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

77–032 PDF 2013

EXAMINING THE INCREASE IN DRUG SHORTAGES 

HEARING 

BEFORE THE

SUBCOMMITTEE ON HEALTH 

OF THE

COMMITTEE ON ENERGY AND 

COMMERCE 

HOUSE OF REPRESENTATIVES 

ONE HUNDRED TWELFTH CONGRESS 

FIRST SESSION 

SEPTEMBER 23, 2011 

Serial No. 112–88 

( 

Printed for the use of the Committee on Energy and Commerce 

energycommerce.house.gov 

COMMITTEE ON ENERGY AND COMMERCE 

FRED UPTON, Michigan 

Chairman 

JOE BARTON, Texas 

Chairman Emeritus 

CLIFF STEARNS, Florida 

ED WHITFIELD, Kentucky 

JOHN SHIMKUS, Illinois 

JOSEPH R. PITTS, Pennsylvania 

MARY BONO MACK, California 

GREG WALDEN, Oregon 

LEE TERRY, Nebraska 

MIKE ROGERS, Michigan 

SUE WILKINS MYRICK, North Carolina 

Vice Chairman 

JOHN SULLIVAN, Oklahoma 

TIM MURPHY, Pennsylvania 

MICHAEL C. BURGESS, Texas 

MARSHA BLACKBURN, Tennessee 

BRIAN P. BILBRAY, California 

CHARLES F. BASS, New Hampshire 

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 

HENRY A. WAXMAN, California 

Ranking Member 

JOHN D. DINGELL, Michigan 

Chairman Emeritus 

EDWARD J. MARKEY, Massachusetts 

EDOLPHUS TOWNS, New York 

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 

CHARLES A. GONZALEZ, Texas 

JAY INSLEE, Washington 

TAMMY BALDWIN, Wisconsin 

MIKE ROSS, Arkansas 

JIM MATHESON, Utah 

G.K. BUTTERFIELD, North Carolina 

JOHN BARROW, Georgia 

DORIS O. MATSUI, California 

DONNA M. CHRISTENSEN, Virgin Islands 

KATHY CASTOR, Florida 

SUBCOMMITTEE ON HEALTH

JOSEPH R. PITTS, Pennsylvania 

Chairman 

MICHAEL C. BURGESS, Texas 

Vice Chairman 

ED WHITFIELD, Kentucky 

JOHN SHIMKUS, Illinois 

MIKE ROGERS, Michigan 

SUE WILKINS MYRICK, North Carolina 

TIM MURPHY, Pennsylvania 

MARSHA BLACKBURN, Tennessee 

PHIL GINGREY, Georgia 

ROBERT E. LATTA, Ohio 

CATHY MCMORRIS RODGERS, Washington 

LEONARD LANCE, New Jersey 

BILL CASSIDY, Louisiana 

BRETT GUTHRIE, Kentucky 

JOE BARTON, Texas 

FRED UPTON, Michigan (ex officio) 

FRANK PALLONE, JR., New Jersey 

Ranking Member 

JOHN D. DINGELL, Michigan 

EDOLPHUS TOWNS, New York 

ELIOT L. ENGEL, New York 

LOIS CAPPS, California 

JANICE D. SCHAKOWSKY, Illinois 

CHARLES A. GONZALEZ, Texas 

TAMMY BALDWIN, Wisconsin 

MIKE ROSS, Arkansas 

JIM MATHESON, Utah 

HENRY A. WAXMAN, California (ex officio) 

(II) 

(III) 

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. John Shimkus, a Representative in Congress from the State of Illinois, 

opening statement ................................................................................................ 5 

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

New Jersey, opening statement .......................................................................... 5 

Hon. Henry A. Waxman, a Representative in Congress from the State of 

California, opening statement ............................................................................. 6 

Hon. Fred Upton, a Representative in Congress from the State of Michigan, 

prepared statement .............................................................................................. 158 

Hon. John D. Dingell, a Representative in Congress from the State of Michigan, prepared statement ...................................................................................... 160 

Hon. Edolphus Towns, a Representative in Congress from the State of New 

York, prepared statement .................................................................................... 161 

WITNESSES

Howard K. Koh, Assistant Secretary of Health, Department of Health and 

Human Services ................................................................................................... 7 

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

Jonathan M. Kafer, Vice President Sales and Marketing, Teva Health Systems ....................................................................................................................... 66 

Prepared statement .......................................................................................... 69 

John M. Gray, President and CEO, Healthcare Distribution Management 

Association ............................................................................................................ 78 

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

Kevin J. Colgan, Corporate Director of Pharmacy, Rush University Medical 

Center, on behalf of the American Society of Health-System Pharmacists .... 87 

Prepared statement .......................................................................................... 89 

Mike Alkire, Chief Operating Officer, Premier, Inc. ............................................. 101 

Prepared statement .......................................................................................... 103 

W. Charles Penley, Chair, Government Relations Committee, American Society of Clinical Oncology ....................................................................................... 117 

Prepared statement .......................................................................................... 120 

Richard Paoletti, Vice President, Operations: Pharmacy, Laboratory, and Radiology, Lancaster General Health ..................................................................... 131 

Prepared statement .......................................................................................... 133 

Robert S. DiPaola, Director, The Cancer Institute of New Jersey ...................... 141 

Prepared statement .......................................................................................... 144 

SUBMITTED MATERIAL

Statement, dated September 23, 2011, of the National Coalition for Cancer 

Research, submitted by Mr. Pallone ................................................................... 25 

Statement, dated September 23, 2011, of the National Community Pharmacists Association, submitted by Mr. Pitts ...................................................... 32 

Letter, dated September 22, 2011, from J. Evan Sadler, President, American 

Society of Hematology, to subcommittee leadership, submitted by Mr. Pitts . 35 

Statement, dated September 23, 2011, of the Generic Pharmaceutical Association, submitted by Mr. Pitts ................................................................................ 39 

Statement, dated September 23, 2011, of Fight Colorectal Cancer, submitted 

by Mr. Pallone ...................................................................................................... 151 

(1) 

EXAMINING THE INCREASE IN DRUG 

SHORTAGES 

FRIDAY, SEPTEMBER 23, 2011 

HOUSE OF REPRESENTATIVES, 

SUBCOMMITTEE ON HEALTH, 

COMMITTEE ON ENERGY AND COMMERCE, 

Washington, DC. 

The subcommittee met, pursuant to call, at 9:36 a.m., in room 

2322 of the Rayburn House Office Building, Hon. Joseph Pitts 

(chairman of the subcommittee) presiding. 

Members present: Representatives Pitts, Burgess, Shimkus, 

Myrick, Murphy, Blackburn, Gingrey, Lance, Cassidy, Guthrie, 

Walden, Pallone, Dingell, Schakowsky, Matheson, DeGette, and 

Waxman (ex officio). 

Staff present: Clay Alspach, Counsel, Health; Ray Baum, Senior 

Policy Advisory/Director of Coalitions; Marty Dannenfelser, Senior 

Advisor, Health Policy and Coalitions; Andy Duberstein, Special 

Assistant to Chairman Upton; Debbee Keller, Press Secretary; Jeff 

Mortier, Professional Staff Member; Katie Novaria, Legislative 

Clerk; John O’Shea, Professional Staff Member, Health; Chris 

Sarley, Policy Coordinator, Environment and Economy; Alan 

Slobodin, Deputy Chief Counsel, Oversight; Heidi Stirrup, Health 

Policy Coordinator; John Stone, Associate Counsel; Phil Barnett, 

Democratic Staff Director; Stephen Cha, Democratic Senior Professional Staff Member; Alli Corr, Democratic Policy Analyst; Eric 

Flamm, FDA Detailee; Ruth Katz, Democratic Chief Public Health 

Counsel; Elizabeth Letter, Democratic Assistant Press Secretary; 

and Karen Lightfoot, Democratic Communications Director and 

Senior Policy Advisor. 

Mr. PITTS. This subcommittee will come to order. The chair recognizes himself for 5 minutes for an opening statement. 

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

OF PENNSYLVANIA 

In 2005, 61 drug shortages were reported to FDA. By 2010, there 

were 178 reported drug shortages, 132 of which involved sterile 

injectable drugs. So far this year, FDA has continued to see an increasing number of shortages, especially those involving older sterile injectable drugs. These shortages have involved cancer drugs, 

anesthetics used for patients undergoing surgery, as well as drugs 

needed for emergency medicine, and electrolytes needed for patients on IV feeding. 

2 

It appears that there are many potential causes of these drug 

shortages. In some cases, shortages have been caused by quality 

and manufacturing issues. Additionally, production delays at the 

manufacturer level, including limited production lines for certain 

older drugs, and difficulty in receiving raw materials and components from suppliers have caused drug shortages. Many raw material suppliers also experience capacity problems at their facilities, 

causing delays that ripple through the drug production process. 

Shortages can also result from a company discontinuing a particular drug. Certain drugs are susceptible to shortages, particularly those that are complex to manufacture, such as injectable 

drugs, or require longer lead times. FDA cannot compel a company 

to manufacture a particular drug, and, if there is a shortage of that 

drug, it cannot compel other firms to increase their capacity. Further, companies are not required to notify FDA in advance of a potential drug shortage, unless a company is discontinuing a sole 

source, medically necessary drug. In that case, a company must inform FDA 6 months in advance. 

Drug shortages have real effects on real patients. Due to shortages, patients have not received the appropriate drugs for their 

conditions, often getting a less effective drug or a more costly substitute as a result. According to a study done by Premier 

Healthcare Alliance of 228 hospitals, retail pharmacies, and other 

health care facilities, nearly 90 percent of hospitals reported a drug 

shortage in the last half of last year that may have caused a patient safety issue, resulted in a procedure’s delay or cancellation, 

required a more expensive substitute, or resulted in a pharmacist 

compounding a drug. 

I look forward to hearing from our witnesses today about their 

experiences with drug shortages and learning what remedies they 

believe are necessary. I would like to say a special hello to Richard 

Paoletti, Vice President, Operations; Pharmacy, Laboratory, and 

Radiology at Lancaster General Hospital in my home district. 

Lancaster General is the largest employer in the 16th Congressional District, and, for 10 of the past 13 years, it has been named 

among the ‘‘Top 100 Hospitals in America’’ by Thomson Reuters, a 

leading source of healthcare business intelligence. The hospital is 

also helping to revitalize the northwestern part of Lancaster City 

through a partnership with Franklin and Marshall College. 

Again, thank you to our witnesses, and I will yield the balance 

of my time to Congressman Shimkus from Illinois. 

[The prepared statement of Mr. Pitts follows:] 

3 


77032.001
4 


77032.002
5 

OPENING STATEMENT OF HON. JOHN SHIMKUS, A REPRESENTATIVE IN CONGRESS FROM THE STATE OF ILLINOIS 

Mr. SHIMKUS. Thank you, Mr. Chairman. And we want to welcome our folks at the 2 panels. Obviously, this is of concern. I am 

a market-based conservative capitalist, and whenever there is a lag 

in a commodity good or product, you have to really wonder about 

the demand and the supply and the available cost because when 

there is limited supply and a high demand, cost should go up. 

So that begs a question is, what is constraining the market signals from producing the product that the consumers need? Is that 

insurance companies? Is that government reimbursement rates? Is 

that the State Medicaid provisions? That is what I will be looking 

at because the bigger the government is, the more manipulative it 

gets in the market services, the less its ability to provide goods and 

services to consumers. 

So we appreciate that and look forward to it, and I yield back 

my time, Mr. Chairman. Thank you. 

Mr. PITTS. The chair thanks the gentleman and recognizes the 

ranking member of this subcommittee, Mr. Pallone, for 5 minutes. 

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

Mr. PALLONE. Thank you, Mr. Chairman. I want to thank you for 

holding today’s hearing on this important issue. I am encouraged 

by the bipartisan nature of this effort and thank our witnesses for 

joining us. 

Today, we will discuss the recent increase in drug shortages that 

have been the subject of numerous reports. Drug shortages appear 

to be on the rise at an alarming rate and are threatening the supply of some of our most important medications from lifesaving oncology drugs to antibiotics that rid us of infection to antiseptics 

that get us through the most minor surgical procedures. These 

drugs have become an important part of our healthcare system. 

No patient must be told that their chemotherapy must be postponed because the only drug used to treat their type of cancer is 

unavailable. And likewise, no anesthesiologist wants to begin their 

workday with the realization that they will have to use subpar 

drugs on a patient because the one they normally rely on is out of 

stock indefinitely. So we can’t let this become the new norm. 

We are dependent upon the medications on the FDA’s drug 

shortage list for years and continue to look for them for our health 

and wellbeing. It is alarming that drugs that have been around for 

so long would suddenly be the most difficult to keep hospitals, 

pharmacies, and doctors’ offices supplied with. Furthermore, these 

drugs tend to be low-cost generics, which are an essential component of healthcare for most Americans as they seek to keep their 

healthcare costs low. 

In this fiscal climate, having a readily accessible supply of generic medication is of profound importance, and to that end, it has 

been disheartening to learn that the so-called gray market would 

take advantage of such a dire situation to engage in price-gouging 

at the expense of those desperate enough to pay. 

6 

So I am hoping that we can begin today to identify the cause of 

these shortages and discuss solutions for replenishing our drug 

supply. We must address this sudden increase so that Americans 

can continue to receive high-quality treatments at low cost and remain confident in both the pharmaceutical industry and the 

healthcare providers. 

Unfortunately, companies are not currently required to report to 

the FDA when a shortage will be occurring whether because of 

change in investment strategy or manufacturing difficulties, there 

is currently no policy for notification unless the company is the sole 

manufacturer. 

My colleague, Representative DeGette, has introduced bipartisan 

legislation, H.R. 2245, the Preserving Access to Life-Saving Medications Act of 2011, as the first step in addressing this issue. This 

legislation would require manufacturers to notify the FDA of any 

actual or prospective drug shortages. And I want to commend Representative DeGette on pioneering this effort and hope that as a result of hearing from our witnesses today, we can identify additional 

solutions to this growing problem. 

This hearing will allow us to learn more about why drug shortages are occurring, what the administration and industry are doing 

to address the problem, and what new authorities the FDA might 

need to prevent shortages from happening in the future. And I am 

encouraged that we are exploring this issue in our subcommittee 

today, look forward to working with you, Chairman Pitts, as you 

get to the bottom of this issue. And again, thank you for having 

the hearing. 

I yield back. 

Mr. PITTS. The chair recognizes the ranking member of the full 

committee, Mr. Waxman, for 5 minutes. 

OPENING STATEMENT OF HON. HENRY A. WAXMAN, A REPRESENTATIVE IN CONGRESS FROM THE STATE OF CALIFORNIA 

Mr. WAXMAN. Thank you, Chairman Pitts, for recognizing me 

and for holding this hearing. 

Recent media and other reports indicate that drug shortages are 

now at an unprecedented level. Indeed, according to FDA, the number of drugs in short supply in 2010 was almost triple that of 2005. 

The shortages affect a broad spectrum of critically important 

drugs—including oncology drugs to treat lymphoma, leukemia, 

breast and other cancers—and the seizure drugs without which 

surgeries have to be postponed and antibiotics to remedy lifethreatening bacterial infections. Without these drugs, patients’ 

lives are at risk. 

Drug scarcities generally affect sterile injectable drugs. These 

drugs are technically difficult to make and each drug is usually 

manufactured by only one or a handful of producers. If any one 

company develops manufacturing problems, which is not uncommon, other companies may have little excess capacity to help fill 

the need. 

With the aging of our population, the outsourcing of drug manufacturing, the increasing consolidation of drug companies, and the 

general adoption of a just-in-time approach to drug production and 

7 

distribution, this problem may be significantly worse unless immediate measures including congressional action are taken to address 

its multiple causes. 

Representative DeGette has introduced legislation that would be 

an important first step in this process. H.R. 2245, the Preserving 

Access to Life-Saving Medications Act of 2011, would require manufacturers to notify FDA of any actual or prospective drug shortages. Such advance notice would enable FDA to help avoid or mitigate the shortage by both working with the manufacturer and 

alerting hospitals and physicians of the problem. 

While this is an important piece of legislation that has broad bipartisan support, I don’t think anyone believes it alone can solve 

the drug shortage problem. So I look forward to hearing from our 

witnesses today to better understand the causes of what is already 

a crisis for many patients and to find out what we in Congress can 

do to help prevent shortages in the future. We already had been 

working in bipartisan manner to learn about this very disturbing 

issue, and I trust that we will continue to work together to develop 

and enact legislation to help address it and address it quickly. 

Thank you, Mr. Chairman. I yield back the time. 

Mr. PITTS. The chair thanks the gentleman. That concludes our 

opening statements. 

Our first panel will be Assistant Secretary for Health at HHS, 

Mr. Howard Koh. And Mr. Koh, you may begin your testimony. 

Please summarize in 5 minutes. We will put your entire written 

testimony in the record. You may begin. 

STATEMENT OF HOWARD K. KOH, ASSISTANT SECRETARY OF 

HEALTH, DEPARTMENT OF HEALTH AND HUMAN SERVICES; 

ACCOMPANIED BY SANDRA KWEDER, DEPUTY DIRECTOR, 

FDA OFFICE OF NEW DRUGS 

Mr. KOH. Thank you, Chairman Pitts, Ranking Member Pallone, 

and distinguished members of the committee. I am Dr. Howard 

Koh, the Assistant Secretary for Health at the U.S. Department of 

Health and Human Services. I am very pleased to be joined here 

by my colleague, Dr. Sandy Kweder, Deputy Director of the FDA 

Office of New Drugs. 

As you already heard, the growing problem with drug shortages 

is a troubling situation and one that the Department and the Secretary take very seriously. This growing trend has the potential to 

impact on our entire healthcare system, and as we discuss this 

problem today, we should always remember that our goal is to protect the health of people affected most by these shortages—patients 

and their families. And I say that as a physician who has cared for 

patients for over 30 years. 

