed by such pharmacy or physician, 

unless the state in which the pharmacy is located has entered into a memorandum of 

understanding (MOU) with the Agency that addresses the distribution of inordinate 

amounts of compounded drugs interstate and provides for an appropriate investigation 

by the state of complaints related to compounded products. FDA published a draft 

MOU in 1999, and received over 6,000 comments. However, due to the conflicting 

court rulings that had resulted in uncertainty regarding the validity of section S03A, the 

template MOU was never finalized, and FDA has not been implementing the 

provision. 

However. on November 27, 2013, the President signed DQSA, which removes the 

provisions from section S03A of the FD&C Act that were found to be unconstitutional 

by the U.S. Supreme Court in 2002. By removing the unconstitutional provisions, the 

new law removes uncertainty regarding the validity of section 503A, which will be 

applicable to compOlmders nationwide. FDA has initiated actions to implement the 

new law. 

5. You testified before the Senate HELP committee regarding their legislation on 

May 9, 2013. Under this legislation, would compounded drugs manufactured by 

the new entity (compounding manufacturer) be subject to the same requirements 

as current manufacturers under the Federal, Food, Drug, and Cosmetic Act? 

a. If yes, can you describe those requirements? 

b. If no, how are those standards - different - and why are they different? 

As of the time of the hearing, the legislation proposed by the Senate HELP committee, 

S. 959, would have placed several requirements on "compounding manufacturers" that 

are similar to those imposed on traditional manufacturers. For example, as drafted, S. 

959 would have: 

• Required compounding manufacturers to meet FDA-established product 

quality standards, to register with FDA, and to list the products they produce. 

• Required compounding manufacturers to report serious adverse events, of 

which they become aware, to FDA and to label their products with important 

information for physicians and consumers. 

• Provided FDA with the clear authority to access records of compounding 

manufacturers during an in.~pection to more effectively oversee their 

compounding activities. 
149 


85438.089

Page 13 - The Honorable Joseph R. Pitts 

• Put in place several restrictions-applicable to both traditional compounders 

and compounding manufacturers-on the types of bulk drug substances that 

can be used to compound a drug and would prohibit the compounding of 

copies of marketed FDA-approved drugs, unless they appear on FDA's drug 

shortage list. 

• Provided that compounding of other categories of drug products, such as 

complex dosage forms and biologics, would be prohibited because they are 

particularly difficult to make. 

• Required compounding manufacturers to pay establishment fees and, when 

appropriate, re-inspection fees, to help defray the costs of this increased 

oversight. 

Not all requirements imposed on manufacturers under the FD&C Act, however, would 

have applied to compounding manufacturers under S. 959. For example, compounding 

manufacturers would not be required to submit an NDA for compounded products. 

6. How do drug manufactures today assure the raw materials (or Active 

Pharmaceutical Ingredient "API") used to create a drug are safe? What is the 

certification process? 

For finished dosage forms (FDFs) required to have an application approved before 

marketing, FDA reviews API production processes before granting marketing approval 

of an FDF using the API. In addition, the FD&C Act requires producers of APIs (and 

excipients, or inactive ingredients) and producers of the FDF to follow COMP 

requirements appropriate to the manufacture of the drug (API, excipients, or FDF). 

FDA regulates the manufacture of APls under internationally harmonized COMP 

guidance for industry, known as ICH Q7. The COMP requirements, iffollowed, 

ensure that APIs have the safety, identity, quality, and purity as labeled. FDA inspects 

API production facilities referenced in approved applications to verify conformance 

with ICH Q7 and COMPs. 

FDA requires conventional manufacturers of the FDFs (e.g., tablets, capsules, 

injections) to exercise additional controls over the quality of APIs before use in FDF 

manufacturing. Specifically, the COMP regulations for finished pharmaceuticals 

(primarily at 21 CFR parts 210-211) require FDF manufacturers to examine the 

integrity of each API shipment and to test samples verifying each ingredient's identity 

before it can be released for FDF production. FDA regulations, however, do not 

require FDF manufacturers of non-application drug products (e.g., OTC drugs covered 

by a published monograph at 21 CFR 330·358) to know who actually manufactures the 

API, and some APIs are purchased from wholesalers and brokers. For those products 

requiring an approved new drug application, FDA also re"iews FDF production 

processes before marketing approval, and inspects FDF production facilities on a riskbased schedule to verify conformance with 21 CFR 211 and COMPs. 
150 


85438.090

Page 14 - The Honorable Joseph R. Pitts 

Drug compounders, which are not subject to FDA application approval and CGMP 

requirements, may not routinely evaluate the quality of the APls they use in 

compounding. Compounders that do not check each shipment or that do not verify 

their API supply chain are at significant risk of producing a finished product that does 

110t contain the API they intended, does not function as intended, or contains harmful 

impurities. 

7. How do compounders access the API they use? Is their API FDA-approved? 

The Agency does not generally approve bulk APIs used in the manufacture or 

compounding of drug products, nor are the APIs used in compounding required to be 

FDA-approved. 

8. Don't drug manufacturers pay much more than a compounding manufacturer 

would under the User Fee structures? Why aren't compounders paying more if 

they are making the same product? Or more importantly, if I'm an FDA -

licensed drug maker, why don't I just become a compounder? It would be 

cheaper and a lot less paper work? 

As you note, the user fees paid by drug manufacturers are significantly higher than 

those a compounding manufacturer would pay under the legislation under 

consideration as of the time of the hearing or that an outsourcing facility will pay 

under the DQSA. Pharmacies compounding drugs under the conditions in section 

S03A will continue to pay no user fees at all. However, there are a number of reasons 

that drug manufacturers would not opt to become a compounder. For example, only 

state-licensed pharmacists or physicians may qualify for the exemptions in section 

S03A of the FD&C Act, and the pharmacists or physicians must compound the drugs 

consistent with the conditions of section S03A. Under section S03A, a pharmacy may 

not compound regularly or in inordinate amounts any drug products that are essentially 

copies of a commercially available drug product. Further, under section S03A a 

pharmacy may only distribute interstate compounded drugs in quantities that do not 

exceed S percent of the total prescription orders dispensed or distributed by such 

pharmacy or physician, unless the state in which the pharmacy is located has entered 

into an MOU with the Agency that addresses the distribution of inordinate amounts of 

compounded drugs inte.rstate and provides for an appropriate investigation by the state 

of complaints related to compounded products. 

