[Senate Hearing 112-934]
[From the U.S. Government Publishing Office]





                                                        S. Hrg. 112-934

   PHARMACY COMPOUNDING: IMPLICATIONS OF THE 2012 MENINGITIS OUTBREAK

=======================================================================


                                HEARING

                                 OF THE

                    COMMITTEE ON HEALTH, EDUCATION,
                    
                          LABOR, AND PENSIONS

                          UNITED STATES SENATE

                      ONE HUNDRED TWELFTH CONGRESS

                             SECOND SESSION

                                   ON

 EXAMINING PHARMACY COMPOUNDING, FOCUSING ON IMPLICATIONS OF THE 2012 
                          MENINGITIS OUTBREAK

                               __________

                           NOVEMBER 15, 2012

                               __________

 Printed for the use of the Committee on Health, Education, Labor, and 
                                Pensions


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          COMMITTEE ON HEALTH, EDUCATION, LABOR, AND PENSIONS

                       TOM HARKIN, Iowa, Chairman

BARBARA A. MIKULSKI, Maryland
JEFF BINGAMAN, New Mexico
PATTY MURRAY, Washington
BERNARD SANDERS (I), Vermont
ROBERT P. CASEY, JR., Pennsylvania
KAY R. HAGAN, North Carolina
JEFF MERKLEY, Oregon
AL FRANKEN, Minnesota
MICHAEL F. BENNET, Colorado
SHELDON WHITEHOUSE, Rhode Island
RICHARD BLUMENTHAL, Connecticut

                                     MICHAEL B. ENZI, Wyoming
                                     LAMAR ALEXANDER, Tennessee
                                     RICHARD BURR, North Carolina
                                     JOHNNY ISAKSON, Georgia
                                     RAND PAUL, Kentucky
                                     ORRIN G. HATCH, Utah
                                     JOHN McCAIN, Arizona
                                     PAT ROBERTS, Kansas
                                     LISA MURKOWSKI, Alaska
                                     MARK KIRK, Illinois
                                       

             Pamela J. Smith, Staff Director, Chief Counsel

                 Lauren McFerran, Deputy Staff Director

              Frank Macchiarola, Republican Staff Director

                                  (ii)


                            C O N T E N T S

                               __________

                               STATEMENTS

                      THURSDAY, NOVEMBER 15, 2012

                                                                   Page

                           Committee Members

Harkin, Hon. Tom, Chairman, Committee on Health, Education, 
  Labor, and Pensions, opening statement.........................     1
    Prepared statement...........................................     2
Enzi, Hon. Michael B., a U.S. Senator from the State of Wyoming, 
  opening statement..............................................     4
Roberts, Hon. Pat, a U.S. Senator from the State of Kansas.......     6
Mikulski, Hon. Barbara A., a U.S. Senator from the State of 
  Maryland.......................................................    34
Alexander, Hon. Lamar, a U.S. Senator from the State of Tennessee    36
Hagan, Hon. Kay R., a U.S. Senator from the State of North 
  Carolina.......................................................    39
Blumenthal, Hon. Richard, a U.S. Senator from the State of 
  Connecticut....................................................    41
Bennet, Hon. Michael F., a U.S. Senator from the State of 
  Colorado.......................................................    43

                           Witnesses--Panel I

Bell, Beth, M.D., MPH, Director, National Center for Emerging and 
  Zoonotic Infectious Diseases, Centers for Disease Control and 
  Prevention, Atlanta, GA........................................     8
    Prepared statement...........................................    10
Hamburg, Margaret A., M.D., Commissioner, Food and Drug 
  Administration, Washington, DC.................................    16
    Prepared statement...........................................    18
Smith, Lauren, M.D., MPH, Interim Commissioner, Department of 
  Public Health, Boston, MA......................................    23
    Prepared statement...........................................    25

                           Witness--Panel II

Cadden, Barry, Owner and Director of Pharmacy, New England 
  Compunding Center, Framingham, MA--(Mr. Cadden declined to 
  appear)

                          Witnesses--Panel III

Kainer, Marion, M.D., MPH, FRACP, Director, Healthcare Associated 
  Infections & Antimicrobial Resistance Program, Tennessee 
  Department of Health, Nashville, TN............................    55
    Prepared statement...........................................    57
Miller, David G., R.Ph., Executive Vice President and CEO, 
  International Academy of Compounding Pharmacists, Missouri 
  City, TX.......................................................    65
    Prepared statement...........................................    66
Thompson, Kasey K., Pharm.D., M.S., B.S., Vice President, Office 
  of Policy, Planning and Communications, American Society of 
  Health-System Pharmacists, Bethesda, MD........................    74
    Prepared statement...........................................    76

                          ADDITIONAL MATERIAL

Statements, articles, publications, letters, etc.:
    Senator Casey................................................    87

                                 (iii)
    John J. Dreyzehner, M.D., MPH, FACOEM, Commissioner, 
      Tennessee Department of Health, Nashville, TN..............    88
    Andrew C. Holt, Pharm.D. Executive Director, Tennessee Board 
      of Pharmacy, Nashville, TN.................................    90
    Craig Becker, President, Tennessee Hospital Association, 
      Nashville, TN..............................................    92
    Baeteena M. Black, D.Ph., Executive Director, Tennessee 
      Pharmacists Association (TPA), Nashville, TN...............    94
    Wiley Robinson, M.D., FHM, President, Tennessee Medical 
      Association (TMA), Nashville, TN...........................    97
    Response by Lauren A. Smith, M.D., MPH, to questions of the 
      HELP Committee.............................................    98
    Response by Marion Kainer to question of Senator Whitehouse..   109
    Response by David G. Miller, R.Ph., to questions of:
        Senator Enzi.............................................   110
        Senator Casey............................................   110
        Senator Franken..........................................   112
    Response by Kasey K. Thompson to questions of:
        Senator Enzi.............................................   117
        Senator Casey............................................   119
        Senator Franken..........................................   120
  

 
   PHARMACY COMPOUNDING: IMPLICATIONS OF THE 2012 MENINGITIS OUTBREAK

                              ----------                              


                      THURSDAY, NOVEMBER 15, 2012

                                       U.S. Senate,
       Committee on Health, Education, Labor, and Pensions,
                                                    Washington, DC.
    The committee met, pursuant to notice, at 9:53 a.m., in 
room SD-106, Dirksen Senate Office Building, Hon. Tom Harkin, 
chairman of the committee, presiding.
    Present: Senators Harkin, Enzi, Mikulski, Casey, Hagan, 
Merkley, Franken, Bennet, Blumenthal, Alexander, and Roberts.

                  Opening Statement of Senator Harkin

    The Chairman. The Senate Committee on Health, Education, 
Labor, and Pensions will please come to order.
    We're meeting here today to better understand what caused 
one of the worst public health crises this country has 
experienced in recent years, the meningitis outbreak that has 
claimed the lives of 32 Americans and sickened at least 461 
people. While those affected grapple with side effects and 
complications related to treatment, thousands more are waiting 
to see if they become ill. This outbreak has been traced back 
to pharmaceuticals produced at the New England Compounding 
Center in Framingham, MA, where it is now clear the owners and 
managers demonstrated a complete disregard for basic procedures 
to ensure that the products they were manufacturing were 
sterile.
    The real question we will seek to answer today is: How 
could this have happened? How could 17,000 doses of a product 
so contaminated that, upon recall, black particles were visible 
to the naked eye in some of the samples, have been shipped to 
23 States? How could a pharmacy that the FDA had described in 
2003 as posing, and I quote,

          `` . . . the potential for serious public health 
        consequences if the compounding practices, in 
        particular, those relating to specific sterile 
        products, are not improved . . . ''

How could they have been then licensed to ship drugs to 45 
different States?
    As we have learned over the course of our committee 
inquiry, NECC's shortcomings were well-documented. The FDA and 
the Massachusetts Board of Pharmacy repeatedly found 
significant deficiencies in their operations, including the 
suspected destruction of documents and contaminated lots; 
findings of bacterial contamination in compounded medications; 
findings of sterile injectable products that were both too weak 
or too strong in potency; and repeated complaints about the 
sale of compounded drugs without a patient-specific 
prescription in direct violation of State and Federal law.
    Yet, despite the abundance of documentation, neither the 
Massachusetts Board nor the FDA appears to have taken the 
necessary steps to protect the public from these products.
    I will dispense with the rest of my statement, and I will 
submit it in its entirety for the record.

    [The prepared statement of Senator Harkin follows:]

                  Prepared Statement of Senator Harkin

    The committee will come to order. We are meeting here today 
to better understand what caused one of the worst public health 
crises this country has experienced in recent years: the 
meningitis outbreak that has claimed the lives of 32 Americans 
and sickened at least 461 people.
    While those affected grapple with side effects and 
complications related to treatment, thousands more are waiting 
to see if they become ill. This outbreak has been traced back 
to pharmaceuticals produced at the New England Compounding 
Company in Framingham, Massachusetts, where owners and managers 
demonstrated a complete disregard for basic procedures to 
ensure that the products they were manufacturing were sterile.
    The question we will seek to answer today is: how could 
this have happened? How could 17,000 doses of a product so 
contaminated that upon recall, black particles were visible to 
the naked eye, have been shipped to 23 States? How could a 
pharmacy that the FDA had described in 2003 as posing,

          `` . . . the potential for serious public health 
        consequences if [the] compounding practices, in 
        particular those relating to specific sterile products 
        are not improved, . . . ''

have been licensed to ship drugs to 45 different States?
    As we have learned over the course of our committee 
inquiry, NECC's shortcomings were well-documented. The FDA and 
the Massachusetts Board of Pharmacy repeatedly found 
significant deficiencies in NECC's operations, including the 
suspected destruction of documents and contaminated lots; 
findings of bacterial contamination in compounded medications; 
findings of sterile injectable products that were both too weak 
or too strong in potency; and repeated complaints about the 
sale of compounded drugs without a patient-specific 
prescription, in direct violation of State and Federal law. And 
yet, despite the abundance of documentation, neither the 
Massachusetts Board nor the FDA appears to have taken the 
necessary steps to protect the public from these products.
    Equally troubling is that fact that, when the owners and 
managers of NECC sought a license for a separate company, 
Ameridose, to compound drugs on scale perhaps 10 times the size 
of NECC, these same State and Federal regulators granted that 
license. They did so without referencing the checkered history 
of NECC, even though Ameridose would supply hospitals across 
the country under contract with the largest group purchasing 
organization in the United States. How could that history not 
been deemed relevant? How could NECC's owners have been allowed 
to expand their operations, in light of their history? These 
are questions I am hoping to answer today.
    In the face of such a tragedy it is natural to want to take 
action. And we will. This committee has a demonstrated ability 
to work to find bipartisan solutions that will take into 
consideration the needs of all stakeholders. The hearing today 
will explore not just what happened, but it will begin to help 
us determine how to prevent similar outbreaks in the future.
    What is important to remember, however, is that drug 
compounding is essential and that most pharmacies that compound 
do so on a vastly smaller scale than NECC. We need to ensure 
that these pharmacists can continue to compound without a 
drastic increase in overhead.
    We also know that to address drug shortages, compounding is 
occurring both in hospitals and in pharmacies to replenish 
supply of previously available drugs. Indeed, in the case of 
methylprednisolone acetate, the drug at issue in the outbreak, 
two manufacturers had ceased producing the drug in the last 2 
years.
    We know compounding is critical, and that the need for 
large scale compounding is increasing. But we do not know where 
or how much large-scale drug compounding is being conducted, or 
if these companies are compounding drugs in accordance with 
best practice standards. More importantly, we have no way of 
knowing which facilities are not in compliance. This is a 
problem and indicates to me the need for better Federal 
regulation in this area.
    As a committee, we will work together to identify and plug 
any gaps in our regulators' authority. We want to ensure that 
any pharmacy that takes the kinds of risks with patient lives 
that NECC did will be shut down long before more patients get 
hurt. The only good that can come from a tragic situation like 
this outbreak is the momentum to make changes to prevent it 
from ever happening again. I look forward to hearing the 
thoughts of the panel on this topic and I promise the other 
members of this committee who I know have a history on this 
issue to working together with you to ensure that a problem 
like this cannot occur again.
    In our first panel, we'll hear from Dr. Beth Bell of the 
Centers for Disease Control and Prevention about the public 
health impact of the meningitis outbreak and CDC's role in 
responding to it. Dr. Peggy Hamburg of FDA and Dr. Lauren Smith 
of the Massachusetts Department of Public Health will talk to 
us about the role of their agencies in regulating compounding 
pharmacies in general and in investigating NECC specifically. 
And we'll ask them about their views on what we can do to 
prevent future crises.
    We invited the manager and co-owner of the New England 
Compounding Center, Mr. Barry Cadden, to appear on our second 
panel. We were informed by Mr. Cadden's attorney that he would 
decline to voluntarily appear, and if compelled to appear, 
would invoke his Fifth Amendment right against self-
incrimination and refuse to answer our questions. I am 
disappointed by his failure to appear, but frankly, I believe 
this committee has amply demonstrated the extensive failures of 
Mr. Cadden and NECC, as the record of this hearing will make 
clear.
    On our third panel, we will talk to the physician whose 
critical work led to the initial identification of the outbreak 
and who ably worked with CDC to isolate NECC products as the 
source of the meningitis infections, Dr. Marion Kainer of the 
Tennessee Department of Health. We'll also talk with David 
Miller from the International Academy of Compounding 
Pharmacists and Dr. Kasey Thompson of the American Society of 
Health-System Pharmacists about the use of compounding in 
medical care, and the measures needed to ensure that compounded 
drugs are safe.
    Before we begin, I'd like to submit to the record the 
documents that we have received from NECC, FDA, and 
Massachusetts in response to our investigatory letters.
    The Chairman. But before we begin, I'd like to submit for 
the record the documents that we have received from NECC, the 
FDA, and Massachusetts in response to our investigatory 
letters. Without objection, they'll be submitted for the 
record.
    [Editor's Note: Due to the large volume of documents and 
the high cost of printing, the information referred to is 
maintained in the committee file.]
    And with that, I'll yield to Senator Enzi.

                   Opening Statement of Senator Enzi

    Senator Enzi. Thank you, Mr. Chairman.
    Thirty-two Americans have died, out of 461 total, sickened 
after receiving contaminated steroid injections produced by the 
New England Compounding Center, or NECC. Additionally, 
approximately 14,000 patients in 23 States have been exposed to 
potentially contaminated injections produced by the same 
pharmacy.
    This case represents a catastrophic failure by the 
regulatory agencies that are charged with protecting patients 
from unsafe drugs. Such a failure is unacceptable, and we're 
going to examine what happened in order to determine what needs 
to be done to prevent it from reoccurring.
    The compounding pharmacy that caused these patients' deaths 
and illnesses has a long history of problems with product 
safety and compliance with State regulations. These problems 
began almost as soon as NECC first received its pharmacy 
license in the late 1990's, when complaints began to be made 
about the sterility of the products and its practices around 
the requirement for individual patient prescriptions.
    Both the FDA and Massachusetts Board of Pharmacy became 
aware of the problems with NECC over a decade ago. They jointly 
inspected NECC's facility and held multiple meetings about the 
problems they discovered. The Massachusetts Board entered into 
a consent decree with NECC in 2006. Later that year, FDA also 
issued a warning letter to NECC.
    Despite the multiple warnings, State and Federal regulators 
failed to continue to monitor NECC and take the steps that 
could have prevented the current situation. In particular, the 
Massachusetts Board should have known from its numerous 
inspections of NECC's facility that it was operating a large-
scale drug manufacturing operation. That information, coupled 
with repeated complaints highlighting NECC's pattern of failing 
to require valid prescriptions for specific patients, clearly 
contravened Massachusetts regulatory requirements for 
compounding pharmacies.
    Even after receiving multiple complaints about the 
sterility and safety of drugs compounded by NECC, there is no 
evidence that the Board made any effort to even followup and 
inspect NECC's facility from 2006 until 2011. State boards of 
pharmacy have explicit authority over the practice of pharmacy, 
including compounding products for individual patients. States 
like Massachusetts also have clear and unequivocal authority to 
inspect, suspend, and revoke pharmacy licenses.
    While there have been litigation and conflicting court 
decisions around Federal legislation enacted in 1997 to 
differentiate between compounded and manufactured products, 
this ambiguity alone cannot be blamed for this tragedy. FDA can 
inspect any facility that manufactures, processes, packs, or 
holds products for interstate commerce and has authority over 
unapproved new drugs in interstate commerce. FDA also has the 
ability to take action against misbranded or adulterated 
products.
    NECC was clearly operating outside its pharmacy license in 
violating State laws requiring individual prescriptions. NECC 
also looked like it was operating as a large-scale drug 
manufacturer, pretending to be a pharmacy in order to avoid FDA 
regulation. In every warning letter and legal brief the Food 
and Drug Administration has ever issued concerning this very 
type of conduct, including a 2006 warning letter to NECC, the 
agency said it had clear authority to regulate this very type 
of conduct.
    I hope today we can find out why these State and Federal 
authorities were not used to prevent this tragedy. The 
committee is and will continue to investigate NECC's conduct 
and the oversight of both FDA and the Massachusetts Board of 
Pharmacy. We've sent letters to FDA, the Massachusetts Board, 
and NECC. We've received over 10,000 pages of documents, which 
show NECC has a history of not complying with State and Federal 
law. We expect to receive more documents in the coming weeks 
and will leave no stone unturned.
    I want to take a moment to recognize the longstanding 
interest of my colleagues, Senators Roberts and Burr, regarding 
pharmacy compounding. They've been leaders in this area since 
the late 1990s and released a draft of pharmacy compounding 
legislation with former HELP Committee Chairman Kennedy in 
2007.
    Many other members of the HELP Committee also have a strong 
interest in this matter. Senator Alexander's home State of 
Tennessee has been hit particularly hard by the current 
outbreak. I know that Senators Franken and Blumenthal have 
strong views. Numerous members of the HELP Committee signed 
oversight letters requesting the information from the Food and 
Drug Administration, the Massachusetts Board of Pharmacy, and 
the New England Compounding Center.
    The HELP Committee worked very effectively and in a 
bipartisan manner to reauthorize the FDA user fee legislation 
earlier this year. I am confident we can all work together to 
arrive at a common understanding of this problem and its 
solution.
    I'm also interested in hearing from Dr. Kasey Thompson of 
the American Society of Health-System Pharmacists on our third 
panel. Many patient populations and specialties require 
compounded products, including pediatrics and hospice. Some 
State pharmacy boards, like Wyoming's, also do their jobs 
effectively. I hope he can comment on the benefits of 
traditional pharmacy compounding and the strengths and 
weaknesses of pharmacy regulation by the States.
    Last, I want to thank Dr. Bell from the CDC and Dr. Kainer 
for attending today. Without your hard work, I understand this 
could have been much worse. Patients all over the country owe 
you thanks for immediately acting upon hearing about only one 
case.
    Thank you, Chairman Harkin, for holding this important 
hearing, and I look forward to learning more about how this 
tragedy occurred in order to see that it's not repeated in the 
future.
    The Chairman. Thank you very much, Senator Enzi.
    It has been a longstanding procedure of this committee that 
only the chair and the ranking member give opening statements. 
The chair, with the concurrence of the ranking member, would 
diverge from that for this hearing because of the long-time 
interest in and leadership by Senator Roberts on this issue and 
because he had been a leader on a bill that came up about 5 or 
6 years ago. I would yield for no more than 5 minutes for an 
opening statement by Senator Roberts.

                      Statement of Senator Roberts

    Senator Roberts. Thank you, Mr. Chairman, and Ranking 
Member Enzi. The reason I'm making this statement is very 
simple. I've been involved in this for 12 years. This is not a 
new story. I just appreciate you allowing me to make a short 
statement. I believe it's important to outline some of the 
previous actions that members of this committee and the Senate 
have taken in the past to review and take action on issues 
relating to compounding pharmacy.
    I want to begin by thanking the Chairman and the Ranking 
Member for holding this hearing on a crisis that has gained 
significance and deserves attention over the past few weeks but 
is also an issue that many of us on the committee have worked 
on for many years and for some over a decade.
    First and foremost, I want to start out by reiterating my 
support for pharmacy compounding. I know that compounding 
serves a very important role for patients, such as patients who 
are allergic to certain ingredients found in approved drugs or 
for children who need a pediatric dosage of a drug.
    Legitimate pharmacy compounding occurs when a patient has a 
special medical need that cannot be met by an FDA-approved 
drug. Their physician writes a specific prescription for the 
patient, and then the individual pharmacist makes the 
medication for the individual patient. This type of compounding 
should continue. I want to work to ensure that we don't do 
anything to alter that practice.
    However, and unfortunately, the more traditional pharmacy 
compounding is not why we are here today. We are here today 
because there have been bad actors who are using the good name 
of pharmacy compounding to mass produce products not approved 
by the FDA and provide them to patients. Compounding products 
are made for the individual patient and are, therefore, not 
FDA-approved.
    However, under the guise of traditional compounding, some 
manufacturers have been mass producing and providing products 
without the knowledge of the patient or their doctor. 
Regrettably, this is not a new issue. There have been many 
examples of injuries and deaths from unsafe compounded drugs 
that stretch across the country. In fact, it goes back over a 
decade or more. Throughout that time, I've had the privilege of 
working with many members on this committee, more especially 
Senator Burr, on issues relating to pharmacy compounding.
    This is an issue that hit far too close to home in Kansas. 
Several years ago, a pharmacist in Kansas City was found to be 
diluting cancer drugs for his patients. Unfortunately, over 
4,000 patients were affected before authorities could stop him. 
Senator Kit Bond and I worked together at that time to hold the 
first HELP Committee hearing on pharmacy compounding. We 
requested a GAO report on the status of pharmacy compounding to 
try to get some answers.
    We sponsored what I always thought was a very simple 
amendment to the Medicare Modernization Act to have the FDA 
establish a committee to look into pharmacy compounding and 
make any recommendations to improve and protect patient safety. 
This committee was to terminate after 1 year. It was an 
amendment supported in the Senate. Unfortunately, it was 
stripped during the conference because some folks incorrectly 
thought that the States were adequately regulating such 
pharmacies and that additional Federal regulation would be an 
undue burden.
    I must say I think every member here on this committee time 
and again has fought against additional Federal regulation and 
placing undue burdens on any constituent, including my local 
community pharmacists. I was amazed. Fast forward a few years 
later. With Chairman Kennedy and Senator Burr, we once again 
tried to take a closer look at the regulation and enforcement 
of pharmacy compounding. In an effort to be open and 
transparent, we produced a discussion draft along with Ranking 
Member Enzi and Senator Reed and requested comments and 
feedback.
    While I don't think that discussion draft is anything that 
I would recommend signing into law today, the intent was to 
garner stakeholder feedback and apply it to our policymaking. 
Instead, rather than working with us, we were faced with a full 
grassroots effort to stop the discussion draft from moving 
forward. I said then, and I would repeat now, that my intent, 
and I believe the intent of others, was never to do away with 
pharmacy compounding. What we needed were answers. What we got 
was pushback.
    Now, while it was ultimately Chairman Kennedy's decision 
not to move forward with the discussion draft, I had hoped then 
and continue to believe it is important today to revisit the 
regulation, oversight, and enforcement of pharmacy compounding 
at the Federal and State levels. There are obviously very 
serious patient safety concerns. I have my own opinions on 
where the cracks may be and ways to address these safety 
concerns. To that end, I am working with my colleagues on the 
HELP Committee to discover the appropriate measures we need to 
put in place to protect patient safety.
    Let me be clear. I have not and will not introduce any sort 
of legislation to ban pharmacy compounding. However, the recent 
and repeated loss of life has reiterated the need for 
appropriate measures to be put in place to ensure that bad 
actors can no longer take advantage of patients. Patients have 
a right to know when they are receiving a product that is not 
FDA-approved and the risk that may come with using it. As I 
said during the last hearing we had on this subject, I fully 
recognize the benefits of compounding pharmacy and that they 
fill an important niche in the healthcare delivery system.
    However, many questions need to be answered. How do we 
define manufacturing versus compounding? What are we doing at 
the State level to enforce regulations currently on the books? 
How can we get States that do not have adequate regulations on 
the books to improve? Are those who are inspecting properly 
trained? Should we have a means to test products once they have 
been compounded to ensure they are safe and accurate doses? Are 
schools of pharmacy properly training individuals to compound 
and what steps they should take to make sure they do so safely? 
Why is there not a system of adverse event reporting?
    These questions were important a decade ago and, 
unfortunately, they continue to remain relevant today. My 
expectation from today's hearing is to answer some of these 
questions, learn more about the current state of regulation of 
pharmacy compounding, and I anticipate that all of our 
witnesses will commit to working fully with this committee to 
address any potential gaps in the regulatory structure that 
would potentially affect patient safety.
    I thank the chair and my colleagues for their indulgence.
    The Chairman. Thank you very much, Senator Roberts.
    Now we'll turn to our first panel. We'll hear from Dr. Beth 
Bell of the Centers for Disease Control and Prevention about 
the public health impact of this outbreak and the CDC's role in 
responding to it. Second, we'll turn to Dr. Peggy Hamburg, 
Commissioner of the FDA, and then Dr. Lauren Smith of the 
Massachusetts Department of Public Health to tell us about the 
role of their agencies in regulating compounding pharmacies in 
general and in investigating NECC, specifically. We'll ask them 
about their views on what we can do to prevent future crises.
    With that, all your statements will be made a part of the 
record in their entirety. I'd ask that you limit your opening 
statements to 5 to 7 minutes, and then we'll open it for 
questions. Welcome, all of you. Thank you for being here.
    Dr. Bell, we'll start with you. Please proceed.

 STATEMENT OF BETH BELL, M.D., MPH, DIRECTOR, NATIONAL CENTER 
  FOR EMERGING AND ZOONOTIC INFECTIOUS DISEASES, CENTERS FOR 
          DISEASE CONTROL AND PREVENTION, ATLANTA, GA

    Dr. Bell. Chairman Harkin, Ranking Member Enzi, members of 
the committee, thank you for the opportunity to speak to you 
today about CDC's response and ongoing activities in the 
multistate outbreak of fungal meningitis and other infections. 
CDC disease detectives work 24/7 to save lives and protect 
Americans from harm. The fungal meningitis outbreak is a 
reminder of the importance of CDC's ability to rapidly respond 
to, to characterize, and to stop outbreaks of unexplained 
illness and death.
    My remarks today will focus specifically on the public 
health response to the outbreak associated with injections of 
contaminated preservative-free methylprednisolone acetate 
produced by the New England Compounding Center, NECC. To begin, 
I want to give particular credit to Dr. April Pettit, an 
infectious disease doctor at Vanderbilt University, who 
identified the first meningitis case and notified the State 
health department. If Dr. Pettit had not acted, it is likely 
that many more patients would have been exposed.
    We are also fortunate that Dr. Pettit reached out to Dr. 
Marion Kainer of the Tennessee Department of Health, who 
quickly identified similar cases, reached out to CDC for 
support, and identified the common exposures: three lots of 
methylprednisolone acetate produced by NECC. Dr. Kainer's quick 
response resulted in a voluntary national recall of the 
suspected NECC lots within days of the first case being 
reported. CDC then reached out to other State health 
departments to marshal an enormous nationwide effort, including 
rapidly contacting approximately 14,000 patients at risk.
    The efforts of Dr. Kainer and the hundreds of other State 
public health officials who responded to this outbreak did not 
happen by chance. Despite trying economic times, we have worked 
hard to build and sustain a network of trained public health 
professionals that can rapidly detect and respond to outbreaks. 
As State budget cuts have forced public health personnel 
losses, we are fortunate to have been able to make a real 
difference with CDC's direct financial and in-kind support.
    Many of the outbreak responders are directly supported 
through CDC's Epidemiology and Laboratory Capacity Cooperative 
Agreement. Dr. Kainer is a graduate of CDC's Epidemic 
Intelligence Service Training Program, and Tennessee is one of 
CDC's 10 emerging infections program sites that receive 
additional resources which supported their response in this 
outbreak. The resources available through the Prevention and 
Public Health Fund authored by this committee also made a 
tangible difference in detecting and responding to the 
outbreak.
    I would also like to share information about some of the 
patients affected by the outbreak and what CDC has done to try 
to help them. As of November 14, a total of 461 cases, 
including 32 deaths, have been reported in 19 States. The 
approximately 14,000 people across the country who received the 
contaminated medication include people like Diana Reed and 
George and Lillian Cary.
    Diana Reed of Brentwood, TN, was the primary caretaker of 
her wheelchair-bound husband, Wayne, who suffers from Lou 
Gehrig's Disease. Diana was healthy and physically active, but 
after a neck injury, she turned to steroid injections to help 
with her pain. Tragically, Diana received a contaminated 
injection and became the third Tennessean to die of fungal 
meningitis.
    George Cary of Howell, MI, is husband of Lillian. Both 
received contaminated steroid injections in September. Lillian 
was the first to show symptoms and, tragically, lost her battle 
to fungal meningitis. While grieving the loss of his wife, 
George was also diagnosed with fungal meningitis himself and is 
in the process of undergoing the long and difficult treatment. 
These are just a few of the personal stories associated with 
this tragic event.
    Because this infection is so rare and few doctors have ever 
treated it, CDC stepped in to ensure that patients were getting 
the best possible care. We convened a panel of the Nation's 
leading clinical fungal disease experts to work with CDC 
scientists to help develop diagnostic and treatment guidance. 
Even with treatment, we are seeing many patients return with 
new symptoms and new conditions. We also fear that more exposed 
patients will become ill before the outbreak is over.
    Our focus going forward should be on preventing these 
outbreaks in the future and ensuring that all products, 
materials, and procedures used in healthcare are safe. We are 
fortunate in this case for the clinical and public health 
heroes like Drs. Pettit and Kainer in Tennessee.
    I will end by again noting the thousands of patients and 
families who have been directly affected by this event. Diana, 
George, Lillian, and countless others put their faith in our 
healthcare system. Patients deserve to be safe whenever they 
receive their medical care.
    Thank you.
    [The prepared statement of Dr. Bell follows:]
               Prepared Statement of Beth Bell, M.D., MPH
    Chairman Harkin, Ranking Member Enzi, members of the committee, 
thank you for the opportunity to speak to you today about CDC's 
response and ongoing activities related to the multistate outbreak of 
fungal meningitis and other infections. CDC works 24-7 to save lives 
and protect people from harm and this outbreak illustrates the power of 
public health in action both to identify serious health problems and to 
coordinate a targeted response that protects our Nation and its 
citizens from infectious disease threats.
    I want to extend my sympathies to the patients affected by this 
outbreak. Our hearts go out to the patients and families impacted by 
the debilitation and death from these infections.
    My remarks today will focus specifically on the identification of, 
and subsequent public health response to the outbreak associated with 
injections of contaminated preservative-free methylprednisolone acetate 
(MPA), an injectable steroid produced by the New England Compounding 
Center (NECC). Specifically, I will cover three critical areas related 
to the outbreak:

     a summary of the response by CDC and our partners in State 
public health agencies;
     a description of the fungal infections involved in this 
outbreak and how these infections are affecting patients; and
     a discussion of several early lessons learned.

    As of November 14 at noon (EST), a total of 461 cases, including 32 
deaths, have been reported in 19 States. The cases include fungal 
meningitis, stroke, or other central nervous system-related infections 
plus 10 peripheral joint infections (i.e., knee, hip, shoulder, elbow). 
CDC and our partners at State and local health departments marshaled an 
enormous effort nationwide to determine the source and scope of the 
outbreak, rapidly contact patients at risk, and enlist the individual 
input of leading experts to help us develop novel diagnostic and 
treatment guidance to achieve the best possible patient outcomes. In 
this outbreak, local infectious disease officials, including State 
epidemiologists, healthcare associated infection (HAI) prevention 
coordinators, and others whose positions are directly supported through 
CDC's Epidemiology and Laboratory Capacity (ELC) cooperative agreement 
and CDC's Emerging Infections Program (EIP) were pivotal in the 
original identification of the outbreak and the substantial patient 
notification that followed. Their efforts at the State and local level 
have been extraordinary and in many cases undoubtedly contributed 
directly to saving the lives of exposed patients.
    I would like to highlight some specific efforts by CDC and State 
health agencies:

     The Tennessee Department of Health (TN DOH) identified and 
sounded the alarm on the initial cluster of cases. The TN DOH official 
who alerted others about these cases serves as the State's HAI Program 
Director and is a graduate of CDC's Epidemic Intelligence Service (EIS) 
program. Tennessee also is one of CDC's 10 Emerging Infections Program 
(EIP) sites and as such receives additional resources that helped 
support their response in this outbreak.
     The Virginia Department of Health laboratory, whose staff 
had been trained by CDC in identifying fungi, was the first to identify 
the very rare fungal pathogen, Exserohilum. This discovery saved 
valuable time and provided the Nation with a critical piece of 
information to guide diagnostic and treatment recommendations.
     The Michigan Department of Community Health identified the 
first case of a joint infection associated with these products.
     Over 250 Federal disease control specialists have been 
working out of CDC's Emergency Operations Center to coordinate the 
multistate fungal outbreak response efforts with Federal, State, local, 
tribal, and territorial public health partners. CDC coordination was 
helpful to ensure patient notification, development and dissemination 
of treatment guidance, and rapid communication to the public and the 
health professions community.