According to the FDA’s Center for Drug Evaluation and Research 

(CDER), the number of drug shortages has been rising steadily 

over the last 5 years, as you have already heard. And although 

shortages can occur with any drug, generic sterile injectables currently make up a large and increasing share. And in fact, in 2010, 

74 percent of these shortages involved these older sterile injectable 

agents. So these include critical products such as oncology drugs, 

anesthetics, parenteral nutrition drugs, and many drugs used in 

emergency rooms. 

8 

There is no single reason why drug shortages occur so ultimately, 

in any given situation, many factors are involved and underlying 

causes they operate either alone or in combination to cause a shortage. These factors include but are not limited to industry consolidation, major issues of quality and manufacturing challenges, 

changes to inventory and distribution practices, difficulty in producing a given drug, production delays, discontinuations for business reasons, unanticipated increased demand, and shortages of 

underlying raw materials. These are some of the causes, but more 

importantly, we the Department are trying to focus now on finding 

solutions that protect patients. 

In 1999, the FDA formed the drug shortage program within 

CDER in an effort to proactively begin monitoring and mitigating— 

that is, lessening the impact of—potential and actual drug shortages. And when the FDA becomes aware of any potential shortage, 

it was collaboratively with the affected firm to return the product 

to its usual market availability as quickly and as safely as possible 

while striving to prevent any harm to any patient. Although the 

FDA cannot require firms to continue production of a product or increase production in response to a shortage, it does encourage other 

firms to do so. 

FDA also expedites the review of submissions from manufacturers, which may include request to extend the expiration date of 

products, increase capacity, use a new raw material source, license 

new manufacturers, and prevent changes in product specifications. 

The FDA is committed to working with drug manufacturers to prevent shortages whenever possible, and in fact, as a direct result of 

this commitment and the work of the FDA drug shortages staff and 

experts from across the Agency, last year, 2010, 38 shortages were 

prevented. And so far for 2011, this year, I am pleased to report 

for the first time that 99 shortages have been prevented. 

Also, at the same time, the FDA goes to great lengths to mitigate 

shortages—that is, lessening the impact when they occur. One notable recent example involves the well described shortage of the 

drug cytarabine used to treat certain types of acute leukemia. Crystal formation in the vials of this drug represented a quality and 

manufacturing problem that led to a disruption in production and 

a shortage that received tremendous publicity across the Nation 

within recent months. In this case, the FDA worked with the manufacturer, found that if the vials were warm, the crystals would 

dissolve and the drug could be then safety administered to the patient, and as a result of this collaboration, the manufacturer was 

then subsequently able to ship the vials to healthcare professions 

along with a letter from the FDA notifying them to inspect for crystal formation, and if present, warm the vials to dissolve the crystals. And in this way, the collaboration led to ensuring and upholding patient safety. So as a result of this work, we can report today 

that this well reported drug shortage has been recently resolved. 

In limited circumstances, the FDA can allow the temporary importation of critical drugs when the shortage cannot be resolved immediately. However, there are several factors that limit the applicability of this option. The product may already be in short supply 

abroad, so importation to the U.S. could exacerbate the shortage. 

9 

FDA must also ensure that drugs imported from abroad are manufactured in facilities that meet FDA quality standards. 

To discuss these and other possible solutions, the FDA will be 

hosting a public meeting next Monday, September 26, and this 

meeting is being held to gain additional insight about causes and 

impact of this challenge and possible strategies for solutions. 

Then on Friday, September 30, the FDA is conducting a webinar 

for the general public, and this is an opportunity for people to learn 

more about what the FDA is doing to address this challenge, and 

it will also be a venue for citizens to ask questions directly to FDA 

experts who are working on this topic every day. 

Although I have focused my comments until now on the FDA, I 

should stress that the entire Department of Health and Human 

Services has been fully engaged on this topic for quite some time. 

We view this as a pressing public health challenge, and we want 

to resolve this on behalf of the Department and indeed the entire 

country. 

This past summer, I personally convened a series of meetings 

with representatives from FDA; NCI, our National Cancer Institute; CDC, our Centers for Disease Control and Prevention; the Office of the Assistant Secretary for Preparedness and Respondent; 

the Office to the Assistant Secretary for Planning of an Evaluation; 

the Centers for Medicare and Medicaid Services, CMS; and others. 

We have joined together as one department to explore more deeply 

the root causes of this problem and the possible steps that can be 

taken to address them. These have been productive meetings and 

we pledge to continue them until the problem is solved. We look 

for as many ways as possible to maximize our efforts within the 

Department to protect the public health. 

Also, earlier this morning, Secretary Sebelius, along with other 

senior leaders in the Department hosted a meeting with over a 

dozen representatives from pharmaceutical manufacturers, professional medical organizations, hospitals, insurance companies, 

group-purchasing entities, and patient advocacy organizations, and 

this crucial meeting gave us firsthand insight into these challenges, 

generated a good discussion with the stakeholders, and also served 

as a foundation for our future collaboration. 

Shortly, later on this fall, the FDA will release a report which 

reflects an even more detailed analysis of the problem and updated 

recommendations for the future. Potential solutions are being examined. One suggestion is a mechanism for manufacturers to report impending supply disruptions and discontinuation of drugs, 

which could help to curb shortages and improve the continuity of 

the drug supply. The sooner the FDA learns of a drug shortage, the 

more effective they are going to be in helping to notify providers 

and the public and upholding patients’ safety. 

So we remain committed to working with all parties—manufacturers, providers, patient advocates, and other stakeholders to help 

minimize and solve this problem. So in conclusion, the Department 

is committed to addressing and solving this critical public health 

challenge. It is our goal to advance this dialogue with all interested 

parties both internal and external, and we also recognize and deeply respect the important roles of the Members of Congress, and we 

10 

welcome the opportunity to discuss this important topic with you 

today. 

So thank you very much, and Dr. Kweder and I will be very 

happy now to take any questions you may have. 

[The prepared statement of Mr. Koh follows:] 

11 


77032.003
12 


77032.004
13 


77032.005
14 


77032.006
15 


77032.007
16 


77032.008
17 


77032.009
18 


77032.010
19 


77032.011
20 


77032.012
21 


77032.013
22 


77032.014
23 

Mr. PITTS. The chair thanks the gentleman. Dr. Koh, why have 

drug shortages increased so much in the last few years? 

Mr. KOH. Well, again, there is no one single reason but there are 

changes here that we are seeing in the backdrop of an economic 

and business climate that is leading to market consolidation, a 

complicated manufacturing process that is being conducted increasingly in aging facilities that is leading to quality and manufacturing issues as we have heard now. Sometimes products are discontinued for business reasons. Oftentimes the production of any of 

these agents is a complicated process. So all these factors converge 

to create the issue that we are facing right now. 

Mr. PITTS. Have other countries experienced shortages such as 

we have? 

Mr. KOH. Unfortunately, the United States is not unique in this 

situation and yes, we are indeed seeing similar situations in other 

countries around the world. 

Mr. PITTS. And when a shortage occurs in another developing 

country, how is that situation resolved there? 

Mr. KOH. Well, we want to learn more from our colleagues there. 

I don’t know if Dr. Kweder wants to say more about that particular 

issue. 

Ms. KWEDER. We are often contacted by our regulatory colleagues 

from other countries looking to collaborate on finding solutions to 

particularly when there are worldwide problems. Different countries have different ways of producing drug, as assuring production 

of product, but we work as much as possible with others to try and 

make sure that shortages are limited and mitigated. 

Mr. PITTS. Does Europe have a particular method of resolving 

this situation? 

Ms. KWEDER. I believe the method is pretty much similar to ours, 

particularly since they have multiple countries. They seek other 

sources of supply from other countries. 

Mr. PITTS. And do you know what is causing these drug shortages in these countries in Europe? 

Ms. KWEDER. Many of them are the same sorts of things. They 

are, you know, many of these products are marketed globally. They 

are not just in the U.S. The sources of the drug substances itself, 

most of them are foreign sources, so if there is an interruption of 

a source in the U.S. at a U.S. plant, if a manufacturer in another 

country has the same source, they will be in the same situation 

and everyone will be out looking for alternatives at the same time. 

Mr. PITTS. OK. Dr. Kweder, what specific steps has the FDA 

taken to prevent or alleviate drug shortages? 

Ms. KWEDER. First, we tend to learn in terms of preventing drug 

shortages. When companies let us know that they are experiencing 

a problem, it is usually a problem in production. Sometimes it is 

a business decision to discontinue a product. When they inform us 

in advance that that is the case, we work very closely with them 

to understand the problem and assess whether this shortage would 

be something that would be critical for patients. 

So, for example, if a company is making a product that 20 other 

companies make, that is not likely to be a critical public health situation. But particularly for these sterile injectables, that is usually 

not the case. So we will work with a company to help them develop 

24 

solutions to fix the problem and avoid an interruption in production. That is not always possible. It is just simply not always possible. 

When it is not possible and it looks like the company may have 

to interrupt production, we go to other manufacturers and we talk 

to them about their capacity to increase their production. They 

usually can’t turn that around on a dime, but we work with them 

to facilitate ramping up in order to supply the market with usual 

sources. 

In the original company that is having a problem, we have a 

number of tools in our kit that we can use to help them address 

the problem. Dr. Koh gave you an example of the kinds of things 

that we can do in some cases, you know, to look at the end product 

itself if there is a problem with the end product itself. In that case 

it was crystallization of the actual active drug. And we worked 

with the company. They got right on the case to figure out why 

those crystals were forming, what could be done to mitigate that, 

inform providers, and since then, the crystal problem has been 

fixed. 

Mr. PITTS. Do you feel you need earlier warning than you currently have? 

Ms. KWEDER. We can always use earlier notification. There certainly are circumstances where things happen very, very unexpectedly. But the majority of cases of shortages, we could have been notified, and in the majority of cases, we are not notified in advance. 

It is getting better. I will say it is getting better, but we still have 

a large percentage of actual shortages where we were not aware 

that it was coming. 

Mr. PITTS. Thank you. My time has expired. 

The chair recognizes the ranking member, Mr. Pallone, for 5 

minutes for questions. 

Mr. PALLONE. Thank you, Mr. Chairman. I would like to initially 

ask unanimous consent to enter into the record the testimony of 

the National Coalition for Cancer Research. I think you have a 

copy of it. 

Mr. PITTS. Without objection, so ordered. 

[The information follows:] 

25 


77032.015
26 


77032.016
27 


77032.017
28 


77032.018
29 


77032.019
30 

Mr. PALLONE. Thank you, Mr. Chairman. 

Dr. Koh, we all agree that drug shortages are a real problem facing the country and from what I understand, it is actually getting 

worse. But I guess it is hard to figure out, at least for me, what 

the cause is and I would like to ask some questions about the root 

cause of the problem. 

The FDA has said that in 2010, last year, over half of the shortages were due to manufacturing and product-quality issues, and I 

understand I think you mentioned that many or a majority of those 

are sterile injectable drugs. Why would these drugs be prone to 

manufacturing and product-quality issues in particular? 

Mr. KOH. Well, many of these products are the result of a long 

production process, and those production processes are now occurring in fewer manufacturing sites because of industry consolidation. There is also aging of the facilities where this work is ongoing. There are business and economic factors in the background 

that are lowering the profit margin. So oftentimes, businesses will 

make a decision to perhaps discontinue a particular product for 

business reasons, and as a result, we are seeing the quality in 

manufacturing issues, Congressman, that you are referring to. 

Some of these quality issues are quite disturbing where we literally are tracking products that have particulate matter, even 

pieces of glass and pieces of metal in what should be sterile products that are injected into patients. So this is the reason why the 

FDA continues to uphold this mission of safe and effective drugs, 

also high-quality drugs in the middle of this challenging environment. 

Mr. PALLONE. Now, Teva is on the next panel, but in their written testimony, they state that it takes 2 or 3 years to get FDA approval for a new supplier for ingredients or an alternative manufacturing site. Is that really true? Does it really take 2 or 3 years 

to get the FDA approval? And why would that be if it is true? And 

does it take that long if there is a drug shortage issue involved? 

Mr. KOH. Well, let me start, and I am sure Dr. Kweder can add. 

One of the advances of the FDA in this situation is to prioritize generic drug applications, expedite and accelerate approval in every 

way possible, particularly if the public health is threatened. So 

there are efforts to try to advance that time frame. That is also the 

goal of the Generic Drug User Fee Act, which is under review right 

now. So these are issues that are very important to the FDA and 

they take it seriously. 

Mr. PALLONE. But I mean is that time period that Teva mentioned, would that generally be true and is there any kind of flexibility that you have to expedite review and inspections of new facilities so they could address the shortage when it exists? 

Ms. KWEDER. There absolutely is flexibility, and we do that routinely when we are aware that, say, a new facility is needed or a 

new supplier is needed and when there is a circumstance that 

might lead to a potential shortage of an important medical product. 

We do it routinely. We can often turn things around in a matter 

of weeks. 

Mr. PALLONE. But I mean you haven’t answered that 2- or 3-year 

time span. 

31 

Ms. KWEDER. Sure, I would be happy to do that. The 2- or 3-year 

time span is what is being referred to under usual conditions when 

there is not a shortage situation or not a shortage situation pending. 

Mr. PALLONE. But if there is, then you deal with it quicker? 

Ms. KWEDER. Absolutely. But even the 2- to 3-year time frame, 

as Dr. Koh said, we are working and we are happy to see that 

there has been agreement on generic user fees that will change 

that and make that a matter of months and not years. 

Mr. PALLONE. I mean my concern is, you know, we face these extraordinary fiscal pressures. The House passed budget for FDA 

contained a 21 percent cut in appropriated funds. I mean is this 

cut, would that adversely affect your ability to work with companies to avoid or mitigate shortages? And, you know, I know you 

mentioned generics. Are you negotiating with the generic industry 

to develop a user fee and can that help prevent or alleviate drug 

shortages? This is about the funding now. 

Ms. KWEDER. We are negotiating and have reached agreement 

with the generic industry about user fees. And that will be coming 

up for discussion by yourself, you know, within the next year. 

Mr. PALLONE. And what about this House budget cut, the 21 percent? 

Ms. KWEDER. There is no question that resources matter and 

these are not automated processes. They take people with judgment and knowledge and having enough people makes a big difference. 

Mr. PALLONE. All right. Thank you very much. 

Thank you, Mr. Chairman. 

Mr. PITTS. The chair thanks the gentleman. 

And I would like to request the following statements be entered 

into the record. I think you have copies. The statement of the National Community Pharmacist Association, the letter from the 

American Society for Hematology to the House Energy and Commerce Subcommittee on Health, and the statement of the Generic 

Pharmaceutical Association. 

Mr. PALLONE. I have no objection, no. 

Mr. PITTS. Without objection, so ordered. 

[The information follows:] 

32 


77032.020
33 


77032.021
34 


77032.022
35 


77032.023
36 


77032.024
37 


77032.025
38 


77032.026
39 


77032.027
40 


77032.028
41 


77032.029
42 


77032.030
43 


77032.031
44 


77032.032
45 


77032.033
46 

Mr. PITTS. I recognize this time the gentleman from Illinois, Mr. 

Shimkus, for 5 minutes. 

Mr. SHIMKUS. Thank you, Mr. Chairman. 

I think all would agree that resources matter in this tough fiscal 

period, as the ranking member said. I think also part of our issue 

would be prioritization, especially in life-saving issues and what 

are agencies doing to put first things first and what can they do 

obviously redirect funds in a different direction. 

For Dr. Koh, going in line with my opening statement, how have 

cost and payment factors impacted these drug shortages? 

Mr. KOH. Well, again, this is an industry that is producing products in an environment where they are facing increasing economic 

pressures. The profit margin for any particular agent is declining 

for them, so they have to make business decisions but also keep 

their products moving until the decision is made, perhaps to discontinue a product. On the quality manufacturing issues and possibly delay issues and what is often a complicated production process, it just all contributes to the situation that we are seeing now. 

Mr. SHIMKUS. And who are the big payers? 

Mr. KOH. Well, there is a process where purchasers—hospitals 

and physicians and providers—buy these products but there are 

also group-purchasing organizations and pharmacy benefit managers who are trying to drive down the price for understandable 

business reasons. So these are all the stakeholders who are involved in the purchasing chain. 

Mr. SHIMKUS. And I do appreciate your opening testimony because we had a series of questions and really you answered them 

in your opening statement. And I am just going to highlight one 

of the things was a question we were going to ask was closely collaborating and you gave the example of the drug with the crystallization, and I thought that was very helpful. 

The other issue I was going to focus on was alternative sponsors, 

and that is where you talked about maybe temporary easing import 

restrictions or importation or—I can’t even read my writing—temporarily doing something else. But you said that is constrained 

based upon if there is a shortage overseas of the same product, and 

something that we have talked about over the past years with 

Ranking Member Dingell is the ability to make sure that the drugs 

that we are importing are inspected by our inspectors so we know 

the efficacy and safety of that. 

I have always been a risk-based person on the focus point of saying that those that are more questionable facilities ought to get a 

lot of look. If they have been operating safely and they have inspected like a U.S. facility every year, then it might make that you 

could go every 2 years or maybe every 18 months. And that is the 

whole issue of shifting sources, too, to the more critical elements 

and safety versus known products and industries that you all have 

real confidence in. We want to expect you to do that in industries 

that have a poor record, but those that you have really good confidence in, that is the funding issue. 

You also mentioned, you know, business reasons and aging facilities and I think you mentioned increased regulations. Is that part 

of your testimony? 

47 

Mr. KOH. Well, the quality standards that the FDA puts forward 

in areas like this have been unchanged for the last 4 decades. And 

in fact the FDA has really gone the extra mile in my view to show 

tremendous regulatory flexibility here. So again, since we can’t require any manufacturer to do much of anything, all we can ask is 

for information, communication, collaboration, and then the FDA 

shows maximum regulatory flexibility. This re-warming of the 

cytarabine that I mentioned to you is one example of filtering out 

particular matter so again these medications can be used and not 

put aside is another example. 

Mr. SHIMKUS. Yes, I only have 12 seconds—— 

Mr. KOH. Sure. 

Mr. SHIMKUS [continuing]. I will go back to the testimony—— 

Mr. KOH. Um-hum. 