9. There is some talk that compounding manufacturers could be utilized to help end 

drug shortages. Currently, how are drug shortages determined? Are there 

different levels of drug shortages? 

The CDER Drug Shortage Staff (DSS) utilizes information from manufacturers, other 

FDA offices, external entities, and market-share data to determine or verify that a 

shortage exists. 
151 


85438.091

Page 15 - The Honorable Joseph R. Pitts 

Consistent with FDASIA, DSS defines a drug shortage. with respect to a drug, to mean 

a period oftime when the demand or projected demand for the drug within the United 

States exceeds the supply of the drug. 

The severity of the drug shortage situation for a given product may vary depending on 

certain circumstances, such as the length of the potential shortage/supply interruption 

and the number of other available manufacturers for that product, and whether they are 

also experiencing a shortage situation or whether they are able to increase production 

to meet the anticipated market shortfall. 

10. Is the FDA drug shortage list the only list used? 

The American Society of Health-System Pharmacists2 (ASHP) lists drug shortages and 

additional information on its website. Although both ASHP and FDA maintain drug 

shortage lists, the information received and displayed regarding drug shortages varies 

between the two lists. For example, FDA's drug shortage list focuses mainly on drugs 

that are considered medically necessary,> while ASHP's list includes more drugs; 

some that are not medically necessary because there are suitable alternatives available. 

11. How does a drug get off the drug shortage list? Who determines that? 

For the drug products listed on the drug shortage list, DSS is in regular communication 

with relevant manufacturers regarding their current and projected drug supply and 

utilizes this information to help determine the supply status and potential path forward, 

if applicable. DSS may also consider information from other FDA offices, external 

entities, and market-share data. Once a drug product is available from the involved 

manufacturers and supply is sufficient to meet the demand or projected demand, DSS 

removes the drug product listing from the current drug shortage list and places it in the 

resolved drug shortage list, which is also on the FDA drug shortage website.4 

12. For products on the drug shortage list, many of which are sterile injectable drugs, 

should a compounder be held to the same level of standards and requirements as 

the current manufacturers? 

Patients expect and deserve high-quality drugs. Patients should have access to 

compounded medicines that are safe, pure, and potent. 

FDA's testimony referenced a series of adverse events associated with compounded 

drugs, primarily sterile injectables, over the last 10 years, and FDA is concerned about 

1. http://'''~''f.ashp.orW 

3 A medically necessary drug product is a product that is used to treat or prevent a serious disease or medical 

condition for which there is no other alternative drug in adequate supply that is judged by medical staff to be 

an adequate substitute. Off-label uses are taken into account when making medical-necessity determinations. 

FDA's drug shortage list includes all shortages that the Agency has been informed of and verified, which are 

mostly shortages of medically neccSSlll)' drugs. 

4 htlp:llwwwfda.govIDrugsIDtllgSajelyIDrugShor/Clgesillcm3 J 47 39. 111m 
152 


85438.092

Page 16 - The Honorable Joseph R. Pitts 

compounders that produce such high-risk sterile drugs without the necessary controls 

to ensure quality. 

Under FDA's proposed framework (please see attached document, April 16, 2013, 

Statement of Dr. Margaret Hamburg Before the Subcommittee on Health, Committee 

on Energy and Commerce), as presented at the time of the hearing, phannacies that 

produce sterile drugs in advance of or without a prescription and ship those drugs 

interstate would be subject to Federal oversight and uniform quality standards. These 

types of sterile compounding operations pose higher risks and, therefore, should be 

su~ject to uniform quality standards, established by FDA and appropriate to the 

activity, including when they are making drugs on the drug shortage list. 

Since the hearing, President Obama signed the DQSA, which created a new section 

503B in the FD&C Act. Under section 503B, a compounder can become an 

outsourcing facility and can compound drugs in shortage, so long as certain criteria are 

met, including compliance with CGMPs. 

U. How many drug shortages would be relieved if compounders mass-manufactured 

product? 

The Agency cannot estimate the number of drug shortages that may be relieved if 

compounders produced drug products in shortage. However, we note that under the 

recently enacted DQSA, which added section 503B to the FD&C Act, outsourcing 

facilities may now begin to playa role in compounding drug products that are in 

shortage. (please see Question #6, from Ms. Ellmers, for additional information on 

requirements for APIs in FDA-approved products.) 

With respect to drug shortages generally, it is often difficult to forecast the drug 

product(s) that may become in short supply or the duration of such shortages, since 

immediate and projected supply from drug manufacturers can change rapidly and 

unexpectedly due to many factors. FDA works hard, within its legal authority, to 

address and prevent drug shortages, which can occur for many reasons, including 

manufacturing and quality problems, delays, and discontinuations. 

14. How would the safety ofthese compounded drugs be assured? What are the 

testing processes? 

Under the. legislation being considered at the time of the hearing, compounded drugs 

produced by compounding manufacturers would have been subject to Federal 

standards to help ensure that the compounding could be performed without putting 

patients at undue risk, and FDA would inspect against and enforce these Federal 

standards. 

To further ensure the safety of compounded drugs, FDA proposed that it have clear 

ability to collect and test samples of compounded drugs and to examine and collect 

records in a compounding phannacy, just as the Agency does when inspecting other 
153 


85438.093

Page 17 - The Honorable Joseph R. Pitts 

manufacturers. FDA also proposed that it have clear authority to examine records, 

such as records of prescriptions received, products shipped, volume of operations, and 

operational records such as batch records, product qUality test results, and stability 

testing results. Such inspections are necessary to determine when a pharmacy exceeds 

the bounds of traditional compounding, to respond to public health threats, and to 

enforce Federal standards. 

15. Will there be any differences between the standards and regulations of the 

compounding manufacturer and today's manufacturers? 

As of the time of the hearing, the legislation proposed by the Senate HELP committee, 

S. 959, would have created a new category of drug producers called "compounding 

manufacturers." The recently enacted DQSA created a new category of drug 

producers called "outsourcing facilities." Among other significant differences, unlike 

conventional manufacturers, outsourcing facilities are not required to obtain an 

approved new drug application (NDA) for their compounded drugs, provided they 

meet certain conditions_ 

16. Can YOIl provide more clarity/detail on the differences between the two levels of 

standards between today's manufacturers and the compounding manufacturer? 

FDA cannot provide more clarity or detail on what the differences in the standards 

applicable to conventional manufacturers and compounding manufacturers would have 

been under the legislation being considered at the time of the hearing, because that 

legislation was ncver enacted or implemented. 