          State and local public health departments, health 
        care facilities, and CDC tracked down and contacted over 14,000 
        exposed patients in 23 States with facilities which received 
        the implicated medication.
          CDC engaged the Nation's leading clinical fungal 
        disease experts to receive their individual input on the 
        development of diagnostic and treatment guidance appropriate 
        for identifying and treating patients that develop infections. 
        This panel has met repeatedly as the outbreak has evolved to 
        adjust clinical advice to very complex and rare infections. CDC 
        has educated over 4,200 clinicians through our clinician 
        conference calls (COCA calls) on the interim diagnostic and 
        treatment guidance.
          CDC has prioritized transparent and rapid 
        communication with the public in this outbreak. To date, CDC's 
        meningitis outbreak and fungal diseases web pages have been 
        accessed over 1 million times and have sourced media outlets 
        with direct links and resources to ensure accurate reporting 
        and broad dissemination of health messages. CDC has used the 
        Health Alert Network (HAN) to release multiple health 
        advisories as the outbreak has unfolded. HANs are directly 
        distributed to health care providers nationwide. CDC has also 
        responded to over 4,500 calls to our public inquiry line (CDC-
        INFO).

     CDC's mutually reinforcing laboratory and surveillance 
systems have been critical in confirming the cause of the outbreak:

          CDC's fungus laboratory is the national reference 
        laboratory and in this outbreak has served as an indispensable 
        resource to public health and FDA laboratories to identify and 
        confirm the variety of fungal species recovered from patient, 
        product, and environmental samples. Because there were no 
        available rapid diagnostic tests to identify the fungal 
        organism(s) associated with this outbreak, CDC scientists 
        developed and refined a real-time polymerase chain reaction 
        (PCR) to detect fungal ribosomal DNA, and then performed DNA 
        sequencing to identify the specific fungus by its DNA barcode.
          CDC's HAI laboratory is working with FDA to identify 
        other microorganisms from sealed medication vials. Few 
        laboratories nationwide have the technical expertise and 
        capacity to perform such complicated and exact testing to 
        assess the presence of any bacterial contamination.
          CDC's Infectious Diseases Pathology laboratory has 
        been testing biopsy and autopsy samples from the outbreak. 
        Information from these analyses provides vital clinical 
        information on how this rare disease is affecting patients, and 
        such information is used to inform development of CDC's interim 
        clinical guidance.
                       evolution of the outbreak
    On September 18, an astute clinician alerts the Tennessee 
Department of Health (TN DOH) of a patient with culture-confirmed 
Aspergillus fumigatus meningitis after epidural steroid injection at an 
ambulatory surgical center (ASC).\1\ The patient received an epidural 
steroid injection on July 30 and was admitted to the hospital in late 
August.
---------------------------------------------------------------------------
    \1\ www.cdc.gov/mmwr/preview/mmwrhtml/
mm61e1012a1.htm?s_cid=mm61e1012a1_w.
---------------------------------------------------------------------------
    This type of infection is exceedingly rare, and we are extremely 
fortunate that the clinician chose to test the patient's cerebrospinal 
fluid (CSF) for a possible fungal infection (which is not a routine 
test ordered by clinicians) and then notify the State health department 
when those results came back positive. After further consultation with 
the clinician in Tennessee, the TN DOH contacts CDC on September 20 to 
ask if CDC has received similar reports of unexplained fungal 
meningitis infections. CDC relays that it had not received reports of 
unexplained fungal meningitis infections and recommends that the TN DOH 
conduct a site visit to the ambulatory surgical center where the 
epidural injection was administered.
    On Friday, September 21, the TN DOH follows up with CDC about the 
results of the site visit. TN DOH relays that multiple products and 
exposures could be the source of the infection, including epidural 
injection tray kits, preservative-free contrast media, povidone-iodine, 
lidocaine, and preservative-free MPA from NECC.\2\ External 
contamination of supplies in a common storage area at the ASC was also 
considered as a possible source of infection. CDC recommends that TN 
DOH continue to gather detailed information, including lot numbers on 
all of the products and sources of exposure, to facilitate further 
investigation. Over the weekend, the TN DOH works with the ASC and area 
hospitals to gather additional information and checks if there are any 
other Aspergillus or unexplained meningitis cases.
---------------------------------------------------------------------------
    \2\ Kainer, M., et al. Outbreak of Neuroinvasive Fungal Infections 
Associated with Epidural Steroid Injections, Tennessee, 2012.
---------------------------------------------------------------------------
    On Monday, September 24, CDC and TN DOH discuss the investigation. 
The discussion focuses on additional patients with meningitis from the 
same ASC with similar procedures and product exposures uncovered by the 
TN DOH over the weekend. CSF cultures from the additional patients with 
meningitis were negative, but all presented with a clinical picture 
similar to the index patient. CDC and TN DOH coordinate on next steps 
of the investigation. The TN DOH contacts the Massachusetts Department 
of Public Health (MA DPH) in an effort to obtain more information about 
NECC and its products. TN DOH notifies MA DPH about its cluster of 
meningitis cases following epidural steroid injections \3\ and that use 
of MPA distributed by NECC is one of the common exposures under 
investigation.
---------------------------------------------------------------------------
    \3\ Kainer, M., et al. Outbreak of Neuroinvasive Fungal Infections 
Associated with Epidural Steroid Injections, Tennessee, 2012.
---------------------------------------------------------------------------
    On Tuesday, September 25, CDC notifies FDA that CDC and the TN DOH 
are investigating a cluster of meningitis cases in a single ASC in 
Tennessee that may be related to product contamination. CDC notes that 
they are investigating several product exposures as possible sources of 
infection. Also on Tuesday, the MA DPH and the MA Board of Pharmacy 
organize a call with NECC, the TN DOH, and CDC to inform NECC of the 
ongoing investigation and inquire about product information and adverse 
event reporting. Public health authorities learn about how the MPA 
steroid is prepared, request distribution lists for the three lots \4\ 
identified by the TN DOH and inquire about any reports of illnesses 
related to MPA.\5\ NECC states that it has not received reports of 
illnesses and that sterility testing, as well as environmental 
monitoring, has not demonstrated any concerning results. The MA Board 
of Pharmacy asks if NECC has a voluntary recall process in place if the 
investigation confirms contamination. NECC affirms that it does have a 
voluntary recall process in place.
---------------------------------------------------------------------------
    \4\ Lot #05212012@68, BUD 11/17/2012; Lot #06292012@26, BUD 12/26/
2012; Lot #08102012
@51, BUD 2/6/2013.
    \5\ www.cdc.gov/mmwr/preview/mmwrhtml/
mm61e1012a1.htm's_cid=mm61e1012a1_w.
---------------------------------------------------------------------------
    The following day (September 26), the MA Board of Pharmacy 
initiates an inspection of NECC \6\ and NECC issues a voluntary recall 
of the three lots of MPA identified by the TN DOH. Approximately 3,000 
doses of MPA are quarantined or returned.\7\ CDC is provided an invoice 
list of all facilities that received possibly contaminated lots and 
begins work with TN DOH and other State health departments to contact 
other clinics from the NECC distribution list to see if they are aware 
of any meningitis cases of unknown etiology. CDC also provides an 
update to FDA about the NECC call and informs FDA that NECC initiated a 
voluntary recall of the three lots of MPA though there was no specific 
evidence of product contamination. CDC asks FDA to query MedWatch 
reports for any related cases; the MedWatch query ultimately identifies 
the previously known cases from the Tennessee ASC. During this time, 
CDC continues to pursue other possible sources of the outbreak and 
contacts the New York Department of Health for assistance in contacting 
the company that produced the epidural injection trays used at the 
Tennessee ASC.
---------------------------------------------------------------------------
    \6\ MA DPH NECC Preliminary Investigation Findings: ``. . . 
investigators found NECC employees cleaning sterile compounding areas 
and conducting environmental testing. MA DPH investigators also 
detected signs of bleach decontamination in the compounding areas.''
    \7\ MA DPH NECC Preliminary Investigation Findings.
---------------------------------------------------------------------------
    On September 27, FDA and MA DPH begin coordination for a 
collaborative investigation of NECC.\8\ A case is identified in another 
State \9\ as North Carolina reports its first patient with meningitis 
of unknown etiology following epidural spinal injection to CDC late 
that evening. This is significant because it is the first evidence that 
the exposure may not be isolated to the TN ASC. CDC begins working with 
the TN DOH and NC DOH to identify common exposures in new cases from 
both States which include MPA from NECC as well as the same brands of 
povidone iodine and lidocaine. Of the patients identified thus far, 
only one has a culture-confirmed Aspergillus fungal meningitis 
infection. The additional patients have a similar clinical presentation 
of meningitis as the index case with Aspergillus, but no 
microbiological data yet link them together. The microbiological key 
comes later in the outbreak when the Virginia Department of Health (VA 
DOH) in consultation with CDC's infectious disease pathology laboratory 
links an unexplained death to the outbreak and identifies Exserohilium 
as the fungal pathogen related to that case.
---------------------------------------------------------------------------
    \8\ MA DPH NECC Preliminary Investigation Findings.
    \9\ http://www.cdc.gov/mmwr/preview/mmwrhtml/
mm61e1012a1.htm?s_cid=mm61e1012a1
_w.
---------------------------------------------------------------------------
    On Friday, September 28, CDC requests all 23 States with clinics 
that received the three MPA lots from NECC begin contacting patients 
who received epidural injections to see if there are any other 
meningitis cases of unknown etiology. Through the weekend of September 
29-September 30, CDC posts outbreak information to ClinMicroNet (a 
network of clinical labs) and the Emerging Infections Network (EIN, a 
network of infectious disease physicians) to help identify any 
additional Aspergillus meningitis cases or meningitis cases of unknown 
etiology.
    On Monday, October 1, FDA and MA Board of Pharmacy initiate a joint 
inspection of NECC.\10\ Investigators find violations of MA pharmacy 
regulations \11\ and the MA DPH issues a formal quarantine notice.\12\
---------------------------------------------------------------------------
    \10\ http://www.cdc.gov/media/releases/2012/
t1004_meningitis_outbreak.html.
    \11\ MA DPH NECC Preliminary Investigation Findings--Investigators 
found that methyl-
prednisolone products labeled as patient specific were not individual 
prescriptions but lists of patients generated by a clinic and provided 
to NECC to obtain the product which is a violation of MA pharmacy 
regulations.
    \12\ MA DPH NECC Preliminary Investigation Findings--``The Notice 
directed that all methylprednisolone acetate raw materials (chemicals), 
all non-sterile products located at NECC used in the compounding of 
methylprednisolone acetate, and all inventory on the premises prepared 
for dispensing and stored at the pharmacy, or received by recall should 
be quarantined and not disposed of without the express approval of the 
DPH.''
---------------------------------------------------------------------------
    The following day, CDC initiates a call with the 23 States that 
received the three NECC lots of MPA to provide updates on the 
investigation and share information on meningitis cases of unknown 
etiology as well as common exposures. While NECC products are 
considered the likely source of the outbreak, the investigation does 
not find conclusive evidence of NECC product contamination until 
October 4 when FDA announces it has identified by microscopy visible 
fungal contamination of previously sealed vials of MPA from NECC from 
one of the three lots identified by TN DOH.
    With conclusive identification of fungal contamination, CDC 
activates its Emergency Operations Center on October 4 and intensifies 
outreach to patients and clinicians to ensure appropriate patient 
diagnosis and treatment. CDC also launches a fungal meningitis outbreak 
Web site to provide continual updates to patients, clinicians, and the 
public, and by October 5, CDC posts the lists of the clinics that had 
received the three implicated lots of MPA to facilitate patient 
followup. Additionally, CDC and FDA laboratories work on pathogen 
identification in patient, product, and environmental samples. This 
combined laboratory effort ultimately recovers multiple bacterial and 
fungal contaminants from sealed NECC products labeled as sterile.
  the patient experience with fungal meningitis and related infections
    We do not yet have a full picture of the extent of the impact of 
this tragic outbreak, which clearly has devastating impacts on patients 
and their families. Contaminated medication was administered by 
injection to thousands of people, resulting in an outbreak of fungal 
meningitis and other infections. Exserohilum rostratum, the predominant 
fungal species in this outbreak, is a common brown-black mold found in 
soil and on plants, especially grasses, that thrives in warm and humid 
climates. Fungal infection caused by Exserohilum rostratum is rare and 
when it does occur it has generally been documented as a cause of sinus 
and skin infections. Diagnosis of fungal meningitis, particularly with 
molds, is extremely difficult because traditional diagnostic methods 
such as culture have limited yield.
    The clinical syndromes of these infections are rare and thus lack 
clinical trials or other experience that provide evidence for optimal 
treatment. Available treatments are not straight-forward because of 
potential adverse events and variability among patients. With little 
literature describing these types of infections and limited clinical 
experience available, CDC solicited the individual input of outside 
mycology experts to help develop novel diagnostic and treatment 
guidance for patients at risk for these fungal infections. CDC has 
worked with these experts throughout the outbreak to update our interim 
guidance as more information has become available about the clinical 
experience of patients. Adequate duration of antifungal treatment is 
unknown although we expect a minimum of 3 months' treatment be 
considered. CDC has sent staff to States and worked with State and 
local health departments to abstract medical charts and gather 
information on patients' ongoing clinical experiences. CDC has 
disseminated our treatment guidance through web postings, blast e-mails 
to professional societies, and multiple clinician-specific conference 
calls.
    As of November 13, the median age of the patients is 65 years 
(range: 16-92 years) and over 60 percent are female. While most of the 
cases have presented with meningitis, we have also seen cases of 
stroke, epidural abscess (infection between the outer covering of the 
brain and spinal cord and the bones of the skull or spine), 
osteomyelitis (bone infection), and septic arthritis (joint infection). 
Many patients with meningitis had only a few mild symptoms, such as 
headache and/or nausea or vomiting.
    The incubation period has ranged from 0 to 120 days with a median 
of 20 days. Based on current data, the highest risk is likely to be in 
the first 42 days (6 weeks) after last injection. Maximum incubation 
period for infection is not known, and the incubation period could be 
longer for some patients. Thus, asymptomatic but exposed patients 
should remain vigilant for symptoms and seek medical attention should 
symptoms develop. The clinical situation is still evolving. Even with 
treatment, we are seeing many patients return after being discharged 
from the hospital with new symptoms and other conditions such as 
arachnoiditis (inflammation of the membranes that surround nerves) and 
abscesses at the original injection sites. This suggests that there may 
be long-term complications for patients that have not yet become 
apparent.
    To support ongoing clinical efforts, CDC has developed a Clinicians 
Consultation group consisting of a network of leading clinical 
infectious disease and fungal disease experts nationwide who have 
volunteered to provide consultation with clinicians providing direct 
patient care. CDC is also planning to continue to follow cases to help 
track the course of treatment and provide ongoing information on 
patient outcomes.
                         early lessons learned
    Outbreak responses require skilled, trained public health personnel 
in State and local agencies. In this outbreak, we were fortunate that 
trained individuals were already ``on the ground'' in key positions, 
reinforced by already-established surveillance and laboratory capacity. 
Personnel cuts at the State and local levels have made CDC support to 
State infectious disease programs key to these efforts. CDC's 
Epidemiology and Laboratory Capacity (ELC) cooperative agreement and 
the Emerging Infections Program (EIP) support this critical infectious 
disease capacity and networking.
    This outbreak is also a reminder of the importance of CDC's 
infectious disease epidemiologists and laboratories to rapidly respond 
to and characterize outbreaks of unexplained death and illness. This 
outbreak exemplifies the work of CDC's disease detectives to track down 
and solve public health problems. CDC's laboratory capacity for 
infectious diseases has been a critical element in the response, 
identifying rare or obscure pathogens and providing added capacity as a 
backstop to States. With declining local resources, many States have 
cut back on maintaining fungal testing and instead rely upon CDC's 
fungus laboratory. During the peak of laboratory testing, CDC's fungus 
laboratory was operating 7 days a week to test the hundreds of 
outbreak-related samples. This outbreak has also underscored the 
importance of bioinformatics and genomics technologies that can help 
CDC and States more rapidly and decisively detect, respond to, and 
control large outbreaks like this one.
    CDC plays a vital role not only in responding to these outbreaks 
but in preventing them as well. For years, CDC and its State public 
health partners have been the first-responders to multiple outbreaks 
stemming from suboptimal practices in handling sterile medications in 
clinics and in pharmacies. We are learning that many of these outbreaks 
are the result of a widespread lack of knowledge of or adherence to 
well-recognized regulatory and professional standards for properly 
handling sterile medications.
                           concluding remarks
    This outbreak demonstrates the essential role that public health 
plays in identifying and responding to infectious disease outbreaks 
large or small. Our national public health capacity is disseminated to 
State and local responders who work on a daily basis to keep our 
country safe from infectious diseases--whether they are from naturally 
emerging threats such as a new influenza pandemic or from human-made 
problems such as contaminated medicines. CDC will continue to work with 
State partners, national experts, front-line clinicians and others to 
respond to the critical public health needs related to this outbreak. 





    The Chairman. Thank you very much, Dr. Bell.
    Now we'll turn to Dr. Peggy Hamburg, the Commissioner of 
the Food and Drug Administration. Dr. Hamburg and Dr. Smith, I 
know you were both at the House hearing yesterday. I hate to 
have you do double duty, but that's the way this system works. 
We wanted you over here also to be able to speak with us, so we 
could also engage you in questions about the role of both the 
FDA and the Massachusetts inspections.
    Dr. Hamburg, please proceed.

STATEMENT OF MARGARET A. HAMBURG, M.D., COMMISSIONER, FOOD AND 
              DRUG ADMINISTRATION, WASHINGTON, DC

    Dr. Hamburg. Thank you very much, Mr. Chairman and members 
of the committee. I appreciate the opportunity to testify about 
this tragic fungal meningitis outbreak associated with an 
injectable steroid product distributed by NECC as well as to 
focus on the safety concerns related to compounding and 
legislation that is needed to prevent such incidents from 
happening again.
    I want to, of course, begin by offering my sympathies to 
the patients affected by this outbreak and their families. This 
event has had devastating effects on patients across the 
country, many of whom were likely unaware that they were 
receiving a drug that was compounded, not reviewed or approved 
by the FDA.
    Our foremost goal is the protection of the public health. 
Since the onset of this outbreak, we've targeted FDA resources, 
from experts in our headquarters to inspectors and scientists 
in district offices and labs across the country, to do 
everything we can to stem the toll of this terrible event.
    Together, with CDC and the States, we've sought to identify 
potentially contaminated products and ensure that they are 
removed from market and don't reach patients. We've collected 
and analyzed hundreds of samples from the relevant firms, as 
well as from medical facilities and State and local agencies, 
to isolate the cause and determine the extent of the 
contamination. We're working daily to ensure that timely, 
clear, and accurate information is disseminated about the 
findings of our investigation, what products are affected, and 
what providers should do with any product still on their 
shelves. We're working to alleviate existing drug shortages 
that could be exacerbated by product recalls.
    We've also been reviewing actions taken in the past with 
regard to NECC. In a tragedy of this magnitude, you always look 
back to see what more could have been done. Certainly, we 
should have sent the warning letter more swiftly and done the 
inspection originally planned. From our review thus far, we 
have no reason to believe that any of those specific actions in 
question, more timely issuance of the 2006 warning letter or 
inspectional follow-up, would have prevented this recent 
tragedy.
    What we do know is that stronger, clearer authority would 
enable more effective regulation of the drug compounding 
industry, especially when it's been evolving so significantly. 
As it is, our authority over compounding is limited, unclear, 
and contested. In the face of differing views in Congress and 
the courts about FDA's authority and continuing challenges by 
industry, the agency has struggled with how to chart an 
effective course to protect the public health.
    Like Senator Roberts, we recognize that traditional 
compounding provides an important service for patients who, for 
example, can't swallow a pill or are allergic to an ingredient 
in a drug product. The industry has evolved well beyond a 
neighborhood pharmacist. In particular, the movement by many 
hospitals to outsource pharmacy compounding has created a 
market for compounding operations that produce drugs that reach 
far larger numbers of patients.
    When these facilities operate well, they may serve an 
important function in terms of safety and efficiency. However, 
when they fail to follow safety and quality standards, many 
patients may be harmed. Our best information is that there are 
thousands of other compounders out there producing what should 
be sterile products made to exacting standards, and thus many 
other firms with the potential to generate a tragedy like this.
    The current oversight framework, in attempting to draw a 
bright line between compounders and manufacturers, fails to 
address the complex issues raised by the changing nature of the 
industry. Additionally, gaps and ambiguities in the law have 
hampered our ability to act to protect patients and to prevent 
rather than to react to safety problems.
    I am committed to working with Congress and other 
stakeholders to design a system of rational, risk-based 
regulation that takes into account both the Federal and State 
rules. As I outlined in my testimony, we have developed a 
proposed framework that would tier the degree of oversight to 
the risk posed by the type of product and practices. 
Traditional compounding would remain the purview of the States.
    The higher risk posed by nontraditional compounding would 
be addressed by Federal standards, including standards for 
quality control. Under this framework, certain products 
carrying the highest risk could not be compounded. They could 
only be produced by entities willing to meet the standards 
currently required of drug manufacturers.
    We would also like to explore with you authorities that 
would be important to support this new regulatory paradigm, 
including clear authority to access records, mandatory 
reporting of adverse events, additional registration 
requirements to facilitate appropriate oversight and 
coordination with State regulators, clear label statements to 
allow prescribers and consumers the opportunity to make 
informed judgments, and adequate funding to support the 
inspections and oversight activities outlined in the framework.
    Because a key piece of any plan involving oversight of 
pharmacy compounders will continue to be performed at the State 
level, we must work closely with our State partners as we 
develop the framework for new authorities. FDA will be inviting 
representatives from all 50 States to participate in a full-day 
meeting on December 19 to facilitate these important 
discussions and to strengthen our working relationship with the 
States.
    We have a collective opportunity and responsibility to help 
prevent future tragedies. If we fail to act, this type of 
incident will happen again. It is a matter of when, not if, I'm 
afraid. If we fail to act now, it will only be a matter of time 
until we're all back in this room asking why more people have 
died and what could have been done to prevent it.
    I am happy to answer any questions you have and look 
forward to working with you on this very important public 
health issue.
    [The prepared statement of Dr. Hamburg follows:]
            Prepared Statement of Margaret A. Hamburg, M.D.
                              introduction
    Mr. Chairman and members of the committee, I am Dr. Margaret 
Hamburg, Commissioner of Food and Drugs at the Food and Drug 
Administration (FDA or the Agency), which is part of the Department of 
Health and Human Services (HHS). Thank you for the opportunity to be 
here today to discuss important issues related to the tragic fungal 
meningitis outbreak associated with compounded methyl-
prednisolone acetate (MPA), a steroid injectable product distributed by 
the New England Compounding Center (NECC), and to discuss more broadly 
safety issues related to pharmacy compounding.
    I want to begin by offering my deepest sympathies to the patients 
affected by this outbreak and their families. This outbreak has had 
devastating effects on individuals and families across the country. The 
Centers for Disease Control and Prevention (CDC) has reported 32 deaths 
among 438 individual cases (428 cases of fungal meningitis and 10 cases 
of peripheral joint infections) \1\ across 19 States. Approximately 
14,000 patients may have received injections with MPA from three 
implicated lots. In addition, two other NECC products have been found 
to be contaminated with different bacteria. We have found no adverse 
health effects to date from these additional products, but continue to 
investigate the public health implications of this contamination.
---------------------------------------------------------------------------
    \1\ Four-hundred and twenty-eight cases of fungal meningitis, 
stroke due to presumed fungal meningitis, or other central nervous 
system-related infection meeting the outbreak case definition, plus 10 
peripheral joint infections (e.g., knee, hip, shoulder, elbow).
---------------------------------------------------------------------------
    Although the investigation is ongoing, we want to provide you with 
an update on the actions that FDA has taken, and is continuing to 
respond to this outbreak. We also want to suggest steps that Congress 
can take to strengthen FDA's authority to help prevent tragedies like 
this from happening in the future.
                 fda's response to the current outbreak
    FDA's primary goal since the onset of this outbreak has been to 
protect the public health. With the State and Federal partners, we are 
conducting thorough investigations of the relevant facilities, 
monitoring the voluntary recalls associated with these products to 
ensure that contaminated and potentially contaminated product is off of 
the shelves, and ensuring that information is communicated promptly and 
clearly to health care professionals and patients.
    Let me briefly summarize the sequence of key events regarding the 
outbreak. On September 25, 2012, CDC notified FDA that it was working 
with the Tennessee Department of Health to investigate a cluster of 
meningitis cases at a single clinic, which might be associated with 
product contamination. When we learned of the potential contamination, 
we joined CDC in investigating. On September 26, NECC began a voluntary 
recall of three implicated lots of MPA and voluntarily ceased 
manufacturing of MPA. The Massachusetts Board of Registration in 
Pharmacy, which has primary oversight responsibility for pharmacies in 
its State, oversaw the recall, and initiated a 1-day inspection of 
NECC's Framingham, MA, facility. FDA also began to coordinate with the 
Massachusetts Board of Registration in Pharmacy to plan for inspection 
of NECC. We coordinated closely with the State on this adverse event 
inspection, because the State has authority to compel certain actions 
where our authority is more limited.
    FDA and the Massachusetts Board of Registration in Pharmacy 
initiated a joint inspection of NECC on October 1, 2012. On October 4, 
FDA and CDC held a joint press conference announcing the investigation 
of the meningitis outbreak.\2\ On October 5, after FDA had observed 
fungal contamination by direct microscopic examination of foreign 
matter taken from a sealed vial of MPA collected from NECC, FDA issued 
a MedWatch Safety Alert to 220,000 health professionals to notify them 
of the fungal contamination. Out of an abundance of caution, the Safety 
Alert took the additional step of recommending that health care 
professionals and consumers not use any product produced by NECC. FDA 
also requested that health care professionals retain and secure all 
remaining products purchased from NECC until FDA provided further 
instructions about how to dispose of these products. In addition, the 
Safety Alert encouraged health care professionals and patients to 
report to the Agency's MedWatch Safety Information and Adverse Event 
Reporting Program any adverse events or side effects related to the use 
of these products. On October 6, at FDA's recommendation, NECC agreed 
to recall all products.
---------------------------------------------------------------------------
    \2\ ``CDC and FDA Joint Telebriefing on Investigation of Meningitis 
Outbreak'' (October 4, 2012); transcript available at http://
www.cdc.gov/media/releases/2012/t1004_meningitis_
outbreak.html.
---------------------------------------------------------------------------
    As our investigation continued, on October 11, we announced our 
findings showing the presence of a fungal contaminant in multiple 
sealed vials of MPA injection, made at the NECC's Framingham, MA site. 
CDC confirmed the specific type of fungus related to the patient 
disease--Exserohilum--in this briefing as well.\3\ On October 15, based 
on FDA's ongoing investigation and out of an abundance of caution, we 
further advised health care professionals to followup with patients who 
were administered any NECC injectable product on or after May 21, 2012, 
including an ophthalmic drug that is injectable or used in conjunction 
with eye surgery or a cardioplegic solution. After working closely with 
the State on October 22, the Agency made available two lists of 
customers (consignees) who received products that were shipped on or 
after May 21, 2012, from NECC's Framingham, MA facility, advising those 
customers to check their stocks to identify whether they had any 
products from NECC, and if so, to immediately isolate any identified 
product from their drug supplies and contact NECC to obtain 
instructions on how to return products.
---------------------------------------------------------------------------
    \3\ ``CDC, FDA, Massachusetts Department of Public Health: Joint 
Telebriefing Updating Investigation of Meningitis Outbreak'' (Oct. 11, 
2012); transcript available at http://www.cdc.gov/media/releases/2012/
t1011_meningitis_outbreak.html.
---------------------------------------------------------------------------
    On October 26, FDA released a copy of the FDA Form 483 (list of 
observations made during the on-site inspection) issued to NECC. FDA 
observed, and has since confirmed, that contaminated products were made 
at NECC's Framingham, MA facility, and listed a number of observations 
made during the course of the inspection regarding conditions in the 
clean room at this facility.
    Most recently, on November 1, FDA and CDC laboratories announced 
that bacteria had been identified as present in three separate lots 
(batches) of NECC-supplied, preservative-free injectable betamethasone, 
with each lot producing different culture results (identifying 
different contaminants), and in a single lot of NECC cardioplegia 
solution. FDA stated that although final laboratory results on 
additional samples were still pending, the previous finding of fungal 
contamination of MPA and recent finding of bacterial contamination of 
injectable betamethasone and cardioplegia solution reinforced the 
Agency's concern about the lack of sterility in products produced at 
NECC's compounding facility and served to underscore that hospitals, 
clinics, and health care professionals should not use any NECC-supplied 
products.
    The Agency has been working closely with CDC, numerous State health 
departments, and the Massachusetts Board of Registration in Pharmacy to 
investigate the outbreak of fungal meningitis. This is a far-ranging 
investigation across the United States. FDA, in conjunction with our 
State partners, is in the process of inspecting several facilities 
associated with this outbreak. This includes compounders, wholesale 
distributors, active pharmaceutical ingredient (API) suppliers, 
contract laboratories, and others. The Agency's first priority has been 
to detect any contaminated or potentially contaminated products, to 
prevent them from reaching U.S. consumers by ensuring they are 
effectively recalled and removed from the market, and, as discussed 
more fully below, to communicate key information about these products 
to the providers and patients who need it. In connection with this 
investigation, FDA has collected and analyzed hundreds of samples from 
firms associated with this outbreak, as well as from medical facilities 
and State and local agencies. In addition to staff at FDA headquarters, 
staff in FDA district offices in New England, New York, Dallas, 
Seattle, Chicago, Los Angeles, Detroit, Cincinnati, Kansas City, and 
Florida, and laboratory personnel in Denver, San Francisco, Atlanta, 
New York, and Boston, are assisting in this investigation.
    FDA also inspected Ameridose LLC's facility in Westborough, MA as 
part of the Agency's ongoing fungal meningitis outbreak investigation. 
Ameridose and NECC share some of the same management. Ameridose entered 
into a voluntary agreement with the Massachusetts Board of Registration 
in Pharmacy to temporarily cease all pharmacy and manufacturing 
operations starting on October 10, 2012. After FDA's preliminary 
inspectional findings raised concerns about a lack of sterility 
assurance for products produced at and distributed by Ameridose's 
Westborough facility, the company voluntarily recalled all of its 
unexpired products in circulation. FDA completed its inspection on 
November 9, 2012.
    FDA is currently conducting recall audit checks of NECC's 
customers. In an audit check, FDA contacts a subset of the firm's 
customers, which in this case were health care facilities, to confirm 
that they received notice of the recall and took the action requested 
in the recall notice.
    In this case, the facilities were instructed to immediately 
segregate and quarantine the material and to work with NECC to 
coordinate return of the products. As of November 5, 2012, FDA had 
completed 587 audit checks of NECC's health care facility customers. 
FDA found no product remaining for use at any of the NECC customers 
that it audited, and all customers had knowledge of the recall. 
Ameridose commenced its product recall on October 31, 2012; FDA 
initiated its audit check process for the Ameridose recall on November 
5, 2012.
    FDA has identified six Ameridose products that were on the FDA drug 
shortage list prior to the recall (sodium bicarbonate injection; 
succinylcholine injection; atropine sulfate injection; bupivacaine 
hydrochloride injection; lidocaine hydrochloride injection and 
furosemide injection).
    These six drugs were in shortage before the Ameridose shutdown due 
to manufacturing problems, delays, and discontinuations by commercial 
manufacturers. FDA's Drug Shortage Program is using every tool 
available to work with manufacturers to address these shortages. For 
five of the drugs, we expect the shortages to decrease based on all of 
the ongoing efforts of FDA and the manufacturers to address these 
shortages and do not anticipate the Ameridose shutdown to create 
additional issues. For sodium bicarbonate injection, we are continuing 
all efforts to address the shortage, including exploring temporary 
importation to assist with supplies until demand is being met by the 
U.S. manufacturers.
    FDA has communicated throughout this investigation with the media, 
Congress, State health officials, health care professionals, and the 
public to keep them apprised of important findings and developments as 
we move forward in our investigation. FDA's Web site is updated on a 
frequent basis to provide broad access to any new public information. 
This information is being further disseminated through the Agency's 
electronic listserves and through Twitter and Facebook. Along with CDC, 
FDA is providing health care professionals with information they need 
on an ongoing basis, and as new information comes to light, to advise 
and treat patients affected by this situation.
    Targeted alerts have been sent to 150 health care professional 
organizations, including the national specialty-specific societies that 
work with spinal injections, such as the American Society of 
Anesthesiologists, the American Academy of Physical Medicine and 
Rehabilitation, and the North American Spine Society, and also to all 
State medical, pharmacist, nursing, and physicians' assistant 
societies, as well as all State boards of pharmacy. Regular phone 
updates are provided to State health departments, in collaboration with 
CDC, and written updates are also distributed to national pharmacy and 
ophthalmology professional organizations. FDA also contacted patient 
and health care professional groups and consumer groups and worked with 
the American Hospital Association as part of our response.
    FDA pharmacists are fielding calls from the public and we have 
extended their hours of availability for the last several weeks to help 
respond to the public's concerns. We also continue to respond to calls 
and e-mails from health care professionals, hospitals and clinics, and 
others with questions about the NECC and Ameridose recalls.
    The far-ranging investigation is ongoing and FDA will continue to 
update stakeholders as quickly as possible as information becomes 
publicly available.
    FDA's past activities with respect to NECC include: a 2002 
inspection in response to adverse event reports (followed by a State 
inspection and action under Massachusetts' authority) and a 2006 
Warning Letter focused on lower risk issues associated with copying 
approved drugs, marketing and packaging. Throughout this time, NECC has 
repeatedly disputed FDA's jurisdiction over its facility.\4\ The 
Massachusetts Board of Pharmacy re-inspected NECC in 2011 in response 
to a letter from the firm indicating that NECC was ``updating its 
facility and moving into adjacent space''; that inspection included a 
tour of the facility, security review, licensing review, and inspection 
of NECC's sterile and non-sterile processing areas.\5\ The 
Massachusetts Board of Pharmacy inspection found the facility to be 
``Satisfactory.'' \6\
---------------------------------------------------------------------------
    \4\ Inspection Report for April 2002 inspection, at PP. 2, 3, 5; 
Establishment Inspection Report for 2002/2003 inspection, at p. 11; 
Inspection Memorandum for 2004 inspection, at p. 3; Warning Letter 
Response, at PP. 3-4.
    \5\ A copy of MABRP's May 24, 2011, Inspection Report for NECC is 
available on MABRP's Web site at http://www.mass.gov/eohhs/docs/dph/
quality/boards/necc/03-new-england-compound
ing-pharmacy-incnew-england-compounding-center-inspection-report.pdf.
    \6\ See MABRP's May 24, 2011 Inspection Report for NECC, id., at p. 
10.
---------------------------------------------------------------------------
              fda's legal authority over compounded drugs
    FDA regards traditional pharmacy compounding as the combining or 
altering of ingredients by a licensed pharmacist, in response to a 
licensed practitioner's prescription for an individual patient, which 
produces a medication tailored to that patient's special medical needs. 
In its simplest form, traditional compounding may involve reformulating 
a drug, for example, by removing a dye or preservative in response to a 
patient allergy. Or it may involve making a suspension or suppository 
dosage form for a child or elderly patient who has difficulty 
swallowing a tablet. FDA believes that pharmacists engaging in 
traditional compounding provide a valuable medical service that is an 
important component of our health care system. However, by the early 
1990s, some pharmacies had begun producing drugs beyond what had 
historically been done within traditional compounding.
    After receiving reports of adverse events associated with 
compounded medications, FDA became concerned about the lack of a policy 
statement on what constituted appropriate pharmacy compounding. In 
March 1992, the Agency issued a Compliance Policy Guide (CPG), section 
7132.16 (later renumbered as 460.200) to delineate FDA's enforcement 
policy on pharmacy compounding. It described certain factors that the 
Agency would consider in its regulatory approach to pharmacies that 
were producing drugs.
    The compounding industry objected to this approach and several 
bills were introduced, some with significant support, to limit the 
Agency's oversight of compounding.\7\ In May 1996, in a House Commerce 
Committee hearing on FDA reform legislation, FDA Commissioner David 
Kessler testified that the compounding provision being considered by 
the committee was likely to encourage large-scale manufacturing under 
the guise of pharmacy compounding, and could allow for potentially 
dangerous compounding of sterile products, leading to serious safety 
problems or death.\8\
---------------------------------------------------------------------------
    \7\ H.R. 5256, Pharmacy Compounding Preservation Act of 1994, 
introduced Oct. 7, 1994, 1 co-sponsor; H.R. 598, Pharmacy Compounding 
Preservation Act of 1994, introduced Jan. 20, 1995, 141 co-sponsors; 
H.R. 3199, Drug and Biological Products Reform Act of 1996, introduced 
March 29, 1996, 205 co-sponsors; H.R. 1060, Pharmacy Compounding Act, 
introduced March 13, 1997, 152 co-sponsors; H.R. 1411, Drug and 
Biological Products Modernization Act of 1997, introduced April 23, 
1997, 16 co-sponsors.
    \8\ Statement by David A. Kessler, M.D., Commissioner of Food and 
Drugs, Dept. of Health and Human Services, before the Subcommittee on 
Health and Environment, Committee on Commerce, House of Representatives 
(May 1, 1996).
---------------------------------------------------------------------------
    In November 1997, S. 830, the Food and Drug Administration 
Modernization Act of 1997 (FDAMA) was signed into law as Public Law 
105-115.\9\ FDAMA added to the FD&C Act's Section 503A, which addresses 
FDA's authority over compounded drugs.\10\ Section 503A exempts 
compounded drugs from three critical provisions of the FDCA: the 
premarket approval requirement for ``new drugs''; the requirement that 
a drug be made in compliance with current good manufacturing practice 
(cGMP); and the requirement that the drug bear adequate directions for 
use, providing certain conditions are met. These conditions include, 
among other things, that the compounding be performed by a licensed 
pharmacist or physician, that there be a prescription for the 
compounded product for an individual patient, and that the compounded 
product be necessary for an identified patient. It allows FDA to 
restrict the compounding of certain categories of drugs (after notice-
and-comment rulemaking), and limits the quantity of compounded drugs 
that a pharmacy could ship out of State to 5 percent of the total 
prescription orders, unless the State enters into a Memorandum of 
Understanding with FDA that addresses the distribution of ``inordinate 
amounts'' of compounded drugs out of the State, and the handling of 
complaints about compounded products shipped out of the State. Section 
503A also contains restrictions on the advertising or promotion of the 
compounding of any particular drug, class of drug, or type of drug, and 
on the solicitation of prescriptions for compounded drugs from 
prescribers. These provisions were the subject of subsequent court 
challenges, which have produced conflicting case law and amplified the 
perceived gaps and ambiguity associated with FDA's authority over 
compounding pharmacies. We look forward to working with Congress to 
address these issues.
---------------------------------------------------------------------------
    \9\ Public Law 105-115, FDAMA, 111 Stat. 2296 (Nov. 21, 1997), 
available at http://www.gpo
.gov/fdsys/pkg/PLAW-105publ115/pdf/PLAW-105publ115.pdf.
    \10\ Id.
---------------------------------------------------------------------------
Looking Ahead
    FDA believes that there is a legitimate role for traditional 
compounding to provide needed drugs to patients that, for example, need 
a drug that is allergen free or have a medical need that cannot be met 
with an approved FDA product. However, we have grown increasingly 
concerned about certain compounding practices, and we have seen an 
increasing number of incidents related to compounded drugs. The NECC/
meningitis situation is the latest, and most serious, incident. As 
described above, FDA's ability to take action against compounding, that 
exceeds the bounds of traditional pharmacy compounding and poses risks 
to patients, has been hampered by gaps and ambiguities in the law, 
which have led to legal challenges to FDA's authority to inspect 
pharmacies and take appropriate enforcement actions.
    The Administration is committed to working with Congress to address 
the threat to public health from gaps in authorities for effective 
oversight of certain compounding practices. To that end, FDA has 
developed a framework that could serve as the basis for the development 
of a risk-based program to protect the public health.
Risk-based Framework
    Recognizing the history of compounding practice, FDA supports the 
long-standing policy that all compounding should be performed in a 
licensed pharmacy by a licensed pharmacist (or a licensed physician), 
and that there must be a prescription or order for an individual 
patient who has a documented medical need for the compounded drug.
    Further, we recommend that the statute recognize two categories of 
compounding: traditional and non-traditional. ``Traditional 
compounding'' would include the combining, mixing, or altering of 
ingredients to create a customized medication for an individual patient 
with an individualized medical need for the compounded product, in 
response to a valid patient-specific prescription or order from a 
licensed practitioner documenting such medical need. Traditional 
compounding plays an important role in the health system and should 
remain the subject of State regulation of the practice of pharmacy.
    ``Non-traditional compounding'' would include certain types of 
compounding for which there is a medical need, but that pose higher 
risks based on one or more of the factors identified below. Non-
traditional compounding would be subject to Federal standards adequate 
to ensure that the compounding could be performed without putting 
patients at undue risk. For example, enforcement could be by the FDA or 
by a State willing to effectively oversee the compounding activities, 
as determined by FDA.
    Factors that could place a product into the ``non-traditional 
compounding'' category might include some statutorily specified 
combination of: the type of product/activity (e.g., sterile 
compounding); the amount of product being made; whether the production 
is being done before the receipt of a prescription or order for a 
particular patient (so-called ``anticipatory compounding''); whether 
the compounded drug is being shipped interstate; or whether the drug is 
being dispensed to someone other than the ultimate user when it leaves 
the facility where it was produced.
    Non-traditional compounding should, because of the higher risk 
presented, be subject to a greater degree of oversight, with the 
riskiest products subject to the highest level of controls, such as 
appropriate current good manufacturing practice (``cGMP'') standards 
established by FDA. In addition, FDA believes that with noted 
exceptions, certain products are not appropriate for compounding under 
any circumstances. These products would include: (1) what are 
essentially copies of FDA-approved drugs, absent a shortage 
justification based on the drug appearing on FDA's shortage list; and 
(2) complex dosage forms such as extended release products; transdermal 
patches; liposomal products; most biologics; and other products as 
designated by FDA. Producing complex dosage forms would require an 
approved application and compliance with cGMPs, along with other 
requirements applicable to manufactured drug products. We would seek to 
permit the Secretary to have sufficient flexibility in this area to 
make these exceptions necessary to address issues of public health.
    FDA would like to explore with Congress other authorities that 
would be important to support this new regulatory paradigm. For 
example, FDA should be given clear, full authority to collect and test 
samples of compounded drugs and to examine and collect records in a 
compounding pharmacy, just as the agency does when inspecting other 
manufacturers. FDA should have clear statutory authority to examine 
records such as records of prescriptions received, products shipped, 
volume of operations, and operational records such as batch records, 
product quality test results, and stability testing results. Such 
inspections are necessary to determine when a pharmacy exceeds the 
bounds of traditional compounding, to respond to public health threats, 
and to enforce Federal standards.
    FDA also believes that pharmacies engaged in non-traditional 
compounding should register with FDA so that FDA can maintain an 
accurate inventory of such pharmacies to facilitate appropriate 
oversight and coordination with State regulators. In addition, FDA 
would like to explore with Congress several other ideas such as clear 
label statements identifying the nature and source of the non-
traditionally compounded product, and requiring non-traditional 
compounders to report adverse events. The labeling statements would 
provide prescribers and consumers with valuable information about the 
products they are using or taking so that they can make informed 
judgments about their use. Requiring non-traditional compounders to 
report adverse events, as drug manufacturers are required to do, would 
allow FDA and the States to identify trends and to proactively take 
steps to curtail dangerous compounding practices. Other appropriate 
regulatory and enforcement tools might also be useful. Funding will be 
necessary to support the inspections and other oversight activities 
outlined in this framework. We look forward to working with Congress to 
explore the appropriate funding mechanisms to support this work, which 
could include registration or other fees, as Congress has authorized 
and FDA has implemented in other settings.
    In light of growing evidence of threats to the public health, the 
Administration urges Congress to strengthen Federal standards for non-
traditional compounding. Such legislation should appropriately balance 
legitimate compounding that meets a genuine medical need with the 
reality that compounded drugs pose greater risks than those that are 
evaluated by FDA for safety and efficacy and subject to manufacturing 
controls to ensure consistently high product quality. We recommend that 
it recognize the appropriate State role in regulation of traditional 
compounding, while authorizing Federal standards and oversight for non-
traditional compounders that produce riskier products. We look forward 
to working with Congress in striking the right balance.
                               conclusion
    Protecting Americans from unsafe and contaminated drugs is not just 
an important responsibility of FDA--it is part of our core mission. To 
fulfill our mission, we must be able to proactively identify dangerous 
practices before they result in actual harm, and when necessary, 
intervene to minimize the damage and to prevent future similar events. 
Tragically, there have been 32 deaths to date associated with this 
outbreak. However, we are hopeful that our actions thus far and the 
ongoing investigation are preventing unknown numbers of further deaths, 
which might have occurred had we and our partners not acted 
aggressively after we became aware of the outbreak.
    We look forward to working with Congress on legislation that will 
balance the need to allow legitimate forms of traditional pharmacy 
compounding with the need for adequate Federal oversight of higher risk 
pharmacy compounding practices.
    I am happy to answer any questions you may have.