Mr. SHIMKUS [continuing]. Because I did scribble a note a comment on increased regs, and I will have to go back and look at that. 

But why doesn’t the shortage of a product in this sector then send 

an increased price signal to manufacturers for them to then 

produce the good? 

Mr. KOH. Well, we have come to learn that the standard economic principles of supply and demand—— 

Mr. SHIMKUS. And the question is why is that distorted? I think 

that is the basic fundamental question of this problem. What has 

distorted the fundamental principle of supply and demand, and my 

time has expired, but I think that is the heart of this issue. I yield 

back my time. 

Mr. KOH. Sure. And I am sure Dr. Kweder can add, too. First of 

all, these agreements are made often through these long-term contracts and so also this whole process involves multiple stakeholders, especially and including the pharmacy benefit managers 

and the group purchasing organizations. So it complicates this environment and sort of does not make relevant the sort of standard 

supply and demand economic principles that we see in other businesses. 

Mr. PITTS. Dr. Kweder? 

Ms. KWEDER. You have said what I would say. Thank you. 

Mr. PITTS. The chair thanks the gentleman and recognizes the 

gentlelady from Illinois, Ms. Schakowsky, for 5 minutes for questions. 

Ms. SCHAKOWSKY. Thank you, Mr. Chairman. 

I, too, am sponsor of the DeGette legislation that would ask for 

early notification. I just wanted to mention we actually have a Chicago-based injectable drug company Hospira that has endorsed the 

bill and they already do many of the things including proactively 

reporting to the FDA about potential drug shortages. 

You have explained, Dr. Koh and Dr. Kweder, the advantage of 

that early notification. Let me just raise a question that some have 

raised. Early warning could exacerbate the problem and lead to 

hoarding of critical drugs. Is this anything we need to watch out 

for, account for? I mean I am hoping that that is not the result of 

this legislation, obviously, which I support. Have you heard of that? 

Ms. KWEDER. I will respond to that question. When we are notified of a potential shortage, we do not automatically turn around 

and put that on our Web site and notify the public of a potential 

48 

shortage, which would have the opposite effect of what we want. 

We judge very carefully when is the right time to make a public 

announcement about a potential shortage. First, we assess what 

are we talking about? Is this a true product shortage or is it an 

imbalance in distribution? Because sometimes you see things that 

seem to be in shortage in one part of the country but there is plenty of it and more so in another part. 

So we take that potential for making things worse very, very seriously. We meanwhile are working on it to assess it and assess 

what we might do to mitigate it if it is real. If it is real, we usually 

announce the fact that it exists and try to let the public know what 

we are doing to try to address it. 

Ms. SCHAKOWSKY. So early notification, then, is something that 

is a very useful tool? 

Ms. KWEDER. Right, early notification to FDA is a very useful 

tool. We see that as different than early publication. 

Ms. SCHAKOWSKY. Got it. Let me ask you this. The FDA has limited authorities. Let me run through some of those. At this point 

you can’t require manufacturers to do this early notification, you 

have no authority to require companies to increase production of a 

drug during a shortage, you can’t impose an allocation plan when 

a shortage causes life-threatening conditions, and FDA has limited 

ability to post timely information on its Web site for healthcare 

professionals and patients regarding reasons for shortages and 

timelines for resolution. I don’t really understand that one. But in 

addition to early notification, are there other authorities that you 

need that would help mitigate this problem? 

Ms. KWEDER. I think there are 2 things. One, in the early notification is something that helps us in the mitigation and prevention 

greatly. What we need to be able to do is we need to be able to 

have the industry assure that they are making a quality product 

and upholding their responsibility to produce high-quality products 

where these things won’t happen. Our goal is to prevent even the 

potential for a shortage from occurring, not always possible. 

In the case of many of these threatened and real shortages, as 

Dr. Koh said, these are in plants that manufacture multiple, multiple products. If you look at the record, the things that led to the 

actual problem with production are things that we have been telling the companies about in routine inspections for years but only 

became critical in order that they needed to address these, modernize, so that they could continue producing quality product without a glitch. 

So that is first and foremost from our standpoint, assuring that 

we are aware so that we can step in and use every possible communication tool and flexibility and regulatory action. 

Ms. SCHAKOWSKY. Let me just ask you to what extent is the 

issue of business decisions—what percent of those cases where we 

have shortages would you say this is a business decision? 

Ms. KWEDER. You know, I can’t give you an exact percentage. I 

will be happy to provide that follow up. 

Ms. SCHAKOWSKY. Is it a major issue and is there anything that 

we can do about that? 

Ms. KWEDER. I would say that it is not. That is not the major 

issue. 

49 

Ms. SCHAKOWSKY. OK. 

Ms. KWEDER. I would say by far and away the more common scenario has something to do with manufacturing and product quality. 

Ms. SCHAKOWSKY. Thanks you. Thanks to both of you for being 

here. 

Mr. KOH. Thank you. 

Mr. PITTS. The chair thanks the gentlelady and recognizes the 

gentlemen from Kentucky for 5 minutes for questioning. 

Mr. GUTHRIE. Thank you for being here. I am just going to follow 

up a little bit on Congressman Shimkus. I mean you answered a 

lot of the questions in your opening testimony. But I had a group 

of oncologists in the other day. These aren’t people that make 

drugs, they aren’t people that sell drugs, people that—FDA issues 

or whatever you want to—these are guys just are taking care of patients, and they say they literally have to make choices about who 

they take care of because they don’t have the drugs available. So 

I ask kind of the questions, say, well, I can’t believe a company 

won’t make them if you have the demand for them. And they told 

me that this particular type of drugs, the generic are priced different in the Federal Government. So the Medicare actually prices 

these different than other drugs. Was that what they were saying 

was true? 

Mr. KOH. Well, I can start with that. And first of all, Congressman, thank you again for your attention to the patient. This is a 

dire situation for patients and I have actually trained in cancer as 

well as other fields so this is very personally and professionally important to me. 

We have a rule of Medicare here that reimburses according what 

is called the average sales price, so that is one factor here, but we 

don’t view that as a significant issue in driving the shortages that 

we are seeing here. 

Mr. GUTHRIE. But these generics are a different system than others because what we are seeing is you mentioned that pharmacy 

benefit managers, all these are driving down drug costs where they 

are doing it, you know, a pharmacy benefit manager is trying to 

do all drug costs. 

Mr. KOH. Sure. 

Mr. GUTHRIE. But we seem to see this particular class of drugs 

having a bigger problem than others and the only thing that I can 

see that is different is the way the Federal Government treats 

them. They treat them different than other drugs. 

Ms. KWEDER. I am not sure I can answer your question but these 

are generic drugs. They are off patent for the most part. You know, 

there are some that—so they are at a point in time where the profit margin for the drugs—generally because they are generic and 

you can have multiple manufacturers—is lower. 

Mr. GUTHRIE. Right. 

Ms. KWEDER. And it wouldn’t be just—you mentioned Medicare, 

CMS, but there are many other group purchasers—some of them 

are government-related, others are private insurance companies 

that are negotiating in bulk basically of prices. And they are no different than what the Federal Government does. It is the same. 

Mr. GUTHRIE. But why isn’t that happening in other classes—I 

mean this seems to be particularly more than others. 

50 

Ms. KWEDER. Well, in the other classes, in the non-generic world, 

there is one source. 

Mr. GUTHRIE. Um-hum. 

Ms. KWEDER. And so they are in a great bargaining position because they are a sole source, the innovator product, they have a 

patent. 

Mr. GUTHRIE. But there is a different system for generic drugs 

in Medicare than—— 

Ms. KWEDER. They tend to be priced lower. 

Mr. GUTHRIE. Priced lower? 

Ms. KWEDER. Absolutely. And that, of course, is the access point 

for the public. 

Mr. GUTHRIE. Right, if you have lower costs, which we all want 

to drive lower costs, believe me. We are all trying to save—but you 

have lower cost, then you get less supply as you are saying because 

the prices are obviously lower and you have less quality of people 

producing. And so according to the oncologists there is not a mechanism where if just you pay just a little bit more, you are going 

to get the drug that is going to take care of—you know, there is 

not a price mechanism to say we have got a low supply that Congressman Shimkus is talking about. Therefore, if we can adjust the 

price, we get the supply that we need to take care of patients. 

Mr. KOH. Well, the situation is summarized by Dr. Kweder, but 

Congressman, I think you were raising some interesting points 

where we can get you more information—— 

Mr. GUTHRIE. OK. 

Mr. KOH [continuing]. And work with you. 

Mr. GUTHRIE. Because whatever we can do—I mean the things 

that you mentioned, business decisions, that is all part of the mix 

but there are some things we can do from this side. 

Mr. KOH. Thank you. 

Mr. GUTHRIE. And one other thing just quickly on the FDA, the 

2 to 3 years you said, now you have got the flexible teams, is that 

relatively new? Because after these oncologists said this I reached 

out to some people and they did talk about some issues with inspection and inspection time like Congressman Shimkus. So it is 

being addressed—— 

Ms. KWEDER. Absolutely, it is being addressed. It absolutely is 

being addressed. 

Mr. GUTHRIE. OK. Maybe just hear from the ones who have the 

worst experiences I guess but that is good because I know with 

your physicians and the oncologists I met, you take care of patients, so I appreciate your attitude in moving forward to do so. 

So thank you and I yield back. 

Mr. PITTS. The chair thanks the gentleman and now recognizes 

the ranking member emeritus of the full committee, the gentleman 

from Michigan, Mr. Dingell, for 5 minutes for questions. 

Mr. DINGELL. Mr. Chairman, thank you for your courtesy and 

thank you for holding this hearing. 

Let me begin by asking this question yes or no. Do you have authority at FDA or at HHS to waive any of the requirements with 

regard to efficacy, good manufacturing practices, or safety, yes or 

no, in the event of shortage? 

Ms. KWEDER. Yes. 

51 

Mr. DINGELL. You do have it? 

Ms. KWEDER. We have the authority to use flexibility in how we 

implement the regulations. 

Mr. DINGELL. OK. 

Ms. KWEDER. Regulatory discretion. 

Mr. DINGELL. I would like to have a further answer on that particular point. 

Ms. KWEDER. But the requirements are the same. How one 

reaches them is flexible. 

Mr. DINGELL. OK. I would like to have further statement on that 

for the record so we can understand what your authority there is. 

It is my understanding that the FDA has been working to address shortages of medically necessary drugs. Can you please define what medically necessary means, please? 

Mr. KOH. Medically necessary is defined as a product used to 

treat or prevent a serious disease or condition for which there is 

no other product available to act as a substitute. 

Mr. DINGELL. I believe you have indicated in your testimony that 

the vast majority of shortages experienced in the United States is 

attributable to sterile injectables. Is that correct? 

Mr. KOH. Yes, sir, that is correct. 

Mr. DINGELL. And according to your testimony, the majority, 

some 54 percent of these shortages were due to ‘‘product quality 

issues such as particulates, microbial contamination, impurities, 

stability changes resulting in crystallization.’’ Is that right? 

Mr. KOH. That is right, Congressman. 

Mr. DINGELL. Were you finding those in American pharmaceuticals or imports? 

Mr. KOH. We were finding them here in the United States. 

Mr. DINGELL. What about imports? 

Mr. KOH. Well, those are exactly issues we try to prevent which 

is why importing is always a challenging issue. In fact—— 

Mr. DINGELL. Yes, but you have really no authority to address 

the question of the manufacturing practices abroad. You have no 

real authority to deal with good manufacturing practices. You have 

no real authority to see to it that the requirements that are imposed on American manufacturers for safety, efficacy are there, and 

you have very little power to effectively inspect those foreign manufacturers either of finished pharmaceutical products or components 

and constituents, right? 

Mr. KOH. That is correct, Congressman. 

Mr. DINGELL. And you have no ability, really, to know who is 

manufacturing these things or to trace them through the product 

line, is that right? 

Mr. KOH. That is right. That is why the importation process is 

done very carefully and selectively. 

Mr. DINGELL. I have got some legislation to address that and I 

hope that we will be shortly addressing it here in this committee. 

I have a bill, as I mentioned, where we address the problem of 

quality problems in drug manufacturing process by requiring the 

drug manufacturers implementing effective quality system that 

complies with GMP. The quality system would also be required to 

ensure risk management procedures that would address all relevant factors through the supply chain, including original source 

52 

materials and their origin, onsite audits, and methods to detect or 

include potentially risky substances. Manufacturers would also 

have to maintain records and establish that the drug was manufactured and distributed under conditions that ensured its identity, 

strength, quality, and purity. Would legislation of this kind help 

you address quality issues? 

Mr. KOH. Yes, tracking quality every step of the way would certainly uphold patient safety. 

Mr. DINGELL. This is a matter on which I have worked with the 

gentleman, my colleague Mr. Shimkus. Now, it has been widely reported that when information becomes public about a drug shortage, an active gray market tries to sell drugs in short supplies to 

pharmacists or hospitals. Does this present a safety concern? 

Mr. KOH. Yes, it does, Congressman. 

Mr. DINGELL. Why and how and what can you do about it? 

Mr. KOH. Well, this is largely unregulated. The Federal Trade 

Commission is involved to some degree but unfortunately—— 

Mr. DINGELL. They don’t have the expertise that you have and 

would you submit to us a proper answer informing me what we 

have to do to address that particular problem? 

Mr. KOH. I would be happy to do that, um-hum. 

Mr. DINGELL. Now, when drugs are purchased in the gray market, do we know if these drugs have been stored properly to ensure 

effectiveness, whether the drugs have been diluted, or whether the 

drugs are free of filth contaminants or adulterates? Yes or no? 

Mr. KOH. No. Unfortunately, we know very little about the products in the gray market. 

Mr. DINGELL. Now, as I mentioned, I have a bill that would require manufacturers to maintain records establishing where the 

drug and its raw materials were produced, including all information relative to producers, manufacturers, distributors, and importers. Would such legislation and such power assist Food and Drug 

in assuring the safety of these kinds of pharmaceuticals? Yes or no? 

Mr. KOH. Yes, we want to uphold the safety and quality, so 

thank you for that. 

Mr. DINGELL. At the end of the day, American consumers and patients are facing 3 problems: 1) the drugs, they need to be available 

and affordable; 2) are there drugs they need safe; and 3) are they 

efficacious? Do they work? 

I believe the committee needs to examine these issues carefully 

and swiftly. Our colleagues in the Senate, Mr. Harkin and Mr. Enzi 

have already called on Food and Drug to improve its oversight of 

the pharmaceutical supply chain. I would hope this committee 

would follow suit, but I would like to have you give us a statement 

of what authorities you need to adequately carry that out. I don’t 

believe that sending you a letter asking you to do something for 

which you have no authority works. Would you submit, please, for 

the record because my time is up what it is that has to be done 

to give you the authority to address those problems? 

Mr. KOH. I would be happy to, Congressman. Thank you. 

Mr. DINGELL. Thank you. Mr. Chairman, I thank you for your 

courtesy. I ask unanimous consent that the responses be inserted 

in the record upon receipt? 

Mr. PITTS. Without objection, so ordered. 

53 

Mr. DINGELL. Thank you. 

Mr. PITTS. The chair thanks the gentleman and recognizes the 

gentleman from Louisiana, Dr. Cassidy, for 5 minutes for questions. 

Mr. CASSIDY. Hello. Thank you. 

Now, you do have the ability to import from overseas obviously, 

and there were issues raised regarding adequacy of quality control 

if you will. We think of Hepburn from China causing many deaths, 

correct? One of the issues that was raised here in a previous hearing was that the inspectors, as part of their union contract, can 

refuse to go overseas. And so I think Mr. Pallone spoke about inadequate resources, but the issue was that here there was enough 

money to inspect or a requirement to inspect a pharmaceutical 

every 2 years and there is happening only every 9, and when I ask 

could we just redirect resources to send that person over to maybe 

alleviate some of these by expanding importation, the point was 

that the unions would not allow this to occur. They had the right 

to refuse the overseas assignment. Is that true and to what extent 

is that limiting our ability to approve the APIs—I forget the acronym but you know what I am speaking of. 

Ms. KWEDER. In the terms of a shortage situation, that has not 

been a big issue. For the most part, when we have a circumstance 

where some inspection activity is necessary in order to prevent a 

drug shortage, we find that our staff are extremely cooperative and 

willing to roll up their sleeves and step in. We are addressing the 

issue of our inspection force more broadly in parallel to this, but 

it has not been a critical issue in mitigating or preventing drug 

shortages. 

Mr. CASSIDY. But there are a heck of a lot of generics being manufactured in India and other Third World countries so are they just 

not producing the ones that we are in short supply of or are we just 

not confident of the quality of the product which they produce? 

Ms. KWEDER. I am not sure I understand your question. 

Mr. CASSIDY. So is there a worldwide supply of drugs that are 

currently in shortage here? It is just that we are not trusting the 

manufacturing process by which they are produced and therefore 

do not allow their importation? 

Ms. KWEDER. I would say the lack of allowance to import a product has been unusual. If there is a foreign source, we are usually 

able to work through and get it approved. There have certainly 

been circumstances where there have been important problems 

that would prevent that, but in most cases if there is a foreign 

source and going to a foreign source is necessary, we are able to 

work through that. 

Mr. CASSIDY. OK. In the gentleman who is going to testify from 

Teva, he speaks about how DEA has a quota for controlled products and that if somebody goes out of business, that quota might 

not necessarily be assigned to another manufacturer, and so you 

have a kind of centrally planned economy-induced shortage. Any 

comment on that and any way we can address that? 

Mr. KOH. I can start. I know that controlled substances represent 

only a very small part of the drug shortage situation that we are 

talking about, so we do work with DEA but it is limited only to several instances. And Dr. Kweder might add more. 

54 

Ms. KWEDER. And it is more complicated having the DEA involved for obviously good reasons. It does create an additional step 

and complicates this, but we work closely with the DEA when a 

controlled substance shortage is at issue. 