Under the recently enacted DQSA, outsourcing facilities are subject to section 

50 1 (a)(2)(B) of the FD&C Act, which requires compliance with COMPs. FDA is 

looking at its COMP regulations to determine what requirements are appropriate for 

outsourcing facilities. 

17. If the full requirements and standards are different for products on the drug 

shortage list produced by a compounding manufacturer than those oftoday's 

manufacturers, how will this ensure the greatest level of confidence and safety in 

the products? 

As stated above, under the legislation being considered at the time of the hearing, 

compounded drugs produced by compounding manufacturers would be subject to 

Federal standards to help ensure that the compounding could be performed without 

putting patients at undue risk, and FDA would inspect against and enforce these 

Federal standards. 

18. Do doctors and hospitals tell a patient that the drugs they are receiving are 

manufactured by a compounding manufacturer? 
154 


85438.094

Page 18 - The Honorable Joseph R. Pius 

Health care providers and patients often are unaware that they administered or received 

a compounded product, which limits their ability to associate any adverse events with a 

compounded product. This hinders FDA's ability to effectively identify adverse 

events for compounded products in our adverse event reporting system. At the time of 

the hearing, FDA was working with Congress on its proposed framework, which 

included potential improvements such as label statements for compounded products to 

help patients and providers make more infonned choices. 

19. Should hospitals and providers require a patient to sign a release for any liability 

if the hospital or provider gives a compounded drug that is not manufactured 

under the same safety requirement of the drug manufacturers? 

FDA does not have a position on this. 

Additional Information for the record 

During the hearing, Members asked FDA to provide additional information for the record. 

Descriptions of the requested infonnation, based on the relevant excerpts from the hearing 

transcript regarding these requests. are provided below. We have restated each Member's 

questions below in bold, followed by our responses. 

The Honorable Joseph R. Pitts 

1. You testified during the hearing that several companies have challenged your 

authority while the FDA was conducting inspections. Please provide a list to the 

committee of companies that the FDA inspected those that challenged your 

authority, and the grounds by which the companies challenged your authority. 

The response below was e-rnailed to Representative Pitts' Health Policy Analyst on 

July 16,2013, in response to this question. 

In a sample of 226 pharmacy inspections5 between 2002 and 2012 that FDA has 

conducted on practices related to phannacy compounding of human and veterinary 

drugs, pharmacies have refused at least one FDA request in more than 25 percent of 

inspections. For example, 4 percent offirms refused FDA entry into their facility, and 

ofthose firms that did grant entry, 12 percent refused FDA access to records (e.g., 

shipping records, dispensing records, product formulas, andlor standard operating 

5 These 226 inspections represent the number of inspections recorded under the human and veterinary 

pharmacy compounding Program Assignment Codes (PAC Code) between 2002 and September 25, 2012, that 

FDA has conducted of pharmacies based on practices related to pharmacy compounding of human and 

veterinary drugs. Not all compounding pharmacy inspections were recorded under this PAC Code, in part, 

because some firms engage in multiple types of activities. In addition. some inspectionaI activities may have 

been coded as "investigations" rather than "inspections" and, therefore, not captured in this figure. Thus, we 

know that FDA conducted additional inspections of firms that could be classified as compounding pharmacies 

that are not accurately reflected in OUf databases. 
155 


85438.095

Page 19 • The Honorable Joseph R. Pitts 

procedures). Other refusals include the ability to observe drug production processes, 

collect samples, access portions of the facility, or take photographs. 

FDA encountered refusals of at least one FDA request during inspections of the 

following compounding pharmacies between 2002 and September 25, 2012. This may 

not be an exhaustive list: 

2002 

• Lee and Company, Inc. dba Lee Pharmacy, Fort Smith, AR (July 2002) 

• Med-Mart Pacific Pulmonary Services Pharmacy, Bakersfield, CA (November 

2002) 

2003 

• Plum Creek Pharmaceuticals, Inc., Amarillo, TX (February 2003) 

• Med 4 Home Pharmacy, Kansas City, MO (March 2003) 

• Med-Mart Pacific Pulmonary Services Pharmacy, Bakersfield, CA (May 2003) 

• Unique Pharmaceutical, Ltd., Temple, TX (August 2003) 

• Monument Pharmaceutical Co., Inc., Winchester, VA (September 2003) 

2004 

• Keyes Drug, Nevliton, MA (April 2004) 

• Reliant Pharmacy, Southaven, MS (May 2004) 

• Reliant Pharmacy, Southaven, MS (June 2004) 

• Essential Pharmacy Compounding, Omaha, NE (August 2004) 

• Pet Script, Inc., Paris, TX (August 2004) 

• University Rx Specialties, Inc. (September 2004) 

• ApotheCure, Inc., Dallas, TX (September 2004) 

• Kubat Custom Healthcare, Omaha, NE (September 2004) 

2005 

• PharMEDium Services, Sugar Land, TX (March 2005) 

• Pulmo-Dose Inc., Murray, KY (August 2005) 

• Civic Center Pharmacy, Scottsdale, AZ (October 2005) 

• Pharmacy Creations, Randolph, NJ (October 2005) 

• Wedgewood Village Pharmacy, Swedesboro, NJ (October 2005) 

• Alchemist Shoppe, P.C., Denville, NJ (November 2005) 

• Spoonamore Drug Co., Inc., Louisville, KY (December 2005) 

2006 

• Pharmacy Creations, Randolph, NJ (February 2006) 

• D.R. Pharmacy, Inc., Midland, TX (March 2006) 

• Oakdell Pharmacy, Inc., San Antonio, TX (April 2006) 

• Hopewell Phannacyand Compounding Center, Hopewell, NJ (October 2006) 
156 


85438.096

Page 20 - The Honorable Joseph R. Pitts 

2007 

• Newman Inc. dba Medi-Stat, Mobile, AL (February 2007) 

• ApotheCure, Inc., Dallas, TX (May 2007) 

• Advanced Physician Solutions, Inc., North Hollywood, CA (July 2007) 

• Leiter's Pharmacy, San Jose, CA (September 2007) 

• Calvert-Gamble Pharmacy, Inc. dba Southern Meds Joint Venture, Biloxi, MS 

(October 2007) 

• Delta Pharma, Inc., Ripley, MS (October 2007) 

• Wellness Pharmacy, Birmingham, AL (November 2007) 

• Bellevue Pharmacy Solutions, Inc., Saint Louis, MO (November 2007) 

• Spoonamore Drug Co., Inc., Louisville, KY (December 2007) 