    The Chairman. Thank you, Dr. Hamburg.
    Dr. Smith, welcome. Again, as I said, your statements will 
be made a part of the record in their entirety. If you could 
sum it up, I'd appreciate it.

  STATEMENT OF LAUREN SMITH, M.D., MPH, INTERIM COMMISSIONER, 
            DEPARTMENT OF PUBLIC HEALTH, BOSTON, MA

    Dr. Smith. Good morning, Senator Harkin and Ranking Member 
Enzi and members of the committee. Thank you for having me here 
today. My name is Dr. Lauren Smith, and I'm the Interim 
Commissioner for the Massachusetts Department of Public Health.
    I must begin by saying that my thoughts are with the 
victims and their families of this tragic outbreak--some of the 
poignant stories described by Dr. Bell. I know that the numbers 
that represent those made ill and those who lost their lives 
actually represent real people with real stories. That only 
strengthens my resolve to ensure that no other families have to 
suffer the heartbreak that these have.
    As a mother, a pediatrician, and a public health leader, I 
have devoted my life and career to protecting the health of 
others. These events invoke in me the same outrage that you and 
the rest of the public feel. For many of you, I know this hits 
very close to home.
    For nearly 2 months, our department, along with the FDA, 
has conducted a joint investigation of the New England 
Compounding Center, the source of the devastating fungal 
meningitis outbreak. We have also investigated and shut down 
NECC's sister companies. NECC knowingly disregarded sterility 
tests, prepared medicine in unsanitary conditions, and violated 
their pharmacy license, which endangered thousands of lives as 
a result. NECC bears the primary responsibility for the harm 
that they have caused with these actions.
    I was given the responsibility as interim commissioner less 
than 3 weeks ago to lead my department through this crisis. And 
like you, I have been trying to put together the pieces of the 
puzzle. First licensed by Massachusetts in 1998, NECC and its 
owner, Barry Cadden, have been the subject of numerous 
complaints resulting in a series of investigations by the State 
and the FDA.
    These investigations led the Board of Pharmacy to propose 
reprimand and probation in 2004. This proposal was inexplicably 
weakened in 2006, allowing NECC to continue to operate without 
any disciplinary actions pending an independent evaluation of 
its progress under a consent agreement. The Board of Pharmacy's 
failure to take decisive disciplinary action in 2006 on these 
complaints contributed to these tragic events.
    In addition, in April 2006, the Board of Pharmacy staff 
learned that the principal of PSI, the evaluator for NECC, had 
been convicted of Federal crimes that resulted in 18 people 
being blinded. However, the staff did not share this 
information with the Board members before they accepted the 
report from PSI indicating that NECC's compliance with the 
consent agreement had been completed. These same staff members 
failed to act on a July 2012 report from a Colorado Board of 
Pharmacy that NECC had violated both Colorado and Massachusetts 
pharmacy regulations. These staff members have been removed 
from their jobs.
    Poor judgment, missed opportunities, and lack of action 
have allowed NECC to continue on this troubling path. We 
acknowledge that some of these lapses were preventable, but, 
clearly, all are unacceptable.
    From the early days of this outbreak, the department has 
acted swiftly and decisively. We secured a surrender of NECC's 
license, shut down its operations, and secured a total recall 
of NECC products. We moved to permanently revoke NECC's 
license, as well as the licenses of the three principal 
pharmacists who oversaw their operations. We also secured the 
suspension of operations of Ameridose and Alaunus, which are 
two other drug manufacturers also owned by Barry Cadden, which, 
as I'm sure you know, have been found to have substandard 
practices.
    While taking these strong and necessary actions, we have 
reexamined our own State regulations regarding compounding 
pharmacies. Although our regulations are comparable to those in 
most States, they clearly need to be strengthened to address 
the realities of this evolving industry. On November 1, 
Massachusetts enacted a series of emergency regulations to 
bring greater scrutiny to this industry and require sterile 
compounding pharmacies to report both volume and distribution 
information to us.
    In addition, licensed pharmacies will also have to report 
when they are the subject of either a State or a Federal 
investigation. We have also begun unannounced inspections of 
all sterile compounding pharmacies. Teams are conducting those 
inspections even as we speak.
    To further strengthen our oversight over sterile 
compounding pharmacies, we must also explore changes in State 
law. We have created a special commission to review best 
practices in other States and to identify stronger mechanisms 
of oversight of pharmacies such as these in Massachusetts.
    As we work to raise our standards in Massachusetts, we urge 
Congress to act to strengthen the Federal oversight. 
Congressman Markey's leadership on this issue is laudable, and 
we hope this will address the regulatory black hole that exists 
currently between State and Federal oversight.
    As a pediatrician who has cared for acutely ill children 
and their families for close to 20 years, I understand that 
patients place a significant amount of trust in our healthcare 
system. We must use these terrible events as an impetus to work 
together as public health leaders and legislators to institute 
reforms to restore this trust and ensure that something like 
this never happens again. I know that we will keep the victims 
and their families always in our thoughts as we work to 
identify responsibility and to implement policies and practices 
that will be both effective and lasting.
    Thank you. I appreciate this committee's interest in this 
matter, and I commend you for moving so swiftly to bring us 
together to discuss it.
    [The prepared statement of Dr. Smith follows:]
             Prepared Statement of Lauren Smith, M.D., MPH
                                summary
     For nearly 2 months, the Massachusetts Department of 
Public Health has conducted a joint investigation of New England 
Compounding Center (NECC) with our Federal partners at the Food and 
Drug Administration (FDA) to determine what caused the devastating 
fungal meningitis outbreak that has sickened hundreds and led to dozens 
of deaths across the country. DPH has also been jointly investigating 
sister companies Ameridose and Alaunus, Westborough, MA-based drug 
manufacturers.
     NECC knowingly disregarded sterility tests, prepared 
medicine in unsanitary conditions and unlawfully engaged in 
manufacturing, endangering thousands of lives as a result.
     This testimony provides a chronology of events based upon 
documents, reports, and e-mails recently reviewed, beginning with 
NECC's licensure in July 1998. It is a troubling history.
     The Massachusetts Department of Public Health has taken 
swift and decisive actions since we became aware of the outbreak.

          DPH secured a surrender of NECC's license, shut down 
        its operations and issued a total recall of NECC products.
          Massachusetts sterile compounding pharmacies have 
        been required to attest under penalty of perjury that they are 
        meeting all State laws and regulations.
          The Massachusetts Board of Pharmacy approved 
        emergency regulations to enhance oversight of compounding 
        pharmacies.
          We have begun unannounced inspections of the State's 
        25 sterile compounding pharmacies to review how they function 
        when they are not aware that an inspection is scheduled.
          We have named Christian A. Hartman, an expert in 
        pharmacy practice and patient safety, to chair a Special 
        Commission on compounding pharmacies. We will look at best 
        practices in other States, explore new ideas, and consider the 
        interplay between State and Federal authority.
          We have removed three key employees from their jobs 
        due to their failures to act at key junctures.

     Massachusetts will continue to do whatever we can, make 
any changes, and identify any areas of new law to make sure something 
like this never happens again.
                                 ______
                                 
    Good morning, Chairman Harkin, Ranking Member Enzi, members of the 
committee, thank you for having me here today. My name is Dr. Lauren 
Smith, I am the Interim Commissioner of the Massachusetts Department of 
Public Health and I welcome the opportunity to have this discussion.
    I want to say from the outset that my thoughts are with the victims 
and families affected by this tragic outbreak. As a mother, a 
pediatrician, and a public health leader, I have devoted my life and 
career to protecting the health of others. Have no doubt that these 
events invoke in me the same outrage that you and the rest of the 
public feel. The natural first question we all ask is ``How could this 
possibly have happened?'' The necessary second question is ``What can 
we do to ensure that this terrible situation does not happen again?''
    For nearly 2 months, our Department has conducted a joint 
investigation of New England Compounding Center (NECC), alongside our 
Federal partners at the Food and Drug Administration (FDA), to answer 
these questions.
    NECC is a Framingham, MA-based pharmacy that compounds sterile 
medications. It was identified as the source of the devastating fungal 
meningitis outbreak that has sickened hundreds and led to dozens of 
deaths across the country. For many of you, and for those with cases 
among your constituents in particular, I know these losses hit close to 
home.
    NECC knowingly disregarded sterility tests, prepared medicine in 
unsanitary conditions and unlawfully engaged in manufacturing, 
endangering thousands of lives as a result. NECC bears the primary 
responsibility for the harm they have caused with these actions.
    I was given the responsibility as interim commissioner less than 3 
weeks ago, to lead my department during this crisis. And like you, I 
have spent the last several weeks trying to put together the pieces of 
this troubling puzzle.
    Although the majority of these events happened in the previous 
administration and well before I came to the Department, I offer the 
following chronology based on a review of documents and reports from 
the time.
    Let me begin by noting that by statute, the Massachusetts Board of 
Registration in Pharmacy, supported by the Department of Public 
Health's Division of Health Professions Licensure, has primary 
responsibility for oversight of the practice of pharmacy in the 
Commonwealth.
    The Board of Pharmacy is an independent body, with 11 members 
appointed by the Governor. The Board has the responsibility and legal 
authority to license and regulate pharmacies and pharmacists. DPH staff 
investigators, lawyers, administrators, and an executive director 
support the Board's operations.
    The Massachusetts Board of Registration in Pharmacy's interaction 
with NECC began on July 16, 1998, when it obtained its initial license. 
On February 2, 1999, the Board received the first complaint against 
NECC, which alleged that the pharmacy had provided a prescriber with 
pre-printed prescriptions that specifically listed NECC medications. 
State law prohibits pre-printed prescriptions. Prescriptions are 
required to be patient-specific, and based upon the patient's 
diagnosis, medical history, allergies, tolerance, and the specific 
constellation of symptoms that the patient is presenting. This 
complaint was resolved in October 1999 with an informal reprimand 
letter, a non-disciplinary action.
    In April 2002, working with the FDA, the Board visited NECC and 
obtained records related to a recent MedWatch report concerning 
betamethasone, a compounded steroid suppository. The FDA investigator 
met with Barry Cadden, owner of NECC, and conducted an inspection on 
April 9, concerning procedures, sterility and recordkeeping.
    In October 2002, the Board initiated a joint investigation with the 
FDA at NECC related to the April 2002 betamethasone complaints as well 
as MedWatch reports associated with the use of methylprednisolone 
acetate, the injectable steroid medication implicated in this current 
outbreak. The MedWatch reports pertained to two patients who received 
the steroid and experienced pain and headaches and were hospitalized 
with meningitis-like symptoms. Laboratory tests from these 
investigations identified subpotency of betamethasone and superpotency 
of methylpredni-solone acetate. The FDA also noted contamination of one 
lot of methylprednisolone acetate with bacteria. These investigations 
continued into 2003.
    Also in 2002, Board of Pharmacy member Karen Ryle convened a Task 
Force to study Board oversight of the compounding pharmacy industry. 
Barry Cadden served on this Task Force, which met for nearly 2 years. 
The Task Force discussed proposals to change regulations around 
compounding, but records do not show whether formal recommendations 
were made, and the Board did not adopt new regulations.
    In February 2004, the Board conducted a followup inspection of NECC 
and noted that all deficiencies surrounding sterility, safety, quality 
and procedures from the 2002-3 investigations had been resolved. Just 
weeks later, however, the Board received a complaint, from a pharmacist 
in Wisconsin, expressing concerns with the safety of a topical 
anesthetic product. The complaint alleged that NECC advised the 
pharmacy to unlawfully use a staff member's name rather than an 
individual patient's name in filling a prescription. The Board then in 
place resolved this complaint with a disciplinary warning letter on 
September 30, 2004.
    Based on this series of investigations, in September 2004, the 
Board voted unanimously to sanction NECC with a reprimand, a 3-year 
probation, and a requirement that Barry Cadden obtain additional 
training in sterile compounding. NECC objected to these sanctions, but 
the Board reaffirmed this approach through an additional unanimous vote 
on November 23, 2004.
    More than a year later, on January 10, 2006, NECC entered into a 
non-disciplinary consent agreement with the Board that was 
significantly weaker than the earlier version. The signed consent 
agreement stipulated a 1-year probation to be stayed with the condition 
that NECC hire an independent evaluator. The Board's staff identified 
Pharmaceutical Systems, Inc. (PSI) as the evaluator to conduct 
inspections of NECC's compounding practices.
    Despite interviews with Board and staff members involved with these 
decisions and a thorough review of the limited records retained from 
this period, troubling questions remain about what influenced the more 
lenient consent agreement resolution, given NECC's track record. I will 
not be satisfied until we know the full story behind this decision.
    What we know now is that from January to April 2006, the 
independent evaluator PSI conducted an assessment of NECC's compliance 
with United States Pharmacopeia Standards, and oversaw development of 
policies and procedures. PSI also issued recommendations for process 
improvement and provided training for NECC staff. An April 7, 2006 
report from PSI described NECC's compliance with the evaluation.
    Our investigation has revealed that in late April 2006, some Board 
of Pharmacy and Health Professions Licensure staff, including the 
Board's executive director and legal counsel, learned that PSI 
executives were convicted of Federal crimes related to defrauding the 
FDA and selling unapproved sterilization equipment to hospitals. 
However, we have found no evidence to indicate that the executive 
director or staff attorney of the Board provided this crucial 
information to the Board. Nor did they see fit to send inspectors back 
to NECC in 2006 to determine if they were fulfilling the requirements 
of the corrective action plan.
    In May 2006, the Board voted to affirm that NECC was in compliance 
with the terms of the consent agreement, thus accepting PSI's findings 
in overseeing NECC's compliance.
    Consistent with Board policy at the time, which was to inspect 
pharmacies only upon a change in licensure status or upon receipt of a 
complaint, the next time a Board investigator returned to the pharmacy 
was 5 years later on May 24, 2011 to inspect NECC following its 
renovation and expansion. This inspection included a full review of the 
facility space, operations, sterility protocols, and compliance with 
United States Pharmacopeia among other factors. The inspector found no 
evidence to suggest that NECC was violating patient-specific 
prescription requirements, and no deficiencies were cited.
    In March 2012, the Board received a complaint pertaining to an 
insufficiently potent eye anesthetic distributed by NECC. This 
complaint focused on the potency of the medication but did not 
reference sterility concerns. This investigation continues.
    In July 2012, some of the same staff members who failed to inform 
the Board of the issues surrounding PSI received a report from the 
Colorado Board of Pharmacy documenting violations of Colorado and 
Massachusetts pharmacy laws. The information provided to the Board 
executive director and legal counsel by Colorado showed that NECC had 
distributed bulk shipments of drugs to many hospitals in that State 
between 2010 and 2012 without patient/specific prescriptions, in 
violation of NECC's Colorado and Massachusetts licenses. The Colorado 
Board of Pharmacy issued a cease and desist order to stop NECC from 
engaging in the unlawful distribution of prescription drugs in the 
State in April 2011. Colorado informed the FDA of the adverse action, 
and provided them with the report, supporting evidence, and copy of the 
order. However, there is no record of Colorado providing similar notice 
to the Board or DPH.
    Colorado contacted Board staff in July 2012 because NECC was 
violating the April 2011 cease and desist order by continuing to 
prepare and dispense bulk shipments without patient-specific 
prescriptions. However, after receiving the July report, both the 
executive director and legal counsel failed to order an investigation, 
inform the Board of the complaint, or take any other action on the 
Colorado complaint.
    The first two lots of contaminated methylprednisolone acetate 
linked to the meningitis outbreak were prepared in May and June 2012. 
The Colorado report was received 2 weeks prior to the production and 
shipping of the third lot of contaminated vials, which were prepared in 
August. Though issues of contamination with NECC products were not 
included in the Colorado report, given NECC's history and the evidence 
from Colorado that the company was violating Massachusetts pharmacy 
regulations, prompt action was warranted.
    The individuals responsible for this failure to act have been 
removed from their jobs. These steps are consistent with the swift and 
decisive actions of DPH since we became aware of the outbreak.
    Late in the evening of September 24, the Tennessee Department of 
Health notified our Department about a cluster of six exceedingly rare 
fungal meningitis cases. All six cases shared common risk factors, 
including an epidural injection of a steroid prepared by NECC. The 
Massachusetts DPH secured a list of medical facilities in 23 States 
that had received shipments of the steroids from three suspect lots 
identified by the Centers for Disease Control and Prevention. A day 
later, we secured a recall of those three lots, totaling 17,676 vials, 
and began our on-site investigation at NECC.
    On October 1, we were joined on-site at NECC by the FDA and 
commenced our joint investigation. Among a list of troubling findings, 
investigators observed visible black particulate matter in sealed vials 
that had been returned to NECC through the recall. Several batches of 
the drugs had been shipped by NECC prior to the completion of internal 
sterilization tests. Investigators also found evidence that NECC had 
been dispensing medication in bulk shipments rather than filling a 
patient-specific prescription for each dose dispensed.
    We secured a surrender of NECC's license, shut down its operations 
and issued a total recall of NECC products.
    Our aggressive investigation not only focused on NECC, but also 
companies with shared ownership. On October 10, we secured the 
voluntary suspension of operations of Ameridose, a Westborough, MA drug 
manufacturer also owned by Barry Cadden. This closure allowed for a 
full investigation by DPH and the FDA, and eventually led to a total 
recall of Ameridose products. Ameridose remains closed as the 
investigation continues.
    The Board of Registration in Pharmacy moved to permanently revoke 
NECC's license, as well as the individual licenses of the three 
principal pharmacists who ran NECC so they may never practice pharmacy 
in Massachusetts again. The Board also issued a cease and desist order 
to all pharmacy staff at NECC to bar them from any compounding 
activities.
    While taking these forceful and necessary actions, we have also 
reexamined our own approach to regulating this industry.
    It is clear that the compounding pharmacy industry has changed 
drastically from the days of neighborhood businesses that served a 
local clientele. We recognized that our State regulations needed to be 
strengthened to address the realities of this industry, which has 
evolved over time, and again we took action.
    On November 1, Massachusetts enacted a series of emergency 
regulations to bring greater scrutiny to the industry and ensure that 
we have the tools to prevent such a tragedy from happening again.
    Our new regulations stem from the lessons learned from this tragedy 
and require sterile compounding pharmacies in Massachusetts to report 
volume and distribution figures to the State, for the first time. This 
will alert us to any pharmacy that is acting like a manufacturer by 
producing medication on an industrial scale, which requires an FDA 
license and the additional scrutiny and adherence to high manufacturing 
standards for safety and quality that FDA oversight requires. We are 
also requiring all licensed pharmacies to report to the State when they 
are the subject of investigations by any other States or the Federal 
Government. This will allow us to know when other entities have 
identified issues with pharmacies in Massachusetts, including other 
States that issue non-resident licenses to pharmacies in Massachusetts.
    The Board of Pharmacy's prior approach to inspecting pharmacies 
when they first apply for a license, and then again only if they move 
or if there is a complaint, though not out of line with the approach 
used by most States, is no longer sufficient to keep pace with the 
changing nature of the industry. Since the outbreak we have begun 
unannounced inspections of the State's 25 sterile compounding 
pharmacies to review how they function when they are not aware that an 
inspection is scheduled. Teams are in the process of conducting 
additional inspections as we speak.
    Massachusetts sterile compounding pharmacies have also been 
required to attest under penalty of perjury that they are meeting all 
State laws and regulations.
    To further strengthen our oversight over sterile compounding 
pharmacies, we need to explore changes to State law. We created a 
Special Commission, and named Christian Hartman, an expert in pharmacy 
practice and patient safety, as its chairman. The Commission will 
include members of the Massachusetts' Legislature and experts in 
pharmacy practice, regulatory affairs, and patient safety. We will look 
at best practices in other States, explore new ideas, and consider the 
interplay between State and Federal authority. The first meeting of the 
Commission is scheduled for this month and this body will report its 
findings to the Governor by December 31.
    As we work to raise standards in Massachusetts, we urge Congress to 
act to strengthen Federal oversight. It is clear that the patchwork of 
disparate State regulations is not enough to keep the public safe.
    Congressman Markey's leadership in putting forward legislation is 
laudable and would help fill what he has aptly called a ``regulatory 
black hole'' that exists between State and Federal oversight. 
Congressman Markey's report also shows that at least 34 States have had 
deaths or illnesses stemming from violations at compounding pharmacies 
nationwide before this current meningitis outbreak. We join Congressman 
Markey in supporting immediate Federal action.
    As a pediatrician who has looked into the faces of children and 
families at their most vulnerable moments, I understand the faith and 
trust that patients place in our health care system. I would never have 
contemplated that a medicine I might prescribe to my patients could 
actually be the source of such harm. We must use these terrible events 
as an impetus to work together, as public health officials and 
legislators, to reaffirm the trust that has been broken by the 
circumstances surrounding this outbreak.
    I pledge to you that Massachusetts will continue to do whatever we 
can, make any changes, and identify any areas of new law to make sure 
something like this never happens again. We intend to identify 
responsibility but also focus on reforms that will be effective and 
lasting.
    As the victims and their families remain always in our thoughts, we 
accept the challenge of reform that lies ahead.
    Thank you. I am happy to take your questions.