Mr. CASSIDY. And I understand that but is there any plans to 

make it so that if somebody stops producing their quota it is transferred to someone who would? Because I gather that is not the situation now. And although we are working closely, that is an obvious 

solution that I am not sure is being implemented from your statement. 

Ms. KWEDER. We are continuing to try and figure out how to expedite these kinds of issues with DEA. And I don’t have an answer 

for you about exactly when that will be resolved, but we are committed to doing it, as are they. 

Mr. CASSIDY. OK. Teva also mentioned—just because I, you 

know, I like to read what the other panels say so I refer to this— 

that the ‘‘speaking of a source or an active pharmaceutical ingredient,’’ they say that the qualification process to identify a supplier 

for such can be very onerous, the qualifying gain after you get approval for a new API supplier or alternative manufacturing site for 

an already-approved supplier can take as long as 2 to 3 years. Now, 

I am channeling my inner Teva wherever Teva is. You don’t have 

to testify anymore, but what would be your response to that? 

Mr. KOH. Again, these are areas where we are trying to show as 

much regulatory flexibility as possible to accelerate approvals when 

necessary. So we often address these themes through the maximum 

flexibility possible. 

Ms. KWEDER. And we already do. Whenever there is an issue related to a supplier where it requires FDA to approve a new supplier or even a new facility, I think that was one of the other concerns. We turn those around very, very quickly. 

Mr. CASSIDY. What would—— 

Ms. KWEDER. In a matter of weeks to months. These are not 

business as usual where there is a long wait time. We understand 

that patients are at the end of this line and we need to do everything possible to get on the case and work with the companies. And 

we have done that with Teva. 

Mr. CASSIDY. OK. I yield back. Thank you. 

Mr. PITTS. The chair thanks the gentleman and recognizes the 

gentleman from Utah, Mr. Matheson, for 5 minutes for questions. 

Mr. MATHESON. Thank you, Mr. Chairman. I appreciate your 

yielding time to me and I appreciate you holding this hearing. I 

think we have established the problem. I am sure lots of people 

have talked about circumstances in their district. I represent the 

University of Utah. They project more than 360 products having 

shortages and that many products by the end of this year. And I 

was at the Huntsman Cancer Institute just 2 weeks ago and they 

were talking to me about the challenges they are facing. So I guess 

everybody up here has a story, but I thought I would tell you it 

is in my backyard as well. 

I was wondering if you could address for me some of the concerns 

about gray market activity as a result of these drug shortages and 

the integrity of what is out there, the quality of the medications 

55 

if they are counterfeit or how we can address some of these challenges of a gray market when these medications have shortages. 

Mr. KOH. Well, I can start. And first of all, thank you, Congressman, for your commitment to research. We didn’t say explicitly but 

we can say now that this drug shortage issue is dramatically affecting clinical trials as well in cancer and infectious disease in many 

parts of NIH, so that is very, very troubling to us as a Nation that 

prizes scientific advances. 

The gray market, unfortunately, is very poorly understood and, 

as we have mentioned already, it is largely unregulated. And to 

have now this dimension complicating an already complicated situation is very disturbing. So we appreciate your attention to that 

and we want to address that as well as all the other factors that 

are involved here. 

Mr. MATHESON. Are there actions we should be taking on addressing the gray market specifically or should we really just be 

addressing on the underlying problem of the shortage of these 

medications? Is that the more valuable way to address—that would 

eliminate the gray market problem I guess if we don’t have shortages? 

Ms. KWEDER. One of the questions that was asked previously 

was about what we know about the products that appear on this 

gray market. 

Mr. MATHESON. Right. 

Ms. KWEDER. Do we understand when they expired, where they 

came from, and are they made by the company that is experiencing 

the shortage or are they counterfeit products? We don’t because we 

don’t have a tracking system within the drug supply to know what 

product comes from where. 

Mr. MATHESON. I appreciate that. I will do my 30-second advertisement. I just introduced with Mr. Bilbray this week our track 

and trace legislation, pedigree legislation for maintaining the integrity of the drug supply in this country. We are operating on rules 

that were created in 1988 and the world has changed. I don’t think 

this is going to be on the topic of this hearing, but there is just too 

much money on the table for the counterfeiters in terms of the U.S. 

pharmaceutical marketplace, and I hope this committee can take a 

look at this legislation Mr. Bilbray and I have introduced because 

I do think it is an important safety factor for the integrity of our 

supply in general. 

I appreciate your coming here for this hearing. Mr. Chairman, I 

yield back. 

Mr. PITTS. The chair thanks the gentleman and recognizes the 

gentlelady from Tennessee, Mrs. Blackburn, for 5 minutes for questions. 

Mrs. BLACKBURN. I want to thank our witnesses for being here, 

and as you know, some of us arrived a little bit late. We did have 

the Solyndra oversight hearing going on downstairs, so we completed that one before coming up. But we are grateful that you are 

here and our second panel of witnesses we are also looking forward 

to. And I am glad we have a Tennessean on that panel who will 

be joining us. 

Just a couple of questions. As you can see, we are going to look 

at how we address this issue and having you here helps to inform 

56 

our decision-making process. So a couple of things I would like 

know, and if you don’t have the answer for me, please submit it 

to us so that we can include it in our record. 

I wanted to see if each of you had any examples where you had 

worked closely and collaboratively with your agencies with manufacturers’ drugs where there was a known or a projected shortage 

and see if you could articulate what that process was, the interface 

that transpired there. And if you have those examples, ma’am, 

please go ahead and give them, and if not, we will accept those in 

writing. 

Mr. KOH. So Congresswoman, I can repeat the example that we 

are very proud to share actually here for the first time that had 

to do with cytarabine, which is a—— 

Mrs. BLACKBURN. OK. 

Mr. KOH [continuing]. Lifesaving drug used for acute leukemia. 

And this shortage received tremendous national publicity and represented a dire challenge for cancer patients. And so when the FDA 

worked with the industry on this particular drug, they found that 

one of the issues complicating the production was the crystallization of the drug in the solution and that re-warming it would restore the safety features that would allow infusion into patients. So 

with that collaboration between the FDA and industry, that issue 

has now been recently resolved and we are very, very pleased to 

report that. And I know my colleague has other examples. 

Ms. KWEDER. I actually would like to expand on that one—— 

Mr. KOH. OK. 

Ms. KWEDER [continuing]. Because before the issue of the crystals in the vials, where the cytarabine shortage began was it was 

being made by 3 companies but the majority of the supply was 

being made by one firm. They were experiencing significant production delays, so what FDA did was we contacted the other manufacturers to work with them to increase their production in order to 

be able to supply the market. In the course of them increasing 

their production and trying to produce product rapidly, the crystallization occurred in both facilities. So that preceded the crystals. 

We then resolved that activity as well. So in that case, we also, 

when there was concern about whether we would find a solution 

to the crystallization, we also investigated alternative manufacturers, whether there were any overseas. We were not able to identify 

any alternative manufacturers. They were all U.S. firms. 

Mrs. BLACKBURN. Let me interject there. Do you have examples 

other than this one? Are there examples where you worked with 

some of those alternative manufacturers and brought them into the 

fold, and then once you identify that there is a near-shortage that 

is approaching, do you think that there is a way through the production process or the compensation model to provide incentives so 

that you have a more predictable supply? 

Mr. KOH. Well, another example that we can provide for you, 

Congresswoman, has to do with purple fall, which is an agent that 

is used in anesthesia. And when those shortages started occurred, 

the FDA could facilitate temporary importation of a substitute 

agent to help ameliorate that situation. So that is yet another example and I know the FDA has many others. The economic issues 

here are so complex that offering any economic solution requires 

57 

first a careful analysis. And we are trying to do more of that, especially through our assistant secretary for planning an evaluation 

and we hope we can come out with some more definitive recommendations for you in that area in the near future. 

Mrs. BLACKBURN. Thank you. We appreciate that, and in the interest of time, I will yield back. 

Mr. PITTS. The chair thanks the gentlelady and recognizes the 

gentlelady, Mrs. Myrick, for 5 minutes for questions. 

Mrs. MYRICK. Thank you, Mr. Chairman. And thank you all, all 

of our witnesses for being here. I was also at another hearing so 

I am sorry I missed your testimony and some of the questions. 

Like everybody else, our area is experiencing the same problems 

and our doctors, we meet with them constantly. But particularly in 

anesthesiology and oncology as you well know, we have the problems. And it is scary from the standpoint of what could happen 

with somebody if they are given another drug that really doesn’t 

either work or they, you know, have a reaction to it or something. 

And thank you very much for any efforts in trying to get to the bottom of it. 

And I wanted to ask if really the consolidation has taken place 

in the drug industry over the last few years and continues to place, 

you know, what effect or how does that contribute to the problem 

that we are seeing today? I mean is this a large contributing factor 

because of fewer manufacturers available? 

Mr. KOH. Thank you, Congresswoman, for your interest and support. And yes, we view industry consolidation as one of the driving 

causes here, and as you can imagine if you are a denominator of 

or a manufacturer shrinks and then any one of them has a manufacturing problem or delay, it really puts the onus on the others, 

and if the others don’t happen to produce that product and if this 

particular company is a sole source producer, then you have the 

number of occasions that we are seeing right now. So there is no 

doubt that industry consolidation has contributed to this. 

Mrs. MYRICK. So what if any recommendations do you have of 

how we get over this hump? Because, you know, you mentioned the 

generics which we are all very much aware of and the fact that are 

just as popular to do because of the cost factors and other things 

that have entered into it. I mean what is it that you think we 

should be doing or looking at to try and get to the bottom of how 

we can help with this. 

Mr. KOH. Well, we again want to stress the importance of communication and early notification because that will help all parties 

to work together. And as the number of industries involve shrinks, 

we want to really maximize our communication with those manufacturers, and we are doing so as we speak. And then as Dr. 

Kweder mentioned, we also want to have more assurances that the 

products that are being produced have high quality so that we 

don’t run into these quality and manufacturing issues. So those are 

2 things that would be very helpful to us. 

Mrs. MYRICK. And you find the companies work well with you? 

Mr. KOH. We have had excellent dialogue to date and I want to 

do much more of that, not just the FDA but the entire department 

and also engage the public in this as you have heard. 

Mrs. MYRICK. Thank you. I will yield back, Mr. Chairman. 

58 

Mr. PITTS. The chair thanks the gentlelady and recognizes the 

gentleman from Pennsylvania, Dr. Murphy, for 5 minutes for questions. 

Mr. MURPHY. Thank you. And I thank this distinguished panel 

and we appreciate your concern for our citizens of this country. 

A couple areas here. Are you meeting with the manufacturers? 

I want to ask a couple questions to find out here with regard to 

what are some of the causes of this drug shortage. You laid out a 

number of these things very well, thank you. But let us say, for example, cancer drugs. Why the shortages with cancer drugs? We 

know they are very expensive in many cases. What specifically is 

the reason for that? 

Mr. KOH. Well, it is very distressing, Congressman, some of these 

time-honored lifesaving medications now being caught in the middle of this public health crisis and some of the agents we have 

mentioned here, cytarabine, vincristine, bleomycin, time-honored 

agents that have been shown to be effective for decades are now 

stuck in these shortages. So again these are older generic sterile 

injectable drugs that are typical of the ones that are being—— 

Mr. MURPHY. But can I ask specific things. Do we not have 

enough manufacturers, for example, working on these things? Is 

that part of the problem? 

Mr. KOH. That is part of the problem, again, because the industry has consolidated and so we don’t have the dozens and dozens—— 

Mr. MURPHY. Of those who are there, are they not working at capacity? Do we know if that is an issue? 

Mr. KOH. I am not sure I can address that directly. 

Ms. KWEDER. I think that what often happens in a lot of these 

companies, they make dozens of products. 

Mr. MURPHY. Um-hum. 

Ms. KWEDER. These sterile injectables can only be made in certain types of facilities so there are a limited number of those. And 

because of the market and the few number of producers, there is 

pressure to produce and continually produce. And so maintenance 

of the facilities themselves is often put off because it requires an 

investment on these low profit margin—— 

Mr. MURPHY. They are expensive, the low profit margins? 

Ms. KWEDER. Right. Some of them are not terribly expensive but 

low profit margin. So there is—— 

Mr. MURPHY. That is important what you just said. So this is one 

of the concerns we have. Certainly, we want medications to be affordable. I mean why window shop when you can’t afford, but in 

our push to make sure that drugs are affordable, are we also tripping over ourselves? It is hurting the patients when we say we 

want there to be such a low profit margin that it ends up backfiring and we don’t end up with the medications that save lives? 

Is that part of our policy that is getting away for us? 

Mr. KOH. Well, thank you for posing those questions and obviously ultimately our goal is to protect the patient and give timely 

delivery of a lifesaving medication—— 

Mr. MURPHY. And even if you don’t have the information today, 

is that something you could advise us on? I am looking for anything politics aside. I really want to know from the standpoint of 

59 

myself as a healthcare provider. If we are doing something that is 

saying we want drugs to be affordable but we are cutting the price 

so much that people don’t want to make them, that is a serious 

concern. And so my question is policy interference. If you can’t answer that today, I just want to know if you will get back to us with 

that. 

Mr. KOH. Sure, Congressman. Those are precisely the issues that 

we are wrestling with as a department and as a country. So thank 

you for posing that. 

Mr. MURPHY. And I say this from the standpoint of, look, what 

oftentimes what goes around the Hill is lots of accusations and politics. We can’t afford to engage in any of that on these lifesaving 

issues. And so I am trusting you to give us those honest answers 

and I really appreciate it from one colleague to another here. 

Mr. KOH. Thank you so much, Congressman. 

Mr. MURPHY. And also with regard to inventories, I am hearing 

that hospitals are saying they are having a hard time keeping their 

inventory. It is not an issue that they are not purchasing enough, 

correct? Or is it? If a hospital says we can’t have some of these 

things in supply because it may be too expensive or too difficult for 

us to keep these in inventory because of special requirements for 

how to maintain them, how to secure them, the special conditions 

under which they might be—is that part of the problem, too, they 

may not be ordering enough because for themselves it is also very 

expensive? 

Ms. KWEDER. I believe that it can be a problem. There also has 

been a trend—this is certainly not 100 percent but there has been 

a trend in the industry to have what some people call just-in-time 

production. 

Mr. MURPHY. Um-hum. 

Ms. KWEDER. They don’t have the long lead time at production 

that may be—particularly for these sterile injectables that there 

may be for other products that have longer shelf lives. So they tend 

to make less and distribute it out in smaller amounts—— 

Mr. MURPHY. Um-hum. 

Ms. KWEDER [continuing]. Which certainly contributes to hospitals not being able to maintain a large supply and cushion in addition to what the other concerns that you mentioned—— 

Mr. MURPHY. And again, the just-in-time inventory is one where 

they are thinking that they also have a small margin. I mean it 

is one of these things, look, we understand healthcare is expensive. 

Sickness is more expensive and we all want to work together. And 

so I do appreciate and look forward to seeing your information on 

this. Thank you very much. 

I yield back, Mr. Chairman. 

Mr. PITTS. The chair thanks the gentleman and recognizes the 

gentleman from Georgia, Dr. Gingrey, for 5 minutes for questions. 

Mr. GINGREY. Mr. Chairman, thank you very much. I am sorry 

I missed a lot of your testimony, witnesses, but thank you for being 

here. 

Let me first address to Secretary Koh, in your testimony you cite 

that there were 178 drug shortages in 2010 and that sterile 

injectable drugs make up a large and increasing share of these 

shortages and by my count, roughly 132 of the 178 were for sterile 

60 

injectables. Of these injectable drugs, can you tell me how many 

were in shortage in previous years? Has it been a long-term problem or just more recently? 

Mr. KOH. This is a long-term problem, Congressman, and unfortunately, the trend is going the wrong way. The shortages are increasing year by year. We did it back through 2006 and the trend 

is getting worse since then. 

Mr. GINGREY. And then tell me this. Are there any other common 

characteristics that you are aware of among these 132 besides the 

fact that they are generic and they are sterile injectables? For instance, are these drugs typically newer generics or drugs that have 

been on the market for years? Actually, you just answered that and 

I thank you. Well, the other thing on that is are the profit margins 

typically very low or any other issues that you might be aware of? 

Mr. KOH. So on the first question, Congressman, the irony here 

is that these are older generic drugs that we understand are very 

helpful if not lifesaving and so to have this situation is really quite 

ironic and tragic. And you are right, there is an issue with respect 

to business forces here and the profit margin is understood to be 

quite low for many of these individual products. 

Mr. GINGREY. And my last question can really go to either one 

of you, Mr. Secretary or Dr. Kweder. Am I saying that correctly? 

Good. Help me understand something. Mr. Shimkus earlier addressed this. Many of the drugs we are talking about are these 

older generics, not just the sterile injectables, where the profit margins can often be very low. These low profit margins can oftentimes 

lead to very little competition or even drugs for which only one 

company make the product. Mr. Shimkus raised this point about 

the market prices and I understand maybe, Secretary Koh, you 

tried to answer this for him. I just want to be clear. Do either one 

of you have any thoughts as to why you get to the point where 

there is a limited number of manufacturers of a particular generic, 

why the prices at that point remain low? I mean the market should 

be able to work—the market of supply and demand and obviously 

when a brand name drug, which is very expensive, first goes generic and you have several manufacturers jumping in an producing 

that generic at a much, much lower price, and then finally it gets 

too low for some of them to survive, they stop doing it and go on 

to something else, maybe another generic and a couple or maybe 

even one company hangs on. It would seem because of supply and 

demand that that company would be able to raise their prices. Are 

there any government rules, regulations, laws, pharmacy benefit 

managers, something that would cause them not to be able to raise 

their prices even though the market would certainly let them do 

that otherwise? 

Mr. KOH. Yes, Congressman, so we have come to understand that 

this is a complex business situation where the standard economic 

principles of supply and demand do not easily apply. And we have 

manufacturers, we have purchasers, providers, hospitals, we have 

group purchasing organizations and pharmacy benefit managers, so 

we have multiple forces here all working to the final outcome that 

ordinarily you would see with a rise in pricing profit, but that 

doesn’t apply here. So this is why we need the extra analysis that 

our department is doing and others and we welcome new informaVerDate Aug 31 2005 13:50 Mar 13, 2013 Jkt 037690 PO 00000 Frm 00064 Fmt 6633 Sfmt 6633 F:\112-08~4\112-88~1 WAYNE
61 

tion and modeling to really help us understand the root causes better. 