2008 

• PharMEDium Services LLC, Cleveland, MS (January 2008) 

• AnazaoHealth Corporation, Tampa, FL (May 2008) 

• Hopewell Pharmacy and Compounding Center, Hopewell, NJ (June 2008) 

• Specialty Pharmacy of Saint Louis, Saint Louis, MO (July 2008) 

• National Respiratory Services LLC, Louisville, KY (July 2008) 

• Precision Pharmacies, LLC, Bakersfield, CA (August 2008) 

• Advanced Physician Solutions, Inc .. North Hollywood, CA (August 2008) 

• University Pharmacy, Salt Lake City, UT (November 2008) 

2009 

• Medaus, Inc., Birmingham, AL (February 2009) 

• Lee and Company, Inc. dba Lee Pharmacy, Fort Smith, AR (February 2009) 

• Prescription Lab Compounding Pharmacy, Tucson, AZ (February 2009) 

• Franck's Lab, Inc. dba Franck's Compounding Lab, Ocala, FL (May 2009) 

• Franck's Lab, Inc. dba Franck's Compounding Lab, Ocala, FL (June 2009) 

• Central Admixture Pharmacy Services, Inc., Chicago, IL (August 2009) 

• Franck's Lab, Inc. dba Franck's Compounding Lab, Ocala, FL (December 2009) 

2010 

• Preckshot Professional Pharmacy, Peoria Hill, IL (June 2010) 

• Health & Wellness Compounding Phannacy, Nashville, TN (August 2010) 

• Delta Pharma, Inc., Ripley, MS (September 2010) 

• Alwan Pharmacy, Peoria, IL (December 2010) 

2011 

• Infupharma LLC, Hollywood, FL (September 2011) 

2012 (January 2012 through September 25, 2012) 

• Weatherford Compounding Pharmacy LLC, Weatherford, TX (February 2012) 

• Franck's Lab, Inc. dba Franck's Compounding Lab, Ocala, FL (May 2012) 
157 


85438.097

Page 21 - The Honorable Joseph R. Pitts 

In addition, between 2002 and October 2012, FDA sought administrative warrants in 

25 cases, of which nearly half were for compounding pharmacies. 1ms covers all 

product areas, not just firms producing drugs. Below are some specific examples of 

situations in which FDA need~d to obtain warrants to inspect compounding 

pharmacies. Although FDA was ultimately able to obtain warrants to inspect, in many 

of these cases, the firms' refusals hindered FDA's ability to rapidly investigate reports 

of serious patient i~ury, including infections and death. This is not an exhaustive list: 

Lee Pllarmacy (2002) 

FDA initiated an inspection of Lee Pharmacy on July 17, 2002, to investigate a 

complaint from a physician reporting foreign material in a preservative-free sterile 

injectable drug product made by this firm. Lee Pharmacy's owner refused to provide 

records, including distribution information identifYing consignees of this product. 

reportedly based on advice from his attorney. Because of these refusals, FDA's 

inspection ended prematurely on July 18, 2002. FDA attempted another inspection on 

December 2,2002, and again was refused. FDA obtained an Administrative Warrant 

on December 10, 2002, to complete the inspection. 

ApothiCure, Inc. (2007) 

FDA initiated an inspcction of ApotheCure, Inc. on April 26, 2007, to investigate 

reports of three deaths follo'Wing administration of injectable colchicine that was later 

fOlUld to be 640 percent superpotent. When the scope of FDA's inspection went 

beyond the firm's preparation of colchicine, the owner refused to provide records or 

allow further access to the facility, causing the inspection to conclude prematurely on 

May 3,2007. On August 3, 2007, FDA obtained an Administrative Warrant to 

complete its inspection. OCI investigated the incident and referred the case to the 

Department of Justice for criminal prosecution. On April 24, 2012, ApotbeCure and 

its owner pleaded guilty to two misdemeanor counts of introducing a drug that was 

misbranded into interstate commerce. 

Health and Wellness Compounding Pharmacy, LLC (2010) 

FDA attempted an inspection of Health and Wellness Compounding Pharmacy on 

April 28, 2010, after learning of a cluster of Streptococcus endophthalmitis infections 

in patients who received injections of A vastin repackaged by this firm. The owner 

asserted that his firm was not under FDA's jurisdiction and refused to allow FDA to 

inspect. On August 2,2010, FDA obtained an Administrative Warrant to inspect the 

firm. 

I1ljupharma, LLC (2011) 

FDA attempted to inspect Infupharma, Inc. beginning on July 18, 2011, after receiving 

reports of 12 cases of Streptococcus endophthalmitis infections following intravitreal 

injections of repackaged Avastin. After a few days, the owner asserted that his firm 

was not subject to FDA regulations and, although he agreed to suspend repackaging of 

Avastin, he would not agree to cease sterile operations. The owner refused FDA 

access to observe processing of sterile injectable drugs, and, therefore, FDA's 

inspection ended prematurely on July 22, 2011. After receiving sample analysis 
158 


85438.098

Page 22 - The Honorable Joseph R. Pitts 

results confmning microbial contamination and information suggesting that 

lnfupharma intended to resume repackaging of Avastin, FDA obtained an 

Administrative Warrant on September 15,2011, (0 complete the inspection and later 

issued a Warning Letter citing the firm for adulteration, unapproved drug, and 

misbranding violations. 

Notably, despite recent events, and although vlie are often working with the state 

inspectors, our investigators' efforts are being delayed because they are denied full 

access to records at some of the facilities they are inspecting. For example, during 

both of our recent proactive and for-cause pharmacy compounding inspections, several 

pharmacies delayed or refused FDA access to records. FDA encountered refusals of at 

least one FDA request during recent inspections of the following firms and had to seek 

Administrative Warrants in three cases as noted: 

• Wedgewood Pharmacy, Swedesboro, NJ (November 20 12) (obtained warrant) 

• JCB Labs, Wichita, KS (February 2013) 

• Triangle Compounding Pharmacy, Cary, NC (February 2013) 

• University Pharmacy, Salt Lake City, UT (February 2013) 

• Avella, Phoenix, AZ (February 2013) 

• Foundation Care, Earth City, MO (March 2013) 

• Olympia Compounding Pharmacy, Orlando, FL (March 2013) (obtained warrant) 

• MedQuest Pharmacy, North Salt Lake, UT (March 2013) 

• Pine Pharmacy, Williamsville, NY (July 2013) (obtained warrant) 