    The Chairman. Thank you, Dr. Smith, and thank you all. 
We'll start a round of 5-minute questions.
    I wanted to have Dr. Bell here today. I know you weren't at 
the hearing in the House yesterday. I thought it was extremely 
important for us and for the public to know just how important 
the intervention of CDC was in this. I'm going to read your 
concluding remarks which I read last night.

          ``The outbreak demonstrates the essential role that 
        public health plays in identifying and responding to 
        infectious disease outbreaks, large or small. Our 
        national public health capacity is disseminated to 
        State and local responders who work on a daily basis to 
        keep our country safe from infectious diseases, whether 
        they are from naturally emerging threats such as a new 
        influenza pandemic or from human made problems such as 
        contaminated medicines. CDC will continue to work with 
        State partners, national experts, frontline clinicians 
        and others to respond to the critical public health 
        needs related to this outbreak.''

    Again, I think the public needs to be aware that we have an 
infrastructure in this country with CDC, with our State 
departments of public health, with our field epidemiologists 
who instantaneously can intervene, track these threats down, 
keep our public safe. That's why I thought it was so important 
for CDC to be here today, both to outline--and I know we have 
another witness from Tennessee who will be here. You mentioned 
this person, Dr. Kainer--to let the public know that things 
happen, and we're never going to be 100 percent safe, either 
from human-made problems or infectious diseases, as you 
mentioned, like influenza pandemics.
    I think it's also important for us to know that the more we 
constrain the budgets of the Center for Disease Control and 
Prevention and the budgets of our public health entities around 
the United States, the more we put the public at risk. We have 
for too long treated public health as sort of a stepchild of 
healthcare in America, something that, well, we just don't have 
to pay attention to. It's to our detriment, and people die, and 
people get sick if we don't continue our support for public 
health in the United States.
    Senator Mikulski and I worked very closely in the 
Affordable Care Act to make sure that we had a strong component 
of public health in that bill. I just hope that my colleagues 
and others who are watching the proceedings will, again, note 
what has happened to public health funding in America. I know 
this is not an Appropriations Committee meeting, but I wear two 
hats, and I'm sorry, but I'm going to wear that one here right 
now.
    In fiscal year 2009, CDC funding was $6.239 billion. Got 
that? In 2009, $6.239 billion. In fiscal year 2012, it's down 
to $5.644 billion, and yet we have more emerging diseases. We 
have more people. We have people moving more rapidly around the 
country. We have people moving from this country to other 
countries, back and forth, through commerce, through travel. 
Yet we continue to turn a blind eye to the need for public 
health infrastructure in this country.
    Dr. Bell, thank you, and I look forward to our witness from 
the State of Tennessee also and what they did to intercede in 
this.
    Dr. Hamburg, when I see the history of this and I read the 
history of this and I see the two court cases, Fifth Circuit 
and Ninth Circuit--I'm not going to go into all that. You 
understand it. I have some sympathy for the FDA not knowing 
exactly what its role is going to be. But that's OK. That's the 
past. We have to do something now. And, of course, I'm going to 
look to Senator Roberts and others who have been more involved 
in this in the past for some guidance and direction.
    Why don't we just have a demarcation line? If a compounding 
pharmacy makes anything that goes outside the State boundaries, 
that's FDA jurisdiction--anything. If it stays within a State, 
it can be State or it can be dual, depending. But anything that 
goes beyond State borders, that must be under FDA purview.
    Dr. Hamburg. That isn't the way the law is currently 
written. You're asking a larger question of why don't we do 
that. The problem is----
    The Chairman. I know that's not the way the law is, but I'm 
saying why don't we do that?
    Dr. Hamburg. The problem is that there is not a clear 
distinction between what is a compounder and what is a 
manufacturer, either in law or in practice. The industry is 
evolving in ways that can be very, very important to the 
healthcare system and the needs of patients.
    For example, it used to be in a hospital that the hospital 
pharmacy in the basement would make up intravenous bags with 
potassium chloride or other substances added in to be used on 
the floor. Because of volume and because of concerns about 
making sure that this is actually done under the best and most 
safe and most efficient circumstances, hospitals have started 
outsourcing some of those kinds of activities where they're 
repackaging a drug or a medical product, and that can have real 
benefits.
    If we treat all of those individuals as manufacturers, 
we'll have to have them submit drug applications for every one 
of those products. They'll be subject to user fees. We could 
hold them to stronger standards of compliance to good 
manufacturing practice, et cetera, and that would really have 
benefits. I think the challenge is we have to think about how 
to address this.
    The Chairman. Dr. Hamburg, I understand. I get all that. 
But, really, the essential thing is what is in the best 
interest of protecting the public health.
    Dr. Hamburg. I think----
    The Chairman. That's the essential question.
    Dr. Hamburg. Yes.
    The Chairman. Now, if some people can't protect the public 
health by making things in their basement, maybe they shouldn't 
be making things in their basement.
    Dr. Hamburg. I guess what I would really propose is that we 
have an antiquated system, trying to fit a square peg into a 
round hole. What we have proposed in terms of a tiered system, 
I think, could get at these issues in a very responsible way. 
Traditional compounding on a small scale would remain under the 
purview of the States.
    Nontraditional compounding that gets us into this area 
would be addressed in a different way. For one thing, they'd 
have to register with us, so we'd know who they were and what 
they were making. We would have Federal standards that they 
could be held to, either enforced by the States or by the FDA. 
We would have to, in statute, through a combination of factors, 
define what puts you into this category; what kinds of products 
you're making, like sterile products; what volume of products; 
are you shipping interstate; other issues about shipping 
directly to the user or through a third party. We can do that 
together.
    Then there's some products that clearly should only be 
under the purview of a full-fledged manufacturer and that 
simply should not be compounded because of the nature of those 
products, biologics and transdermal patches, extended release, 
and other things. Then copying an FDA-approved drug is also 
clearly not appropriate.
    The Chairman. OK. Thank you. I'm over my time. I will hold 
for Senator Enzi when he returns.
    Next I would recognize--oh, he's not coming back? Then I 
would yield to Senator Roberts or Senator Alexander. This is in 
terms of how people appear on the committee. Senator Roberts 
appeared----
    Senator Roberts. It looks like I have appeared first.
    Dr. Hamburg, your past interactions with NECC, the New 
England Compounding Center, prior to the current crisis, which 
spanned over 6 to 10 years, depending on how you look at it--we 
were taking a look at your testimony before the House. Were you 
Dingellized over there or, did you get around all that?
    Dr. Hamburg. That's a term I'm not familiar with.
    Senator Roberts. There are a lot of us that are very much 
familiar with it.
    [Laughter.]
    You said that NECC has repeatedly disputed FDA's 
jurisdiction over its facility. You cited a number of times 
during your interactions that NECC had done so. Isn't it also 
true that each time the NECC disputed the FDA authority, the 
FDA responded, reasserting its authority to regulate the NECC? 
Now, that culminated in the final communication between the FDA 
and the NECC in 2008 prior to the current crisis.
    The FDA wrote to the NECC to outline in no less than four 
pages--and we don't need to get into reading the four pages, I 
hope--the numerous reasons why the FDA did have the authority 
to regulate and, furthermore, use its enforcement authorities 
with the NECC. I think that's correct.
    Now, in fact, that letter went on to tell the NECC not only 
to clean up its act or there would be specific consequences, 
but also to confirm future inspections would occur to ensure 
the firm's compounding practices are consistent with the 
policies articulated in the compounding guidelines. If this is 
correct, then I think we need a yes or no answer from you. That 
didn't come in the House. One more time, did the FDA actually 
have the authority to regulate and engage in enforcement 
actions against the NECC? Can you give us a yes or no?
    Dr. Hamburg. I'll make you mad the same way I made Dingell 
mad in terms of it's not a yes or no question, per se. We have 
authority, but it's limited and----
    Senator Roberts. I think you said it was a gray area. I 
don't want a gray area. I want a black or white answer. Do you 
have that authority? Did you have that authority?
    Dr. Hamburg. We have limited--we have authority, but it is 
limited and unclear and contested.
    Senator Roberts. That's a hell of an authority. In May 
2011, from the Colorado Board of Pharmacy, the FDA was informed 
of a cease and desist letter and related report accusing the 
NECC of illegal distribution of compounded drugs. FDA 
officials, including Bruce Ota, the signatory to the 2008 FDA 
letter I was referring to, to the NECC threatening enforcement 
for such conduct and asserting jurisdiction over NECC, was 
individually notified according to the May 2011 email that was 
introduced into the record.
    The FDA then waited until July 2012, over a year, to 
suggest to Colorado they contact the Massachusetts Board of 
Pharmacy. I don't know how you can explain this, with over a 
year. The State of Massachusetts fired and suspended the 
individuals who ignored the Colorado complaint about the NECC. 
By the time the FDA suggested in July 2012 that Colorado 
contact the Massachusetts Board for action, the NECC had 
already compounded some of the drugs that led to this tragedy.
    Indeed, if the FDA had acted in 2011, according to their 
letter, either to investigate or to notify Massachusetts of the 
NECC's continued violation, 30 lives could have been saved. Did 
the FDA take any action against the FDA personnel who ignored 
this problem for over a year?
    Dr. Hamburg. Obviously, in the context of the situation, 
looking at that, questions are raised. When the communication 
came from Colorado, it was around an issue of NECC acting out 
of compliance with the Colorado Board of Pharmacy Registration 
and Licensure and the question of whether they were, in fact, 
registered with us as a manufacturer.
    I wish, in retrospect, that we had alerted the 
Massachusetts Board of Pharmacy at that time. It's also 
important to underscore that that communication really was not 
about the kinds of sterility concerns and safety quality issues 
that underlie this ongoing outbreak.
    Senator Roberts. OK. I appreciate that. My time is almost 
up. If you had inspected upon receipt of the Colorado complaint 
in the summer of 2011 and found the unsanitary conditions and 
the scale of production that existed at NECC, is it your 
position that you could not have shut the operation down 
despite a decade of evidence that NECC was a bad actor? That's 
the first part.
    Last part: If that is the case, why do you assert the 
authority to cease, enjoin, or otherwise prosecute the 
recipients of your warning letters? Why in the hell send the 
warning letters if you can't act on them? That's just an empty 
threat. Why do we even have an FDA and why do you have a job if 
the FDA can't stop back-alley, large-scale drug manufacturing 
that it knows about and writes letters about?
    Dr. Hamburg. If we had gone in in 2011, as you had 
suggested, and found unsanitary conditions and contaminated 
product, we could have acted with the full force of FDA 
authority as we have acted in other cases of compounding 
failures that have resulted in contaminated products. However, 
in terms of our routine oversight responsibility of NECC, that 
does rest with the State board of pharmacy if they are behaving 
as a compounder.
    Massachusetts was actually in that facility in 2011 and 
found that the conditions were satisfactory. It speaks to the 
fact that inspections are only one piece of what can make a 
difference. What we are really trying to seek is a legislative 
framework that would enable us to hold these kinds of large-
scale, nontraditional compounders to a set of standards, 
proactively in a preventive way, rather than using authority--
--
    Senator Roberts. That's what you want us to provide, a 
legislative framework to really define that you do have the 
authority to act on your own letters?
    Dr. Hamburg. At the present time, our authority, because it 
is limited and unclear and contested, really forces us into a 
position of being reactive rather than proactive. With drug 
manufacturers, we can require and hold them to a different set 
of standards in terms of compliance with good manufacturing 
practice and the requirement of preapproval review for safety, 
quality, and manufacturing controls.
    Senator Roberts. Thank you. I'm done.
    The Chairman. We've got to go around. Thank you.
    Senator Mikulski.

                     Statement of Senator Mikulski

    Senator Mikulski. Mr. Chairman, thank you very much for 
holding this hearing. I, too, wish to express my condolences to 
the families who have passed away--one in Maryland. Today, 
their Sun paper reports a constituent whose name I can use 
because it's already in a public domain--Mr. Gerald Cohen, 71, 
retiree, filling his free time with gardening, enjoying the 
company of his grandchildren, and being active in the 
community. Treated with steroids, he now is so sick from 
nausea, fever, and he eventually had a stroke. He told his 
wife, ``I thought I was dying.''
    This is why we are here today, to look for the right 
regulation. Also, at the same time, regulation without 
resources is a hollow exercise, and then resources without a 
workforce--the fact that we have to recruit people in science 
and train them to enforce these also needs to be part of this 
discussion.
    Mr. Chairman and colleagues, I hope this is the first of a 
series of hearings on not only regulatory reform but also on 
resource need and also on workforce need. I would hope today, 
too, we would look at not only what is not working but what did 
work. Obviously, Tennessee was really doing their public health 
job. Obviously, Colorado was really doing their job, because 
they sent an alert. So, we need to do those lessons learned.
    In the area of regulation, I'm very interested in the black 
hole of when do we go from the traditional role of 
compounding--with Senator Roberts we all agree exists--to where 
they're now manufacturers. Even when they do do traditional 
compounding, when are they just sloppy, dilatory, or dangerous? 
How do we get to that? The other is then the resources that 
Senator Harkin talked about and referenced.
    Dr. Hamburg, I'd like to come back to you. Do you feel that 
what you are suggesting with your two-tiered system would get 
us to the problem, or would you also think that there needs to 
be--that this would be a down payment on getting to this? As 
the market is evolving, market forces are evolving on 
compounding, and then our tendency in Congress is to be anti-
regulatory, dump everything on the States, until there is a 
problem. Then we pound our chests and want the Federal 
Government to be involved.
    We've got a lot of convergent forces, even within this 
institution. Do you think your framework would get us to this, 
or do you think also we need additional work, say, through a 
commission, as suggested by Senator Roberts, or through the 
Institute of Medicine to go for an even more deep dive in this?
    Dr. Hamburg. I think that the tiered approach that we are 
proposing would make an enormous difference. Right now, really, 
what is a compounder versus a manufacturer is very unclear. 
503A was Congress' attempt to really clarify it, but it doesn't 
define compounding anywhere. It doesn't set an absolute limit 
on volume. It doesn't set an absolute prohibition on 
compounding in advance of getting a prescription.
    Senator Mikulski. That's the methodology. What would be the 
outcome achieved?
    Dr. Hamburg. What would be the outcome achieved?
    Senator Mikulski. In other words, if we go your way, yes.
    Dr. Hamburg. Oh, I think there would be many, many 
benefits. We would, No. 1, be able to really know what the 
landscape looks like, who's out there doing what. We would have 
a set of Federal standards that would be strong and really 
support quality. We would have authorities for adverse event 
reporting and an ability to have labels so people would know 
whether the product was compounded or not. We would clarify the 
issue around inspections so that when we went in, we'd be able 
to get access to the records that we need.
    Senator Mikulski. OK. Thank you. I want to go to Dr. Bell 
and Dr. Smith for my next set of questions.
    Dr. Bell, you referred consistently in your testimony about 
something called the Epidemic Intelligence Service, and then 
how also those people trained in that service are working in a 
variety of States, one of which was Tennessee that, again, did 
such a superb job.
    Senator Alexander, we'd like to compliment the public 
health people in Tennessee.
    Could you, then, talk about the role of CDC, not only in 
this, but this Epidemic Intelligence Service, and how it would 
be of use in terms of ultimately bio surveillance at the local 
level which acted so quickly, because we can't be in every 
place, everywhere, all the time? And it must go through the 
States.
    Dr. Bell. Yes. Thank you, Senator. The Epidemic 
Intelligence Service is a training program that CDC has had in 
place for actually many decades. Many of us--and I hazard to 
say maybe most of us, even me with the gray hair--who have been 
at CDC for decades started our careers in CDC in the Epidemic 
Intelligence Service. There is a very, very large cohort of 
epidemiologists in the State and local health departments who 
also trained at CDC.
    This is an extremely important resource that we have. There 
are other aspects----
    Senator Mikulski. Just tell me what it does.
    Dr. Bell. Basically, it's a training program, so----
    Senator Mikulski. What do you train them to do?
    Dr. Bell. We train them to do field epidemiology. We train 
them to investigate outbreaks. We train them in how to work 
with the laboratories. We train them in how public health 
works.
    Senator Mikulski. Then they don't stay at CDC. Some do.
    Dr. Bell. That's correct.
    Senator Mikulski. Like the ones who were so pioneering in 
the work on early detection of Legionnaire's Disease and 
others. But then they go to States.
    Dr. Bell. That's right.
    Senator Mikulski. Then they work in State health 
departments or in a variety of other areas of the public health 
human infrastructure.
    Dr. Bell. That's right. In fact, we have some Epidemic 
Intelligence Service officers that are assigned to State health 
departments during their training. For example, this outbreak 
is a good example of how this EIS program works.
    Senator Mikulski. I have limited time, Dr. Bell.
    Dr. Bell. OK. Just to say that we have done what we call 
Epi-Aids. These are, in outbreaks, assistants that we provide. 
In this situation, we've sent EIS officers out five or six 
times to help quickly--including to Tennessee very early on in 
the outbreak--to help the State health departments quickly 
identify the problem.
    Senator Mikulski. Now, tell me how much these people get 
paid, and what is their education?
    Dr. Bell. I can't tell you how much they get paid. They 
generally----
    Senator Mikulski. Are they GS-15s? Do they get paid 
$180,000 a year? Do they get paid $45,000 a year?
    Dr. Bell. I think it depends on their level of training. 
They have to have an advanced degree. It could be a Ph.D., an 
M.D., or they could be a nurse with a master's degree. They 
could be a veterinarian. They could be a pharmacist. They have 
many different ways of entering CDC.
    Senator Mikulski. Thank you. My time is up.
    I would like to say to my colleague, Mr. Chairman, with 
your indulgence--to my colleague from Kansas, Senator Roberts--
I would like, really, Mr. Chairman, to work with you to--we 
have the FDA recommendations. We have the Roberts Commission. I 
remember when you did that during the Affordable Care Act, and 
it was an impressive piece of work.
    We're possibly going to IOM, the Institute of Medicine, 
where we have the appropriate regulation, where we don't over-
regulate so we strangulate. But at the same time, we have to 
really move on it. While we're working to pass legislation, 
perhaps we need a process to get us to the right legislation 
and maybe a down payment on what we need to do, while we also 
look at the resources, which you identified, Mr. Chairman, and 
then these workforce needs, because if you have the right roles 
without the right people, you don't have anything.
    Thank you, and I appreciate this hearing.
    The Chairman. I want to reassure you, Senator Mikulski, and 
others on this committee that I have asked my staff to work 
with Senator Enzi's staff and other staff on this committee to 
get a good bipartisan process going, to work together to 
achieve exactly the end that you say. That is ongoing right 
now. I want to reassure you of that.
    Senator Alexander.

                     Statement of Senator Alexander

    Senator Alexander. Thanks, Mr. Chairman, for the hearing, 
and thanks to Senator Roberts for your leadership in the area. 
I certainly intend to work with Senator Harkin and Senator 
Roberts, Senator Mikulski and others.
    I hope it's our first order of business to answer these 
questions, not just whose job was it to prevent this tragedy, 
but whose job will it be to make sure it doesn't happen again. 
That's our job here today. This has been a nightmare for 
Tennesseans, as it has been for any Americans affected. We've 
had 32--13 Tennesseans died, 81 Tennesseans are sick, and 1,000 
more exposed.
    All of us are shaken, because we live in this country where 
we have this miracle that we walk into one of our 60,000 drug 
stores or pharmacies or go to our doctor or our pain clinic, 
and we get medicine, and we don't think about it. We just 
assume it's safe. And then to suddenly go home and find that 
you've got fungal meningitis and you may die or be permanently 
disabled is a nightmare, not just for the families involved, 
especially them, but for all of us. I want to do everything I 
can to help solve this problem.
    Now, my experience as Governor, Mr. Chairman, was that 
whenever I gave a job to more than one person, sometimes it 
came back not done. When I put somebody on the flagpole, it was 
surprising to see how fixing that responsibility got it done. 
Let's start on what went right.
    Obviously, we had incompetence in the Massachusetts State 
Board of Pharmacy. We had confusion at the FDA. We had a 
textbook case of A-plus excellence at the CDC, the Centers for 
Disease Control, and at the State of Tennessee and at 
Vanderbilt University, their partner, where they uncovered this 
within literally a matter of a couple of days, and in a few 
more days were able to alert everybody about it.
    Dr. Bell, whose job is it? Is it your job at CDC, once 
something like this is discovered, to let the world know about 
it? Is that your job, or is that the job of a lot of different 
people?
    Dr. Bell. Senator, that's our job.
    Senator Alexander. So it's clear. If that hadn't been done, 
that would have been your responsibility, really. Right?
    Dr. Bell. Yes, sir. It's our responsibility to let the 
world know about public health threats.
    Senator Alexander. Right. And you did a superb job. Let's 
go back. What we're hearing from the FDA is they had some 
authority, but it was confusing. We hear from Massachusetts--or 
I'll just say it. Massachusetts--well, let me ask Dr. Smith.
    Massachusetts clearly had the authority to regulate this 
compounding pharmacy. Correct?
    Dr. Smith. That's correct.
    Senator Alexander. So Massachusetts clearly had the 
authority. FDA had some authority, but there was confusion. It 
seems to me that one guiding principle in terms of working this 
out is let's stop this dual responsibility. Let's put either 
the State board of pharmacy on the flagpole or the FDA on the 
flagpole and get the other one out of it.
    Now, I'll give you an example of that. In surface mining, 
we have a procedure in the State where the EPA and the 
Department of Interior may delegate to States the whole 
responsibility for regulating surface mining, or they may take 
it back. If something bad goes wrong, and Tennessee has that 
responsibility, it's Tennessee's fault. If Tennessee gave it 
back to the Federal Government, it's the Federal Government's 
fault. At least everybody knows who's on the flagpole for that.
    Dr. Hamburg, would you be in favor of a system that would 
say to a State like Massachusetts that for 10 years has been 
incompetent in managing a compounding facility like this that 
it should take over completely compounding of pharmaceutical 
drugs?
    Dr. Hamburg. There are many different models that----
    Senator Alexander. No. I'm asking you would you be in favor 
of that model? Do you think it makes sense to have a model 
where you may delegate to Massachusetts or any State, for 
example, the responsibilities for even sterile compounding or 
advanced com-
pounding, or you may keep it?
    Dr. Hamburg. I think first----
    Senator Alexander. But if you kept it, it would be your 
responsibility, and you couldn't say you were confused about 
it.
    Dr. Hamburg. Traditional compounding on the local level 
should remain the responsibility of States. Nontraditional com-
pounding----
    Senator Alexander. How much of that goes on? Traditional 
compounding, as I understand it, happens in most pharmacies. Is 
that right?
    Dr. Hamburg. Most pharmacies. We don't know the numbers 
because they don't register with us. There are many, many, 
many, many thousands.
    Senator Alexander. I've heard an estimate of 60,000 
pharmacies or drug stores.
    Dr. Hamburg. Yes.
    Senator Alexander. That's traditional compounding. Advanced 
compounding--how much of that is there?
    Dr. Hamburg. We think there are about 7,500 pharmacies 
doing so-called advanced compounding, and then about 3,000 that 
are doing sterile processing. For those, we should have Federal 
standards that could be enforced by the State or by the Federal 
Government.
    Senator Alexander. Now, that's my problem. Why would you 
say ``or by the Federal Government?'' Then we have a hearing 5 
years from now, and we have another tragedy, and the State 
says, ``Well, we could have done it,'' and you say, ``We could 
have done it.'' I'd like to see one of you say, ``It was our 
job,'' just like Dr. Bell said.
    Dr. Hamburg. I guess I'm saying that's a subject for 
discussion. Some States are very strong in terms of their 
boards of pharmacy. Others are much weaker.
    Senator Alexander. How do we pick and choose? If I'm 
sitting down in Gainesboro, TN, I don't care which one it is. 
Whether it's the Federal Government or the State government, I 
want the one that's going to do the job. How do you decide 
that?
    Dr. Hamburg. I think it should be made explicit.
    Senator Alexander. So you agree that one person should 
have----
    Dr. Hamburg. I do think we should make it explicit.
    Senator Alexander. With advanced compounding, either 
Federal or State should be in charge. Is that right?
    Dr. Hamburg. For nontraditional compounding, there should 
be Federal standards that apply to certain types of practices 
that go to issues of quality and safety.
    Senator Alexander. Instead of telling somebody else what to 
do, why don't you just do it? Is it too big a job to put all 
here?
    Dr. Hamburg. It would certainly enormously expand what we 
do presently. We've got about 5,600 drug manufacturers and 
facilities that we routinely are responsible for oversight of 
and inspection.
    Senator Alexander. Let me answer my own question and say 
it's too big a job to put it all here. Would you then certify 
State agencies as adequate to do sterile compounding or 
inadequate to do it? And what if they fail to do it?
    Dr. Hamburg. We need to discuss the range of options. That 
would certainly be one model that could work. I would like to 
see, though, some consistency of the standards applied, and I 
think a Federal standard would enable us to do that.
    Senator Alexander. Thank you, Mr. Chairman.
    The Chairman. Thank you. I just want to say we will have a 
second round here for this panel.
    Senator Hagan.

                       Statement of Senator Hagan

    Senator Hagan. Thank you, Mr. Chairman, and thank you and 
Senator Enzi for holding this hearing today and the continued 
bipartisan leadership of this committee. I also want to thank 
our witnesses for coming today, and I certainly have heartfelt 
and sympathy condolences to all of the families and individuals 
who have gotten sick from this, ultimately have died, and then 
all of the other people who are very worried about what might 
happen.
    Confronting this outbreak is a pressing national concern. 
Over 451 people in 19 different States have developed fungal 
meningitis, and 32 people have died, one of those individuals 
in my State, a woman, Elwina Shaw. I actually had an 
opportunity to speak with her son and with her husband. She was 
77 years old. She was very active. Her husband said you 
couldn't slow her down. She was busy from the morning until she 
went to bed--active. She loved to garden. She had back pain 
this summer. She went to get treated and had three steroid 
injection shots. When she ended up getting a migraine headache, 
she just didn't know what to do. She had nausea, and she really 
just wanted to stay in bed.
    She went to the hospital, and they treated her for 
migraines. The headaches returned. Her family took her back, 
and that's when they diagnosed the fungal meningitis. She 
stayed at the hospital for over a month. She then had two 
strokes. She was left without speech and motor functions. Her 
son, Scott, said this was a horrible death, that she had black 
fungus that had to be swabbed from her mouth and suctioned, and 
it was just a horrible situation.
    Fifty-two days after the injection to relieve her back 
pain, she passed away. What is really ironic about today--today 
would have been her 78th birthday. We all know that these are 
terrible situations, and we are committed to acting to be sure 
that something like this never happens again in the United 
States.
    Dr. Hamburg, what I'm trying to understand is--if you can 
help give some thought and guidance to--why in February 2003 
the FDA designated the New England Compounding Center a 
pharmacy rather than a manufacturer? The investigation then was 
into the same pharmacy compounding the same drug that led to 
the same result of fungal meningitis. I'm just wondering if 
this scenario could have been avoided 10 years ago.
    Dr. Hamburg. We were actively involved in the investigation 
beginning in 2002 of the contaminated products, working to get 
the products off the shelves and limit the damage. In terms of 
the ongoing efforts to remediate the sterility concerns, we 
were working with the State board of pharmacy. Together we 
determined that NECC--as I understand it. I, of course, wasn't 
commissioner at the time, so I'm relying on records and what 
I've been told.
    As I understand it--and I've looked at the notes, the 
minutes of the meeting--there was a determination that NECC was 
behaving as a compounding pharmacy, and under the existing 
legal framework, that is the appropriate authority of the State 
board of pharmacy for regulatory oversight. They took the lead 
and began a series of steps with NECC to address the sterility 
concerns. We tried to be as helpful as we could be. It was 
clearly determined that it was the Massachusetts Board of 
Pharmacy's responsibility to work with NECC on this important 
issue.
    Senator Hagan. We certainly see what has happened in the 
interim. That's why we're obviously holding this hearing and 
looking at the actions that we need to take. And I know we're 
on a short timeframe today.
    Dr. Smith, I wanted to also thank you for coming. I know 
you recently became the interim commissioner. Given the 
integral role that the Massachusetts Board of Pharmacy has 
played in the current outbreak, I want you to shed some light 
on its failure to properly discipline the New England 
Compounding Center over a longer period of time.
    Yesterday, when I spoke to Elwina Shaw's son, Scott, he 
said, ``These companies are allowed to make drugs in the back 
end of a recycling facility?'' The disturbing thing is--and 
this is his quote--is that ``someone in this Nation thought 
that was a good idea. It makes no sense.''
    I have to ask you, Dr. Smith, why in April 2011 did the 
NECC receive a permit to expand its facilities when the FDA 
later found out that its building was 100 feet from the 
mattress and plastics recycling plant, and that black 
particulate matter near the HVAC system was contaminating 
sealed vials of the steroid now causing this current meningitis 
outbreak? When the Board granted that request, did it know that 
the same family that owns NECC also owns that recycling plant? 
Any comments?
    Dr. Smith. Certainly. When the board of pharmacy did the 
on-site inspection that you're referring to, it was in the 
situation of NECC requesting an expansion or a change in its 
physical plant. The inspector at the time did the on-site 
inspection, looked at about 10 or 12 different areas, including 
sterility, quality assurance, staff training, among a number of 
others. At that time, the inspector's report, which I know 
we've shared with this committee, indicated that there were no 
issues.
    Now, it is not a specific aspect of the report to look at 
the broader outside environment and the siting of the facility. 
However, going forward, that is certainly something that we can 
look at.
    Senator Hagan. But in the FDA report, it did show that this 
black particulate matter was close by and, obviously, could 
have tainted some of the medicine.
    Dr. Smith. There were a number of substandard practices 
that NECC had, including the interior contamination that you're 
discussing, as well as a disregard for their own policies and 
procedures regarding sterility, and, obviously, their disregard 
of Massachusetts pharmacy law.
    Senator Hagan. Obviously, there are many issues that we 
have to determine, and I appreciate you holding this hearing. 
Thank you.
    The Chairman. Thank you, Senator Hagan. As I said, we'll 
have an extra round for Senators to followup on.
    Senator Blumenthal.