Mr. GINGREY. Dr. Kweder? 

Ms. KWEDER. I think the questions that you raise are exactly 

some of the questions that we have as we really try to understand 

the roots of this problem. What are the things that could be done 

to try and prevent these shortages from occurring or even being at 

risk in the first place. 

Mr. GINGREY. Well, I thank both of you for those answers because, you know, the Federal Government tries to do the right 

thing in many instances—I would hope in all instances and it 

seems that far too much of the time they screw it up. And so that 

is why I ask you those questions and I hope that you will continue 

to look at that so that market forces can continue to prevail. Then 

I don’t think we would be faced with these shortages. 

Mr. PITTS. The gentleman yields back? This is the round of questions for the subcommittee members. We have a couple of members 

of the committee who have joined us. The chair recognizes the gentleman, Mr. Walden, for 5 minutes for questions. 

Mr. WALDEN. I thank the chairman very much, first of all, for his 

recognition since I am not a member of the subcommittee but also 

for having this hearing. And I appreciate the testimony from the 

2 witnesses today. I got involved in this issue some time ago because of an oncology doctor in my district, Dr. Chuck Dibs, who 

brought this issue to my attention, my staff’s attention. And the 

drug specifically that I recall he mentions was—and I will try and 

say this right—doxorubicin. Is that right? I understand it is an 

ovarian cancer drug which he has prescribed for a very long time, 

apparently a very effective drug. And I am not a doctor but that 

is what he tells me. What was the FDA’s role in interrupting the 

production of that drug? Can you speak to that? 

Ms. KWEDER. I can speak to that very generally. There were several companies that produced doxorubicin. One of them which was 

the major supplier also was the same producer for the cytarabine, 

APP, that Dr. Koh mentioned earlier. Some of the issues were exactly the same. There were facility issues, production delays because of, you know, chronic problems in an aging facility is probably the best way to summarize it. What FDA did was we worked 

with the other 2 producers to facilitate their ability to increase production. It did take a while. As I said, these are complex products 

to make. Companies can’t just ramp up production overnight. 

Mr. WALDEN. Right. 

Ms. KWEDER. But in the meantime, a fourth company came in 

with a new version of the product and helped to make up the supply. So we make sure to expedite review of that fourth company’s 

application and the inspections, et cetera, that were necessary in 

order to turn this around. 

Mr. WALDEN. Now, Dr. Koh, do you have any comment on that? 

Mr. KOH. I think Dr. Kweder summarized it well. 

Mr. WALDEN. So you feel like you have taken all the steps? This 

drug is now available on the market again and without shortage? 

Is this accurate? 

Ms. KWEDER. My expert tells me, yes. Yes, doxorubicin itself is. 

There is another version of the drug that is sort of a special formuVerDate Aug 31 2005 13:50 Mar 13, 2013 Jkt 037690 PO 00000 Frm 00065 Fmt 6633 Sfmt 6633 F:\112-08~4\112-88~1 WAYNE
62 

lation that has a sole source that continues to be a problem, but 

again, that is a different company. 

Mr. WALDEN. All right. I know, Dr. Koh, you mentioned glass 

and metal in injectables I think you were discovering which sends 

sort of shivers up everybody’s spine. I have also heard though that 

with the new technologies, the scientists are able to see deeper into 

the drugs we had ever seen before in parts per billion or whatever. 

Again, this is your field, not mine. But are we looking deeper and 

finding things that we never knew was there before and is that 

really a problem from a health standard or is it a question that 

may play a role? 

Mr. KOH. Well, again, those examples, Congressman, are very 

graphic examples on the quality issues that we are facing. I must 

say though that again the FDA has worked with companies so in 

the case of particulate matter—pieces of glass, pieces of metal— 

first to identify the issue but also there have been advances in developing filtering systems so we can filter those out and make 

those drugs then safe to inject into patients. So that is another example of regulatory flexibility that has marked this chapter of our 

history. So I guess the end of my time is about to expire but—I 

mean my time to ask questions is about to expire. I just want to 

clarify that. 

It is this sense of urgency. I applaud you for bringing people together and trying to figure this problem out, but as I am hearing 

from both Dr. Dib and others in my district there is this, you know, 

patient comes in, the drug is not available, they have been prescribed it for years, it is effective, it works, and they can’t get it. 

I know my own mother had ovarian cancer and died from it and 

so I have just this sense of patient urgency. I know you feel that, 

both of you. We all do. And so if there is a way we can play a constructive role here, whether it is Ms. DeGette’s bill on notification, 

I mean she has put a lot of work into this. You know, we just need 

to do everything we can to be a partner in this to find a solution. 

I look forward to working with both of you and members of this 

committee to the extent they will let me play a role. So with that, 

I would yield back the balance of my time. 

Mr. PITTS. The chair thanks the gentleman and recognizes the 

gentlelady from Colorado, Ms. DeGette, for 5 minutes for questions. 

Ms. DEGETTE. Thank you very much. And I want to thank my 

colleague from Oregon for the free commercial announcement. 

Mr. Chairman, thanks for letting me participate. It is good to be 

back in my old stomping grounds of the House subcommittee. As 

I know you have been discussing, Congressman Rooney and I have 

introduced in a bipartisan way the Preserving Access to Lifesaving 

Medications Act, which creates an early warning system between 

FDA drug companies and providers so that we can respond to these 

drug shortages quickly and efficiently. Do I think that this bill will 

solve the root problems of the drug shortage crisis? No. But do I 

think it is a necessary first step? Absolutely. And I appreciate the 

witnesses coming here to talk to the members of this committee. 

This bill came up because Mr. Rooney and I independently were 

going around meeting with our hospitals and our doctors and suddenly, they started saying to us, you know, I was in the middle of 

a chemotherapy treatment of a child and suddenly I couldn’t get 

63 

the drug. And I am sure it didn’t happen immediately but it 

seemed like it did. Doctor, you are shaking your head. Do you want 

to comment on that? 

Ms. KWEDER. Well, to the prescriber, you know, they are not following, you know, Web sites. They just know that they can’t get 

the drug and they have a patient who is ill and needs it today or 

tomorrow and not in 2 months when the supply can be re-upped, 

and that is a very difficult position to be in as a physician and even 

worse as a patient. 

Ms. DEGETTE. And is there some reason why these shortages 

have increased recently? Either one of you? 

Ms. KWEDER. We are trying to understand that. Some of the 

things that we have identified is that these are products that are 

complicated. Most of the products that have been problematic are 

complicated to produce, there are a limited number of producers, 

and many of them are working in facilities that are aging and have 

had chronic challenges in maintaining production or product quality. 

Ms. DEGETTE. Yes. And you know, I think before I got here, Mr. 

Chairman, you had discussed the current reporting system, which 

is the reporting system for companies that don’t have competition 

and it is a voluntary system. Even though it is much more limited, 

it has really worked. In 2010, 38 drug shortages were avoided 

when the Agency was given advance notice. And I just want to give 

a couple of examples. In August of 2009, Hospira notified FDA of 

their intention to discontinue the drug potassium phosphate in 

2010 due to low volume. The drug is often critical for neonatal care. 

Hospira received a note back from the FDA drug shortage in September 2009 thanking them and then in March 2011 the other supplier of potassium phosphate, American Regent, recalled its product because of a quality issue. So what happened then is in April 

2011, the FDA made Hospira aware of the drug shortage caused by 

the recall and asked them to assess their ability to return to manufacturing. And then in that same month, Hospira told the Agency 

that they would return to manufacturing potassium phosphate so 

that the patients could be served. And so it worked. But that is on 

a very limited basis. And so I just think that this could really work. 

And I guess I want to ask you, Dr. Koh, in my minute remaining, 

how will it work if we enact legislation like this to get the information into the providers’ hands that there is an impending drug 

shortage? Because you folks have had some experience with it. 

Mr. KOH. Sure. And Congresswoman, first of all, thank you for 

your leadership on this issue. It is very, very much appreciated. 

And we all feel that establishing the highest level of communication as early as possible about any potential shortage could give us 

the opportunity all to be proactive. And that is not just FDA and 

HHS but also providers and hospitals and patients. So if we can 

do this together, understand that a potential shortage is on the horizon as soon as possible, make that information available to relevant parties and ultimately to patients and the public, then we 

can all work together in a proactive way. 

Right now we are in a situation that you have summarized very 

well where the reporting is voluntary. Oftentimes the FDA does not 

know until too late and then patients are stuck in this dire situaVerDate Aug 31 2005 13:50 Mar 13, 2013 Jkt 037690 PO 00000 Frm 00067 Fmt 6633 Sfmt 6633 F:\112-08~4\112-88~1 WAYNE
64 

tion, which is just not acceptable. So we are looking forward to 

greater emphasis on early notification and communication. 

Ms. DEGETTE. Great. Thank you so much, Mr. Chairman. My 

time has expired. 

Mr. KOH. Thank you, Congresswoman. 

Mr. PITTS. The chair thanks the gentlelady. 

Before we go to Panel 2, we have one request for a follow-up for 

Panel 1. Without objection, we will let Dr. Cassidy ask that followup question. 

Mr. CASSIDY. Thank you. My office had looked into I think maybe 

it had been cysteine. And there was a problem that we heard back 

from you of endotoxin being in the product and it was unclear 

where in the manufacturing process that endotoxin had been introduced. Now, obviously that is an issue and frankly, I called my constituent. I said FDA did the right thing. We don’t know whether 

endotoxin was introduced. It is very disturbing to me that 

endotoxin should be in the product so we are kind of 

euphemistically speaking about manufacturing problems but really 

they are significant. So is it a pattern? And when we are saying 

manufacturing that know there is actually some sort of contamination such as endotoxin for which in their GMP they do not know 

where it is entering. Because that is a process problem that is of 

tremendous concern. 

Ms. KWEDER. The answer is yes. That is exactly the kind of thing 

that we are concerned about. When you find end product that has 

endotoxin in it, the first thing one needs to do is figure out how 

that endotoxin is getting in there in the first place. And there are 

multiple steps in production where that could be occurring and figuring it out is not easy and it can take a very long time to determine that and then a long time to fix it. And particularly we see 

this with metal shavings in medicine, glass shards in vials, all 

things that would be unconscionable to give to patients. But the 

key is being on top of those good manufacturing practices and 

maintaining facilities to avoid those kinds of events. And where 

you have facilities that are in 100 percent production mode all of 

the time, it is often difficult to maintain your facilities and modernize them in a way for a company to assure that they are producing a reliably high-quality product. 

Mr. CASSIDY. Thank you, Mr. Chairman. 

Mr. PITTS. The chair thanks the gentleman. I believe Mr. Pallone 

has a follow-up as well. 

Mr. PALLONE. Dr. Koh, as Mr. Shimkus said earlier, classic economics would suggest that when a product is in demand, prices 

should rise and the market establish a new equilibrium, yet we are 

now in the seventh consecutive year with more shortages than the 

year before. I am also curious why the market has failed to establish an equilibrium because both Mr. Shimkus and Mr. Guthrie discussed public program pricing constraints, and as I understand 

these constraints, they apply to brand name drugs and not 

generics. Is that correct that they only apply to the name brand 

and not generics? 

Mr. KOH. Well, Congressman, those economic issues are precisely 

the ones that we are analyzing right now. And we have especially 

our assistant secretary for planning and evaluation and health 

65 

economists looking at the economic principles and the modeling 

that could help us predict where we need to go in the future. So 

thank you again for raising these issues. These are very, very complicated business and economic models we have come to find. 

Mr. PALLONE. The generic drugs are where we have seen most 

of the drug shortages in recent years. 

Mr. KOH. That is right. 

Mr. PALLONE. I mean if there is that distinction, is that the problem? 

Mr. KOH. Well, we do know that is it older generic sterile 

injectables that are making up about 3/4 of these shortages. And 

so that is where we are indeed focusing our attention. 

Mr. PALLONE. I don’t know if either Mr. Shimkus or Mr. Guthrie 

asked you if you said you were going to get back to them, but, you 

know, I would really like to get some answers, you know. I mean 

obviously you are not prepared or you don’t feel you have an answer today, but I would like you to get back to us through the 

chairman if you could. 

Mr. KOH. I would be happy to, Congressman. So again I did mention we have an upcoming report from the FDA that is going to 

give further economic analyses that are also intensely underway 

right now. 

Mr. PALLONE. Is that going to relate to this or you don’t know 

for sure? 

Mr. KOH. Hopefully we will get a better understanding of root 

causes. 

Mr. PALLONE. Mr. Chairman, if he could get back to us on that 

because I know many of us have sort of asked the same question 

and I would really like to know. 

Mr. KOH. Sure. Thank you. 

Mr. SHIMKUS. If the chairman would yield just on this point. 

Mr. PITTS. Go ahead. 

Mr. SHIMKUS. And I thank my friend for following up on this debate and this question. But in my opening statements, I didn’t just 

focus on the government pricing. I did say insurers, too, so I mean 

we are all kind of in this together and the market going to work 

it has got to work. So I just wanted to just correct the record. I 

wasn’t just picking on—— 

Mr. PALLONE. Oh, no, I understand. I just wanted to bring up the 

public program aspect. Whenever, you know, you can get back to 

us on it because I think, you know, I mean I understand to be perfectly honest, I mean a lot of the questions that we have asked 

today we have gotten a response and we have a little better idea, 

but I almost feel like more questions have been raised than answered today. And that is not anybody’s fault but that is kind of 

where I feel we are right now, Mr. Chairman. 

Mr. PITTS. All right, thank you. If you will respond to the questions in writing, we will get those to the committee members—— 

Mr. KOH. Thank you, Chairman. 

Mr. PITTS [continuing]. And I look forward to reading your report. The chair thanks the first panel for your—— 

Mr. KOH. Thank you very much. 

Mr. PITTS [continuing]. Testimony. Thank you. We will call at 

this time Panel 2. And our second panel consists of 7 witnesses. 

66 

Our first witness is Mr. Jonathan Kafer, Vice President of Sales 

and Marketing for Teva Health Systems and testifying on behalf of 

Teva Pharmaceuticals. Next is Mr. John Gray, the President and 

CEO of Healthcare Distribution Management Association. Our 

third witness is Kevin Colgan. He is the corporate director of pharmacy at Rush Medical Center in Chicago. Our fourth witness is Mr. 

Mike Alkire, Chief Operating Officer of Premier, Inc. Next, we will 

hear from Dr. Charles Penley, who is testifying on behalf of the 

American Society of Clinical Oncology. We also have Mr. Richard 

Paoletti, the Vice President of Operations at Lancaster General 

Health. And finally Dr. Robert DiPaola, Director of the Cancer Institute of New Jersey. 

We thank all of you for coming. Your written testimony will be 

entered into the record. We ask that each of you would summarize 

your testimony in 5-minute opening statements. 

And Mr. Kafer, you may begin your testimony. 

STATEMENTS OF JONATHAN M. KAFER, VICE PRESIDENT, 

SALES AND MARKETING, TEVA HEALTH SYSTEMS; JOHN M. 

GRAY, PRESIDENT AND CEO, HEALTHCARE DISTRIBUTION 

MANAGEMENT ASSOCIATION; KEVIN J. COLGAN, CORPORATE DIRECTOR OF PHARMACY, RUSH UNIVERSITY MEDICAL CENTER, ON BEHALF OF AMERICAN SOCIETY OF 

HEALTH–SYSTEM PHARMACISTS; MIKE ALKIRE, CHIEF OPERATING OFFICER, PREMIER, INC.; W. CHARLES PENLEY, 

CHAIR, GOVERNMENT RELATIONS COMMITTEE, AMERICAN 

SOCIETY OF CLINICAL ONCOLOGY; RICHARD PAOLETTI, 

VICE PRESIDENT, OPERATIONS: PHARMACY, LABORATORY, 

AND RADIOLOGY, LANCASTER GENERAL HEALTH; ROBERT 

S. DIPAOLA, DIRECTOR, CANCER INSTITUTE OF NEW JERSEY 

STATEMENT OF JONATHAN M. KAFER 

Mr. KAFER. Thank you, Chairman. Chairman Pitts, Ranking 

Member Pallone, and distinguished colleagues within the subcommittee and full committee, thank you very much for the opportunity to be here today. As referenced by the chairman, my formal 

testimony has been submitted to you. I am more than willing to answer questions specific to that testimony throughout the questioning period and I will summarize my remarks in my opening. 

I am John Kafer. I am vice president of sales and marketing for 

Teva Health Systems, representing Teva Pharmaceuticals. Teva 

Pharmaceuticals is a global leader in brand, generic, and biologic 

pharmaceutical products. We are a market leader in many of the 

markets in which we serve. Here in the United States, we are the 

market leader in generic products. We have a vast portfolio including many dosage forms, including oral solid presentations, 

injectable presentations, including a significant portfolio of oncology generic injectable presentations, and I look forward during the 

questions period to share some insights specific to that very important category. 

As referenced, we are a market leader. Teva is a market leader 

and we understand and embrace the responsibility that does come 

with being a market leader, and in that context, I am very happy 

to be here today. 

67 

One side note, as all of us have been, we all have personal stories 

as it relates to family, friends, people we know, individuals that 

have been impacted by not being able to get medications. In my 

particular situation, I have friends and family as well. Given the 

role I play, they reach out to me hoping I may be able to make a 

difference. Unfortunately, there is many times I can’t and it is very 

challenging. At the same time, given the role I play, I hear from 

patients, I hear from family members of patients, I hear from constituents, I hear from physicians looking to the manufacturer to 

ask the question, ‘‘Why?’’ And we respond and we certainly understand that. 

And at the same time, I see every day when I go to work hundreds and hundreds of people working tirelessly around the clock, 

sparing no expense to do whatever we can to return to historical 

production volumes so that we can get these critical products back 

to market. 