The Honorable Michael Burgess 

1. There was a discussion regarding the level of difficulty of obtaining an injunction 

from a judge. Please provide a list of how many times you have not prevailed in 

obtaining an injunction? (pg. 35) 

Tn general, the decision whether to pursue an injunction or a seizure is a fact-specific 

determination that is made by FDA on a case-by-case basis. In considering an 

injunction or a seizure, FDA will evaluate factors such as pending and adjudicated 

actions involving the same charges, the seriousness of the offense, the actual or 

potential impact of the offense on the public, whether other possible actions could be 

as effective or more effective, whether a voluntary recall by the firm was refused or 

would be inadequate to protect the public, whether violative practices have not been 

corrected through use of voluntary or other regulatory approaches, andlor whether 

FDA would be able to demonstrate the likelihood of the continuance of the violation in 

the absence ofa court order. Additional information is available in FDA's Regulatory 

Procedures Manual, Chapter 6. Due to the many legal challenges at the time of the 

hearing (questions regarding the validity of section S03A of the FD&C Act), 

identifying and pursuing civil enforcement actions against compounding pharmacies 

has been difficult. 
159 


85438.099

Page 23 - TIle Honorable Joseph R. Pitts 

Between 2002 and September 25,2012, FDA brought one injunction against a 

compounding pharmacy. In 2009, 2Ipolo ponies died after being administered a 

compounded animal drug made by Franck's Lab in Florida. In 2011, the U.S. District 

Court denied FDA's requested injunction, stating that FDA's "statutory authority to 

regulate traditional state-licensed veterinary pharmacr, compounding was 

questionable." FDA appealed that decision to the lIt' Circuit Court of Appeals. In 

October 2012, the parties filed ajoint motion to dismiss the appeal and vaeate the 201) 

U.S. District Court decision because it was moot after Franck's sold its assets and 

stopped engaging in animal drug compounding. On October 18, 2012, the 11th Circuit 

Court of Appeals granted this motion, dismissing the appeal and vacating the lower 

court's decision. 

Although FDA did not bring additional civil injunction cases against compounding 

pharmacies, since 2002, FDA has criminally investigated at least six pharmacies 

regarding their compounding practices, which resulted in successful prosecutions by 

the Department of Justice, including: 

• On April 24, 2012, ApotheCure, a compounding pharmacy, and its owner pleaded 

guilty to two misdemeanor counts of introducing a misbranded drug into interstate 

commerce. The government's charges were based on ApotheCure's February 2007 

shipment of 72 vials of compounded colchicine. FDA testing of the vials revealed 

that some of the vials were superpotent, containing 640 percent of the level of 

colchicine declared on the label. Other vials were determined to be subpotent and 

contained less than 62 percent of the declared levels on the labels. Three patients 

who were administered colchicine from ApotheCure died shortly afterward, and the 

cause of death for all three patients was determined to be colchicine toxicity. 

• In February 2012, the fonner Vice President of National Respiratory Services, LLC 

(NRS), a compounding pharmacy, pleaded guilty to charges of misbranding and 

adulterating drugs and to committing healthcare fraud. The government's charges 

were based on NRS providing compounded medications to patients, but leading both 

Medicare and patients' doctors to believe that NRS was providing FDA-approved, 

commercially manufactured products. The government also alleged that the former 

Vice President ofNRS, aided and abetted by others, misbranded inhalation drugs 

because the labeling misrepresented the strength and potency of their active 

ingredients, or the type of drug actually provided and adulterated inhalation drugs, 

because their strength differed from what it was purported or represented to possess 

and because the drugs were contaminated and non-sterile. 

• In January 2010, the owner and operator of College Pharmacy, a compounding 

pharmacy, was convicted on 31 counts related to the distribution of human growth 

hormone (HGH) that was smuggled into the United States from China, and the 

distribution of an anabolic steroid to customers with no legitimate relationship to 

physicians. He was found guilty on two counts of conspiracy, including conspiracy 

to facilitate the sale of misbranded and unapproved Chinese-made HGH and 

conspiracy to manufacture, distribute, dispense, and possess with intent to distribute 
160 


85438.100

Page 24 - The Honorable Joseph R. Pitts 

anabolic steroids; 27 counts of distribution of HGH; one count of facilitating the sale 

of smuggled HGH; and one count of possessing with intent to distribute HGH. 

• In January 2006, the o\\-ner of City Pharmacy, a compounding pharmacy, pleaded 

guilty to health care fraud and misbranding drugs. The government's charges were 

based on findings that the pharmacy dispensed compounded inhalation solutions to 

Medicare patients in different strengths than the commercially available drugs 

prescribed, while leading Medicare and the patients' physicians to believe that the 

pharmacy was providing the FDA-approved, commercially manufactured products. 

• In August 2004, pharmacists of Tricare Pharmacy Network, a compounding 

pharmacy, were convicted of misbranding of a drug after receipt in interstate 

commerce. This was based on evidence that the pharmacy dispensed drugs bearing 

fictitious patient and doctors' names or that were invoiced to disguise the drug that 

was shipped. In addition, the pharmacy did not receive or require prescriptions for 

drug products dispensed. 

• In July 2002, the o\\ner of The Medicine Shoppe was convicted on three counts of 

manufacturing a Schedule II Controlled Substance without a prescription, two counts 

of misbranding and adulterating drugs, and one count of health care fraud. The 

government's charges were based on evidence that the pharmacy dispensed 

compounded drugs instead of commercially available, FDA-approved drugs to 

numerous patients without their knowledge and without authorization from their 

physicians, as well as laboratory results indicating that samples of drug products 

collected at the firm were ineffective. 

The Honorable John D. Dingell 

1. Please explain the authority the FDA needs to require all compounding 

pharmacies to register with the agency. 

2. Please explain the authority the FDA needs to require all componnding 

pharmacies to report adverse events. 

3. Please explain the authority the FDA needs to require all compounding 

pharmacies to follow good manufacturing practices. 

4. Please explain the authority the FDA needs to reqnire nontraditional 

compounders to be subject to appropriate good manufacturing practices the way 

manufactures are. 

5. What authority does the FDA need to ensure risked-based inspection schedules 

are appropriate for non-traditional compounders? 
161 


85438.101

Page 25 - The Honorable Joseph R. Pitts 

6. Please explain the authority the FDA needs to see all records wben inspecting a 

compounding pharmacy. 

7. Please explain the autbority tbe FDA needs for a fee system for tbe approval of 

pbarmaceuticals and medical devices. 