                    Statement of Senator Blumenthal

    Senator Blumenthal. Thank you, Mr. Chairman. I want to join 
in my thanks to you and Senator Enzi for holding this hearing 
as I suggested and urged that you do in the wake of this 
tragedy and express my sympathy to the families and individuals 
who have been affected by it, and also my respect for 
Commissioner Hamburg and the excellent institution that you 
lead.
    Unfortunately, having reviewed many of these documents, 
having spoken to experts in the field, having reviewed the 
history here, the conclusion is inescapable that this tragedy 
could and should have been prevented by more effective 
enforcement of existing laws. NECC was a known risk to both 
Federal and State regulators, but both failed to take any 
dispositive and effective action to stop this kind of tragedy, 
action that could have been taken against both NECC and 
Ameridose. In effect, they were disasters waiting to happen. In 
fact, they waited to happen for about a decade.
    Going through the history, I understand your view that the 
FDA's authority was, as you have said--and I think you've used 
this formulaic expression a number of times--contested, 
limited, and unclear. But so is a lot of Federal authority and 
State authority, and it's used effectively to prevent 
wrongdoing and law breaking by companies like NECC that cannot 
only imperil the health of people but actually kill them, as 
this company did through its contaminated product.
    I think that a lot of the questioning that you're seeing 
here reflects a skepticism on the part of Congress and the 
public about whether the FDA will use this enhanced authority 
more effectively than it has used the authority that it has had 
to date. I think that the assurance that the FDA now has to 
give is that it will be vigorous and zealous in using new 
authority, if it's given that authority, and I think that that 
is a challenge for the agency at this point.
    It's a challenge for the Federal Government and certainly 
for State authorities as well. We don't have jurisdiction over 
them. I would suggest to you that the jurisdictional question 
ought to be resolved very simply and starkly. If a company 
manufactures drugs, you regulate them now, do you not?
    Dr. Hamburg. Drug manufacturers we regulate, yes.
    Senator Blumenthal. Correct. In other words, if a company 
produces pharmaceutical drugs without a specific patient 
prescription, they are regulated by the Federal Government. 
That ought to be the rule.
    Dr. Hamburg. As I understand it, that is not currently, in 
fact, in the law.
    Senator Blumenthal. It certainly was the intent of 
Congress. Those decisions that so swayed the FDA to avoid 
asserting its authority and jurisdiction were also unclear, 
limited, and contested. An enforcer knows, in that situation, 
the only way to protect the public is to use what authority he 
or she has.
    Dr. Hamburg. Yes.
    Senator Blumenthal. In this instance, whether it's in 2004, 
the inspection report that involved the FDA; 2006, where a 
warning letter was issued and NECC never responded until 2007 
and then the FDA never got back to them until 2008, the FDA 
failed to use its existing authority. I'm suggesting to you 
that the jurisdiction ought to be asserted as widely and 
effectively as possible and that there be no ambiguity in the 
law as there is now.
    To the extent you use a multi-tiered, complicated, 
differentiated approach, you will embark on the same kind of 
perilous voyage that you have in the past.
    Dr. Hamburg. If I can make two quick points, one is I 
completely agree with what you're saying. Frankly, I wasn't 
there, but I wish that the responses had been more timely, 
there had been better communication with the States, and that 
the outcome had been different. As far as using our existing 
authorities, during my tenure, we have tried to be proactive or 
aggressive in responding to problems that come before us.
    There have been a series of incidents where we've had 
problems with contaminated products for intraocular injection 
or problems with other compounded products, and we have moved 
in quickly, as soon as we heard about the cases, done the 
inspections, gotten the companies to recall the products. In 
some cases--in most of the cases, in fact, they've stopped 
compounding sterile products.
    In one instance that was actually a veterinary case that 
occurred right before I became commissioner, we decided to go 
after the compounding pharmacy after 21 horses were killed 
because of super potent medication that they were provided with 
by a compounding pharmacy. We lost in court. Later, we had a 
problem with that same compounding pharmacy for an important 
human medical product, and there was serious injury as a 
result. We went back in, we recalled the product, we got them 
to stop practices, and they're not compounding now.
    We have tried to use the authority that we have, but it is 
reactive. What I would like would be to have a system in place 
that was statutorily defined, that would assign roles and 
responsibilities, that would define standards of quality 
practice, that would help us to prevent problems from happening 
in the first place. Just looking at the map in terms of how the 
statute governing our oversight of compounding pharmacies 
currently exists, it applies in some parts of the country and 
it doesn't in others, and there's a big gray area. That can't 
be good for anyone.
    What I'm saying is that--as Senator Roberts said, this is 
certainly the most tragic of the events that we've seen. For 
more than a decade, there have been problems in this area, and 
there will be more problems unless we really work together, to 
make sure that we have the overriding, legal authorities that 
are strong and clear and explicit. I just think we can do 
better.
    Senator Blumenthal. I agree.
    And I apologize, Mr. Chairman, because my time has long 
expired.
    Overriding is the key word, overriding local authorities 
that may be reluctant to enforce. Your job--and it is uniquely 
and always the job of the Federal Government to establish 
standards that protect the public health and safety where there 
is a national impact, and, clearly, there is a national impact 
here. When a drug compounding pharmacy--whatever terminology 
you want to use, traditional, nontraditional, big, small--if 
they manufacture a drug, if they make it without a specific 
individual prescription, that's manufacturing. You do that now. 
Why not for these as well?
    Thank you, Mr. Chairman.
    The Chairman. Thank you very much, Senator Blumenthal.
    I will, for the record, say that the first phone call I 
received after this outbreak occurred was from Senator 
Blumenthal, urging us and urging this committee to really 
engage in this. Based on that, we got our committee staff 
involved in it immediately.
    I thank you for your diligence and being on top of this, 
Senator Blumenthal.
    Senator Blumenthal. Thank you, Mr. Chairman.
    The Chairman. Senator Bennet.

                      Statement of Senator Bennet

    Senator Bennet. Thank you, Mr. Chairman. I want to thank 
you and the Ranking Member for holding this hearing.
    This may be the most needless tragedy that I've seen since 
I've been here. I've appreciated the work that we've done over 
the last several years with the FDA to try to figure out how we 
get a drug supply in this country that's actually safe. When I 
learned, for example, that 80 percent of the active ingredients 
in our pharmaceuticals are coming from abroad and there was no 
regulatory framework in place, we all went to work on that. 
We're working together, and I appreciate the chairman's 
leadership on a track-and-trace system in this country.
    This was an event that never had to happen. I wanted to ask 
a question to Dr. Smith and Dr. Hamburg about this.
    Thank you for being here today. Thank you all for your 
testimony.
    Dr. Smith, as you relayed in your testimony, the Colorado 
Board of Pharmacy issued a cease and desist letter to the New 
England Compounding Center in both April 2011 and July 2012, 
twice, because NECC had continued to violate its licensure in 
both Colorado and Massachusetts by issuing numerous compounded 
drugs without patient-specific prescriptions. Both times, our 
board of pharmacy in Colorado also informed the Massachusetts 
Board of Pharmacy, as well as the local Denver office of the 
FDA.
    I've been informed that upon receipt of both complaints, 
the executive director of the Massachusetts Board failed to 
assign an investigator to this complaint. After the outbreak, 
they also failed to alert the Massachusetts Department of 
Public Health officials of this complaint. Obviously, our State 
had the diligence and resources to be on the lookout for NECC 
products. Others, for some reason, did not and as a result this 
tragedy occurred all over the United States of America.
    Dr. Smith, I want to know whether you felt the response to 
the Colorado Board of Pharmacy was adequate, and, if not, how 
you're going to fix this problem going forward.
    And, Dr. Hamburg, I'd like to ask you about when a State 
board of pharmacy serves in its good actor role by issuing 
these cease and desist letters and notifies the Massachusetts 
Board and their local FDA office, how we can better prioritize 
this at the Federal level. As Senator Alexander said, how can 
we better strengthen the role of either the States or the 
Federal Government to take responsibility in a circumstance 
like this one?
    Dr. Smith, I'll turn it to you.
    Dr. Smith. Thank you. Just to be clear, while the executive 
director of the Board of Pharmacy did receive notification from 
the Colorado Board of Pharmacy regarding the cease and desist 
that was done in April 2011, we have not found any record that 
there was any communication from the Colorado Board of Pharmacy 
at that time back in 2011.
    Now, that said, clearly, when we got the information from 
the Colorado Board of Pharmacy in July----
    Senator Bennet. I don't think I understood what you just 
said. Can you say that again?
    Dr. Smith. I'm sorry. If I heard you correctly, you 
indicated that back in 2011 and then again in 2012, the 
Colorado Board of Pharmacy communicated with the Massachusetts 
Board of Pharmacy. What I was saying is that we haven't found 
any record of a communication between Colorado and the 
Massachusetts Board until July 2012.
    Now, that said, it is clear that it was a serious and, 
grave lapse of judgment executed by the board's executive 
director not to followup on what Colorado sent. The report was 
clear. It indicated with sufficient detail that NECC was 
clearly operating outside of Massachusetts pharmacy laws. The 
board certainly knew of NECC at that time and that it had 
issues. It should have been a red flag that was followed up on, 
and it wasn't. That clearly was, frankly, a mistake, a grave 
one, and we have acted since then to remove that employee.
    Senator Bennet. It's one of those things where it doesn't 
even feel like it's a gray area. It feels to us like it was a 
flashing red light.
    Dr. Smith. I agree. What I can say is when I learned of 
this email exchange and the fact that we, the board of 
pharmacy, knew this in July 2012, I was astounded, baffled, and 
incredibly angry, because that was something we should have 
acted on.
    Senator Bennet. Dr. Hamburg.
    Dr. Hamburg. In retrospect, clearly, I would have hoped 
that there would have been greater communication. That speaks 
to the issue that was raised about ensuring the appropriate 
level of back and forth communication and coordination with our 
State partners. When this email was received, it was in the 
context of a violation of State pharmacy registration and 
licensure. While there was an indication that they had sent 
product in the absence of specific patient prescriptions, there 
was no indication of a safety or quality concern that was being 
raised.
    We really felt that it was--as I understand, those kinds of 
issues are often handled by the State board of pharmacy. We 
should have made sure that Massachusetts was aware, and it 
underscores the need for greatly enhanced communication and 
coordination. The other aspect speaks to the larger question 
that we really need to work on clarifying and trying to figure 
out how to address this issue of compounding versus 
manufacturing and when does one authority kick in and when does 
the other apply.
    Senator Bennet. I think Senator Alexander hit the nail on 
the head. It's a question of clarity, of what the roles and 
responsibilities here really are, so that what, at the best, is 
bureaucratic in difference--and it's probably worse than that, 
I suspect--causes this kind of thing.
    Mr. Chairman, thank you for holding this hearing.
    The Chairman. Thank you, Senator Bennet.
    I'm starting another round. I don't know how many Senators 
would like to have more questions. I just have a couple.
    Dr. Hamburg, unlike NECC, where there is a lack of clarity, 
as we now know, regarding the FDA's authority, there's another 
company called Ameridose.
    Dr. Hamburg. Yes.
    The Chairman. Owned by the same people, run by the same 
people, closely aligned. Ameridose is registered with the FDA. 
Although it is essentially a large-scale compounder--it is a 
large-scale compounder--it provides products to hundreds of 
hospitals all over the country. Now, given that the two 
companies are owned and run by the same people, that the FDA 
inspectors documented many similar serious problems at 
Ameridose and NECC, could the contamination just have easily 
occurred at Ameridose?
    For example, in 2008, the regional inspector for the FDA 
recommended a warning letter to be issued to Ameridose, but it 
never got sent. I'm wondering whether what you're recommending 
is clarifying enough, that compounders like NECC are subject to 
FDA's authority. Is that really enough, if FDA already had the 
authority with regard to Ameridose?
    Dr. Hamburg. I can't speak to the specifics of Ameridose 
because it is the subject of an ongoing investigation. It 
speaks to this issue of these hybrids of compounding pharmacies 
that are merging more into manufacturing, and the fact that we 
do need a system that is clearer.
    Registration with the FDA does not necessarily mean that 
they become a drug manufacturer. People register with us for 
all kinds of reasons and never even are putting anything into 
commerce. It means, we get their name and address. We never got 
listings of products that Ameridose was manufacturing, but we 
were engaged with them in terms of inspections and responding 
to some specific complaints and concerns.
    I really think we need to work together to figure out how 
to address this evolving field of nontraditional compounding, 
because it can serve an important need. We need to be able to 
define it more and be able to really apply the right 
enforcement approaches.
    The Chairman. I got it. I got that. I just keep saying that 
FDA had authority over Ameridose but didn't exercise that 
authority. This was clear.
    Dr. Hamburg. We were in Ameridose and took some actions 
related to some specific concerns in the facility. In 2010, I 
think it was, we were in there around an issue with a 
particular product, nicardipine, I believe.
    The Chairman. I will take a look at that. I just know that 
in 2008----
    Dr. Hamburg. There was a--my colleague was just reminding 
me--a recall of a super potent----
    The Chairman. Oh, this.
    Dr. Hamburg [continuing]. Fentanyl product.
    The Chairman. That's very true. One was super potent and 
one was subpotent.
    Dr. Hamburg. There was one that was dramatically super 
potent and one that was less potent. We were in there and we 
did take actions. Again, I can't speak to all the specifics 
because we're still investigating, looking at that internally 
as to what we should have done, and it's part of a broader 
investigation.
    The Chairman. OK. I got that. I'll look at Ameridose, but 
it seems to me that that was a clear cut case but we still 
weren't exercising authority.
    I did have one more question, Dr. Smith. You know, I look 
at this history, and I'm pointing it out not just to point a 
finger at something and to chastise, but to understand that 
certain structures don't accomplish what people think they 
accomplish. In 2003, staff from the FDA met with the staff from 
the Massachusetts Board of Pharmacy to discuss,

          `` . . . the potential for serious public health 
        consequences if NECC's compounding practices, in 
        particular, those relating to sterile products, are not 
        improved.''

    That was in 2003.
    At that meeting, consensus was reached that primary 
jurisdiction over NECC rested with the board, Massachusetts. 
The board then took 1 year to get a staff investigator to 
recommend censure, 6 months to actually issue a censure in the 
form of a draft consent decree, another whole year to arrive at 
a signed consent decree which then lasted for all of 6 months.
    In all, it took the board 4 years from the time MPA-caused 
meningitis was reported to make NECC hire a third party to 
review and improve its sterility procedures. Again, this is not 
effective oversight.
    Maybe I'm making a statement more than a question. I'm 
saying that sometimes we set up these structures, and we people 
them with the very people that they're supposed to be policing. 
In this case, I'm informed that a member of this board is a 
person who actually works for Ameridose, and his or her 
paycheck--I forget the gender of the person--their paycheck 
comes from the very company that they're supposed to be 
overseeing.
    We see this happening in a lot of different States, where 
boards are set up but they're peopled with the very people that 
they're supposed to be policing. They're all friends. They go 
to the same clubs. They belong to the same this and the same 
that, and it's sort of a wink and a nod and a pat on the back. 
Sometimes that's why I think that for effective oversight, you 
need the expertise of people in the field, but only to inform a 
board, not to actually exercise that kind of jurisdiction.
    Dr. Smith. You bring up very important points. The Board of 
Pharmacy in Massachusetts, by statute, indicates who is allowed 
to be on the board. Certainly, in evaluating as part of this 
review the function of the board, that's something that's also 
going to be taken up by the special commission that we've 
established to be able to really provide us with best practices 
about what kind of board makeup might be better suited or 
better balanced to be able to perform the oversight function 
that is so crucial.
    If I could just say one other thing about the lapses that 
you clearly point out, I would say that the emergency 
regulations that we issued on November 1st include two that I 
think are very important. One would be to require pharmacies in 
Massachusetts who are the subject of State or Federal 
investigations to disclose that and make that known to us. That 
would get at the issue that Senator Bennet raised of 
Massachusetts not being aware at the time that Colorado issued 
a cease and desist letter. That would be very important.
    The other would be that sterile compounding pharmacies must 
supply information about volume and distribution patterns to 
the State board. Right now, that is not required. And, clearly, 
compounding pharmacies like NECC who are acting in a de facto 
manufacturing-like role would then have to tell us information 
about how much they're making, what they're making, and where 
they're shipping it to.
    That would allow us to identify pharmacies that are doing 
that kind of practice, as opposed to the neighborhood 
compounder that's doing that necessary compounding or the ones 
that are doing it within State law, which is one prescription 
at a time. NECC was violating that as well.
    The Chairman. Got it. Thank you.
    Senator Roberts.
    Senator Roberts. Thank you, Mr. Chairman, and thank you for 
citing the timeframe that is most frustrating to this.
    Doctor, you said that if there were sterility issues, you 
could have shut the manufacturer down. I'm having a lot of 
trouble here with this. On 4/16/2002, FDA report cited 
sterility issues and lack of accountability by NECC and Mr. 
Cadden as the former CEO or director, he took the Fifth over in 
the House yesterday, we asked him to appear and he did not.
    I might add that this timeline was prepared by our staff, 
the committee staff, the chairman's staff. We asked for a 
timeline from you in regards to any actions that you have taken 
against any compounding manufacturer. We have yet to receive 
that, and I would hope that we could get it.
    But this is 2002. Mr. Chairman, we go through 2002--a 
complaint, 2002 adverse event, FDA inspections, FDA 483. By the 
way, the 483 is like a 1099 in regards to your taxes. You don't 
want to get a 483. That says you're in trouble, and you've got 
to answer. I have the answer by the New England Compounding 
Center. Then I have the warning letter back.
    I could go down all of the things that have happened here--
investigation, complaint, board action, board action, 
inspection. We go clear down here, another whole page of it--
letter, board action, board consent, board compliance, 
compliance, other licensing, advisory letters, licensing. 
Finally, in 2006, a warning letter. Finally, we get something 
done.
    Here's the warning letter. In the warning letter--and here, 
by the way, is the 483 that says you're in trouble--2002. 
Finally, after all of these things happen, in 2006, we have a 
warning letter. All right. What happens with a warning letter? 
And then New England Compounding Centers respond, and then you 
respond to them about the warning letter. So this is a warning 
letter after the response to the warning letter.
    And you say,

          ``Your firm must promptly correct the violations 
        noted in December 4, 2006, warning letter and establish 
        procedures to assure that such violations do not 
        reoccur. Its failure to do so will result in 
        enforcement action, including seizure of the firm's 
        products and an injunction against the firm and its 
        principals. In a future inspection, we will confirm the 
        commitments that you made in your response and verify 
        that your firm's compounding practices are consistent 
        with the policy articulated,''

et cetera, et cetera, et cetera.
    That's a pretty strong response. What happened? Actually, 
nothing happened until 2008, and then there was another 483. 
I'm not going to go through all that. We went through that. 
That involved Colorado. And, finally, we get to a 483 of 
October 26, 2012, finding multiple sources of contamination and 
air sampling showing contaminants 6 months prior to compounding 
of MPA. This has been going on since 2002. This is amazing.
    These are steroid injections, by the way, that when there 
was an inspection, there were vials of the product and there 
was black fungus in the vials. Who on earth would put an 
injection needle into a vial with black fungus to put into 
somebody's knee or shoulder or whatever? Maybe that's the 
problem I have with my knees. Hell, I don't know.
    I'm just saying it took all that time, Mr. Chairman, and 
nobody did anything. You say that you have the ability to shut 
down somebody if they have sterility issues. I have two or 
three 483s here and letters back and forth from 2002 until now, 
and the thing that shut the manufacturer down was 30 lives. 
Holy mackerel.
    Senator Alexander is precisely correct. I don't know 
whether you need a State flagpole or a Federal flagpole or 
something to get us off the dime here so that if somebody gets 
into this kind of a problem and you feel that you have to issue 
a 483, you can shut them down. Now, what am I missing here, 
other than I'm over time and I made a long statement and I 
didn't allow you to have a question. By the way, thank you for 
wearing purple because Kansas State is rated No. 1 in the BCS 
poll.
    Dr. Hamburg. Obviously, it's a very long answer and we're 
out of time. Just quickly, the 2002 contaminated product issues 
were responded to very swiftly in terms of going in and 
inspecting. We worked with the Massachusetts Board of Pharmacy. 
The products, in fact, were taken off the shelves. A decision 
was made, as we discussed earlier, that because this was a 
compounding pharmacy, it was under the purview of the 
Massachusetts Board of Pharmacy who licenses and oversees the 
day-to-day operations.
    They took on that responsibility of working with the 
company to resolve the sterility issues, including the consent 
decree in 2006, which turned out to have serious flaws, as Dr. 
Smith indicated. The belief was that the company had made 
progress, working with the Massachusetts Board of Pharmacy, to 
address the sterility issues.
    The 2006 warning letter from the FDA actually concerned a 
completely different set of issues at the facility. It had to 
do with three specific products where we did have very real 
concerns with the practices at NECC. It didn't have to do with 
sterility failures. It had to do with basically copying FDA-
approved drugs or making unapproved drugs. They were things 
that were taken seriously.
    As I said earlier, I wish that we had been much prompter in 
the followup on that, and perhaps we should have been more 
aggressive. The response to those warning letters--and had we 
taken the legal action that you indicated that we were citing 
authority to take, it would have been on a set of issues 
involving these specific products, and it probably--maybe we 
would have been successful and it would have made a difference. 
Maybe we wouldn't have been.
    I wasn't at the agency at the time. I know that there was a 
lot of internal debate about how to proceed. That's why it was 
slowed, because of the ambiguity in the law and the fact that 
there was ongoing litigation and differing opinions about the 
scope of our authority coming in. I think that doesn't fully 
answer your question, and I think we all wish that we had done 
more. It is complicated.
    Senator Roberts. OK. I've gone over and it's my fault, not 
your fault--3 minutes. You're just saying basically that your 
statement was erroneous. You do not have the authority to shut 
people down if there's a sterility issue because you don't know 
whether it's State, whether it's Federal, or whether it's 
specific to this product or that product, and all of the 
laundry list of things that went on here with staff and 
everything else. Then you have a crisis on your hands, and 
that's what happened.
    It's a pretty sad situation, Mr. Chairman.
    Can we get your timeline?
    Dr. Hamburg. We will get you the timeline. We are still 
collecting information, going through documents. This did 
happen at a time when many of the people involved are no longer 
at the agency. We're working hard to respond to the ongoing 
public health crisis, and many of the same people that we need 
to pull the documents are involved in that.
    We are very focused on it. We recognize the work that you 
need to do. We want to work with you, and we appreciate your 
patience.
    The Chairman. Thank you, Senator Roberts.
    Senator Blumenthal.
    Senator Blumenthal. Thank you, Mr. Chairman. I'd like to 
pursue, Mr. Chairman, your questions at the very outset here 
about the Ameridose matter, which, for me, in many respects, is 
more serious even than the NECC from a Federal enforcement 
standpoint.
    I have reviewed all the documents, 483s, and inspection 
reports. Clearly, serious, egregious violations of basic 
standards were found by your inspectors in 2008 and then again 
in 2010. Now, I take it that the recommendation was made for a 
warning letter to be issued. There is no evidence in the 
documents submitted to this committee that any warning letter 
was ever sent. Do you disagree?
    Dr. Hamburg. That is my understanding.
    Senator Blumenthal. There was no warning letter ever sent.
    Dr. Hamburg. No.
    Senator Blumenthal. Despite findings about the lack of 
potency in the drugs, the lack of proper sterility standards, 
the basic cleanliness, and other kinds of minimal standards in 
a company that is many times the size of NECC manufacturing 
hundreds of different kinds of products sent across the Nation, 
no warning letter was issued. Is that correct?
    Dr. Hamburg. The product was recalled, however. My 
understanding is no warning letter was sent.
    Senator Blumenthal. Why was no warning letter issued?
    Dr. Hamburg. We are looking into that. As I said, some of 
the specifics are part of an ongoing investigation internally 
and more broadly.
    Senator Blumenthal. There's no question in your mind, is 
there--because there wasn't in any of the inspectors who did 
these reports--that FDA had full and complete authority over 
Ameridose?
    Dr. Hamburg. As I said, it was something of a hybrid in 
terms of being a repackager-pharmacy. It wasn't a drug 
manufacturer, like Merck or Pfizer, but----
    Senator Blumenthal. You're telling the committee it was not 
a drug manufacturer?
    Dr. Hamburg. It was not a drug manufacturer in the sense of 
a drug manufacturer that we have the oversight of in terms of 
new products that undergo product review and approval before 
licensure, that are subject to all that that entails.
    Senator Blumenthal. Your inspector in the jurisdiction 
section of the report in 2010 said the firm currently repacks 
and manufactures prescription drug products which are FDA-
regulated drug products.
    Dr. Hamburg. As I said at the outset, Ameridose is actually 
the subject of an ongoing investigation, and you understand 
what that entails. I have been asked not to try to characterize 
Ameridose at this time as we're looking into those very 
questions that you're asking.
    Senator Blumenthal. Let me ask you a broader question which 
looks to the future rather than the past. I want to reiterate 
that much of the documents and issues that have been brought to 
the committee relate to a time before you took over the 
position that you have now, and we're asking both you and Dr. 
Smith to answer questions about institutional performance well 
before your responsibility.
    Looking to the future, if there is an NECC and an Ameridose 
continuing to operate out there, do you know who they are? In 
other words, if you had that authority today, do you know where 
you would go in terms of where the problems are, the future 
tragedies waiting to happen?
    Dr. Hamburg. We do not know the universe of compounding 
pharmacies that might fit into this category of activity 
because they are not required to register.
    Senator Blumenthal. Shouldn't you know?
    Dr. Hamburg. I do think that we should know, and I would 
like to see that as part of new legislation if we would do it.
    Senator Blumenthal. You can begin that task right now, 
can't you?
    Dr. Hamburg. We are beginning to reach out to our 
colleagues at the State level to learn more information. We are 
enhancing our activities around some of the large compounding 
facilities that we know about to really make sure that we have 
as much information about what they're doing and how they're 
doing it.
    Senator Blumenthal. Let me just suggest--and I don't mean 
to sound simplistic, because I know your task is resource 
challenged and we haven't really discussed the resource issue. 
I know it's one that is very much a challenge for the FDA at 
this point.
    Dr. Hamburg. Absolutely.
    Senator Blumenthal. The Congress really should be meeting 
its obligation to provide those resources that are necessary 
for the tasks that we're all implying you should have been 
carrying out.
    I would suggest very respectfully that the FDA ought to 
make it a priority to scrutinize the 3,000 compounding 
pharmacies, the documents that are public--and most of these 
documents are public right now, as we've seen from the media. 
They're available to folks who want to go into the records to 
find them--and where are the next tragedies going to occur; who 
will cause them; what kind of standards are they failing to 
meet--so that when you're provided with that authority that is 
not as limited, unclear, and contested, as you say it is now, 
you can swoop down on them and shut them down or at least 
require that they correct the problems that exist.
    Dr. Hamburg. I really appreciate your observations, 
including the one on resources, because that is a huge 
challenge. We have enormous responsibilities for the protection 
of the public health across a huge domain of areas of activity. 
I hope that I can work with you to address the crazy quilt of 
regulatory oversight that we currently have, because that will 
enable us to act in a much more efficient and targeted way.
    I also do think that the more we can be preventive, as you 
say, rather than reactive, using our authorities that are 
clearly in the law to address a contaminated product--but we 
don't want to have to wait until there's a contaminated 
product. We want to be able to make sure that these facilities 
are operating with the kind of preventive controls and 
standards of quality that the American people expect and 
deserve.
    Senator Blumenthal. I would just suggest that you be 
preventive with a capital P, and that you regard these 
renegade, outlier drug manufacturers as the threat to public 
health which, clearly, they are.
    Dr. Hamburg. Yes.
    Senator Blumenthal. Thank you, Mr. Chairman.
    The Chairman. Thank you, Senator Blumenthal.
    Senator Alexander.
    Senator Alexander. Mr. Chairman, I'd like to ask to place 
in the record statements from the Tennessee Department of 
Health, the Tennessee Board of Pharmacy, the Tennessee Hospital 
Association, the Tennessee Pharmacists Association, and the 
Tennessee Medical Association, all of which I asked for this 
hearing.
    [The information referred to may be found in Additional 
Material.]
    Senator Alexander. As much as I would like to focus my time 
on whose fault it was, I think the families of those who were 
hurt in Tennessee would like me to find out how we can make 
sure this doesn't happen again. I'd like to pursue the line of 
questioning that Senator Blumenthal and I and others have asked 
about, for lack of a better word, the flagpole theory.
    As I listen to this--and the reason I haven't asked Dr. 
Smith many questions is she said, and we know, that the 
Massachusetts State Board of Pharmacy had the clear authority 
to deal with this problem. They just were incompetent in 
dealing with it. And if anybody's going to be shut down, I 
think they should be shut down. That would be where I would go.
    Now, as we move over to the FDA, thinking about looking 
ahead, I'm not sure--listening to the FDA's confusion and 
reading their record about this, I wouldn't trust the FDA more 
than I would trust the Tennessee Department of Public Health to 
keep our medicines safe. In fact, the evidence that we've heard 
already and that we're going to hear from the second panel is 
that an example of doing things well in part of this area came 
because of the alliance between Vanderbilt University and the 
Tennessee Department of Health.
    It leads me back to this solution, Mr. Chairman, to how we 
fix accountability here. I'm trying to think through different 
ways we do things in the Federal Government. I'm thinking of 
our nuclear program. Admiral Rickover in the 1950s set up our 
nuclear submarines, and he had a very novel idea. He 
interviewed every single captain, and he told them their career 
depended upon whether or not there was ever an accident on the 
reactors on their submarines.
    Since the 1950s, there's never been a death in connection 
with any activity on a nuclear submarine, and I'm pretty sure 
the reason is because if there's an accident on a nuclear 
submarine, that captain's career is basically over or seriously 
diminished. There's clear responsibility. It's the captain's 
responsibility.
    I'd like to be able to come back to a testimony 6 months 
from now, after we've worked together to pass a law, and hear 
representatives of State boards of pharmacy say, ``This is my 
responsibility, and this is what we're doing about it,'' and 
hear the FDA say, ``This is our responsibility.'' I don't want 
to hear this joint responsibility that ``they were supposed to 
do it, and we could have done it, but nobody did it.''
    Let me narrow it down a little bit. As I understand it, 
Senator Blumenthal was focusing in on manufacturing, and the 
estimate I have is that there are about 5,600 manufacturers of 
drugs. Is that about right?
    Dr. Hamburg. There are about 6,500 facilities that are 
manufacturing active pharmaceutical ingredients or drugs.
    Senator Alexander. You have the total responsibility for 
that. Right?
    Dr. Hamburg. We do provide ongoing oversight, yes.
    Senator Alexander. That's your job. That's not the 
Massachusetts Board of Pharmacy----
    Dr. Hamburg. Yes, absolutely.
    Senator Alexander. You're on the flagpole for them. And 
then you've said and others have said that the compounding 
actually goes on, traditional compounding, in thousands of 
pharmacies across the country, and we're not talking about 
that. That's under State boards of pharmacy.
    What we're really talking about--and the estimates I have 
may or may not be right--is that there are about 7,500 
pharmacies that specialize in advanced compounding services and 
about 3,000 in sterile compounding. It's somewhere within those 
facilities, where State boards of pharmacy have responsibility, 
and you have some responsibility. Is that right?
    Dr. Hamburg. Yes. That's the area that in our proposed 
framework we'd really like to focus on as needing 
clarification.
    Senator Alexander. Would you like to take over the 
responsibility, the total responsibility, for a certain number 
of those pharmacies?
    Dr. Hamburg. That might well be the best outcome.
    Senator Alexander. How many of those would that be? Is that 
a few hundred, or is that a few thousand, or do you know?
    Dr. Hamburg. We don't know, because at the present time, 
many of those facilities are not reporting information to us or 
are not registered with us. We need to understand--and those 
numbers are not our numbers because they don't----
    Senator Alexander. No, they're my numbers, and I'm not sure 
they're right. I'm just trying to get a rough idea. If you 
already have 6,500 manufacturers, if you were to take over 
several thousand more or several hundred more, it would make a 
difference. Maybe you don't have the capacity to do that.
    Dr. Hamburg. It would be a real challenge. Of course, for 
our other inspectional activities over drug manufacturers, we 
have user fees that help to support our budget. Senator Harkin 
well knows, as we just worked so hard----
    Senator Alexander. Right. I'm trying to get to a point. 
Would it be conceivable that there could be a system where you 
have the responsibility, but you're able to delegate that 
responsibility to some States that are willing to meet 
standards, and your job would be more like, say, the Nuclear 
Regulatory Commission? You'd go around and check and make sure 
that--it wouldn't be your job to regulate--you wouldn't 
regulate the facilities, but you would basically be regulating 
the States who took on that function in addition to their 
supervision of traditional pharmacies.
    Dr. Hamburg. That would be one model, and we could----
    Senator Alexander. Is that a possibility?
    Dr. Hamburg. Also lay out clear Federal standards for 
practice.
    Senator Alexander. Could that be done in a way that made it 
clear that while you were--what that might mean, for example, 
in a case like this, is that you would go to Massachusetts--
you'd have the authority to go to Massachusetts and take away 
their authority completely to deal with sterile manufacturing 
or sterile compounding because of incompetence or failure to 
meet Federal standards, under that model.
    Dr. Hamburg. That would be a possible model. It's well 
worth exploring all the different ways that we could improve 
the system and make sure that it is fully coordinated and 
provides a safety net to protect health.
    Senator Alexander. Mr. Chairman, as you can tell, my 
general drift here is that looking to the future, if the 
definition already is not for these advanced compounding 
units--if they're not already manufacturing--and Senator 
Blumenthal was suggesting they may already be--if they already 
are, then they're under the FDA.
    If they're not, I would suggest we make it clear that 
either the Federal Government or the State government through a 
set of certification from the Federal Government be on the 
flagpole, have the full accountability and responsibility for 
doing it. If they fail to do it, they lose their opportunity to 
do that. That's one model that I would suggest.
    The Chairman. Thank you very much, Senator Alexander. I 
would just say that as part of this ongoing effort, Senator 
Enzi and I and the committee will be sending a letter to each 
State board of pharmacy to learn more about their oversight 
practices in this area, including just how many large-scale 
sterile compounders are operating today and who they are. We 
don't know. We are preparing a letter, and I hope that I can 
get all of the signatures on both sides of the aisle here to 
send that letter out. It's being prepared by our staffs right 
now.
    I will close this panel where I started with Dr. Bell. I 
talked about the need for public health and the funding. We've 
heard a lot about FDA and about the necessity for FDA to take 
more oversight responsibility here. Again, I remind you of what 
Dr. Hamburg just said. This comes down to resources.
    We continually ask the Food and Drug Administration to do 
more and more and more. We ask them to do more in healthcare. 
We ask them to do more in food inspections, more for imports 
coming from overseas, and, to a certain point, the resources 
are going to have to be there. So, I hope that when 
appropriations time comes around--and we're looking at funding 
for both of these, both for CDC and for the FDA--that we can 
meet our obligations in making sure that they're adequately 
funded to carry out the responsibilities we keep asking them to 
do.
    Thank you all very much.
    Now we'll turn to our second panel. I guess we won't turn 
to our second panel. The second panel was Barry Cadden, the 
manager and co-owner of the New England Compounding Center. He 
declined our invitation. We decided not to issue a subpoena. He 
was subpoenaed by the House committee yesterday and showed up 
and continually took the Fifth Amendment. There was no reason 
to go through that charade here today with him.
    On our third panel, we have--and I'll ask them to come up--
David G. Miller, the executive vice president and CEO of the 
International Academy of Compounding Pharmacists, an 
association which represents individual pharmacists involved in 
the com-
pounding industry.
    Then we have Dr. Kasey Thompson, who serves as the vice 
president of the Office of Policy, Planning, and Communications 
at the American Society of Health-System Pharmacies, an 
organization which advises its members on the responsible use 
of compounded medications. Dr. Thompson has extensive knowledge 
regarding the safe use of compounded drugs, as he previously 
served as ASHP's director of the Center of Patient Safety and 
director of the Practice Standards and Quality Divisions.
    Our third witness is one who has been referenced earlier, 
Dr. Marion Kainer. I will yield to my distinguished friend and 
Senator from Tennessee for purposes of introducing Dr. Kainer 
from Tennessee.
    Senator Alexander. Thank you, Mr. Chairman.
    I'd like to welcome Dr. Marion Kainer. Our previous witness 
from the Centers for Disease Control mentioned her. She'll tell 
more about this, and we'll talk about it at the time. An astute 
clinician at Vanderbilt University, who has a partnership with 
the State of Tennessee where Dr. Kainer is director of 
Healthcare Associated Infections and Antimicrobial Resistance 
Program, reported something suspicious to Dr. Kainer. Within a 
matter of a few days, this report led to a recall of the 
material that was being spread around the United States from 
this New England facility, undoubtedly saving many lives and 
helping many others.
    It was called by the executive director of the Association 
of State and Territorial Health Officials, who said this, Mr. 
Chairman:

          ``By the time we learned this was a problem around 
        the country, the information from Tennessee had already 
        narrowed it down to what the problem was. It was a 
        textbook case of how to do it right.''

    Dr. Kainer obtained her medical degree and master of public 
health in Melbourne. She's had a distinguished career in 
Australia and the United States, with over 20 years of 
experience in infection control. I compliment her for her 
astuteness, her leadership, and welcome her to the panel, and I 
thank the chairman for inviting her.
    The Chairman. Thank you, Senator Alexander.
    We welcome you all. All of your statements will be made a 
part of the record in their entirety. We'll proceed in reverse 
order of the introductions. We'll start with Dr. Kainer.
    Dr. Kainer, I'm sure I speak for all the committee. You 
have our highest praise, and we thank you for your diligence--
for being on top of this immediately and for doing exactly what 
needed to be done in getting it to the Center for Disease 
Control. I'll just echo what Senator Alexander said. Your 
timely action and professionalism undoubtedly saved many lives.
    Thank you very much and please proceed. Welcome to the 
committee.

    STATEMENT OF MARION KAINER, M.D., MPH, FRACP, DIRECTOR, 
  HEALTHCARE ASSOCIATED INFECTIONS & ANTIMICROBIAL RESISTANCE 
     PROGRAM, TENNESSEE DEPARTMENT OF HEALTH, NASHVILLE, TN

    Dr. Kainer. Thank you. On behalf of the Tennessee 
Department of Health, I would like to thank Senator Alexander 
for the opportunity to comment on the fungal meningitis 
outbreak. I'm the director of the Healthcare Associated 
Infections and Antimicrobial Resistance Program.
    In Tennessee, we now report 81 cases and 13 deaths. Our 
concerns and prayers for patients, families, and loved ones 
affected by this preventable tragedy are ongoing. There are 
many heartbreaking stories. Some have been reported in the 
media. Diana Reed's death devastated her family. Her husband 
has Lou Gehrig's Disease and Diana was her husband's arms, 
legs, and voice and kept his accounting business going.
    Fungal meningitis is extremely rare. One of our greatest 
challenges was knowing just what we were dealing with as more 
and more patients fell ill. Even though we were looking for 
fungus, because the initial patient reported to us had been 
diagnosed with fungal meningitis, none of the diagnostic tests 
yielded confirmed results until October 3d, 15 days after we 
initiated our investigation of the first case. My written 
remarks include a detailed chronology.
    I would like to direct your attention to some early lessons 
learned from this outbreak. First, compounding of medications 
must be performed safely. Patients and healthcare providers 
should expect safe and effective medications. Compounding 
pharmacies do provide a needed service. If compounded products 
are unavailable to meet the unique needs of some patients, 
providers may perform compounding or repackaging themselves at 
the bedside and may also put patients at risk.
    Second, recent investments in public health infrastructure 
through cooperative agreements from the CDC have supported 
building public health capacity. This capacity was critical in 
identifying and responding to this outbreak, determining the 
cause resulting in product recall only 8 days after initial 
notification, saving lives and limiting the number of patients 
exposed.
    Six members of our Healthcare Associated Infections or HAI 
team are funded through the Prevention and Public Health Fund 
Epidemiology and Laboratory Capacity grant and the Emerging 
Infections Program. In addition, the team has a CDC/CSTE 
fellow. I am the only person on the HAI team not funded by the 
CDC.
    Our HAI team had the expertise to conduct on-site visits, 
to ask the right questions, create a database, and enter and 
analyze the data swiftly to determine the cause of the outbreak 
and those at highest risk of getting sick. We did an analysis 
to assess the potential impact if there had been a delay in the 
recall from NECC by 9 days. In Tennessee alone, we estimate by 
now, we would have seen an additional 59 cases and at least 
five additional deaths.
    To prevent healthcare associated infections, our team has 
built close relationships with infection preventionists. These 
relationships are built on mutual trust and have been 
invaluable in promoting open communication. Surge capacity was 
provided by staff funded under the Epidemiology and Laboratory 
Capacity and the Public Health Emergency Preparedness grants.
    These staff reviewed clinical information and helped track 
down over 1,000 exposed patients. Contact by phone or in person 
was made by local public health staff funded by the State of 
Tennessee. Outreach included frequent telephone calls and 
knocking on doors. Our nurses tracked down one patient by 
contacting a tour operator in Yellowstone Park.
    Third, this outbreak illustrates the tremendous importance 
of inter-facility communication when patients may seek medical 
services in multiple facilities for complications that arise 
from treatment at another facility. It also illustrates the 
critical importance of astute clinicians in alerting public 
health.
    In conclusion, this has been a devastating outbreak for 
patients, their families and friends, healthcare providers and 
clinics. In Tennessee, we still have many patients hospitalized 
and suffering from complications and others who are exposed and 
frightened that they may become affected.
    Sustained commitment to funding from CDC for emergency 
preparedness and reduction of healthcare associated infections 
has supported our productive relationships with partners and 
healthcare providers across the State. These preexisting 
relationships allowed us to respond quickly because we trusted 
each other. We all need to work together to do our best to 
prevent such a tragedy from occurring again and to ensure that 
we have a public health capacity to detect and rapidly respond 
to any future outbreaks.
    Thank you for your time and attention.
    [The prepared statement of Dr. Kainer follows:]
         Prepared Statement of Marion Kainer, M.D., MPH, FRACP
                                summary
    Communication and coordination among healthcare providers and 
public health in Tennessee was unusually strong thanks to major Federal 
grants to the State that have supported tracking and improving rates of 
hospital-acquired infections. Years of close collaboration between 
public health staff in the federally funded healthcare associated 
infection program and hospital-based infection preventionists in the 
State resulted in relationships and mutual trust that permitted easy 
collaboration during the investigation and response to this crisis.
    Despite this close relationship, cracking this investigation was 
difficult because of the significant technical challenges in 
definitively diagnosing fungal meningitis. We had to take actions days 
in advance of being able to confirm that we were definitely dealing 
with a fungus. With CDC's help, we have been able to diagnose people 
much more easily since the early days of the outbreak. A timeline of 
the major events in this investigation is provided in the attached 
written testimony.
    Recent investments in public health infrastructure through 
cooperative agreements from the CDC have built public health capacity 
at the TDH. This capacity was invaluable in identifying and responding 
to the outbreak, determining the cause resulting in product recall only 
8 days after initial notification, saving lives and limiting the number 
of patients administered the contaminated injections. In Tennessee, if 
the recall from NECC had been delayed by 9 days, we estimate that at 
this time we would have seen an additional 59 cases and at least 5 
additional deaths. If treatment guidance from CDC had been delayed, the 
number of deaths would be even higher. Of the 33 Tennessee patients who 
sought medical care before October 3, 9 (27.3 percent) died. Of the 48 
patients who sought medical care on, or after October 3, when the first 
CDC treatment guidance was issued, four (8.3 percent) died.
    Six members of the Healthcare Associated Infections (HAI) team are 
funded through the Prevention and Public Health Fund Epidemiology and 
Laboratory Capacity Cooperative agreement and the Emerging Infections 
Program. In addition, the team has a CDC/Council of State and 
Territorial Epidemiologists (CSTE) fellow. The only person not funded 
by CDC is the director of the HAI program, Dr. Kainer. The team had the 
expertise to ask the right questions, conduct on-site visits, create 
relevant standardized investigation forms, create a data base, enter 
and analyze the data swiftly to determine the cause of the outbreak and 
those at highest risk of getting sick. Surge capacity was provided by 
staff funded under the Epidemiology and Laboratory Capacity (ELC) grant 
and the Public Health Emergency Preparedness (PHEP) cooperative 
agreements as well as an additional CDC/CSTE fellow and an Epidemic 
Intelligence Service (EIS) officer assigned to Tennessee. State-funded 
public health nurses in the field were mobilized to contact hard to 
reach patients, going door to door when necessary, and maintaining 
regular phone and in person contact with patients for weeks.
    This has been a devastating outbreak for patients, their families 
and friends, healthcare providers and clinics. In Tennessee we still 
have many patients hospitalized and suffering from complications and 
others who are exposed and frightened that they may become infected. 
Sustained commitment to funding for emergency preparedness and 
reduction of healthcare associated infections through cooperative 
agreements from the CDC has supported our productive relationships with 
our partners and healthcare providers across the State. These pre-
existing relationships allowed us to respond quickly because we trusted 
each other. We all need to work together to do our best to prevent such 
a tragedy from occurring again and to ensure that we have the public 
health capacity to detect and rapidly respond to any future outbreaks.
                                 ______
                                 
    On behalf of the Tennessee Department of Health, I would like to 
thank Senator Alexander for the opportunity to comment on the recent 
fungal meningitis outbreak. I hope to provide some insights from this 
tragic outbreak to the Health, Education, Labor, and Pensions (HELP) 
Committee which I hope will assist the committee to gain an 
understanding of potential opportunities to prevent and respond to such 
devastating outbreaks in the future.
    As of November 13, Tennessee reported 81 cases and 13 deaths. 
Behind each one of these numbers is a lot of suffering of the patients 
affected, their loved ones and the communities in which they 
participated. One example: The death of Diana Reed who, according to 
her brother, was her husband's arms, legs and voice, has been 
devastating. Her husband has Lou Gehrig's Disease and Diana was 
instrumental in keeping his accounting business going and in helping 
her husband get in and out of bed, the shower and his wheelchair. The 
family is trying to figure out how they will carry on and enable her 
husband the ability to maintain his dignity and to keep his work 
without her; they shared their story with the New York Times.
    Fungal meningitis is extremely rare. One of our great challenges 
was knowing just what we were dealing with as more and more patients 
fell ill. Even though we were looking for a fungus because the initial 
patient reported to us had been diagnosed with a fungal meningitis, 
none of the diagnostic tests yielded confirmed results until October 3, 
15 days after we initiated our investigation of the first case.
    Below is an outline of the timeline of major events of this 
outbreak and the role of the Tennessee Department of Health in this 
investigation. I will also discuss lessons learned in the context of 
this investigation.

                        Timeline of Major Events
------------------------------------------------------------------------
                                                         Case count as
              Date                   Major events     known at that time
------------------------------------------------------------------------
Day 1: Tuesday, Sept. 18........  Dr. Marion Kainer,  1 case of
                                   Director of the     Aspergillus
                                   Tennessee           meningitis
                                   Department of
                                   Health (TDH)
                                   Healthcare
                                   Associated
                                   Infections and
                                   Antimicrobial
                                   Resistance
                                   Program, receives
                                   an email sent by
                                   Dr. April Pettit,
                                   Infectious
                                   Diseases
                                   Physician,
                                   Vanderbilt
                                   University
                                   Medical Center
                                   (VUMC) about a
                                   patient with
                                   meningitis caused
                                   by a fungus,
                                   Aspergillus
                                   fumigatus, who
                                   had a recent
                                   epidural
                                   injection at a
                                   pain clinic.
                                   Dr. Kainer and Dr
                                   Pettit discuss
                                   the case.
                                  Dr. Kainer speaks
                                   with Ms. Candace
                                   Smith, infection
                                   preventionist
                                   (IP) at St Thomas
                                   Hospital (STH),
                                   which is
                                   organizationally
                                   affiliated with
                                   the St Thomas
                                   Outpatient
                                   Neurosurgical
                                   Center (STONC)
                                   where the patient
                                   received the
                                   injection. Dr.
                                   Kainer requests
                                   details of the
                                   procedure, states
                                   that the
                                   infection is a
                                   sentinel event of
                                   concern, which
                                   deserves a
                                   careful
                                   investigation and
                                   requests that Ms.
                                   Smith commence an
                                   inspection of the
                                   pain clinic
                                   (e.g., evidence
                                   of any
                                   construction,
                                   water damage) and
                                   to inquire about
                                   any potential
                                   additional cases.
Day 3: Thursday, Sept 20........  IP from STH         1 case of
                                   contacts Dr.        Aspergillus
                                   Kainer and          meningitis
                                   confirms that      2 cases of
                                   index case had an   meningitis,
                                   epidural steroid    unknown cause,
                                   injection (ESI)     both seeming to
                                   at STONC;           be improving
                                   provides details   No national
                                   of the procedure.   reports of
                                   Because the         Aspergillus
                                   facility manager    meningitis
                                   of STONC is on
                                   vacation, the IP
                                   at STH continues
                                   to help in the
                                   investigation.
                                  Dr. Kainer
                                   contacts Dr. Perz
                                   at the Division
                                   of Healthcare
                                   Quality Promotion
                                   (DHQP), Centers
                                   for Disease
                                   Control and
                                   Prevention (CDC)
                                   to ask whether
                                   any cases of
                                   Aspergillus
                                   meningitis had
                                   been reported to
                                   CDC from any
                                   other ambulatory
                                   surgery centers
                                   (ASC) or pain
                                   clinics. Fungal
                                   meningitis is
                                   rare, but is not
                                   required to be
                                   reported to the
                                   CDC. Even without
                                   any requirement,
                                   clinicians or
                                   States often
                                   contact CDC about
                                   unusual
                                   infections;
                                   however, no one
                                   had recently
                                   contacted the
                                   Mycotics Branch
                                   at CDC to report
                                   any cases of
                                   Aspergillus
                                   meningitis.
                                  STH reports two
                                   additional
                                   patients with
                                   meningitis with
                                   high levels of
                                   white blood cells
                                   but no known
                                   cause. Both had
                                   undergone ESIs at
                                   STONC. Diagnoses
                                   were complicated
                                   because the
                                   patients appeared
                                   to be getting
                                   better and the
                                   cause of their
                                   meningitis was
                                   unknown. Dr.
                                   Kainer worked
                                   with clinicians
                                   to request
                                   exhaustive
                                   diagnostic tests.
                                   They also had ESI
                                   performed by same
                                   anesthesiologist
                                   at STONC. The
                                   preservative-free
                                   methylprednisolon
                                   e acetate used in
                                   their ESIs was
                                   obtained from New
                                   England
                                   Compounding
                                   Center (NECC).
                                  Arrange for one on
                                   Dr Kainer's staff
                                   to visit STONC
                                   the next morning,
                                   with the IP and
                                   the ID physician
                                   from STH..
                                  On this day, STONC
                                   closes
                                   voluntarily,
                                   sequesters
                                   supplies and
                                   orders new
                                   supplies from
                                   other
                                   distributors.
Day 4: Friday, Sept 21..........  Visit to STONC by   1 case of
                                   TDH staff for a     Aspergillus
                                   careful review of   meningitis
                                   all procedures     2 cases of
                                   and the physical    meningitis of
                                   environment: no     unknown cause
                                   evidence observed  1 case of stroke
                                   of environmental    and meningitis,
                                   conditions that     unknown cause
                                   would have led to  1 case of stroke,
                                   fungal              no spinal tap was
                                   contamination of    done
                                   procedures.
                                  TDH contacts CDC
                                   and describes
                                   findings of site
                                   visit. TDH asks
                                   CDC to help with
                                   laboratory
                                   testing of
                                   patients with
                                   meningitis of
                                   unknown cause
                                   (because fungus
                                   is very hard to
                                   diagnose) and
                                   also for testing
                                   of environmental
                                   samples from the
                                   clinic, if needed.
                                  Another patient
                                   with meningitis
                                   and stroke with a
                                   history of ESI at
                                   STONC is
                                   identified, while
                                   VUMC also reports
                                   yet another
                                   patient who had a
                                   stroke and had an
                                   epidural
                                   injection, but at
                                   the time it was
                                   not clear where
                                   the ESI was done
                                   (it was confirmed
                                   as STONC on Day
                                   7).
                                  TDH sent out a
                                   Health Alert
                                   using our TN
                                   Health Alert
                                   Network (THAN),
                                   asking clinicians
                                   to look for and
                                   report any cases
                                   of meningitis
                                   following
                                   epidural
                                   injection to the
                                   TDH.
                                  At this time, the
                                   leading suspected
                                   causes of
                                   meningitis were
                                   the contrast
                                   media and
                                   methylprednisolon
                                   e acetate (MPA)
                                   from NECC because
                                   both were used in
                                   each patient (and
                                   are commonly
                                   given together
                                   for an ESI).
                                   Other less likely
                                   possibilities
                                   included local
                                   anesthetic, local
                                   skin preparation
                                   and needles used
                                   for the injection.
Day 6: Sunday, Sept 23..........  IP at STH contacts
                                   Dr. Kainer about
                                   one new patient
                                   and one patient
                                   re-admitted with
                                   meningitis; both
                                   had ESI at STONC.
Day 7: Monday, Sept 24..........  Facility manager    1 case Aspergillus
                                   from STONC has      meningitis
                                   returned from      4 cases of
                                   vacation and        meningitis
                                   provides            unknown cause
                                   additional         1 case of stroke,
                                   information on      but no spinal tap
                                   the facility        done
                                   practices. TDH
                                   staff arrange to
                                   begin collecting
                                   data on patients
                                   to try to find
                                   out what
                                   distinguishes the
                                   case patients
                                   from those who
                                   did not get sick.
                                   TDH and CDC
                                   communicating
                                   closely.
                                  Dr. Kainer
                                   contacts State
                                   epidemiologist at
                                   Massachusetts
                                   Department of
                                   Health, Dr. Al
                                   DeMaria, to
                                   request a
                                   conference call
                                   with TDH, CDC, MA
                                   staff and NECC to
                                   obtain
                                   distribution list
                                   of clinics that
                                   got MPA from NECC
                                   in order to look
                                   for other cases
                                   of meningitis
                                   among patients
                                   who received ESI
                                   with MPA
                                   compounded by
                                   NECC.
Day 8: Tuesday, Sept 25.........  2 new cases of      1 case Aspergillus
                                   meningitis          meningitis
                                   reported to TDH.   6 cases of
                                   Both had ESI        meningitis
                                   using MPA from      unknown cause
                                   NECC at STONC;     1 case of stroke,
                                   however, one of     but no spinal tap
                                   the patients did    done
                                   not receive the    1 case of other
                                   suspected           neurologic
                                   contrast and the    problems and
                                   procedure was       abnormal spinal
                                   done by a           tap (unknown
                                   different           cause)
                                   anesthesiologist.
                                  Conference call
                                   with TDH, CDC,
                                   Massachusetts
                                   Department of
                                   Health and Board
                                   of Registration
                                   in Pharmacy
                                   (MABRP) and NECC.
                                   NECC stated no
                                   adverse events
                                   reported, no new
                                   suppliers of
                                   ingredients or
                                   changes in
                                   procedures. TDH
                                   described
                                   severity of cases
                                   and that
                                   preservative free
                                   MPA was leading
                                   hypothesis. TDH
                                   requested
                                   distribution list
                                   and verified that
                                   voluntary recall
                                   procedures were
                                   in place.
                                  TDH staff begin
                                   collecting all
                                   the medical
                                   information
                                   needed to conduct
                                   their
                                   epidemiologic
                                   studies.
                                  STONC starts
                                   contacting
                                   potentially
                                   exposed patients.
                                  A new patient who
                                   had an ESI at
                                   STONC was
                                   admitted to STH
                                   with numbness and
                                   bowel/bladder
                                   control problems,
                                   but no headache
                                   or fever. Her
                                   spinal tap shows
                                   signs of
                                   meningitis of
                                   unknown cause,
                                   but with a much
                                   lower white blood
                                   cell count than
                                   the other cases
                                   of meningitis.
Day 9: Wednesday, Sept. 26......  NECC issues
                                   voluntary recall
                                   for three lots of
                                   preservative free
                                   MPA and provides
                                   distribution list
                                   of consignees to
                                   MABORP and FDA.
                                  TDH and CDC draft
                                   an Epi-X Alert
                                   (national
                                   emergency alert
                                   system for public
                                   health
                                   professionals) to
                                   report cases of
                                   meningitis
                                   related to
                                   epidural
                                   injections.
                                  TDH continues to
                                   followup on
                                   patients who
                                   received ESI at
                                   STONC to look for
                                   any other unusual
                                   illnesses or
                                   complications.
                                  CDC helps TDH by
                                   making available
                                   a medical doctor
                                   with expertise in
                                   treating fungus
                                   to assist TN
                                   clinicians in
                                   caring for
                                   patients.
Day 10: Thursday, Sept. 27......  TDH staff complete
                                   first round of
                                   epidemiologic
                                   studies;
                                   preliminary
                                   findings supports
                                   that MPA is a
                                   likely source..
                                  TDH asks STONC to
                                   contact all
                                   patients who had
                                   procedures since
                                   July 30.
                                  Analysis of the
                                   NECC distribution
                                   list shows two
                                   other clinics in
                                   TN received MPA.
                                   These clinics are
                                   contacted and all
                                   MPA is
                                   sequestered. Both
                                   clinics cease
                                   performing ESIs.
                                  The first clear
                                   evidence that the
                                   meningitis cause
                                   is not related to
                                   the STONC clinic:
                                   North Carolina
                                   (NC) reports a
                                   patient with
                                   meningitis
                                   exposed to MPA
                                   from NECC.
Day 11: Friday, Sept. 28........  It is still not
                                   absolutely clear
                                   that the MPA from
                                   NECC is the only
                                   possible source
                                   of contamination:
                                   the NC case
                                   patient had also
                                   received
                                   lidocaine and
                                   povidone iodine
                                   from the same
                                   manufacturers
                                   used by STONC.
                                   The lidocaine was
                                   the same lot
                                   number.
                                  CDC notifies all
                                   State Health
                                   Departments of
                                   situation and
                                   urges them to
                                   contact clinics
                                   who do ESIs to
                                   ask them to
                                   contact and check
                                   on the health of
                                   recipients of MPA
                                   using a script
                                   prepared by CDC.
                                   They ask that
                                   this be done
                                   immediately, not
                                   waiting until
                                   after the weekend.
                                  CDC issues another
                                   national Epi-X
                                   alert indicating
                                   that this now is
                                   a multistate
                                   outbreak and
                                   requesting
                                   reports of
                                   meningitis, other
                                   neurological
                                   infections, and
                                   stroke. TDH sends
                                   its own alert
                                   through THAN to
                                   clinicians and
                                   hospitals in TN
                                   to look for and
                                   report
                                   meningitis,
                                   stroke and focal
                                   infections in
                                   patients who have
                                   had epidural
                                   injections.
                                  Still, all
                                   diagnostic tests
                                   on these cases
                                   remain negative.
                                   The only patient
                                   with a confirmed
                                   diagnosis remains
                                   the first case
                                   patient reported.
                                   This highlights
                                   the difficulty of
                                   diagnosing a
                                   fungal infection,
                                   even when one is
                                   looking very hard
                                   to find it.
                                  TDH continues to
                                   work on
                                   epidemiologic
                                   studies to learn
                                   more about these
                                   patients, despite
                                   not yet having a
                                   confirmed
                                   diagnosis. TDH
                                   requests
                                   assistance from
                                   CDC to abstract
                                   clinical data
                                   from patient
                                   records (help
                                   arrives on Day
                                   14).
Day 13: Sunday, Sept 30.........  TDH and STONC
                                   staff continue to
                                   abstract data on
                                   patients who had
                                   procedures since
                                   July 1.
Day 14: Monday, Oct 1...........  TDH holds its       11 cases, 2 deaths
                                   first press
                                   conference and
                                   initiates a daily
                                   scheduled press
                                   briefing.
                                  TDH partners with
                                   the State Poison
                                   Control Center to
                                   assist in
                                   responding to
                                   questions from
                                   the general
                                   public.
                                  Other TN clinics
                                   continue to
                                   contact patients
                                   exposed to MPA
                                   from NECC. CDC
                                   and TDH staff
                                   work on gathering
                                   patient data to
                                   continue studies.
                                  TDH participates
                                   on call with
                                   expert fungal
                                   clinical panel
                                   convened by CDC,
                                   discuss need for
                                   CDC to provide
                                   interim
                                   suggestions/
                                   advice to
                                   clinicians on
                                   diagnosis and
                                   treatment.
Day 15: Wednesday, Oct 3........  CDC issues interim  18 cases, 2 deaths
                                   guidance on
                                   diagnostics and
                                   clinical
                                   management using
                                   input from an
                                   expert fungal
                                   clinical panel
                                   convened by CDC.
                                  For the first time
                                   since the initial
                                   report, a tissue
                                   biopsy from a
                                   case patient
                                   shows a fungus.
                                   However, the
                                   fungus looks
                                   different than
                                   Aspergillus. More
                                   tests must be
                                   done to identify
                                   it.
                                  TDH issues another
                                   alert through
                                   THAN to
                                   clinicians to
                                   help them
                                   identify,
                                   diagnose and
                                   treat ill persons
                                   exposed to MPA
                                   from NECC.
                                  TDH analysis of
                                   STONC patients
                                   suggests that one
                                   particular lot of
                                   the three NECC
                                   MPA lots present
                                   at STONC is the
                                   most likely to
                                   make patients
                                   sick: Lot
                                   06292012.
Day 16: Thursday, Oct 4.........  A final
                                   identification of
                                   the fungus
                                   causing illness
                                   is still not
                                   made, but a
                                   specimen from
                                   another patient
                                   who died shows a
                                   fungus that is
                                   not Aspergillus.
                                  FDA announces
                                   fungus was seen
                                   on microscopic
                                   examination of an
                                   unopened vial of
                                   MPA from Lot
                                   08102012. This
                                   now is very
                                   strong evidence
                                   that MPA is the
                                   cause of the
                                   outbreak.
                                  TDH alerts TN
                                   healthcare
                                   facilities using
                                   THAN to cease use
                                   of all
                                   medications and
                                   products from
                                   NECC.
Day 17: Friday, Oct 5...........  TDH opens State     29 cases, 3 deaths
                                   health operations
                                   center to assist
                                   in case tracking,
                                   active
                                   surveillance
                                   (contacting,
                                   reaching out to
                                   all persons who
                                   received MPA from
                                   NECC at any of
                                   the three
                                   Tennessee
                                   clinics--a total
                                   of 1,009
                                   persons).
                                   Mobilize regional
                                   health operations
                                   centers and use
                                   public health
                                   nurses to contact
                                   hard to reach
                                   patients, going
                                   door to door when
                                   necessary. Public
                                   health nurses
                                   maintained
                                   regular phone and
                                   in person contact
                                   with affected
                                   patients for
                                   weeks, changing
                                   messaging as
                                   required to
                                   adjust to a fluid
                                   and constantly
                                   changing
                                   scientific
                                   understanding and
                                   related patient
                                   needs.
                                  The CDC has
                                   another meeting
                                   of its expert
                                   fungal panel.
Day 18: Saturday, Oct 6.........  NECC announces      29 cases, 3 deaths
                                   voluntary recall
                                   of all NECC
                                   products.
                                  FDA issues
                                   Medwatch alert
                                   asking providers
                                   to stop using any
                                   NECC products.
Day 24: Friday, Oct 12..........  MMWR (CDC           50 cases, 6 deaths
                                   publication) is
                                   published on
                                   clinical
                                   presentation of
                                   cases.
Day 26: Sunday, Oct 14..........  FDA call with       53 cases, 6 deaths
                                   States and CDC on
                                   concerns about
                                   sterility of any
                                   product from NECC.
Day 27: Monday, Oct 15..........  FDA issues          53 cases, 6 deaths
                                   Medwatch alert.
                                  TDH works with the
                                   Tennessee
                                   Hospital
                                   Association
                                   (THA), the TN
                                   medical
                                   association
                                   (TMA), the
                                   ambulatory
                                   surgery center
                                   association and
                                   the TN pharmacist
                                   association to
                                   assist in
                                   alerting
                                   hospitals,
                                   providers and
                                   clinics to
                                   identify and
                                   notify patients
                                   who received NECC
                                   products.
Day 29: Wednesday, Oct 17.......  TDH identifies      61 cases, 8 deaths
                                   that patients who
                                   received older
                                   vials are much
                                   more likely to
                                   get sick.
                                   Questions begin
                                   about whether or
                                   not to test these
                                   patients even if
                                   they are not
                                   sick, if testing
                                   might prevent
                                   serious illness
                                   such as stroke.
Day 30: Thursday, Oct 18........  TDH works with CDC  63 cases, 8 deaths
                                   experts to
                                   develop a
                                   mathematical
                                   model used for
                                   decision analysis
                                   by CDC about what
                                   to do for high
                                   risk patients.
                                  For the first
                                   time, CDC and FDA
                                   confirm presence
                                   of Exserohilum
                                   rostratum in
                                   unopened vials
                                   from Lot
                                   0810210@51.
                                  This is now
                                   definitive
                                   evidence that
                                   contaminated MPA
                                   is the cause of
                                   the outbreak.
Day 35: Tuesday, Oct 23.........  MA Board of         70 cases, 9 deaths
                                   Registration in
                                   Pharmacy issues
                                   report of initial
                                   preliminary
                                   findings.
Day 38: Friday, Oct 26..........  FDA releases copy   74 cases, 10
                                   of FDA form 483.    deaths
                                   All 50 vials of
                                   MPA tested showed
                                   contamination
                                   (likely fungal).
Day 48: Tuesday, Nov 6..........  The New England     78 cases, 13
                                   Journal of          deaths
                                   Medicine
                                   publishes an
                                   article written
                                   by TDH and CDC
                                   investigators on
                                   this outbreak:
                                   http://
                                   www.nejm.org/doi/
                                   full/10.1056/
                                   NEJMoa1212972 .
Day 51: Friday, Nov 9...........  TDH invited to      81 cases, 13
                                   provide testimony   deaths
                                   to the Senate
                                   HELP committee.
                                  TDH requests on-
                                   site assistance
                                   again from CDC to
                                   describe later
                                   complications of
                                   fungal infection,
                                   such as epidural
                                   abscess,
                                   arachnoiditis and
                                   risk factors. Two
                                   EIS officers will
                                   arrive on-site on
                                   Nov 13.
------------------------------------------------------------------------