As referenced in earlier testimony, this is a very complex multistakeholder issue and it is going to require the coordination and 

communication amongst all those stakeholders in order for us to resolve this issue. As noted in earlier testimony as well, there are 

many factors that impact the drug shortage issue, whether it be 

API being sourced and available. We have discussed that. The industry has experienced manufacturing challenges. I will go into 

greater detail specific to how it impacts a sterile facility versus an 

oral solid facility. And there has been regulatory impacts on facilities. 

As appropriate and as required, the FDA regulates these complex 

facilities and these products to assure that the manufacturing community is operating within full CG&P compliance, ultimately to 

provide the highest quality of products to all of us in this room. We 

understand that and, as a manufacturer, we certainly embrace 

that. 

Most of the shortages, however, are unanticipated. Those unanticipated shortages can have boomerang effects up and down the 

supply chain. And as noted in earlier testimony, as we will get into 

in greater detail, there are a handful of manufacturers that sometimes are unable to pick up the lost supply from another manufacturer, and we will go into detail around that as well. 

What is Teva doing specifically to address some of the drug 

shortage issues? We have made a significant investment in enhancement of our facilities as well as our quality systems. We have 

unrestricted access to our resources globally to prioritize those people in those facilities that require the work that needs to be done 

to get the products back to market. We have embarked on a very 

aggressive redundancy plan. There is no requirement to a manufacturer to have a secondary or tertiary facility qualified to manufacture these products. We have identified, in combination with drug 

shortage division, those most critically medically necessary products and we have 5 FDA-approved facilities and we have put a 

team in place that is actively working on redundancy planning for 

these critical products. 

As referenced also from the testimony of Dr. Kweder and Dr. 

Koh, there has been extraordinary collaboration within the FDA 

branches as it relates to resolving and mitigating these challenges. 

68 

I can speak to a couple of different references. 1) There was a discussion earlier in testimony around coordination of importation of 

products to alleviate critical drug shortages. There was a specific 

instance in which we worked with the FDA to bring in a product 

called leucovorin that is used in combination with chemotherapy 

twofold to enhance the effectiveness of that treatment as well as 

to mitigate side effects. We brought it in, we had a significant 

amount of resources to work collaboratively with that, and we were 

able to help mitigate that problem. 

The solutions that we are looking at, recognizing it is a multistakeholder issue, I do need to comment that as it exists today, 

there is tremendous cooperation within the drug shortage group 

and the manufacturing community. As referenced earlier, there is 

no formal process. It is an informal process. And I can speak on 

behalf of Teva and the other leading manufacturers in this space 

that we do all collaborate with the FDA, as testified earlier, and 

we take that very seriously and we are responding where we can. 

The doxorubicin example mentioned earlier, I received a phone call 

from York shortage, do what we can. We were able to work in collaboration with them and get product released to market and we 

continue to prioritize those types of products. 

During questioning, I would be more than happy to go into greater detail around how we are seeing the coordination and the effectiveness and how we would like to see a greater communication 

amongst multiple stakeholders beyond the manufacturer and FDA. 

Going forward, we had seen discretion by the Agency deployed to 

allow earlier available of key products. That is working. We would 

like to see a process in which we can get that on the front end as 

well to potentially mitigate potential problems while incorporating 

remedial steps that have no impact or concern to the patient. 

I know I am over my time share, so I apologize. 

[The prepared statement of Mr. Kafer follows:] 

69 


77032.034
70 


77032.035
71 


77032.036
72 


77032.037
73 


77032.038
74 


77032.039
75 


77032.040
76 


77032.041
77 


77032.042
78 

Mr. PITTS. The chair thanks the gentleman. Mr. Gray, you are 

recognized for 5 minutes. 

STATEMENT OF JOHN M. GRAY 

Mr. GRAY. Good morning, Chairman Pitts, Ranking Member 

Pallone, and the members of the Energy and Commerce Subcommittee on Health. I am John Gray, President and CEO of the 

Healthcare Distribution Management Association, Arlington, Virginia. I appreciate the opportunity to come here today, provide 

some overview of the pharmaceutical distribution system and inform your committee on efforts regarding some critically important 

issue around drug shortages. 

A little history—HDMA is a national association representing 

America’s primary healthcare distributors, a vital link in our Nation’s system of healthcare distribution. Each business day, our 34- 

member companies ensure that nearly 9 million prescriptions, 

medicines, and healthcare products are delivered safely and efficiently to nearly 200,000 pharmacies and clinics, hospitals, nursing 

homes, and other providers nationwide. Approximately 90 percent 

of all pharmaceutical product sales in the United States flow 

through our member companies. Continuous innovation and operation efficiency have really set our members apart in trying to annually contribute an estimated about $42 billion in value to the 

Nation’s healthcare system. 

Now, Federal law defines wholesale drug distribution as ‘‘the distribution of prescription drugs to other than the consumer or patient.’’ Wholesale distributors are licensed entities that are bound 

by a range of Federal and State laws. In addition, our distributors 

must comply with licensure requirements in every State in which 

they operate. 

It is important to note HDMA members are primary distributors. 

I said that earlier; I will reiterate it. But they buy predominantly 

from pharmaceutical manufacturers and sell only to appropriate licensed customers, the vast majority of which are pharmacies or 

healthcare providers. 

Pharmaceutical products are distributed through a highly coordinated supply chain in this country to provide maximum efficiency 

and effectiveness and safety. Pharmacies and other healthcare entities generally place orders for prescription medicines by 8 o’clock 

in the evening and receive deliveries from their distributors the 

next morning. The average distribution center in this country processes nearly 2,000 orders a day. On the average, a warehouse 

maintains about 30 days of inventory level. This number varies by 

product, is subject to demand, seasonality, cost, and other factors. 

Pharmaceutical products with special handling requirements typically have shorter cycle times in the system. 

Distributors provide an array of services for manufacturers beyond simply the movement of product, including but not limited to 

receivables risk management for the manufacturer, customer validation, order management, inventory management tracking, processing returns and recalls, and contract management. For pharmacy and provider customers, our distributors provide an equal 

array of services, including aggregate ordering, assistance with 

stocking needs, support for information systems and software, as 

79 

well as accounting and credit support. In the case of inventory 

management, distributors are able to fill customer orders 6 or 7 

days per week, 365 days a year, which limits the need for large inventory levels at the pharmacy level. 

In sum, distributors serve to maximize the efficiency between 

manufacturers and healthcare providers by managing a very complex network of products of systems by efficiently providing mechanisms for this seamless transformation of information and product. 

Through the unique position of distributors and our close relationship with all the stakeholders, we are acutely aware of the impact of drug shortages on patients. Effectively addressing the drug 

shortage is difficult and complex for the entire healthcare community in large part because the shortage typically appears with little 

or no warning and often requires significant resources to manage. 

HDMA and our member companies work hard to improve the communications within the supply chain from manufacturer to distributor to provider where possible and try to mitigate the impact 

of the drug shortage. 

Although distributors do not manufacture product, they do play 

an important role in helping to coordinate and share information 

about drug shortages when those shortages arise. Distributors are 

typically notified of a shortage by a manufacturer or a provider 

partner. Once that shortage information is received, distributors 

communicate with their manufacturer partners about product 

availability to understand the scope and expected duration of any 

shortage. Then the distributor works as quickly as possible with 

customers to fill orders to the extent they are able to do so based 

upon purchasing history or, if necessary, to identify alternative 

products in the supply chain. So as you can appreciate, there is a 

delicate balance between the need to share information at the appropriate level, but at the same time preventing an environment 

for panicked buying. 

HDMA has worked collaboratively with the American Society of 

Health System Pharmacists, Federal agencies and the Congress, 

and other supply chain partners to share expertise about the whole 

drug supplies chain. In addition, we are working with our distributor members and manufacturer providers to update voluntary 

industry guidelines on improving communications between supply 

chain partners in the event of shortages. We hope this effort will 

contribute to the better management of the process in its entirety. 

HDMA strongly believes the healthcare industry as a whole, the 

government, and stakeholders must continue to work together towards some collaborative solutions of this problem that mitigate 

the impact of the shortages, and most importantly, the impact on 

the key stakeholder—the patient. To that end, I thank you again 

for this invitation to participate and I hope the overview has been 

valuable. And I look forward to your questions. 

[The prepared statement of Mr. Gray follows:] 

80 


77032.043
81 


77032.044
82 


77032.045
83 


77032.046
84 


77032.047
85 


77032.048
86 


77032.049
87 

Mr. PITTS. The chair thanks the gentleman. Mr. Colgan, you are 

recognized for 5 minutes for an opening statement. 

STATEMENT OF KEVIN J. COLGAN 

Mr. COLGAN. Good morning and thank you, Chairman Pitts, 

Ranking Member Pallone, and distinguished members of the subcommittee, for holding this hearing. My name is Kevin Colgan. I 

am the corporate director of pharmacy at Rush University Medical 

Center in Chicago, Illinois. I am here today because I cannot serve 

my patients or the caregivers due to shortages of medications, some 

of them critical to patient care. 

While there is no single solution that will immediately solve the 

problem of drug shortages, there are things we can do to help address this issue. First, bipartisan legislation in both houses of Congress would enable FDA to require that drug manufacturers report 

confidentially to the Agency when they experience an interruption 

in the production of their product. This early warning system will 

help the FDA work with other manufacturers to ramp up production when another company experiences a problem. Moreover, the 

bills call upon FDA to work with manufacturers to develop continuity of supply plans which could help to identify backup sources 

of active pharmaceutical ingredients and produce redundancies in 

inventory to serve as reserve supplies. 

While some have argued that this legislation won’t have any impact, we disagree. You have already heard this morning from the 

FDA that in 2010, 38 drug shortages were avoided, and last year, 

99 drug shortages were avoided when the Agency was given advance notice. Further, opponents of this approach argue that it will 

lead to hoarding. We know that hoarding already occurs. How do 

some find out about shortages before others? We don’t know all the 

answers to this question. What we do know is that early warning 

to FDA will help make sure that everyone has the same information at the same time. Simply put, the public benefit of an early 

warning system far outweighs the risk of hoarding. In other emergency preparedness areas such as bioterrorism, flu pandemic, and 

natural disasters, we develop action plans and communication 

channels among necessary responders. Why would we approach 

drug shortages any differently? 

Second, health-system pharmacists have been collaborating with 

other clinicians and members of the supply chain to work with the 

FDA to address this problem. For example, we believe FDA should 

have and devote necessary resources to speed up the regulatory 

process to address drug shortages. Other alternatives include improved communication between FDA field personnel and the drug 

shortages program to assess the comparative risk of public harm 

when a potential enforcement action will cause or worsen a drug 

shortage; exploring incentives for manufacturers to continue or to 

re-enter the market; a generic user fee program to speed approvals; 

and last, ensuring the Agency has the funding it needs to carry out 

its mission. 

Many of you sitting in this room sometime over the next several 

months is going to receive the news that you, a family member, or 

a friend has been diagnosed with cancer, needs surgery, has been 

admitted to an intensive care unit, has a serious infection that reVerDate Aug 31 2005 13:50 Mar 13, 2013 Jkt 037690 PO 00000 Frm 00091 Fmt 6633 Sfmt 6633 F:\112-08~4\112-88~1 WAYNE
88 

quires an IV antibiotic or antiviral medication, or has a premature 

baby or grandbaby that requires nutritional support. And the last 

thing you want to hear is that we don’t have first-line medication 

therapy to treat you; that the medication we have may not work 

as well and could cause heart damage, but it is all we have to offer; 

or that we are delaying your treatment until we are able to obtain 

drugs that are in short supply. These are all situations, I, my clinical pharmacy staff, and the physicians, nurses, and respiratory 

therapists that we work with have had to manage over the past 

year. From our perspective, drug shortages represent a national 

healthcare crisis. We don’t have one single solution, but we have 

offered a number of solutions that together can help resolve this 

problem. 

Again, thank you Mr. Chairman, ranking member, and all members of the committee for the opportunity to provide input on this 

problem. Thank you. 

[The prepared statement of Mr. Colgan follows:] 

89 


77032.050
90 


77032.051
91 


77032.052
92 


77032.053
93 


77032.054
94 


77032.055
95 


77032.056
96 


77032.057
97 


77032.058
98 


77032.059
99 


77032.060
100 


77032.061
101 

Mr. PITTS. The chair thanks the gentleman. We are in the middle 

of votes. We have 14 votes. We are going to try to get a couple more 

before we go and recess for the vote and we will come back. So Mr. 

Alkire, you are recognized for 5 minutes. 

STATEMENT OF MIKE ALKIRE 

Mr. ALKIRE. Thank you. Good morning, Chairman Pitts, Ranking 

Member Pallone, and members of the committee. I am Mike Alkire, 

Chief Operating Officer of the Premier Healthcare Alliance. Premier is owned by not-for-profit hospitals and health systems. We 

use the power of collaboration to lead the transformation to highquality and cost-effective healthcare. One of the ways we do this 

is by aggregating the buying power of 2,500 hospitals to get the 

most effective medical supplies and drugs at the best prices. 

I thank the committee for leading efforts to address drug shortages. As you are aware, the number of drug shortages has tripled 

since 2005 and many of these medicines are essential to patient 

care. Premier set out to understand the extent of the problem 

through a survey. We found that between July and December of 

2010, more than 240 drugs were either in short supply or completely unavailable in 2010. Over 400 generic equivalents were 

backordered for more than 5 days. Many of the drugs noted as 

backordered in 2010 have remained unavailable or in short supply 

in 2011, and 80 percent of the hospitals reported that shortages resulted in a delay or cancellation of a treatment. Drug shortages also carry a cost—an estimated $415 million annually through the purchase of more expensive substitutes and additional labor costs. We don’t have the ability to estimate the financial impact of shortage drugs where there are no alternatives. We 

are working to diminish these costs by determining manufacturing 

capabilities to assess whether a manufacturer can supply the market; we look for alternatives if capabilities don’t meet demand; instituting an early warning system for hospitals to notify us of 

shortages; once notified, we determine the scope of the problem and 

communicate with the FDA; and exploring longer-term contracts 

with manufacturers to create more predictable volumes and stability in the market. 

In this crisis, we hope people will do everything they can to help 

patients get the drugs they need. Instead, we have seen the gray 

market vendors taking advantage of a problem offering to sell 

shortage products at exorbitant prices. Premier analyzed unsolicited offers from gray market vendors on shortage drugs. We compared their prices to Premier’s. We found that average markups 

were 650 percent and the highest markup was 4,500 percent. In 

this case, a vial to treat high blood pressure that sells for 25.90 

was offered for $1,200. Markups were 4,000 percent for drugs to 

treat leukemia and non-Hodgkin’s lymphoma, 3,100 percent for 

drugs to help cancer patients to retain bone marrow. Forty-five percent were marked up 1,000 percent above a normal price and a 

quarter were marked up 2,000 percent. 

Where and how gray market vendors are getting these medicines 

no one knows. And how can the integrity of these drugs be 

ascertained? Again, a question that few know. That is why Premier 

has taken a position that pharmacies should avoid these vendors 

102 

and stick to known primary distributors. But in times of shortage, 

pharmacies may need to look elsewhere. In these cases, we develop 

a set of best practices. These practices include verifying the product’s chain of custody, confirming licensure, verifying that a seller 

is authorized to sell the product, and confirming that the seller is 

a verified, accredited wholesale distributor. 

But in our view, the best way to stop price gouging is to fix the 

drug shortage crisis. We ask the committee and the FDA to consider the following: speed the approval process for medically necessary drugs that appear to be in shortage; encourage FDA to engage stakeholders in discussions determining whether a drug is 

medically necessary—the objective is to prioritize drugs that are 

necessary for treatment and also may be at risk for shortages— 

grant the DEA flexibility to adjust quotas that are limiting the 

amount of active ingredients manufacturers may purchase for controlled substances, thus limiting their ability to ramp up production when a supplier exits the market; fast-track approvals of new 

active pharmaceutical ingredient suppliers for medically necessary 

drugs in shortage; work with manufacturers to slow the trend of 

acquiring raw materials outside the U.S.; require manufacturers to 

notify the FDA of planned supply interruptions—this will allow 

time to work with remaining manufacturers to increase production—and establish an early warning point of contact at the FDA. 

In closing, I thank the committee for the opportunity to share 

what we have learned about drug shortages and the alarming impact it has on the safety and health of our communities, as well 

as our healthcare costs. Premier stands ready to assist Congress in 

finding ways to ensure a safe, reliable drug supply. 

[The prepared statement of Mr. Alkire follows:] 

103 


77032.062
104 


77032.063
105 


77032.064
106 


77032.065
107 


77032.066
108 


77032.067
109 


77032.068
110 


77032.069
111 


77032.070
112 


77032.071
113 


77032.072
114 


77032.073
115 


77032.074
116 


77032.075
117 

Mr. PITTS. The chair thanks the gentleman. And again, we appreciate your patience. We have got 5 minutes left for a vote. I 

think we will break here and come back as soon as the last vote 

is over and continue the testimony. 

The chair recognizes Mr. Pallone. 

Mr. PALLONE. Mr. Chairman, I just wanted to ask unanimous 

consent to submit the written statement for the record of Congressman Matheson. 

Mr. PITTS. Without objection, so ordered. 

At this point, the subcommittee stands in recess until after the 

last vote. 

[Recess.] 

Mr. PITTS. The subcommittee will come to order. Again, I apologize for the schedule, and I appreciate very much your patience 

and your thoughtful testimony. We will resume the testimony with 

Dr. Penley. I believe you are up next, so you have 5 minutes. 

STATEMENT OF W. CHARLES PENLEY 

Mr. PENLEY. Good afternoon, Chairman Pitts, Ranking Member 

Pallone, and the remainder of the subcommittee. I am Charlie 

Penley, and I am a practicing oncologist in Nashville, Tennessee. 