8. Please explain tbe need for a strong user fee program. 

Please see attached document (April 16. 2013. Statement olDr. Margaret Hamburg 

Before the Subcommittee on Health. Committee on Energy and Commerce), provided 

in response to all of Representative Dingell's questions. 

The Honorable H. Morgan Griffitb 

1. The FDA was prepared to release guidance proposals in August of 2012. Please 

explain wby this guidance does not adequately address pbarmacy compounding. 

The needed clarity, predictability, and transparency for effective regulation ofthis 

industry should be set through clear requirements in statute, particularly given the size 

and public health impact of this industry and affected stakeholders, including the 

hospitals, patients, physicians, and states. At the time of the hearing, conflicting court 

decisions had created uncertainty with regard to the validity of section S03A. The 

DQSA removed the provisions of section S03A that had been held unconstitutional and 

removed uncertainty with regard to the validity of section S03A, which will now be 

applicable to compounders nationVl'ide. 

Under the legislation being considered at the time of the hearing, compounded drugs 

produced by compounding manufacturers would have been subject to Federal 

standards to help ensure that the compounding could be performed without putting 

patients at undue risk, and FDA would inspect against and enforce these Federal 

standards. 
162 


85438.102

"A Continuing investigation into the Fungal Meningitis Outbreak and Whether it Could II... Page 1 of 6 

Home News Ii: Events Testimony 

News & Events 

"A Continuing Investigation into the Fungal Meningitis Outbreak and Whether it Could 

Have Been Prevented" 

Statement of 

Margaret A. Hamburg, M.D. 

Commissioner of Food and Drugs 

Food and Drug Administration 

Department of Health and Human Services 

Before the 

Subcommittee on Oversight and Investigations 

House Committee on Energy and Commerce 

U.S. House of Representatives 

April 16, 2013 

INTRODUCTION 

Mr. Chairman and Members of the Subcommittee, I am Dr. Margaret Hamburg, Commissioner of 

Food and Drugs at the Food and Drug Administration (FDA Of the Agency), which Is part of the 

Department of Health and Human Services (HHS). Thank you for the opportunity to be here today 

to discuss important Issues related to pharmacy compounding. 

We are at a critical point where we must work together to improve the safety of drugs produced by 

compounding pharmacies. As the compounding industry has grown and changed, we have seen 

too many injuries and deaths over many years caused by unsafe practices. I testified in front of 

this Subcommittee on November 14, 2012, soon after the emergence of a tragic fungal meningitis 

outbreak associated with compounded methylprednisolone acetate (MPA), a steroid Injectable 

product distributed by the New England Compounding Center (NECq. To date, that outbreak has 

resulted in 51 deaths and over 730 people sickened in 20 States. Sadly, NECC was not an isolated 

incident. Indeed, over the past 20 years we have seen multiple situations where compounded 

products have caused deaths and serious Injuries. For example, in 2001, 13 patients in California 

were hospitalized and 22 received medical care following Injections from contaminated vials of a 

sterOid solution. Three patients died as a result. In 2005, contaminated cardioplegia solution 

resulted In five cases of severe system inflammatory infections; three of these patients died. In 

2007, three people died from multiple organ failure after a Texas compounder sold superpotent 

colchicine that was as much as 640 percent the labeled strength. In 2011, there were 19 cases of 

Serratia marcescens bacterial infections, Including nine deaths, associated with contaminated total 

parenteral nutrition products, and in 2012, 43 patients developed fungal eye Infections from 

contaminated sterile ophthalmic drug products. At least 29 of these patients suffered vision loss. 

These incidents are emblematic of long-standing issues aSSOCiated with the practice of 

compounding and the public health concerns that can result from unsafe practices in compounding 

pharmacies. 

Since the NECC outbreak, there have been seven additional recalls of sterile compounded and 

repackaged drug products by different pharmacies. In one very recent incident, the presence of 

floating particles, later identified to be a fungus, was reported in five bags of magnesium sulfate 

http://www.fda.govlNewsEventsrrestimony/ucm348120.htm 2/24/2014 
163 


85438.103

"A Continuing investigation into the Fungal Meningitis Outbreak and Whether it Could II... Page 2 of 6 

intravenous solution, resulting in a nationwide recall of all sterile drug products produced by the 

pharmacy (over 100 products). Fortunately, we have not received reports of patient injury from 

these products. In another recent recall, all sterile drug products (approximately 60 products) 

from a second pharmacy were recalled as a result of reports that five patients were diagnosed with 

serious eye infections associated with the use of repackaged Avastin. Moreover, we believe that 

presently, there are hundreds of other firms operating as compounding pharmacies, producing 

what should be sterile products and shipping across State lines in advance of or without a 

prescription. However, the current legal framework does not provide FDA with the tools needed to 

identify and adequately regulate these pharmacies to prevent product contamination. 

The history of this issue shows that there is a need for appropriate and effective oversight of this 

evolving industry. It is clear that the industry and the health care system have evolved and 

outgrown the law, and FDA's ability to take action against compounding that exceeds the bounds of 

traditional pharmacy compounding and poses risks to patients has been hampered by gaps and 

ambiguities in the law, which have led to legal challenges to FDA's authority to inspect pharmacies 

and take appropriate enforcement actions. 

The fungal meningitis outbreak has caused the Agency to review our past practices with regard to 

our oversight of compounding pharmacies, and has led to some preliminary conclusions. 

In my view, even in the face of litigation and continuous challenges by industry to our authorities, 

we can nonetheless be more aggressive in pursuing enforcement actions against compounding 

pharmacies within our current limited authority. I can assure you that we are being more 

aggressive now. We have established an Agency-wide steering committee to oversee and 

coordinate our efforts, and we have taken several important steps to identify and inspect high-risk 

pharmacies that are known to have engaged in production of sterile drug products. 

Using a risk-based model, we identified 29 firms for priority inspections focused on their sterile 

processing practices. During these 29 inspections, in two instances, FDA identified secondary firms 

associated with the priority inspections, for a total of 31 finms. We have taken investigators who 

would normally be doing inspections of conventional drug manufacturers and assigned them to 

conduct inspections of those pharmacies whose history suggests a greater risk of potential quality 

issues with their compounded products. We have coordinated our inspections with State officials, 

who have accompanied our investigators in most cases. At the same time, we have also continued 

to conduct for-cause inspections, often at the request of our State counterparts who invited us to 

accompany them on the inspections. When we identified problems during any of the inspections, 

at the close of the inspection, we issued an FDA Form 483 [1] listing our inspection observations. 