                            lessons learned
    1. Compounding and/or repackaging of medications must be performed 
safely. Patients and healthcare providers should expect safe and 
effective medications. Compounding pharmacies provide a needed service. 
If compounded products are unavailable to meet the unique needs of some 
patients, providers may perform compounding or repackaging themselves 
at the bedside and may also put patients at risk.
    2. Recent investments in public health infrastructure through 
cooperative agreements from the CDC have supported building public 
health capacity at the TDH. This capacity was invaluable in identifying 
and responding to the outbreak, determining the cause resulting in 
product recall only 8 days after initial notification saving lives and 
limiting the number of patients administered the contaminated 
injections. Specific examples are provided below:

        a.  Six members of the Healthcare Associated Infections (HAI) 
        team are funded through the Prevention and Public Health Fund 
        Epidemiology and Laboratory Capacity Cooperative agreement and 
        the Emerging Infections Program. In addition, the team has a 
        CDC/Council of State and Territorial Epidemiologists (CSTE) 
        fellow. The only person not funded by CDC is the director of 
        the HAI program, Dr. Kainer.
                  i.  The team had the expertise to ask the right 
                questions, conduct on-site visits, create relevant 
                standardized investigation forms, create a database, 
                enter and analyze the data swiftly to determine the 
                cause of the outbreak and those at highest risk of 
                getting sick.
                 ii.  In Tennessee, if the recall had been delayed by 9 
                days, we estimate that at this time we would have seen 
                an additional 59 cases and at least 5 additional 
                deaths. If treatment guidance from CDC had been 
                delayed, the number of deaths would be even higher.
                 iii.  To prevent healthcare associated infections, the 
                team has built very close relationships with infection 
                preventionists at hospitals, the Tennessee Hospital 
                Association and is building relationships with the 
                ambulatory surgery center community. These 
                relationships are built on mutual trust and have been 
                invaluable in promoting open communication.
        b.  Surge capacity was provided by staff funded under the 
        Epidemiology and Laboratory Capacity (ELC) grant and the Public 
        Health Emergency Preparedness (PHEP) cooperative agreements as 
        well as an additional CDC/CSTE fellow and an Epidemic 
        Intelligence Service (EIS) officer assigned to Tennessee.
                  i.  These staff-funded provided assistance in 
                reviewing clinical information on suspect and confirmed 
                cases, and in tracking down 1,009 exposed patients. 
                Contact by phone or in person was made by local public 
                health department staff, funded by the State of 
                Tennessee, sometimes with assistance from law 
                enforcement. Outreach included frequent telephone calls 
                and door to door tracking, including home visits 
                whenever necessary. Some exposed patients were living 
                in or traveling in other States or were overseas when 
                they developed symptoms.
                 ii.  The State Health Operations Center provided the 
                necessary infrastructure to coordinate activities among 
                the 170 public health staff in Tennessee.
                 iii.  The alert network (THAN) connecting TDH with 
                clinicians and staff at hospitals was invaluable in 
                rapidly getting information out.
                 iv.  We were able to use a database designed for 
                tracking persons in shelters to track patients who were 
                exposed.

    3. Relationships with Federal partners were critical in the 
response to this outbreak.

        a.  CDC provided invaluable assistance throughout the outbreak 
        including weeknights and weekends. Some examples include:

                  i.  Laboratory support: CDC developed a diagnostic 
                test to assist in the outbreak investigation and 
                provided laboratory support for confirming the 
                identities of fungal isolates. The infectious diseases 
                pathology branch has been providing valuable insights 
                on how this fungus behaves and the type of damage it 
                does to tissues. This has greatly assisted the 
                clinicians on the fungal expert working group.
                 ii.  Clinical support: TDH was fortunate to have CDC 
                Epidemic Intelligence Service Officers on-site to 
                assist in clinical data abstraction. CDC regularly 
                convenes the expert fungal panel to develop diagnostic 
                and management guidance that has been constantly 
                updated with the latest clinical information. This has 
                been very helpful to clinicians, many of whom have 
                never treated fungal meningitis before, and this 
                guidance without a doubt saved a lot of lives. Of the 
                33 Tennessee patients who sought medical care before 
                October 3, 9 (27.3 percent) died. Of the 48 patients 
                who sought medical care on, or after October 3, when 
                the first CDC treatment guidance was issued, four (8.3 
                percent) died.
                 iii.  Communications: CDC has provided relevant, up-
                to-date information on case counts, diagnostic and 
                treatment guidance, case definitions, etc, . . . on 
                their Web site, through EPI-X alerts and the Health 
                Alert Network. They have hosted regular conference 
                calls with State partners and other Federal partners to 
                ensure accurate dissemination of information.
                 iv.  Epidemiologic support: CDC has provided technical 
                support (e.g., reviewing logistic regression models, 
                running survival analyses) as well as coordinated the 
                aggregation of data across multiple States to provide a 
                complete national picture. Examples of critical 
                information include distribution of incubation periods. 
                CDC provided expertise in mathematical modeling to 
                review whether guidance needed to be changed for 
                asymptomatic patients at high risk of infection in 
                order to prevent strokes or death.
                  v.  Coordination: CDC has coordinated the national 
                response with other States and the FDA.
                 vi.  Funding through cooperative agreements--please 
                see above note #2 on how these funds were used to build 
                capacity at the TDH.

        b.  FDA provided valuable information on local inspection 
        findings, as well as laboratory testing of products
                  i.  The information provided by FDA was extremely 
                helpful. It also would have been helpful if FDA had 
                shared interim findings with TDH and other State health 
                departments to allow them a better understanding of the 
                extent of the problem at the compounding pharmacy. This 
                type of information is very helpful as State health 
                departments attempt to gauge the level of risk and 
                consider surveillance strategies.

    4. Relationships and Infrastructure

        a.  By focusing on emergency preparedness and on reducing 
        healthcare associated infections, we have made much progress in 
        enabling rapid communication between public health and 
        hospitals; however challenges remain, especially with providers 
        who do not work in hospitals (e.g., ambulatory surgery centers) 
        and with medical specialists who are not traditional emergency 
        response partners.
        b.  Use of electronic health records allowed tremendous savings 
        in time in allowing us to monitor the clinical progress of 
        patients and saved time and resources at the affected 
        hospitals.
        c.  This outbreak illustrated the tremendous importance of 
        inter-facility communication when patients may seek medical 
        services in multiple facilities for complications that arise 
        from treatment at another facility. Reporting to public health 
        is critical, as Dr. Pettit's email illustrated.
        d.  Communication with exposed patients during periods of great 
        uncertainty was very important. Public health played a vital 
        role in finding exposed patients that were difficult to reach 
        and when clinic staff were overwhelmed with the task at hand.
        e.  Communication with media: Frequent press-briefings allowed 
        TDH to effectively communicate important public health messages 
        in a dynamic and rapidly evolving outbreak while allowing staff 
        to continue to do critical work.
                               conclusion
    This has been a devastating outbreak for patients, their families 
and friends, healthcare providers and clinics. In Tennessee we still 
have many patients hospitalized and suffering from complications and 
others who are exposed and frightened that they may become infected. 
Sustained commitment to funding for emergency preparedness and 
reduction of healthcare associated infections through cooperative 
agreements from the CDC has supported our productive relationships with 
our partners and healthcare providers across the State. These pre-
existing relationships allowed us to respond quickly because we trusted 
each other. We all need to work together to do our best to prevent such 
a tragedy from occurring again and to ensure that we have the public 
health capacity to detect and rapidly respond to any future outbreaks.
    Thank you for your time and attention.

    The Chairman. Thank you, Dr. Kainer.
    Now we'll turn to you, Mr. Miller, for your statement.

 STATEMENT OF DAVID G. MILLER, R.Ph., EXECUTIVE VICE PRESIDENT 
             AND CEO, INTERNATIONAL ACADEMY OF COM-
            POUNDING PHARMACISTS, MISSOURI CITY, TX

    Mr. Miller. Thank you, Chairman Harkin. I also thank the 
members of the committee. My name is David Miller. I am the 
executive vice president and I am proud to serve also as the 
CEO of the International Academy of Compounding Pharmacists.
    We are a professional association that represents 
pharmacists in a wide variety of practices, local community 
pharmacies, hospitals, nursing homes, hospice centers. Each one 
of those pharmacists and the pharmacy technicians and the 
student pharmacists that belong to our organization actually 
specialize in the development of customized medication 
solutions that patients need in order to meet their particular 
health needs.
    The tragedy of New England Compounding Center, NECC, is 
quite simple to us as an organization. They were a pharmacy 
that was essentially hiding behind that license and, in 
reality, acting as an illegal drug manufacturer. Plain and 
simple, what NECC did was to violate the trust that every 
member of the public has, specifically, in their local 
pharmacist, but even more so tainted the reputation of 
pharmacists in every practice setting throughout the country 
and placed their trust in jeopardy.
    We know that NECC now acted with impunity. They failed to 
adhere to the quality standards that our organization, our 
profession, and our government require of us at both the State 
and Federal level. We know also that NECC ignored State laws 
and Federal laws as they manufactured illegally and distributed 
bulk quantities of prescription drugs throughout the country.
    We know what NECC did. We do not yet know fully the extent 
of what allowed them to do that. It is clear that the State 
Board of Pharmacy of Massachusetts failed to do their job. They 
failed to protect the citizens of Massachusetts and, most 
importantly, because other States relied upon their action, 
their inspections, and their follow-through, permitted NECC to 
continue its illegal activities and distribute tainted 
medications into States throughout the United States.
    More importantly, we also know that the FDA knew, as we 
heard on the previous panel, of the problems with NECC. One of 
the things that we find particularly appalling, not only as a 
profession but, specifically, a professional association, is 
that there is no question whether or not the Food and Drug 
Administration had regulatory authority over this particular 
business. They were engaged in illegal manufacturing of drugs. 
The FDA is empowered through the FDCA and this Congress to stop 
illegal manufacturing.
    I have heard for 2 days and have seen a map that actually 
was created by IACP being referred to by the agency as a crazy 
quilt. There are questionable overlaps in the regulation of 
compounding pharmacy. Let me reiterate that there is no 
question who has the authority to immediately shut down an 
illegal prescription drug manufacturer. That rests with the 
FDA.
    That is something that we find particularly disturbing, 
that the agency, who knew that NECC was distributing drugs 
without patient-specific prescriptions throughout the United 
States, did nothing to stop them.
    Last, one of the things that we have to ask ourselves as a 
healthcare system is what prompted clinicians, hospitals, 
facilities throughout the United States to obtain medications 
from a pharmacy. We know in this particular case of 
methylprednisolone acetate, the medication at issue, and others 
that NECC produced was a product that was manufactured and 
available in the marketplace.
    What prompted, what allowed, and what permitted physicians, 
hospitals, et cetera, to purchase from an illegal manufacturer? 
As one of the members from the State of Tennessee asked me when 
this first issue came to light, why did a hospital in Tennessee 
buy medicine from a pharmacy outside of Boston? Why did they 
not turn to a local accredited sterile compounding pharmacy? 
Why did they do that?
    That's a question, Mr. Chairman and members of the 
committee, we don't yet know. There's much we don't know. What 
I can tell you is this, as an organization representing and 
comprised of pharmacists and pharmacy technicians, we are 
absolutely committed to making sure this never happens again. 
No compounding pharmacist should be able to hide behind their 
license as a pharmacy or a pharmacist when, in reality, their 
actions are illegal drug manufacturing. We have to stop that.
    I thank the committee, and I look forward to working with 
you as we attempt to solve this problem as expeditiously as 
possible.
    Thank you, sir.
    [The prepared statement of Mr. Miller follows:]
              Prepared Statement of David G. Miller, R.Ph.
                                summary*
    IACP Vice President of Government Affairs Sarah Dodge said,

          ``IACP appreciates the opportunity to provide input as the 
        U.S. Senate HELP Committee seeks to better understand current 
        Federal and State oversight of pharmacy compounding and explore 
        the possibilities for a legislative solution to the tragedy 
        surrounding New England Compounding Center (NECC) business 
        practices.''
---------------------------------------------------------------------------
    * The Summary was provided by the International Academy of 
Compounding Pharmacists, of which, David G. Miller, R.Ph., is Executive 
Vice President and CEO.
---------------------------------------------------------------------------
          ``We believe we share similar goals: an understanding of how 
        this tragedy happened, what can be done to prevent it from ever 
        happening again, and ultimately how do we assure that 
        compounding pharmacists are able to practice their professional 
        expertise without overly burdensome regulations which inhibit 
        quality patient care.''

    The State and Federal regulatory scheme for pharmacy compounding is 
complex--IACP members have valuable experience and technical 
understanding of the laws that govern our industry. IACP stands ready 
to help legislators and regulators to assist in conducting a thorough 
and complete assessment of State and Federal laws governing the 
practice of pharmacy. We believe this assessment must also examine how 
regulators exercise their jurisdiction and discretion in enforcement. 
IACP strongly believes that, in Massachusetts as well as other States, 
many laws and regulations exist that--if they had been followed and 
compliance had been enforced--would have severely mitigated the 
potential for the tragic meningitis infections and the needless deaths 
that have occurred.
    The apparent and tragic results of NECC's alleged behavior 
undermine the fundamental principal of pharmacists' practice--preserve 
patient health by doing no harm. We are determined to help find the 
gaps in the practice, regulatory, and enforcement system which 
permitted this problem to happen and produce real solutions to prevent 
it from occurring in the future. Our profession stands ready to work 
with leaders from across the Federal and State governments to make sure 
that what happened at NECC never happens again.
    Not only does Massachusetts have State sterility requirements and 
United States Pharmacopeia (USP) Standard compliance requirements, but 
it retains the right to pull a pharmacy's license, if that pharmacy is 
practicing outside the scope of its licensing requirements.
    By all current indications, the operations of NECC were clearly 
outside of the scope of their own and other States' licensure 
requirements and their license should have been pulled long ago. The 
Massachusetts Board of Pharmacy had the authority to do so. The FDA 
also had the authority to do so once they identified NECC as engaging 
in the illegal manufacturing and distribution of a prescription drug.
    At a minimum, knowing what they did, both the State and the FDA 
should have worked together to force the pharmacy to register as a 
manufacturer and to comply with Current Good Manufacturing Practice 
Guidelines (cGMP). Unfortunately, NECC showed a blatant disregard for 
existing rules and regulations (no matter what the law was or might 
have been, their behavior suggests that they would not have followed 
it).
    Additionally, and still to be answered by both regulatory agencies, 
is this fundamental question: If both the State and the FDA knew of 
problems at NECC--and we know that they did, based on publicly 
disclosed documents--why did they fail to followup or take action? New 
regulations or new laws are meaningless if the regulatory agencies 
charged with upholding them simply turn a blind eye to problems and 
fail to do their job.
    IACP supports the following State actions, at a minimum, to help 
mitigate further problems with sterility and other potential patient 
hazards:

     All Boards of Pharmacy must be adequately funded by State 
legislatures in a manner sufficient to hire trained/educated 
pharmacists to conduct regular inspections of all pharmacies. Too many 
Boards have been ``de-funded'' by legislatures that have funneled 
revenue from the Boards into the States' general funds leaving 
administrative gaps;
     Board inspectors conducting compounding pharmacy 
inspections in both community and institution settings must receive 
training in both the State regulations pertaining to compounding as 
well as the practice itself;
     All States must adopt mandatory compliance with USP <795> 
and <797> standards. Only 17 currently mandate that in their laws. All 
pharmacies providing compounding services--regardless of practice 
setting--must be held accountable to those standards;
     State Boards must ``police'' themselves and provide the 
necessary assurances to other State Boards which depend upon them for 
conducting inspections for non-resident pharmacies in a regular and 
consistent manner. Massachusetts's Board obviously failed to execute 
its responsibilities both to its citizens as well as patients in other 
States in which NECC was licensed by not conducting regular 
inspections.

    IACP looks forward to the opportunity to testify before the Senate 
HELP Committee on November 15, 2012 to further address these critical 
issues.
                                 ______
                                 
    The International Academy of Compounding Pharmacists (IACP) 
appreciates the opportunity to provide input to the Senate HELP 
Committee as the committee and legislators seek to better understand 
current Federal and State oversight of pharmacy compounding and explore 
the possibilities for a legislative solution to the tragedy surrounding 
New England Compounding Center (NECC) business practices.
    IACP is an international, professional association established in 
1991 to protect, promote and advance the art and science of pharmacy 
compounding. IACP provides support to more than 2,700 members through 
programs and services including reimbursement/third-party advocacy, 
government representation, regulatory analysis, public relations 
support, referral services and a fellowship program. IACP also 
represents more than 164,000 patient and practitioner advocates as part 
of our P2C2 grassroots network.
    IACP members are individuals; IACP does not represent or advocate 
on behalf of specific pharmacies, businesses or companies. Compounding 
pharmacists work directly with prescribers including physicians, nurse 
practitioners and veterinarians to create customized medication 
solutions for patients and animals whose health care needs cannot be 
met by standardized medications manufactured by the pharmaceutical 
industry.
    IACP believes we share similar goals: an understanding of how this 
tragedy could happen, and how to ensure the safest possible practice of 
compounding in the future.
    The State and Federal regulatory scheme for pharmacy compounding is 
complex--IACP members have valuable experience and technical 
understanding of the laws that govern our industry. IACP stands ready 
to help legislators and regulators to assist you in conducting a 
thorough and complete assessment of State and Federal laws governing 
the practice of pharmacy. We believe this assessment should also 
examine how regulators exercise their jurisdiction and discretion in 
enforcement.
    The apparent and tragic results of NECC's alleged behavior 
undermine the fundamentals of pharmacy, which include doing no harm. We 
are determined to help find the problem and solve it. Our profession 
stands ready to work with you and leaders from across the Federal and 
State governments to make sure that what happened at NECC never happens 
again.
    IACP strongly believes that, in Massachusetts and other States, 
laws and regulations currently exist that--if they had been followed 
and compliance had been enforced--would have severely mitigated the 
potential for the tragic meningitis infections that have occurred. Not 
only does Massachusetts have State sterility requirements and United 
States Pharmacopeia (USP) Standard compliance requirements, but it 
retains the right to pull a pharmacy's license, if that pharmacy is 
practicing outside the scope of its licensing requirements.
    By all current indications, the operations of NECC were clearly 
outside of the scope of the State's licensure requirements and their 
license should have been pulled long ago. The State and the FDA should 
have worked together to force the pharmacy to register as a 
manufacturer, but also to comply with Current Good Manufacturing 
Practice Guidelines (CGMP). Unfortunately, NECC showed a blatant 
disregard for existing rules and regulations (no matter what the law 
was, their behavior indicates that they would not have followed it).
    Millions of Americans have unique health needs that off-the-shelf 
prescription medicines cannot meet. For them, customized medicines--
prescribed or ordered by licensed prescribers and mixed safely by 
trained, licensed compounding pharmacists--are the only way to better 
health.
    By definition, compounded medicines are different than commercial 
pharmaceuticals; they are prepared at the direction of licensed 
prescribers to meet patients' individual needs that are not met by 
manufactured pharmaceuticals. As a result, Federal requirements 
designed for large-scale manufacture of uniformly dosed drugs do not 
apply to compounding pharmacies.
    Many patients depend on compounded medicines, including children, 
those with allergies, cancer patients, children with autism, senior 
citizens, menopausal women, hospice patients and those who rely upon 
discontinued drugs. For patients who are unable to take medications 
orally or as injections--the traditional dosage forms for manufactured 
drugs--compounding pharmacists can create alternate methods of 
delivery, like ointments, solutions or suppositories, to fit their 
unique health needs.
    Many, if not most, of the lifesaving intravenous drugs given in 
hospitals and clinics are compounded. Because hospital patients are 
often on multiple medications, compounding them into one treatment 
saves the hospital personnel time and the patient multiple injections 
or administrations.
    Additionally, compounded medications are often used by 
veterinarians and pet owners for the care of their pets. Animals come 
in all shapes and sizes, so one-size-fits-all pharmaceuticals do not 
always meet their needs. In many cases, a compounded medication may be 
necessary for a non-food animal to be satisfactorily treated.
    In 2003, IACP established a 501(c)(3) foundation to further 
research and educational initiatives for the advancement of pharmacy 
compounding. Its mission is to conduct and publish research studies, 
establish academic alliances, and institute educational programs and 
issue forums.
    In 2004, IACP joined a coalition of eight leading pharmacy 
professional and regulatory organizations in the creation of a 
voluntary accreditation program for pharmacy compounding. The Pharmacy 
Compounding Accreditation Board (PCAB) helps to assure quality and 
raise awareness of the profession.
    To begin with, IACP would support the following State actions to 
help mitigate further problems with sterility and other potential 
patient hazards:

     All Boards of Pharmacy must be adequately funded by State 
legislatures in a manner sufficient to hire trained/educated 
pharmacists to conduct regular inspections of all pharmacies. Too many 
Boards have been ``de-funded'' by legislatures that have funneled 
revenue from the Boards into the States' general funds leaving 
administrative gaps;
     Board inspectors conducting compounding pharmacy 
inspections in both community and institutional settings must receive 
training in both the State regulations pertaining to compounding as 
well as the practice itself;
     All States must adopt mandatory compliance with USP <795> 
AND <797> standards. Only 17 currently have that on their books; and 
State Boards must ``police'' themselves and provide the necessary 
assurances to other State Boards which depend upon them for conducting 
inspections for non-resident pharmacies in a regular and consistent 
manner.

    Massachusetts's Board obviously failed to execute its 
responsibilities both to its citizens as well as patients in other 
States in which NECC was licensed by not conducting regular 
inspections.
    Many States address specific compounding standards either through 
existing State laws and regulations and/or through the State's adoption 
of USP standards for compounding pharmacy practices. IACP has submitted 
this information to the committee as part of its responses to committee 
questions issued to stakeholders prior to this hearing.
    Uncertainty about the application of section 503A does not affect 
oversight of pharmacy compounding. As mentioned, the States do address 
compounding, specifically, and provide appropriate governing 
compounding standards. Moreover, some States already (and all should) 
require mandatory compliance with USP <795> AND <797> standards. To 
reiterate, IACP supports adoption of mandatory compliance with USP 795/
595 by all States.
    From the Federal standpoint, the FDCA's existing inspection 
provision, section 704, allows FDA oversight when a pharmacy is not 
operating in conformity with governing State laws, or akin to a drug 
manufacturer. FDCA section 704 contains two very important components:

    1. Pursuant to the first sentence of section 704(a), FDA is 
permitted to inspect ``all pertinent equipment, finished and unfinished 
materials, containers, and labeling therein'' of any pharmacy. FDA can 
glean the information it needs to determine whether a pharmacy is 
engaged in manufacturing through its inspection of these items.
    2. FDA gains enhanced inspection authority to inspect a pharmacy 
that is operating as if it were a manufacturer. This authority exists 
whenever a pharmacy:

    (a) is not operating in conformity with State laws regulating the 
practice of pharmacy;
    (b) is not regularly engaged in dispensing prescription drugs upon 
the prescriptions of licensed practitioners; and
    (c) is compounding drugs for sale other than in the regular course 
of its business at retail. See section 704(a)(2)(A).

    Notably, the enhanced authority granted to FDA under these 
circumstances is the same inspection authority FDA possesses with 
regard to drug manufacturers. Thus, existing FDCA section 704 allows 
FDA to inspect a noncompliant pharmacy such as NECC as a manufacturer, 
subjecting it to inspection for ``all things therein (including 
records, files, papers, processes, controls, and facilities) bearing on 
whether prescription drugs . . . which are adulterated or misbranded 
within the meaning of [the FDCA] . . . have been or are being 
manufactured, processed, packed, transported, or held in any such 
place, or otherwise bearing on violation of [the FDCA]. (Section 704(a) 
(sentence three).
    IACP strongly believes that the States have laws and regulations in 
place that regulate the professional practice of pharmacy, and they 
have for hundreds of years. State laws, for example, govern 
anticipatory compounding (appropriately based on a history between the 
pharmacy and the physician or patient to ensure adequate supply) and 
beyond-use dates for drugs, both of which necessarily limit how much of 
a drug may be compounded in advance.
    Anticipatory compounding is also a required component of most 
States' laws to ensure timely patient access to drugs and thereby 
prevent wait-time and/or unavailability that may be harmful to the 
patient's health. States similarly regulate such things as standards 
for active pharmaceutical ingredients (APIs) used in compounding; 
ability to compound commercial copies; and percentage of compounded 
preparations that may be shipped out of State, i.e., many of the things 
existing section 503A simply attempts to reiterate.
    Notably, when a pharmacy operates outside the scope of its State 
laws and regulations governing the professional practice of pharmacy, 
that pharmacy subjects itself to FDA inspection and oversight, and full 
FDCA application to the same extent as a drug manufacturer. NECC serves 
as a prime example of a pharmacy that both breached State pharmacy 
regulatory laws and that should have been held accountable as a 
manufacturer by FDA. Such a non-State law compliant pharmacy no longer 
operates within the professional practice of pharmacy, which has always 
been effectively and traditionally regulated by the States through 
statutes and regulations developed over the course of more than a 
century.
    IACP believes that, since the practice of pharmacy (much like the 
practice of medicine, veterinary medicine, nursing, etc.) is already 
regulated at the State level, the majority of policy and oversight is 
best if implemented/addressed/enforced at the licensure level. States 
have the ability to remove a pharmacy's license if that pharmacy is not 
operating within its licensure requirements.
    States also already have in place levels of licensure, depending on 
the function and scope of practice. The Federal Government has clear 
oversight and jurisdiction if that pharmacy is acting as a 
manufacturer. Should a pharmacy be acting in a manufacturing fashion, 
they should be licensed as a manufacturer and subject to CGMP, as are 
all other manufacturers.
    Again, IACP believes that all States must adopt mandatory 
compliance with USP <795> AND <797> standards. Only 17 States currently 
have adopted USP standards.
    With regard to ``manufacturing,'' IACP has long maintained and 
continues to maintain, that volume, percentage of sales, use of 
``commercial'' equipment, or interstate sales should not be the 
determining factor in what constitutes a manufacturing practice. A 
pharmacy that focuses much of its practice upon compounding gains even 
greater experience with the activity, and thus has heightened expertise 
and experience that benefit, rather than harm, recipient patients. By 
analogy, an experienced heart surgeon is far more preferable than a 
surgeon who performs heart surgery only sporadically. IACP thus 
believes that rather than indicators such as volume, percentage of 
sales, interstate shipment, etc., it is the activity of the pharmacy 
with regard to what they do with medicines they dispense that must be 
scrutinized to determine whether or not they are engaged in 
manufacturing.
    IACP strongly believes that the current statutory definition of 
manufacturing (as it reads in the Controlled Substances Act) (CSA) 
sufficiently defines, and distinguishes manufacturing from the practice 
of pharmacy compounding (see citation) Notably, the CSA definition 
dovetails nicely with existing FDCA section 704, as described above. 
Both hinge on the status of ``pharmacy'' or, conversely, 
``manufacturer,'' of whether the company preparing the drug operates in 
conformity with applicable State laws governing the practice of 
pharmacy and as an incident to dispensing such drug in the course of 
professional pharmacy practice.
    Should Congress believe it is appropriate, it may be helpful to 
reiterate (mirror) the CSA definition in the Federal Food, Drug and 
Cosmetic Act (FDCA) as an appropriate standard for distinguishing 
between drug manufacturing and the medical practice of pharmacy 
compounding. Such inclusion also promotes uniformity between the two 
Federal acts. The CSA, (21 U.S.C. Sec. 802 (112-90) TITLE 21--FOOD AND 
DRUGS, SUBCHAPTER I--CONTROL AND ENFORCEMENT Part A (15) states:

        ``(15) The term ``manufacture'' means the production, 
        preparation, propagation, compounding, or processing of a drug 
        or other substance, either directly or indirectly or by 
        extraction from substances of natural origin, or independently 
        by means of chemical synthesis or by a combination of 
        extraction and chemical synthesis, and includes any packaging 
        or repackaging of such substance or labeling or relabeling of 
        its container; except that such term does not include the 
        preparation, compounding, packaging, or labeling of a drug or 
        other substance in conformity with applicable State or local 
        law by a practitioner as an incident to his administration or 
        dispensing of such drug or substance in the course of his 
        professional practice. The term ``manufacturer'' means a person 
        who manufactures a drug or other substance.''

    Additionally, the CSA States the following in terms of 
differentiating between interstate and intrastate commerce (21 USC Sec. 
801 (112-90), TITLE 21--FOOD AND DRUGS. SUBCHAPTER I--CONTROL AND 
ENFORCEMENT Part A (5):

        ``(5) Controlled substances manufactured and distributed 
        intrastate cannot be differentiated from controlled substances 
        manufactured and distributed interstate. Thus, it is not 
        feasible to distinguish, in terms of controls, between 
        controlled substances manufactured and distributed interstate 
        and controlled substances manufactured and distributed 
        intrastate.''