I spend the majority of my time taking care of patients, and this 

is why I am pretty uncomfortable in this environment. But I am 

here today to talk about the impact of drug shortages on my patients. I speak today on behalf of the American Society of Clinical 

Oncology. Our 30,000 members and their patients thank you for 

holding this hearing. Drug shortages have indeed reached crisis 

proportions in oncology. We hope that this hearing will better 

frame potential solutions. 

ASCO is hearing from practices all around the country, large and 

small, community-based and hospital-based practices who are having challenges treating their patients. The situation, as you have 

heard this morning, is worsening. Drug shortages in the United 

States have tripled since 2005/2006. Almost all cancer types are affected—leukemia, lymphoma, breast cancer, ovarian cancer, testicular cancer, and colon cancer. Shortages are indeed forcing us to 

change the way we treat our patients. Often, a drug in short supply 

is potentially curative. There is no reasonable substitute. 

Our practice treats many patients who have been diagnosed with 

acute myelogenous leukemia, AML. It is a life-threatening but potentially curable disease. Cytarabine, as you have heard, is one of 

the essential components of treatment for AML but that agent has 

been and remains intermittently in short supply today. Physicians 

have been forced to tell patients that this potentially curative drug 

is not immediately available to them. Treatment delay can result 

in grave consequences in these critically ill patients. 

In other situations, there are alternative drugs, but they are less 

effective, they have more side effects, or they are dramatically more 

expensive. For example, the standard treatment for non-Hodgkin’s 

lymphoma is known as the CHOP regimen. CHOP chemotherapy 

includes doxorubicin, which has been and is in shortage. A colleague shared the story of a young woman who was recently diagnosed with lymphoma during pregnancy. Now, that is a very complex situation which fortunately doesn’t happen very often, but it 

118 

involves potential risks for both the mother and the child. Because 

of the doxorubicin shortage, the woman had to be treated with a 

substitute, one for which the risk for the baby is not as well known 

and which may be less effective treatment for her lymphoma. 

Oncologists and patients should not have to make such difficult 

choices. 

I am currently treating a national firefighter who has an advanced gastrointestinal cancer and who was responding to 5–FU 

based chemotherapy. Earlier this summer, we were unable to obtain 5–FU and had to use an alternative regimen, which both 

caused him more personal side effects and significantly increased 

his out-of-pocket cost. 

The price of substitute drugs can be up to 100 times more expensive than the drug normally chosen, especially if the substitute is 

a brand name drug. As an example, when the mainstay generic 

drug leucovorin went into shortage, oncologists had to treat patients with the substitute, levoleucovorin. Medicare payment for 50 

milligrams of leucovorin is $1.25. An equivalent dose of 

levoleucovorin is approximately $90. 

The clinical trials infrastructure in this country is threatened by 

drug shortages as researchers alter or delay trials because the drug 

that is part of the study becomes unavailable. As many as 60 percent of clinical trials have been delayed, this at a time of great 

promise in cancer research. 

We understand that there are many causes of this problem, a 

number of them involving the manufacturing process. However, 

market factors appear to be a key driver in this rapidly escalating 

crisis. Shortages in cancer drugs are almost exclusively in generic 

sterile injectables, which are generally inexpensive drugs with a 

very low profit margin. Companies that experience manufacturing 

complications may not have the incentives to invest resources required to upgrade facilities or to correct quality problems. 

As we have heard, there does not appear to be a single solution 

to the crisis. Our primary expertise is in patient care, but we would 

offer these potential solutions, which we would encourage the committee to explore. First, Congress should urge expedited abbreviated new drug applications, or ANDAs, for drugs vulnerable to 

shortage in a way that does not compromise safety. Secondly, because this amounts to a public health crisis, Congress could work 

with Medicare to address pricing and payment for ultra-low-cost 

generic drugs. Third, Congress should pass S. 296 and H.R. 2245, 

bipartisan legislation that would give the FDA increased authority 

to manage the shortages. Fourth, consider tax incentives to encourage or enable generic manufacturers to continue to produce vital 

drugs, update their facilities, or enter the market to produce the 

drugs vulnerable to shortage. 

Mr. Chairman, ASCO has been and will remain an active partner 

in seeking resolution to the problem. The stress of dealing with a 

cancer diagnosis and the risks of necessary treatment is a heavy 

enough burden for patients and families to bear. It is absolutely 

unacceptable that the lack of effective oncologic therapeutics should 

add to that stress, or worse, threaten lives. We must do everything 

in our power to resolve this crisis, and we should do it immeVerDate Aug 31 2005 13:50 Mar 13, 2013 Jkt 037690 PO 00000 Frm 00122 Fmt 6633 Sfmt 6633 F:\112-08~4\112-88~1 WAYNE
119 

diately. We appreciate your leadership on this issue, and we stand 

ready to do everything that we can to assist. Thank you very much. 

[The prepared statement of Mr. Penley follows:] 

120 


77032.076
121 


77032.077
122 


77032.078
123 


77032.079
124 


77032.080
125 


77032.081
126 


77032.082
127 


77032.083
128 


77032.084
129 


77032.085
130 


77032.086
131 

Mr. PITTS. The chair thanks the gentleman and now recognizes 

the gentleman from Lancaster, Mr. Paoletti. 

STATEMENT OF RICHARD D. PAOLETTI 

Mr. PAOLETTI. Good afternoon. I want to thank the committee for 

convening this hearing and for the opportunity to participate in 

this important discussion. My name is Rich Paoletti, and I am vice 

president of operations at Lancaster General Health in Lancaster, 

Pennsylvania. My comments today will address the daily challenges hospitals, patients, and providers are experiencing as a result of increasing drug shortages occurring nationwide. 

In the current healthcare climate, hospitals are being asked to 

restructure to meet the quality, safety, fiscal constraint, and community-benefit standards expected in today’s world. Our resources 

are being stretched to the limit. Ongoing drug shortage challenges 

at Lancaster General are further taxing and diverting those resources to respond to the almost-daily patient impacts these shortages create. This pattern is increasingly becoming the norm for 

hospitals, physician practices, emergency responders, and most importantly, patients everywhere. 

At Lancaster General, we work hard to maintain a culture of 

quality and patient safety largely based on fundamental building 

blocks of standardization through elimination of waste and variability. In direct conflict with these safety practices, drug shortages 

add variability, complexity, and additional burden, increasing the 

possibility of medication misadventure, poor outcomes, and patient 

harm. 

The lack of an early warning system regarding impending shortages is one of the greatest challenges we face as healthcare providers, such that sometimes learn about shortages or their severity 

when products are not received in our daily shipments. 

A review of our drug wholesaler orders last month revealed receipt of only 3,452 of the 4,344 line items orders processed, representing a fill-rate of about 80 percent. In other words, 892 line 

items ordered in August were not received. Every disruption to 

medication supply creates new responsibilities to investigate alternative treatments and evidence to update protocols, procedures, 

and various technologies. Additionally, we must disseminate effective education on alternatives not always readily familiar to frontline caregivers. In our fast-paced, complex environment, every substitution adds variation and risk. 

These logistical tasks consume significant dedicated hours from 

multiple stakeholders and staff working collaboratively on detailed 

plans to maintain safety, while requiring execution in limited timeframes. This means working with anesthesiologists and emergency 

physicians in contemplating how we might maintain airway in a 

patient presenting to the trauma center without the availability of 

a paralyzing agent; neonatologists considering how we may best 

provide nutritional care to compromised premature infants; infectious disease specialists searching for alternative anti-infectives; 

and oncologists discussing alternative treatment regimens midway 

through a course of therapy; and more importantly, how we will reveal to patients that we may not have the medication necessary to 

132 

treat their ailments. In our opinion, this issue represents the national healthcare crisis. 

Relieving and minimizing avoidable drug shortages requires both 

short-term interventions and longer-term, permanent solutions. 

These potential solutions require system changes and increased capacity, including the following: establish an early warning system 

as proposed in bipartisan legislation currently in both Houses of 

Congress to immediately help to avert or mitigate drug shortages 

proactively; establish and improve communications between the 

FDA and manufacturers to develop evidence-based allocation plans 

for critical drug therapies; secure the pharmaceutical supply chain; 

and direct available supplies to our most critical patient populations; explore incentives to encourage drug manufacturers to stay 

in, reenter, or initially enter the market critical to specific drugs 

in short supply. These could include creation of a fast-track for approval of new production lines, alternative manufacturing sites, or 

new suppliers of raw materials for medically necessary drugs in 

shortage or vulnerable to shortage without compromising the quality and safety. 

Again, I want to thank the committee for holding this hearing. 

Lancaster General Health offers its continued support and commitment to assist in the development of solutions that will help to prevent and mitigate risks caused by drug shortages. Thank you. 

[The prepared statement of Mr. Paoletti follows:] 

133 


77032.087
134 


77032.088
135 


77032.089
136 


77032.090
137 


77032.091
138 


77032.092
139 


77032.093
140 


77032.094
141 

Mr. PITTS. The chair thanks the gentleman. 

Dr. DiPaola, you are recognized for 5 minutes for your statement. 

STATEMENT OF ROBERT S. DIPAOLA 

Mr. DIPAOLA. Thank you. Good afternoon, Chairman Pitts and 

Ranking Member Pallone and members of the subcommittee. My 

name is Dr. Robert DiPaola. I am director of the Cancer Institute 

of New Jersey, the State of New Jersey’s National Cancer Institutedesignated Comprehensive Cancer Center. I also speak as a member of the American Association for Cancer Research (AACR) and 

its Science Policy and Legislative Affairs Committee. Thank you for 

convening this hearing and recognizing the impact that the current 

drug shortage problem is having on our patients and on our ability 

to advance cancer research and improve patient outcomes. 

You have heard about the effects of drug shortages on treating 

patients. As the director of an NCI-designated Comprehensive Cancer Center and a medical oncologist myself who treats and cares for 

patients, I have the same frustrations regarding the care of our patients and the negative impact of drug shortages. This impact is 

not only immediate for the patients in our clinics today, but also 

affects the future care of cancer patients because the next generation of cancer therapy is driven by today’s clinical trials that are 

critical to meeting the national goal of improving the outcomes for 

cancer patients. Shortages of drugs is actually—as you know and 

you heard today—a very complex problem. 

There are a number of ideas regarding what is causing them, 

and how they can be remedied. I am here today to discuss how this 

growing problem of shortages of already approved drugs, which in 

some cases, as you have heard, have been used and made for decades, is affecting our best cancer care, our clinical trials, and is 

threatening our ability to continue on our trajectory of steadily improving cancer patient outcomes. 

FDA statistics show that the number of drug shortages has more 

than tripled over the past 6 years, with a marked increase in drugs 

involving sterile injectables, which negatively impacts the treatment of cancer patients—again as you have heard—that most 

shortages in oncology are sterile injectables. The medications in 

short supply include cancer treatment drugs, anesthetics, 

antimicrobials, and pain medications. A list maintained by the 

American Society of Health-System Pharmacists recently identified 

193 shortages in 2011, of which 22 are cancer drugs, and the shortage is predicted to worsen. These include drugs that are the standard treatment regimens used to treat patients with many different 

cancers in adults and in children. 

These shortages are now affecting clinical trial options for patients with cancer. Due to the uncertainty of being able to obtain 

many of these drugs, enrollment of patients on clinical trials has 

been delayed or stopped in several of our trials. Many of these 

drugs that are in short supply are a part of the standard regimens 

in which new treatments are added or compared to within a clinical trial. Many of the drugs on the shortage list are also used in 

our large national cooperative group trials. The Coalition of Cancer 

Cooperative Groups reports that approximately 50 percent of active 

cooperative group cancer clinical trials involve drugs subject to 

142 

shortages. Many reports contain examples in which sites are unable to enroll patients on approved clinical trials due to a lack of 

drug supply. Investigators in these clinical studies are unable to 

enroll new patients when the drug supply is not available; patients 

on-study are sometimes receiving alternate drugs when supply is 

not available, and there is concern about interpretation of results 

when drug substitutions occur. 

It is important to remember that the impact from the drug shortages on clinical trials today will also have a long-term effect on 

cancer research and future treatment options for cancer patients. 

Clinical trials represent the final step of a long process of developing new therapies that improve the outcome of patients and add 

treatments for patients in which there were no effective prior options. 

When, after years of effort, a single researcher discovers a potential new drug or treatment, that particular new drug is often best 

added to an existing treatment in combination and/or tested in 

comparison to the best current treatment in a clinical trial. If that 

trial yields positive results, patients can ultimately have access to 

a new and improved drug or treatment combination. Currently, 

however, we are running out of many of the existing drugs. When 

a clinical trial runs out of a drug, even temporarily, the trial results may be compromised, and an enormous amount of work and 

expense is wasted. This means that during a clinical trial, a shortage of only a few weeks in an existing drug might mean delays in 

years for developing a new drug. In other words, the drug shortages of today can have a ripple effect on the availability of new 

drugs and treatment combinations tomorrow. 

Today, we estimate that 1 in 2 men and 1 in 3 women will develop cancer in their lifetimes. This year, over 1.5 million Americans are estimated to be diagnosed with cancer and more than half 

a million Americans are expected to die of their disease. That is 

more than 1,500 people a day or more than 1 per minute. While 

these numbers seem staggering, we have made great strides in our 

ability to diagnose, treat, and prevent cancer and are at a most 

promising time in cancer research. 

Earlier this week the American Association for Cancer Research 

issued a progress report marking 40 years of progress in fighting 

cancer. In fact, thanks to advances made in cancer research, today 

more than 68 percent of adults are living 5 or more years, which 

increased from 50 percent in 1975. It was also reported that in the 

period from 1990 to 2007, death rates for cancer in the U.S. decreased by 22 percent for men and 14 percent for women. 

The challenge we now face is to continue to turn groundbreaking 

science into lifesaving care at even greater speed. By facilitating 

clinical trials, we lay the groundwork for discoveries in basic cancer 

research to be translated into cutting-edge treatments for cancer 

patients. 

The current drug shortage is hindering our ability to treat cancer 

patients overall. We are entering a new era of cancer treatment 

and prevention. However, an inability to have best treatment for 

our patients in general and conduct clinical trials is a serious impediment to our goal and will hamper our ability to reduce the toll 

of cancer for the people of our Nation. 

143 

Thank you. 

[The prepared statement of Mr. DiPaola follows:] 

144 


77032.095
145 


77032.096
146 


77032.097
147 

Mr. PITTS. The chair thanks the gentleman and thanks all of our 

7 witnesses for your thoughtful testimony. And we will begin questioning at this time. I recognize myself for 5 minutes for that purpose. Let me begin with you, Mr. Paoletti. A couple of questions. 

Can you walk us through what happens from your perspective 

when there is a drug shortage? Who notifies you? How much warning do you get? What do you need to do to notify the people in your 

organization? 

Mr. PAOLETTI. It differs in every instance, but like I said, a lot 

of times we find out when a drug order doesn’t come or our buyerand-receiving process, through the receiving process, we learn that 

we didn’t get a medication on order. The buyer then has to follow 

up with the wholesaler to find out if that is a temporary outage, 

when we would maybe next expect that, and then that would relay 

into an investigation of more than probably for us 100 to 150 inventory locations in automated cabinets throughout our facility. So 

we look at what we have on hand, how much we continually use 

on a day-to-day basis, and estimate how much supply we would 

have if we continued business as is. 

Based on that and the information we get, we have to convene 

a team. It is typically pharmacists, nurses, the specific stakeholder 

physicians depending on what medicinal it is. We look at the indications, we look for alternative therapies that we may have available to us, and kind of assess how critical the nature of the shortage is. And then based on that, we have to create action plans. 

Sometimes it involves the pharmacy manually preparing specific 

minimal doses of medications to make our supply last as long as 

conceivably possible. That was the case with one instance last October that to me was the tipping point of the drug shortages with 

a drug called succinylcholine. We came down to the last couple 

days of therapy and really contemplating cancelling surgeries and, 

you know, how we would, you know, manage those situations. 

Mr. PITTS. Is there any way, at present, for you to anticipate a 

shortage? 

Mr. PAOLETTI. Through some online web sources, as good as the 

information is based on what the drug companies reveal and what 

is published, we have an active surveillance program now that goes 

out to the FDA Web site, that goes out to ASHP resources to look 

at that information, which sometimes is published with alternatives. So the University of Utah’s Drug Information Center has 

been very helpful in that regard, but it is only as good as the information that is available. And a lot of times, no information exists 

until we self-report that we are having difficulty. 

Mr. PITTS. Thank you. Let us just go down the line. Mr. Kafer, 

from your company’s experience, what are the main reasons for a 

drug going into shortage, and how does your company work with 

FDA to notify them of the shortage? 

Mr. KAFER. From a notification standpoint, our primary point of 

contact when we become aware of a shortage for any number of 

reasons we could have had a manufacturer lot rejected during release testing. And what that means is after you finish your manufacturing process, every injectable goes through about a 3- to 4- 

week series of tests. If those tests fail for quality reasons or not 

meeting a specification, you reject that lot. If we anticipate a shortVerDate Aug 31 2005 13:50 Mar 13, 2013 Jkt 037690 PO 00000 Frm 00151 Fmt 6633 Sfmt 6633 F:\112-08~4\112-88~1 WAYNE
148 

age, our primary point of contact continues to be FDA drug shortage. As testified this morning by Dr. Kweder, I think the point was 

made that they do not immediately post that information because 

that can trigger additional behavior where the awareness of the potential shortage could lead to purchasing of another generic product or even another comparative therapy which can drain those 

supplies as well. So we coordinate directly with the drug shortage 

group and then we coordinate with our hospital partners and our 

distribution partners. 

Mr. PITTS. And how have you worked with the FDA to alleviate 

a shortage? 

Mr. KAFER. We have worked extremely well with the FDA. There 

has been many instances in which we have collaborated. I think 

through the drug shortage group, they have been playing quarterback on this. I think we mentioned earlier this morning, it is not 

a formal process, but they do a fantastic job in pulling instances 

together. There has been at least 3 occasions where we had submitted a prior approval supplement, and by definition of that, that 

is an extensive review that indicates that we have had significant 

changes to a product or process which would typically take long, 

but they have been able to expedite those reviews and get those approved in about a 3-month period that allowed us to get those critical products to market. 