Thus far, we have issued an FDA-483 at the close of 43 of the 55 inspections we have conducted 

since last fall. We have seen some serious issues, including quality concerns that have led to 

product recalls. Observations have included: lack of appropriate air filtration systems, insufficient 

microbiological testing, and other practices that create risk of contamination. 

Notably, even in light of recent events, and even though we are often working with the State 

inspectors, our investigators' efforts are being delayed because they are denied full access to 

records at some of the facilities they are inspecting. Just during the recent inspections, several 

pharmacies delayed or refused FDA access to records, and FDA had to seek administrative warrants 

in two cases. And although we have been able to eventually conduct the inspections and collect 

the records that we have sought, our ability to take effective regulatory action to obtain lasting 

corrective action with regard to substandard sterility practices remains to be seen. 

As we have noted in the past, our ability to take action against inappropriate compounding 

practices has been hampered by ambiguities regarding FDA's enforcement authority, legal 

challenges, and adverse court decisions, and we have learned that the law is not well-suited to 

effectively regulate this evolving industry. For example, hospitals have come to rely on 

compounding pharmacies that function as "outsourcers" producing sterile drugs previously made by 

http://www.fda.govlNewsEventsrrestimony/ucm348120.htm 2124/2014 
164 


85438.104

"A Continuing investigation into the Fungal Meningitis Outbreak and Whether it Could II... Page 3 of 6 

hospital in-house pharmacies. If FDA brings charges against a pharmacy, alleging that it is 

manufacturing a "new drug" that cannot be marketed without an approved application, the 

pharmacy will have to either obtain individual patient-specific prescriptions for all of its products or 

stop distributing the products until it obtains approved new drug applications for them, something 

most outsourcers are unlikely to do. Several of the pharmacies FDA inspected are some of the 

largest outsourcers in the country. These pharmacies supply large numbers of sterile drugs 

produced in relatively large quantities to hospitals nationwide, and a shut-down at these firms is 

likely to cause disruptions in the supply of drugs to hospitals and other health care providers. FDA 

should have more tailored authorities appropriate for this type of compounding pharmacy. 

Tn my last appearance before this Subcommittee, I presented a framework that could serve as a 

basis for the development of a risk-based program to better protect the publiC health, Improve 

accountability, and provide more appropriate and stronger tools for overseeing this evolving 

industry. We have since met with over 50 stakeholder groups, including pharmacy, medical, 

hospital, payer, and consumer groups, and State regulators, to help further our understanding and 

inform our framework. Today, I will first provide background on FDA's current legal authority over 

compounded drugs, then provide additional details about the framework and suggest specific 

actions that Congress can take to help us better do our job and prevent future tragedies like this 

one. 

FDA's Legal Authority over Compounded Drugs 

FDA regards traditional pharmacy compounding as the combining or altering of ingredients by a 

licensed pharmacist, in response to a licensed practitioner's prescription for an individual patient, 

which produces a medication tailored to that patient's special medical needs. In its simplest form, 

traditional compounding may involve reformulating a drug, for example, by refT)oving a dye or 

preservative in response to a patient allergy. It may also involve making an alternative dosage 

form such as a suspension or suppository for a child or elderly patient who has difficulty swallowing 

a tablet. FDA believes that pharmacists engaging in traditional compounding provide a valuable 

medical service that is an important component of our health care system. However, by the early 

1990s, some pharmacies had begun producing drugs beyond what had historically been done 

within traditional compounding. 

After receiving reports of adverse events associated with compounded medications, FDA became 

concerned about the lack of a policy statement on what constituted appropriate pharmacy 

compounding. In March 1992, the Agency issued a Compliance Policy Guide (CPG), section 

7132.16 (later renumbered as 460.200) to delineate FDA's enforcement policy on pharmacy 

compounding. It described certain factors that the Agency would consider in its regulatory 

approach to pharmacies that were producing drugs. 

The compounding industry objected to this approach and several bills were Introduced, some with 

significant support, to limit the Agency's oversight of compounding.[2l In November 1997, S. 830, 

the Food and Drug Administration Modernization Act of 1997 (FDAMA), was signed Into law as 

Public Law 105-115.(3] FDAMA added Section S03A to the FD&C Act, to address FDA's authority 

over compounded drugs.[4] Section S03A exempts compounded drugs from three critical 

provisions of the FD&C Act: the premarket approval requirement for "new drugs"; the requirement 

that a drug be made in compliance with current good manufacturing practice (cGMP) standards; 

and the requirement that the drug bear adequate directions for use, provided certain conditions are 

met. These provisions were the subject of subsequent court challenges, which have produced 

conAicting case law and amplified the perceived gaps and ambiguity associated with FDA's 

enforcement authority over compounding pharmacies. In 2002, immediately after a Supreme 

Court ruling that invalidated the advertising provisions of Section 503A, FDA issued a reVised 

compliance policy guide on compounding hUman drugs. Several additional legal challenges and 

court decisions then followed. More recently, FDA made significant progress toward issuing 

http://www.fda.govfNewsEventslTestimonyfucm348120.htm 2/2412014 
165 


85438.105

"A Continuing investigation into the Fungal Meningitis Outbreak and Whether it Could II... Page 4 of 6 

another CPG. In fact, FDA was on track to publish a revised draft CPG in the fall of 2012, but the 

fungal meningitis outbreak intervened and we are now reevaluating the draft. It is important to 

note, however, that a CPG is not binding on industry and updating the CPG would not alleviate all 

Issues with Section S03A. 

A look at FDA's attempts to address compounding over the last 20 years shows numerous 

approaches that were derailed by constant challenges to the law. As a result, presently, it is 

unclear where in the country Section S03A is in effect, and Section S03A itself includes several 

provisions that have impeded FDA's ability to effectively regulate pharmacy compounding practices 

including those relating to prescription orders, medical need, and copying FDA-approved products. 

Apart from Section S03A, there are additional prOVisions in the statute that have impeded effective 

pharmacy compounding regulation. For example, if certain criteria are met, the FD&C Act exempts 

compounding pharmacies from registration and the obligation to permit access to records during an 

inspection. As a result, FDA has limited knowledge of pharmacy compounders and compounding 

practices and limited ability to oversee their activities. 

Looking Ahead 

The Administration is committed to working with Congress to address the threat to public health 

from gaps in authorities for effective oversight of certain compounding practices. To that end, FDA 

has developed a framework that could serve as the basis for the development of a risk-based 

program to protect the public health. 