Mr. PITTS. Thank you. Mr. Gray, can inventory management 

practices create the impression of a drug shortage, and how do distributors and others work to avoid that situation? 

Mr. GRAY. Well, inventory management practices or just-in-time 

or whatever you want to call it, those are actually across the supply chain from just-in-time production to just-in-time delivery. Our 

members focus on the delivery side, the manufacturers on the production side. And that actually is a process developed over the last 

25 years in the consumer goods area, which is really to spread out 

the predictability of manufacturing, as well as altering both the 

manufacturer, the wholesaler, and the retailer or pharmacy when 

product potentially is short. It is more real-time information across. 

So the reality is the inventory management programs are really 

there to spot the shortages potentially before they happen, and that 

is really what has been developing since the late 1980s from the 

food industry into the pharmaceutical industry. 

So I am not sure there is a connection there. I have heard that 

today. If you really look at the science of that, the mentality behind 

those is really to identify those shortages early on. 

Mr. PITTS. Now, when a secondary distributor purchases a drug 

product, they often pay more than the primary distributor would 

pay. So if they then charge more for the drug, they are simply responding to market, aren’t they? This is not a gray market practice, is it? Can you contrast that with the gray market? 

Mr. GRAY. I can’t speak to the secondaries. I know our members, 

our 34 primary wholesalers, we are buying directly from manufacturers, and then we sell only to state-licensed entities, be that a 

secondary distributor, a hospital, pharmacy, or whatever. And so, 

usually, we are under contract pricing with the manufacturers for 

those products. So if we are selling them on down to a provider, 

it is usually a contract price already preset. What a secondary 

149 

would do with that product, I do not know. In terms of pricing, I 

have no information on that. 

Mr. PITTS. Thank you. Mr. Colgan, in your testimony, you state 

that there is no one solution to this problem; however, you stress 

the importance of enacting legislation to require manufacturers to 

notify FDA of possible shortages. Can you explain why this requires legislation to accomplish and why it needs to be done on a 

confidential basis? 

Mr. COLGAN. Sure. I think when there is a leak or a hole in the 

dam, I think you need to stick your finger in it first to stop the 

leak, and then you need to explore what the reason is for it, and 

then you need to solve the problem. What this legislation really 

does is sticks your finger in the hole in the dam to stop the leak. 

And basically, we have heard from testimony today from the FDA 

that they have been able to basically abort 99 drug shortages this 

year with regards to early warning systems. So we believe that is 

needed. 

I am definitely not in favor of regulation when regulation isn’t 

needed, but honestly, anything that I am putting in my body or my 

mouth, I want to make sure that it is manufactured in the right 

way, that it is done correctly. And certainly, we support the FDA 

in terms of their role in protecting drug safety within this country. 

Needless to say, they need to be able to have the power and the 

jurisdiction to enforce early reporting of drug shortages. 

And the other thing that I said I think was really most important is get the word out to everybody at the same time. It is beyond 

me sometimes that others have drug product when I don’t have 

drug product. When drugs come back onto market, there are only 

certain places that you can get those drugs from and you can’t get 

it from your normal supply chain. So again, I think we need regulation in order to solve the problems that we have at hand. 

Mr. PITTS. Thank you. Mr. Alkire, we have heard that often the 

end users of drugs that go into shortage have very little advanced 

warning. For example, a surgeon may find out that the preferred 

anesthetic drug is not available only after the patient is prepped 

and on the operating room table. How does this happen? How do 

hospitals give warning of shortages to their own doctors? 

Mr. ALKIRE. For the most part, now, I have not necessarily heard 

that, but for the most part, there is very strong communication 

that actually occurs in the hospitals and doctors are made aware 

of what is happening from a shortage, especially as they are doing 

prep for these procedures. And then they have to go about figuring 

out what are the potential clinical alternatives to ensure that their 

patients are getting the highest quality care. 

Mr. PITTS. OK. Dr. Penley, how many drugs that you use in your 

practice regularly go into shortage? It appears that there are a finite number of drugs that regularly go into shortage. 

Mr. PENLEY. The current number for oncology drugs is around 23 

I believe, and those are very commonly used agents. So we would 

use most of them in our practice on a day-in, day-out basis. 

Mr. PITTS. And is there any way, at present, for you to anticipate 

a shortage? 

Mr. PENLEY. On a practice level, it is difficult. We get information the same way most of these folks do, through the FDA Web 

150 

site or the hospital pharmacist Web site. ASCO, our national organization, serves primarily as an information-gathering and distributing service there for our members, and certainly at times when 

we see that they are going to be prolonged shortages, ASCO convenes expert panels to try to brainstorm and come up with the best 

available work-arounds in situations where we have to make substitutions. We try to bring together the best minds in oncology so 

that they can come up with workable and reasonable solutions for 

our patients when we know that those drugs are going to be in 

shortage for any length of time. 

Mr. PITTS. Thank you. Dr. DiPaola, your description of the impact of drug shortages on future cancer patients because clinical 

trials may have to be stopped or not started in the first place is 

quite compelling. You mention that 50 percent of the cooperative 

group trials involve drugs that are subject to shortage. That sounds 

like it should have a devastating effect on cancer research. Could 

you give us an idea of the magnitude of this problem? 

Mr. DIPAOLA. I think that it is, you know, as we are all concerned with, you know, the shortage even worsening and already 

we are seeing a number of trials even with our cancer center as 

an NCI-designated Comprehensive Cancer Center, we take care of 

patients with both the best standard treatments and then offer 

clinical trials for patients who want that option. And those clinical 

trials are geared towards our new discoveries of new regimens. If 

a clinical trial is compromised because it needed to substitute a 

particular drug for another drug or, in some cases, clinical trials 

won’t allow a substitution, all of the work that went into the discovery getting to the point of the clinical trial is going to be compromised. 

And so, you know, we have made gains on cancer research overall, but ultimately, the discoveries in terms of the targets in the 

lab, the drug development, and then either the comparison to these 

existing drugs or the addition of these new targeted agents to existing drugs make it very, very difficult to continue this. And I agree, 

you know, those statistics relate to data we have been given regarding the cooperative group trials. Those are usually the large 

national trials that do comparisons. And nowadays, most of the 

trials don’t contain a placebo, so at least the existing drug is part 

of the clinical trial. So this already is a very difficult and concerning problem, and the way the stats are looking, may worsen. 

Mr. PITTS. Thank you. I have gone way over my time. I thank 

the ranking member for his indulgence and I will yield to Mr. 

Pallone for such time as he may consume. 

Mr. PALLONE. Thank you, Mr. Chairman. Let me ask unanimous 

consent to put in the record this statement from I guess the Fight 

Colorectal Cancer group on the U.S. drug shortage. You have it. 

Mr. PITTS. Without objection, so ordered. 

[The information follows:] 

151 


77032.098
152 


77032.099
153 

Mr. PALLONE. And I am going to just go back to what you said, 

Mr. Chairman, or follow up on what you asked Dr. DiPaola, who, 

as you know, is from my district. The Cancer Institute is in New 

Brunswick in my district. 

Do you have an example of a clinical trial that was halted at the 

Cancer Institute because of the drug shortage? Is there an actual 

example at the Cancer Institute of New Jersey where you had to 

halt because of the drug shortage? 

Mr. DIPAOLA. Yes. I mean there are actually a number of examples, trials that we were about to launch that we have made, you 

know, the plans and development to start a clinical trial. Most of 

them, Congressman Pallone, have to do with trials where a new 

drug is added to existing therapies. And we have had difficulties 

in at least 1 or 2 trials where a new drug was added to a combination that included TAXOL as one particular example. And the trial 

was held in terms of initiating the trial. What ends up happening 

is is in the clinic, we then have concern in offering patients who 

actually come to the center looking for these new options in terms 

of clinical trials, the trial when we are not assured of the, you 

know, particular drug supply. 

There was another trial where a young patient with breast cancer was enrolled where Doxil was included, along with another set 

of combination of drugs, and it required amendment to the trial to 

allow the patient to be treated, to change the drug from Doxil to 

another agent, which again has concerns about compromising the 

trial, and again the delay involved in trying to look at options and 

then even change the drug because in that case the trial allowed. 

And then in a number of cases, delayed trials where doxorubicin 

was part of the regimen, again with a novel what is called PARP 

inhibitor, which in the case I am referring to is an NCI trial that 

was delayed. So all of these, you know, taken together, any one of 

these, you know, weeks, months delays really delay us getting an 

answer. And more importantly, patients are coming because they 

are concerned that in that case, the standard option may not be 

what they are looking for enough and they are looking for these options in clinical trials. 

Mr. PALLONE. Sure. I mean just give me an idea. I mean how do 

you think the drug shortage impacts the future of cancer research 

and treatment? I mean are you concerned and, you know, just in 

an overall sense? 

Mr. DIPAOLA. Well, I mean I think, you know, it is going to be 

important and that is why I think it is important that everybody 

get together in a collaborative way to look at all of the root causes 

and come up with solutions because it is concerning, especially if 

it does worsen. And, at least as statistics would indicate ,that it is. 

So I think it is concerning. I think that we need to keep pushing 

forward in all areas of research. I mean as you know well, you 

know, it includes the discovery on the basic science end leading 

into the efforts of translating into clinical trials. But it is concerning, especially with the statistics that we are seeing. 

Mr. PALLONE. OK, thank you. 

I wanted to ask Mr. Kafer from Teva a couple things. A frequent 

cited reason for shortages is manufacturing problems, and of course 

we have heard that sterile injectable drugs are hard to manufacVerDate Aug 31 2005 13:50 Mar 13, 2013 Jkt 037690 PO 00000 Frm 00157 Fmt 6633 Sfmt 6633 F:\112-08~4\112-88~1 WAYNE
154 

ture. So if your supplier, I guess, has a problem, that can lead to 

a shortage. So obviously, there are circumstances outside of your 

control that can interfere with your ability to deliver a product. I 

mean are these problems unique to the drugs prone to shortages? 

For example, are all sterile injectable drugs prone to shortage or 

is there something about these drugs that makes controlling their 

manufacture more difficult? Are there things manufacturers can do 

to avoid these problems? 

Mr. KAFER. I think one of the things you need to understand 

from a complexity standpoint, by the nature of a sterile manufacturing facility, it is sterile and it is a very complex manufacturing 

environment. Picture, if you will, people in spacesuits kind of doing 

the prep work. If you are in an oral solid manufacturing facility, 

it is much different. So there is more complexity. 

The other thing within a manufacturing facility, each technology 

has its own defined manufacturing line or manufacturing suite. For 

instance, you cannot manufacture cytotoxic oncology products on 

the same line you would manage hormones or something of that 

nature. Many of the products, some of them are lyophilized, which 

is a powder that has a very unique manufacturing suite. And a liquid fill line is also a very unique manufacturing suite. So it is possible that within one manufacturing facility, you have a disruption 

in just one suite, one of those technologies. And one of the questions we have heard repeatedly from the panel is specific to oncology, and it is a very dynamic complex environment. And unfortunately, over the last couple of years, industry has had some disruptions within those manufacturing suites that we are in the stages 

of recovery so we are manufacturing product, but we are in a slow 

build and it is impacting, obviously, patients as the panel has testified today. 

Mr. PALLONE. Of course, we always worry not only today but in 

so many cases about active ingredients in drugs sold in the United 

States that are supplied from abroad. So I guess I am, you know, 

asking you to what extent that is problem and, you know, in the 

wake of heparin, of course, there is major concern about cracking 

down on some of the ingredients that are sold abroad. I mean to 

what extent does the availability of these ingredients from abroad 

impact this discussion today? I mean it is very likely that, you 

know, we put a lot more regulation and make it more difficult for 

things to come from abroad. 

Mr. KAFER. Regardless if the materials coming from abroad or 

domestically, to your point regarding the heparin scare of years 

ago, the testing requirements and scrutiny that we will go through 

before we will release the active ingredient into production is significant, and we will not jeopardize that. So the testing requirements that we impose on our manufacturing partners on the API 

side are significant. And there has been repeated instances in 

which we are failing API coming in for production because they 

have not met our specifications. If that does happen on a repeated 

basis, then you are obviously going to have a gap in readily available material to produce product. So without question for good reason that we are testing that material to the requirements that we 

are required to and we will not use it unless it passes those tests. 

155 

Mr. PALLONE. Now, you heard me earlier mention your testimony 

in the context that you and Dr. Kweder, I guess, acknowledged in 

your testimony that it can take 2 to 3 years for FDA to approve 

a new facility or API supplier, and obviously, that is not a good situation. However, on the first panel, they also said that FDA has 

the flexibility to adjust resources so that it can approve facilities 

and suppliers very quickly. I mean has that been your experience 

that that flexibility is exercised or works or are you sort of sticking 

to this 2 to 3 years? 

Mr. KAFER. The standard process as it exists today historically 

has been 2 to 3 years for an API secondary manufacturer approval 

or a manufacturing site traditional past. And, you know, those reviews take time because it is a complex review and it does require 

extensive work. At the same time, yes, we have seen expedited reviews in that area. We have been the beneficiary of expedited reviews to handle critical situations. 

But also in my earlier statement, in my opening remarks, I mentioned a lot of the shortages are unforeseen. We are applying a 

great deal of coordination and a great deal of collaboration when 

we are solving the problem. And as a standard of practice, is it possible to expedite some of those reviews as a standard of practice 

was the point of my written testimony. But we do see on a routine 

basis now where applicable, without jeopardizing the product, you 

know, we never jeopardize the product or system, but we have seen 

collaboration to expedite those reviews in a matter of months. 

Mr. PALLONE. And I appreciate that, but I guess what I am trying to say is, you know, when I mentioned your 2 or 3 years in your 

written testimony, I don’t want to put words in their mouth but it 

was sort of suggested at the first panel that maybe it is not so 

much a problem because we can use this flexibility, but I mean is 

it your experience that there is enough flexibility to deal with these 

situations or not? I mean I know that is a difficult question. You 

don’t have to say—— 

Mr. KAFER. I have had experience where we have had expedited 

reviews, collaborative work, and favorable outcomes. You know, the 

volume of work that could be forthcoming based on continued remediation, I can’t predict and I can’t, you know, forecast that impact. 

But prior to significant shortages—which the industry planned 

for—I mean, so we would plan for a 2-year review, we knew what 

that type was, but at the time when we were just making sure we 

had redundancy in place for those critical products, it wasn’t of immediate need. Now that we are seeing immediate need, we are seeing those expedited reviews. 

Mr. PALLONE. All right. Thanks. I just wanted to ask one more 

question of Mr. Colgan here, Mr. Chairman. 

In his written testimony he suggested a number of incentives 

that might be provided to encourage manufacturers to stay in the 

field or enter the field and, of course, I think in principle that incentives are a good idea. If we can get more companies to manufacture these products or to produce excess supply, you would think 

that shortages would be less likely to occur and less severe if they 

do occur. But that being said, the suggestions in your testimony I 

think need a little more fleshing out for me to better understand, 

156 

you know, what you are trying to achieve or how you would achieve 

the goal. 

And I know they are only presented as options to be further explored, but I was puzzled by the suggestion of granting temporary 

exclusivity for a new product line of drug either already in short 

supply or deemed vulnerable to a shortage considering that the 

goal would seem to be to get as many companies into the field as 

possible. It would seem that granting exclusivity would appear to 

be doing the exact opposite, and it is my understanding that exclusivity works best as an incentive when the company is the only one 

manufacturing the product, or in the case of a new generic, is the 

only company offering a generic alternative to a name brand. So it 

is not clear to me that granting exclusivity would be much of an 

incentive. And I am not trying to be critical. I just wanted you to 

walk me through how you think this would actually work practically. 

Mr. COLGAN. Well, there are 2 things here. One is the generic 

user fees and we believe those can be utilized to incent manufacturers to enter in the market or reenter into the market in producing a product that they have produced before or not produced. 

We have drugs that are single-source sometimes or we have drugs 

where we don’t have enough production and throughput. In those 

situations, we think within limits this is a concept that needs to 

be explored in terms of some sort of temporary exclusivity in the 

market so that there is a period of time that would incent a manufacturer to get into the market and produce the product. It could 

be that the FDA provides accelerated review of a supplemental 

NDA to that manufacturer, allows that manufacturer a period of 

6 months or so to put the product together and produce the product. We see the whole idea of incenting the industry to jump into 

the generic market as being really important. 

Let me give you an example of that. Hopefully, that will play out 

and you will understand. Right now, we have production problems 

with carmustine and we use this in non-Hodgkin’s lymphoma as a 

conditioning therapy in getting patients ready for autologous bone 

marrow transplants. Right now, that is not a medically necessary 

drug because we can use bendamustine. If I have a patient who is 

on carmustine, I would pay $938 for that patient’s drug if they had 

a body surface area of 2. For bendamustine I would pay $14,440. 

It advantages us to have other manufacturers in producing 

carmustine so we have adequate supplies and some sort of incentive that would allow them to do that so we are not forced to use 

bendamustine would be very important to us in terms of securing 

a supply line for that drug. And it certainly adds up to the economics of the situation, too, in terms of being able to supply a drug that 

is category one, recognized as the appropriate treatment for the patient, but also provides the lowest overall cost continuum of providing the care to that patient. 

Mr. PALLONE. All right. Thanks a lot. Thank you, Mr. Chairman. 

Mr. PITTS. The chair thanks the gentleman and that concludes 

our round of questioning. Again, I would like to thank the witnesses for your testimony, for answering the questions. We will ask 

you to please respond to any questions in writing. 

157 

In conclusion, I would like to thank all the witnesses and members for participating in today’s hearing and remind members that 

they have 10 business days to submit questions for the record, and 

then I ask the witnesses to please respond promptly to the questions. And members should submit their questions by the close of 

business on October 7. 

There being no further business, the subcommittee is adjourned. 

[Whereupon, at 2:18 p.m., the subcommittee was adjourned.] 

[Material submitted for inclusion in the record follows:] 

158 


77032.100
159 


77032.101
160 


77032.102
161 


77032.103
162 

Æ 


77032.104