Risk-based Framework 

Recognizing the history of compounding practice, FDA supports the long-standing policy that all 

compounding should be performed in a licensed pharmacy by a licensed pharmacist (or a licensed 

physician), and that there must be a medical need for the compounded drug. 

Further, we believe there Should be a distinction between two categories of compounding: 

traditional and non-traditional. Traditional compounding would include the combining, mixing, or 

altering of ingredients to create a customized medication for an individual patient with an 

individualized medical need for the compounded product, in response to a valid patient-specific 

prescription or order from a licensed practitioner documenting such medical need. Traditional 

compounding, while posing some risk, plays an important role in the health care system, and 

should remain the subject of State regulation of the practice of pharmacy. 

Non-traditional compounding would include certain types of compounding for which there is a 

medical need, but that pose higher risks. FDA proposes working with Congress to define nontraditional compounding based on factors that make the product higher risk such as any sterile 

compounding in advance of or without receiving a prescription, where the drug is distributed out of 

the state in which it was produced. Non-traditional compounding would be subject to Federal 

standards adequate to ensure that the compounding could be performed without putting patients 

at undue risk, and FDA would inspect against and enforce these Federal standards. Such a 

definition focuses on the highest risk activities and offers a uniform degree of protection across all 

50 States, for highest-risk compounding activities. 

Non-traditional compounding should, because of the higher risk presented, be subject to a greater 

degree of oversight. Sterile products produced in advance of or without a prescription and shipped 

interstate should be subject to the highest level of controls, established by FDA and appropriate to 

the activity, similar to cGMP standards applicable to conventional drug manufacturers. 

http://www.fda.govlNewsEventsrrestimony/ucm348120.htm 2124/2014 
166 


85438.106

"A Continuing investigation into the Fungal Meningitis Outbreak and Whether it Could II... Page 5 of 6 

In addition, FDA believes that with noted exceptions, certain products are not appropriate for 

compounding under any circumstances. These products would include: 1) what are essentially 

copies of FDA-approved drugs, absent a shortage justification based on the drug appearing on 

FDA's shortage list; and 2) complex dosage forms such as extended release products; transdermal 

patches; liposomal products; most biologics; and other products as designated by FDA. Producing 

complex dosage forms would require an approved application and compliance with cGMP standards, 

along with other requirements applicable to manufactured drug products. 

FDA believes that there are other authorities that would be important to support this new 

regulatory paradigm. For example, FDA should have clear ability to collect and test samples of 

compounded drugs and to examine and collect records In a compounding pharmacy, just as the 

Agency does when inspecting other manufacturers. FDA should also have clear ability to examine 

records such as records of prescriptions received, products shipped, volume of operations, and 

operational records such as batch records, product quality test results, and stability testing reSUlts. 

Such inspections are necessary to determine when a pharmacy exceeds the bounds of traditional 

compounding, to respond to public health threats, and to enforce Federal standards. 

FDA also believes that an accurate inventory of pharmacies engaged in non-traditional 

compounding would facilitate appropriate oversight and coordination with State regulators. In 

addition, FDA looks forward to working with the Congress on potential improvements that may 

include label statements and adverse event reporting that have proven useful In other areas, A 

user-fee-funded regulatory program may be appropriate to support the inspections and other 

oversight activities outlined in this framework. We look forward to working with Congress to 

explore the appropriate funding mechanisms to support this work, which could include registration 

or other fees, as Congress has authorized and FDA has successfully implemented in other settings. 

CONCLUSION 

Given our experiences over the past 20 years and the recent fungal meningitiS outbreak, we must 

do everything we can to clarify and strengthen FDA's authority in this area. We recommend that 

Congress recognize the appropriate State role in regulation of traditional compounding while 

authorizing clear and appropriate Federal standards and oversight needed for non-traditional 

compounders that produce riskier products. We look forward to working with Congress in striking 

the right balance. 

I am happy to answer any questions you may have. 

[1] A form FDA-483 is issued when investigators observe any significant objectionable conditions. 

It does not constitute a final Agency determination of whether any condition is in violation of the 

Federal Food, Drug, and Cosmetic Act (FD&C Act) or any of our relevant regulations, but the 

observations often serve as eVidence of a violation of the FD&C Act and its implementing 

regulations. 

[2j H.R. 5256, Pharmacy Compounding Preservation Act of 1994, introduced Oct. 7, 1994, 1 cosponsor; H.R. 598, Pharmacy Compounding Preservation Act of 1994, introduced Jan. 20, 1995, 

141 co-sponsors; H.R. 3199, Drug and Biological Products Reform Act of 1996, introduced March 

29, 1996, 205 co-sponsors; H.R, 1060, Pharmacy Compounding Act, introduced March 13, 1997, 

152 co-sponsors; H.R. 1411, Drug and Biological Products Modernization Act of 1997, introduced 

April 23, 1997, 16 co-sponsors 

[3] PubliC Law 105-115, FDAMA, 111 Stat. 2296 (Nov. 21, 1997), available at 

http://www.gpo.gov/fdsys/pkg/PLAW-l 05pubI115/pdf/PLAW-l 05publ115.pdf1 

[4)Id. 

http://www.fda.govlNewsEventsffestimony/ucm348120.htm 2/2412014 
167 

Æ 


85438.107

"A Continumg Investigation into the Fungal Meningitis Outbreak and Whether it Could H... Page 6 of 6 

Page Last Updated: 04{18/2013 

Note: If you need help accessing information in different file formats, see Instructions for 

Downloading Viewers and Players. 

Accessibility Contact FDA Careers FDA Basics FOIA No Fear Act Site Map Transparency 

Website Policies 

U.S. Food and Drug Administration 

10903 New Hampshire Avenue 

Silver Spring, MD 20993 

Ph. 1-888-INFO-FDA (1-888-463-6332) 

Email FDA 

r~ . .\,9;2<~ 11 ll1il l~ 

For Government For Press 

Combination Products Advisory Committees Science & Research Regulatory Information Safety 

Emergency Preparedness International Programs News & Events Training and Continuing 

Education Inspections/Compliance State & Local Officials Consumers Industry Health 

Professionals FDA Archive 

:{.. us. Department of Kealth &; Kuman Scrvk:es 

Links on this page: 

1. http://WWW.gpo.gov/fdsys!pkg/PLAW-105pubI115/pdf/PLAW10SpublllS.pdf 

http://W\l;w-fda.govlNewsEventslTestimony(ucm348120.htm 2/24/2014