    Any changes to the statutory definitions of ``manufacture'' in 
either the CSA or the FDCA, or any changes to related regulations and/
or agency policies, should be consistent as they apply to compounding 
pharmacies. For example, under either the FDCA or the CSA, a pharmacist 
should, with a prescription from a licensed physician, be able to 
compound patient-specific medications, controlled substance or not, 
sterile or unsterile, and deliver them directly to the prescribing 
physician for office administration when medically necessary as 
determined by the physician.
    This alone should not trigger a requirement that the pharmacist 
register with either the DEA or the FDA as a ``manufacturer.'' However, 
under current DEA policy, based on the agency's interpretation of the 
CSA, unless the drug (controlled substance) is delivered directly to 
the ``end user,'' (i.e. the patient), registration as a 
``manufacturer'' is required, even when the pharmacist is compounding 
the drug pursuant to a valid prescription and delivering the drug to 
the prescribing physician for medically necessary office 
administration.
    This is a particularly troubling policy by the DEA as it relates to 
sterile, injectable compounds, which often must be surgically implanted 
and delivered via intrathecal pain pump. As the recent tragedy 
involving the NECC has shown, maintaining sterility throughout the 
compounding process and the administration of injectable compounded 
drugs is critical to patient safety.
    DEA's current policy runs counter to both their stated goal of 
preventing diversion of controlled substances, and to standard medical 
practices intended to maintain sterility of the drugs. This has put 
compounding pharmacists in the untenable position of following 
universally accepted medical practice and risking enforcement action by 
the DEA; or, undergoing an expensive and burdensome manufacturer 
registration process that does not accurately reflect the status of 
their traditional pharmacy practice.
    Alternatively, they could refuse to fill prescriptions for 
controlled substances for office administration, which could jeopardize 
patient access to critical medications. Again, changes to the FDCA or 
CSA should be consistent in what actions trigger manufacturer licensing 
requirements and should not impede traditional pharmacists from 
compounding patient-specific medications for office administration when 
medically necessary.
    With regard to standards for sterile and non-sterile compounding, 
IACP feels that these issues are sufficiently addressed by State laws 
and regulations. Where it is not, IACP strongly urges that States adopt 
rules and regulations similar to those in Iowa (Iowa regulations are 
attached). IACP again encourages that the USP <795> and <797> standards 
and practices be adopted by every State, as further safeguard.
    State Boards must ``police'' themselves and provide the necessary 
assurances to other State Boards which depend upon them for conducting 
inspections for non-resident pharmacies in a regular and consistent 
manner. Massachusetts Board obviously failed to execute its 
responsibilities both to its citizens as well as patients in other 
States in which NECC was licensed by not conducting regular 
inspections.
    Additionally, virtually every State requires an out-of-state 
pharmacy to register as such with the recipient State (with one notable 
exception being Massachusetts). In this regard, the pharmacy dispensing 
compounds across State lines is subject to heightened (not diluted) 
oversight and regulation because it must abide by the laws of both its 
home State and the out-of-state recipient.
    With regard to the Active Pharmaceutical Ingredients (APIs) used in 
the profession of compounding, there already exists in Federal statute 
language that requires all drugs compounded in the United States to use 
only active pharmaceutical ingredients (APIs) from FDA registered 
facilities. (See section 510). IACP regularly reminds its members to 
require a bill of lading. This provision was included in the PDUFA 
reauthorization legislation signed into law this year. Please see below 
for statutory language:

           P.L. 112-144, Section 713, The ``Food and Drug 
        Administration Safety and Innovation Act''.

           SEC. 713. STANDARDS FOR ADMISSION OF IMPORTED DRUGS.

           Section 801 (21 U.S.C. 381) is amended--
          (1) in subsection (o), by striking ``drug or''; and
           (2) by adding at the end the following:

           (r)(1) The Secretary may require, pursuant to the 
        regulations promulgated under paragraph (4)(A), as a condition 
        of granting admission to a drug imported or offered for import 
        into the United States, that the importer electronically submit 
        information demonstrating that the drug complies with 
        applicable requirements of this Act.
           (2) The information described under paragraph (1) may 
        include--
                 (A) information demonstrating the regulatory status of 
                the drug, such as the new drug application, abbreviated 
                new drug application, or investigational new drug or 
                drug master file number;
                 (B) facility information, such as proof of 
                registration and the unique facility identifier;
                 (C) indication of compliance with current good 
                manufacturing practice, testing results, certifications 
                relating to satisfactory inspections, and compliance 
                with the country of export regulations; and
                 (D) any other information deemed necessary and 
                appropriate by the Secretary to assess compliance of 
                the article being offered for import.

          (B) PROCEDURE.--In promulgating a regulation under 
        subparagraph (A), the Secretary shall--
                 (i) issue a notice of proposed rulemaking that 
                includes the proposed regulation;
                 (ii) provide a period of not less than 60 days for 
                comments on the proposed regulation; and
                 (iii) publish the final regulation not less than 30 
                days before the regulation's effective date.

          (C) RESTRICTIONS.--Notwithstanding any other provision of 
        Federal law, in implementing this subsection, the Secretary 
        shall only promulgate regulations as described in subparagraph 
        (B).
    (3) DISCONTINUANCE OF REGISTRATION.--The Secretary shall 
discontinue the registration of any commercial importer of drugs that 
fails to comply with the regulations promulgated under this subsection.
    (4) UNIQUE FACILITY IDENTIFIER.--The Secretary shall specify the 
unique facility identifier system that shall be used by registrants 
under paragraph (1). The requirement to include a unique facility 
identifier in a registration under paragraph (1) shall not apply until 
the date that the identifier system is specified by the Secretary under 
the preceding sentence.
    (5) EXEMPTIONS.--The Secretary, by notice in the Federal Register, 
may establish exemptions from the requirements of this subsection.
    (c) MISBRANDING.--Section 502(o) (21 U.S.C. 352) is amended by 
inserting ``if it is a drug and was imported or offered for import by a 
commercial importer of drugs not duly registered under section 
801(s),'' after ``not duly registered under section 510.''
    (d) REGULATIONS.--
    (1) IN GENERAL.--Not later than 36 months after the date of the 
enactment of this Act, the Secretary of Health and Human Services, in 
consultation with the Secretary of Homeland Security acting through 
U.S. Customs and Border Protection, shall promulgate the regulations 
required to carry out section 801(s) of the Federal Food, Drug, and 
Cosmetic Act, as added by subsection (b).
    (2) PROCEDURES FOR PROMULGATING REGULATIONS.--
    (A) IN GENERAL.--In promulgating a regulation under paragraph (1), 
the Secretary shall--
    (i) issue a notice of proposed rulemaking that includes the 
proposed regulation;
    (ii) provide a period of not less than 60 days for comments on the 
proposed regulation; and
    (iii) publish the final regulation not less than 30 days before the 
regulation's effective date.
    (B) RESTRICTIONS.--Notwithstanding any other provision of Federal 
law, in implementing section 801(s) of the Federal Food, Drug, and 
Cosmetic Act, as added by subsection (b), the Secretary shall 
promulgate regulations only as described in subparagraph (A).

    On the issue of where and with whom a pharmacy should be 
registered, pharmacies are already required to register with their 
State Board of Pharmacy and the Drug Enforcement Administration (DEA). 
Adding an additional registration requirement for pharmacies would do 
nothing to further the goal of keeping patients safe--it would amount 
to a paperwork requirement/administrative step that would produce no 
particular positive outcome due to an already overstrained FDA budget 
and the existing broad categories of oversight the agency has to 
prioritize.
    The FDA may inspect an establishment--including pharmacies--to 
ensure that drugs are appropriately handled and stored. In other words 
. . . they can look at what's on the shelf, in the refrigerator, in the 
inventory, etc.
    The FDA may not inspect records and files (e.g., prescriptions, 
compounding formulas, etc.) unless either (a) the pharmacy in 
noncompliant with its State laws, see supra section 704 discussion, or 
(b) FDA has an administrative warrant that demonstrates a sufficient 
cause to do so. A pharmacy may decline such an inspection if it 
believes it is operating in full compliance with the State law unless 
there is some sort of court document authorizing the FDA to do so.
    However, if the pharmacy is registered as a manufacturer, the FDA 
has much broader authority to inspect and cite such a manufacturing 
entity. As a manufacturer, they would also have to comply with CGMP and 
the FDA has clear injunctive authority over them, should they not 
remedy violations. In short, a pharmacy engaged in manufacturing is 
subject to the same laws, inspections, restrictions, and penalties as a 
commercial drug manufacturer.
    There are many patients (both human and animal) needing products in 
various medical scenarios requiring physician input and judgment based 
upon the needs of their patient. States already have limitations to 
this in their regulations and laws as necessary for their particular 
State for citizens/citizens' pets. Pharmacists are required, by State 
law, to have sufficient drugs and preparations on their shelves to 
enable them to service their clients in a timely manner. Any 
requirement that a pharmacist must wait on each and every prescription 
thus works counter to public interest and patient health and safety.
    Regarding the prescription, moreover, there is no need for a 
physician to explicitly order a compounded drug. If a physician orders 
a name brand commercial product, the pharmacy will fill the 
prescription with it. If, however, the physician's prescription is 
specific as to active ingredient, dosage, and/or delivery format, it 
enables the pharmacy to create the medication as needed for the 
particular patient, and as a prescribed physician, without need of 
express direction to compound by the physician.
    IACP acknowledges that many States have already addressed this 
issue through ``office use'' specifications in their laws and 
regulations (IACP has supplied the committee with a state-by-state 
office use regulation guide). Should a State NOT have such standards in 
place, IACP would urge the State to adopt clear and concise guidance 
for the compounding of medications for ``office use.'' IACP adds that 
compounds prepared for office stock are no different than a singular 
compounded drug prescription in terms of pharmacy preparation. The same 
State law remains applicable to each and every one of these compounds. 
Finally, regarding labeling, please see the enclosed IACP statement 
regarding suggested labeling for office use.
    Ultimately, the decisionmaking with regard to what a script 
requires is left to the medical practitioner who writes the scripts in 
the first place. The doctor or veterinarian is best educated and best 
suited to make these determinations on medicines to be used and in what 
dose and dosage form. IACP does not believe the volume of prescriptions 
involved necessarily is the issue. Instead, the issue is one of (a) 
drug preparation--which is the same regardless of number, and (b) 
fulfilling the medical judgments of the practitioner by following the 
practitioner's directions, as determined for the practitioner's 
patient.
    IACP believes that the FDCA's existing inspection provision, 
section 704, which was outlined supra, allows FDA the necessary 
authority and oversight it needs to determine whether a pharmacy is 
operating as a pharmacy or, instead, akin to a drug manufacturer, thus 
subjecting it to full inspection and FDCA application.
    By way of further example, FDA may inspect the equipment, drug 
materials, containers and labeling of any pharmacy. See section 704(a) 
(sentence one). State law requires pharmacy labeling to include, inter 
alia, the name and strength of the active ingredient, the lot number, 
the beyond-use date, the quantity or amount in the container, the 
pharmacy's name, and the physician's name.
    Through this information, FDA can assess the professionals' 
licensure, the exact prescription for the patient, and exactly what the 
patient will receive. Moreover, all this information must be included 
on the label or the pharmacy violates its State's law, thus triggering 
the FDCA section 704 enhanced inspection (sentence three) that applies 
to drug manufacturers. (See section 704(a)(2)(A)).
    It has not been IACP's experience that the FDA has had difficulty 
collaborating with the States. The opposite appears to be true. FDA 
often collaborates with both the State boards of pharmacy and the DEA, 
both of which have full inspection authority over pharmacies. See e.g., 
Wedgewood Village Pharmacy, Inc. v. U.S., 421 F.3d 263, 271 (2005) 
(noting FDA collected all the evidence it needed regarding whether a 
pharmacy was operating as a pharmacy or more akin to a manufacturer 
through collaboration with the State board and DEA); and Medical Center 
Pharmacy v. Mukasey, 451 F.Supp.2d 854 (W.D.Tex. 2006) (noting same).
    IACP stresses the importance of communicating important health 
information to patients whenever any medication is dispensed through 
labeling on the medication. IACP supports State regulations that 
require information on labeling that informs the patient that the 
medication has been compounded.
    With regard to adverse event reporting, IACP argues that MedWatch 
is the Food and Drug Administration's reporting system for an adverse 
event or sentinel event, founded in 1993. This system should also be 
used for compounded medication.
    An adverse event is any undesirable experience associated with the 
use of a medical product. The MedWatch system collects reports of 
adverse reactions and quality problems, primarily with drugs and 
medical devices, but also for other FDA-regulated products (e.g., 
dietary supplements, cosmetics, medical foods, and infant formulas).
    Voluntary reporting by healthcare professionals, consumers, and 
patients is conducted on a single, one-page reporting form (Form FDA 
3500). Reporting can be conducted online, by phone 1-800-FDA-1088, or 
by submitting the MedWatch 3500 form by mail or fax 1-800-FDA-0178.
    Rather than replicating The MedWatch system, IACP contends that 
there already exists a reporting system for all in the Triad of care. 
MedWatch is intended to detect safety hazard signals for medical 
products. If a signal is detected, the FDA can issue medical product 
safety alerts or order product recalls, withdrawals, or labeling 
changes to protect the public health. Important safety information is 
disseminated to the medical community and the general public via the 
MedWatch Web site and the MedWatch E-list.
    On the issue of communication between agencies, IACP would support 
a notification system that requires States to notify the FDA (within 14 
days of such action) when a pharmacy's license has been revoked. 
Additionally, the FDA should notify States when they believe a pharmacy 
is acting as a manufacturer and may be operating outside of its 
registration status allowances.
    Additionally, Congress might want to consider assessing civil 
penalties when a pharmacy owner/operator has willfully misled 
authorities as to the nature of their business.
    IACP appreciates this opportunity to provide input on this critical 
outbreak to the committee and looks forward to further discussing this 
issue. IACP will be happy to respond to any additional questions the 
committee may have.

    The Chairman. Thank you, Mr. Miller.
    Now we'll turn to Dr. Thompson.
    Dr. Thompson, please proceed.

  STATEMENT OF KASEY K. THOMPSON, PHARM.D., M.S., B.S., VICE 
   PRESIDENT, OFFICE OF POLICY, PLANNING AND COMMUNICATIONS, 
  AMERICAN SOCIETY OF HEALTH-SYSTEM PHARMACISTS, BETHESDA, MD

    Mr. Thompson. Thank you, Chairman Harkin and distinguished 
members of the committee, for holding this hearing. My name is 
Kasey Thompson. I am vice president for Policy, Planning, and 
Communications with the American Society of Health-System 
Pharmacists. I am here today to provide ASHP's perspective on 
the recent meningitis outbreak and to explore potential policy 
options to help prevent similar events from occurring ever 
again in the future.
    First and foremost, on behalf of ASHP and our more than 
40,000 members practicing in hospitals, health systems, and 
ambulatory clinics, I want to express our sympathy for the 
victims and their families who were harmed by this terrible 
tragedy. The patients who relied on these medications deserved 
much better.
    Unfortunately, the New England Compounding Center appeared 
to have been operating in a manner that falls far short of 
standards for compounding sterile preparations. Further, the 
scale and scope of NECC's operations more nearly resembles 
pharmaceutical manufacturing than traditional pharmacy 
compounding.
    U.S. hospitals prepare a vast array of compounded sterile 
preparations every day in order to meet the needs of patients. 
In fact, the majority of compounded medications hospitals 
utilize are prepared in-house by pharmacy departments. The 
compounded medications that hospitalized patients need include 
simple intravenous admixtures to complex customized medications 
that are not available off the shelf, such as multi-ingredient 
solutions for heart surgery, epidural pain medication, and 
adult medications prepared with concentrations that can be 
safely administered to babies and children.
    However, hospitals also enlist the help of qualified 
compounding pharmacies for some compounded preparations for 
several reasons. For example, they may not have the necessary 
equipment or facilities to prepare some high-risk preparations, 
or they may face medication shortages from commercial products.
    Hospitals prepare or purchase compounded medications based 
on specific patient needs and individual medication orders or 
in anticipation of needs for patients under their care. 
Importantly, medications that are purchased from outside 
compounding pharmacies are not commercially available from 
brand or generic manufacturers in the individualized form 
needed for specific patients.
    ASHP has dedicated itself to developing the highest 
standards for compounding sterile products in hospitals. We 
began publishing guidelines on sterile and non-sterile 
compounding in the early 1990s. In 2010, ASHP published the 
ASHP Guidelines on Out-
sourcing Sterile Compounding Services to advise pharmacy 
departments on how to conduct due diligence when selecting 
outsourcing vendors. All of our guidelines have always been 
available as a free public service to the healthcare community 
and to others.
    However, even with the availability of these useful 
resources, we cannot rely solely on the diligence of purchasers 
to take the place of proper licensing, inspection, and 
oversight of entities producing compounded medications, 
especially those entities that are manufacturing in large 
quantities and shipping across the country. Pharmacists and 
other healthcare providers should not be expected to perform 
the jobs of regulators by visiting and inspecting pharmacies 
and manufacturers that they do business with.
    The distinction between traditional pharmacy compounding 
and manufacturing appears to be a regulatory gray area between 
State boards of pharmacy and the FDA. As we have seen, however, 
the implications of this gray area are serious.
    We recognize the regulatory challenges of defining the 
activities in this gray area. We firmly believe that specific 
definitions are essential so that mass production of the scope 
and scale done by NECC falls clearly within the regulatory 
jurisdiction of FDA rather than State boards of pharmacy. To 
this end, we have developed policy recommendations for the 
committee, FDA, and other stakeholders to consider as we 
explore ways to address this gap in oversight.
    A number of variables make distinguishing between compound-
ing and manufacturing difficult. Therefore, both functions 
might be better viewed as a continuum of activities stratified 
by the potential risk for patient harm, each requiring defined 
procedures, equipment, training, and quality controls. At one 
end of the continuum, oversight of traditional compounding is 
clearly within the purview of States and the oversight of 
pharmaceutical manufacturing within the purview of the FDA.
    Once compounding activities advance along the continuum to 
manufacturing, the risk to patient safety and public health 
increases. There may be a need for a special category of FDA 
oversight that falls between compounding and manufacturing but 
does not require a drug approval.
    For example, if a compounding pharmacy sells to other 
organizations and not directly to patients, there may be a need 
to be regulated by the FDA. Doing so would allow hospitals, 
clinics, and physician offices to purchase sufficient 
quantities of compounded product as is necessary to meet 
patient needs, while doing so under the assurance that they are 
making those purchases from appropriately regulated entities.
    ASHP recommends stronger communication and collaboration 
between State boards of pharmacy and the FDA to accomplish this 
goal. We also believe that State boards of pharmacy should be 
able to work with FDA to inspect an entity suspected of 
engaging in large-scale drug production beyond the scope of 
traditional pharmacy compounding.
    Finally, we strongly believe the FDA must be provided with 
the resources it needs to perform oversight of compounding 
entities that are potentially engaged in manufacturing.
    Thank you for the opportunity to provide the perspectives 
of the pharmacists who practice in hospitals and health 
systems. ASHP remains committed to working with Congress, the 
FDA, and other stakeholders to ensure that an event like this 
never occurs again.
    [The prepared statement of Mr. Thompson follows:]
     Prepared Statement of Kasey K. Thompson, Pharm.D., M.S., B.S.
                                summary
    U.S. hospitals prepare a vast array of compounded sterile 
preparations every day in order to meet the needs of patients. However, 
hospitals also enlist the help of qualified compounding pharmacies for 
some compounded preparations for several reasons.
    ASHP has dedicated itself to being a leader in developing the 
highest standards for compounding and sterile product preparation in 
hospitals. We have developed an assessment tool based on our guidelines 
that helps pharmacists in hospitals and health systems comprehensively 
evaluate sterile compounding service providers and use comparative date 
for their vendor selection process.
    However, we cannot solely rely on the due diligence of purchasers 
to take the place of proper licensing, inspections and oversight of 
entities producing compounded medications. The distinction between 
traditional pharmacy compounding and manufacturing appears to be a 
regulatory gray area between State boards of pharmacy and FDA. As we 
have seen, however, the implications of this gray area are serious.
    ASHP recommends stronger communication and collaboration between 
State boards of pharmacy and the FDA. We also believe that it may be 
necessary to revisit previous attempts to further define pharmacy 
compounding from large scale, mass-produced medications. Finally, we 
strongly believe that FDA must be provided the resources it needs to 
perform serious and meaningful regulatory oversight.
                                 ______
                                 
    Good morning and thank you Chairman Harkin, Ranking Member Enzi, 
and distinguished members of the committee, for holding this hearing. 
My name is Kasey Thompson and I am vice president of Policy, Planning 
and Communications for the American Society of Health-System 
Pharmacists (ASHP). I am here today to provide ASHP's perspective on 
the recent meningitis outbreak, and to explore potential policy options 
to help prevent similar events from occurring in the future.
    First and foremost, on behalf of ASHP and our more than 40,000 
members practicing in hospitals, health systems, and ambulatory 
clinics, I want to express our sympathy for the victims and their 
families who were harmed by this tragedy. The patients who relied on 
these medications deserved much better. Unfortunately, the New England 
Compounding Center appeared to have been operating in a manner that 
falls far short of standards for compounding sterile preparations. 
Further, the scale and scope of NECC's operation more nearly resembles 
pharmaceutical manufacturing rather than pharmacy compounding.
    U.S. hospitals prepare a vast array of compounded sterile 
preparations every day in order to meet the needs of patients. In fact, 
the majority of compounded medications hospitals utilize are prepared 
in-house by pharmacy departments. The compounded medications that 
hospitalized patients need span from simple intravenous admixtures to 
complex customized medications that are not available off the shelf, 
such as multi-ingredient cardioplegia solutions for heart surgery, 
precisely measured combinations of epidural pain medication and adult 
medications prepared in concentrations that can be safely administered 
to babies and children.
    However, hospitals also enlist the help of qualified compounding 
pharmacies for some compounded preparations for several reasons. For 
example, they may not have necessary equipment or facilities to prepare 
some high-risk preparations, or they may face medication shortages for 
commercial products that can only be replicated by a compounding 
pharmacy.
    Hospitals prepare or purchase compounded medications based on 
specific patient needs and individual medication orders or in 
anticipation of needs for patients under their direct care. 
Importantly, medications that are purchased from outside compounding 
pharmacies are not commercially available from brand or generic 
manufacturers in the individualized form needed for a specific patient 
or patients, unless manufacturers cannot supply them.
    ASHP has dedicated itself to developing the highest standards for 
compounding and sterile product preparation in hospitals. Through our 
peer-reviewed publication, the American Journal of Health-System 
Pharmacy, we began publishing guidelines on sterile and non-sterile 
compounding in the early 1990s. In 1993 we published the ASHP Technical 
Assistance Bulletin on Quality Assurance for Pharmacy-Prepared Sterile 
Products. This was revised in 2000, and is currently in the final 
stages of revision.
    These guidelines formed the basis for the three-tier risk 
assessment structure later incorporated by the United States 
Pharmacopeia into Chapter 797, its standards for compounding sterile 
products. In 2010, ASHP published the ASHP Guidelines on Outsourcing 
Sterile Compounding Services to advise pharmacy departments on how to 
conduct due diligence when selecting outsourcing vendors. In addition, 
we have developed an assessment tool based on our guidelines that helps 
pharmacists in hospitals and health systems comprehensively evaluate 
sterile compounding service providers and use comparative data for 
their vendor selection process. Our guidelines and assessment tool are 
and have been available free as a public service to the health care 
community and others.
                             policy options
    We cannot rely solely on the due diligence of purchasers to take 
the place of proper licensing, inspections and oversight of entities 
producing compounded medications, especially for those entities that 
are manufacturing in large quantities and shipping across the country. 
Pharmacists and other health care providers should not be expected to 
perform the jobs of regulators by visiting and inspecting pharmacies or 
manufacturers that they do business with.
    The distinction between traditional pharmacy compounding and 
manufacturing appears to be a regulatory gray area between State boards 
of pharmacy and FDA. As we have seen, however, the implications of this 
gray area are serious.
    We recognize the regulatory challenges of defining the activities 
in this gray area, but we firmly believe that specific definitions are 
essential so that mass production of the scope and scale done by NECC 
falls within the regulatory jurisdiction of FDA, rather than State 
boards of pharmacy. To this end, we have developed policy 
recommendations for the committee, FDA and other stakeholders to 
consider as we explore ways to address this gap in oversight.
    Previous attempts to define compounding in Federal law contained 
certain elements that should be examined in light of practice changes 
since 1997. Recent legislative proposals merit further discussion and 
exploration, since they may reflect those practice changes and allow 
for the regulatory flexibility among State boards of pharmacy and the 
FDA that would ensure that hospitals continue to be allowed to obtain 
compounded medications in anticipation of patient need.
    Compounding pharmacies range from small pharmacy operations that 
compound medications for individual patients directly under their care 
to large-scale operations that prepare compounded medications in the 
volumes required to serve the needs of patients under the care of 
health systems or physician offices. A number of variables make 
distinguishing between compounding and manufacturing difficult. 
Therefore, both functions might be better viewed as a continuum of 
activities stratified by the potential for risk of patient harm, each 
requiring defined procedures, equipment, training, and quality 
controls. At one end of the continuum, oversight of traditional 
compounding is clearly within the purview of States, as is FDA 
regulation at the other end of the continuum with pharmaceutical 
manufacturing. As legislative proposals are considered, it will be 
important to reaffirm the role of State boards of pharmacy to license 
and regulate traditional compounding while recognizing that large-scale 
compounding of sterile products may require oversight by the FDA in 
cooperation with State boards of pharmacy.
    Once compounding activities advance along the continuum to 
manufacturing and the risk to patient safety and public health 
increases, there may be a need for a special category of FDA oversight 
that falls between compounding and manufacturing but does not require a 
drug approval (e.g., an NDA). For example, if a compounding pharmacy 
sells to other organizations and not directly to patients, then they 
may need to be regulated by the FDA. Doing so would allow hospitals, 
clinics, and physician offices to purchase sufficient quantities of 
compounded product as is necessary to meet patient needs, while doing 
so under the assurance that they are making those purchases from 
appropriately regulated sources.
    ASHP recommends stronger communication and collaboration between 
State boards of pharmacy and the FDA to accomplish this goal. We also 
believe that State boards of pharmacy should be able to work with FDA 
to inspect an entity suspected of engaging in large-scale production 
beyond the scope of pharmacy compounding. Previous court rulings have 
made FDA's authority to inspect these facilities unclear and subject to 
legal action.
    Finally, we strongly believe that FDA must be provided the 
resources it needs to perform serious and meaningful regulatory 
oversight of entities that are potentially engaged in manufacturing. 
Not to do so now will only hinder the agency in implementing 
legislation.
                               conclusion
    To summarize, we are profoundly saddened by what we believe should 
have been an avoidable tragedy. ASHP remains committed to working with 
Congress, FDA and other stakeholders to address these regulatory gaps 
and reduce the likelihood of similar outbreaks from compounded sterile 
products in the future.

    The Chairman. Thank you very much, Dr. Thompson. We'll 
begin a round of 5-minute questions.
    Mr. Miller, do you believe Congress should clarify the 
legal status of section 503A given the current split between 
the Ninth and Fifth Circuits?
    Mr. Miller. Mr. Chairman, there is definitely clear 
confusion about authority based upon the judicial decisions in 
the Fifth and the Ninth. We also know based upon the Medical 
Center v. Thompson decision in the Supreme Court that actually 
struck down sections of the original FDA FDAMA law as being 
unconstitutional. So, yes, we need to go back and revisit this, 
especially in light of this tragedy.
    The Chairman. Let me ask that question one more time. Do 
you believe Congress should clarify the legal status of section 
503A?
    Mr. Miller. Yes.
    The Chairman. Thank you. That's all I wanted to hear. We 
know the background and stuff. We're trying to get a 
clarification of this. So you think that we should give that 
kind of clarification whether it's the flagpole type or some 
kind of clarification on section 503A?
    Let me ask this. I may tend to disagree with you a little 
bit on your sort of absolute statement that FDA had 
jurisdiction in this. I still think that's sort of a gray area. 
But let's assume that they did.
    Mr. Miller. Yes, sir.
    The Chairman. Assuming we agree that they should have 
jurisdiction when a pharmacy like NECC operates in a manner and 
scale that is essentially a manufacturer, shouldn't the FDA 
have access to records such as prescription records to help it 
determine whether the operation is really a compounder or a 
manufacturer?
    Mr. Miller. That's a complex question, and the answer is it 
does. The FDA has the ability to obtain a court order, 
subpoena, or administrative warrant to obtain any records 
within a pharmacy. They also have the ability to work in 
collaboration with a board of pharmacy. The board of pharmacy 
in every State has the ability to look at all documentation and 
materials in any of its licensed sites.
    If the FDA felt compelled, in addition to its Form 482 on-
site inspection of materials, that it needed additional 
information, that's a simple collaboration with a State board 
of pharmacy. We know based on testimony that occurred between 
the FDA and the Massachusetts Board of Pharmacy, and yet that 
system still failed. Does the FDA--should they--actually, 
Senator, although it's not specific, they do have that ability 
currently.
    The Chairman. They do have to go through a lot of hoops. 
They've got to go to court. They've got to get all kinds of 
things before they do that. That takes, obviously, a lot of 
resources. It takes a lot of time. I'm just saying that if we 
agree that FDA should have this jurisdiction, shouldn't they 
have access to records to help them determine whether it's a 
compounder or a manufacturer, because sometimes--as Dr. Hamburg 
kept saying, sometimes they don't know.
    Mr. Miller. Yes. One of the things that also has to be 
addressed--and it's very important--is that as we distinguish 
between a pharmacy engaged in compounding, which more than 50 
percent of all pharmacies in the country do, versus 
manufacturing, we have to look at what they are doing, not 
necessarily how, but what are they doing.
    The Chairman. I know you were here for the first panel. You 
may have heard me say something about State lines.
    Mr. Miller. Yes.
    The Chairman. I don't know if that's right or not. What are 
the features that distinguish NECC from what you would view as 
a legitimate large-scale compounding pharmacy? Again, we heard 
about volume. I mentioned interstate shipment, prescription 
records. Again, do we have some guidelines? What features would 
distinguish that as a legitimate large-scale compounding 
pharmacy?
    Mr. Miller. Mr. Chairman, I am a pharmacist. I tend to 
think black and white. The answer is pretty simple. When I 
receive a prescription, regardless of whether it's a compound 
or an off-the-shelf commercially manufactured drug, that is 
coming from an authorized prescriber in my State. I'm empowered 
to fill it for a patient, or, depending upon the order, I may 
be filling it for a clinic associated with a hospital down the 
street. I fill prescriptions.
    The difference between NECC and a compounding pharmacy was 
they weren't filling prescriptions. They were bulk 
manufacturing and selling. A company like Pfizer creates and 
sells medications. They don't fill prescriptions. A company 
like Ameridose, associated with NECC, creates and sells 
medications. Pharmacies fill prescriptions.
    One of the things that we've heard from conversations with 
many boards of pharmacy is how do I distinguish this? It's 
relatively simple. Any pharmacy inspector, specifically one who 
is a pharmacist and trained, can tell you, based on the 
paperwork in that pharmacy, is this pharmacy filling a 
prescription, or are they essentially creating bulk quantities? 
And those bulk quantities, whether they're 100 or 100,000--are 
they being sold as opposed to being dispensed?
    It's a function of what we do as pharmacists that really 
differentiates between pharmacy practice and manufacturing. 
That's where I think we really went awry here with NECC, 
because it was quite apparent that they were not filling 
prescriptions. They were selling stuff, and that's what 
manufacturers do.
    The Chairman. OK. I'll try to absorb all that.
    Senator Roberts.
    Senator Roberts. I want to be a little insistent here, and 
I apologize for that. In the first place, in my opening 
statement, I said that I hoped that the witnesses today would 
offer their commitment to work with us--and I think you've done 
that--and to do so in good faith--and I know you'll do that--
with the intent to be transparent and forthcoming with your 
thoughts and your suggestions and your concerns. That came from 
my opening remarks.
    Is this something that you are both willing to do, 
remembering that during the early days of trying to get 
something done, we wanted answers and all we got was pushback. 
Could you speak to that, please?
    Mr. Miller. Senator Roberts, as a pharmacist and as an 
organization representing pharmacists, the worst possible thing 
has happened. We have more than 30 people dead. We have 461 
people ill. Right now, the focus must be on working 
collaboratively--professional associations, regulators, 
legislators--to prevent this from ever happening again. IACP 
and all the other pharmacy associations, State and national, 
will be working with you, this committee, and everyone else to 
make sure that we protect the public from organizations, 
businesses, entities like an NECC. You have my commitment on 
that, Senator.
    Senator Roberts. I appreciate that.
    Dr. Thompson, I know that you are providing a legislative 
blueprint to be of help to us, which I appreciate. Is that 
criteria voluntary, or is that mandatory?
    Mr. Thompson. The blueprint that we suggested?
    Senator Roberts. Yes.
    Mr. Thompson. We think that's mandatory. Basically, it's to 
clarify the jurisdiction of the FDA over manufacturing of these 
compounding entities. I call them entities for a reason, 
because it is a gray area--and I'm speaking as a practitioner 
and for our members--in trying to understand who they're doing 
business with out there. And we do believe there are some gray 
areas.
    We think that this is something that would give the FDA the 
authority it needs to regulate these entities that fall between 
the Pfizers and the Mercks and the large-scale manufacturers 
that are manufacturing under approved drug applications and 
abbreviated new drug applications for generic drugs and these 
entities that are compounding medications in large amounts.
    Senator Roberts. In your opinion, either one of you, do you 
think that NECC is a manufacturer? If you do, do you believe 
that FDA has the current oversight and enforcement authority to 
appropriately regulate manufacturers?
    Mr. Thompson. I believe that they were behaving as a 
manufacturer, without question. It's become clear to me, or 
perhaps unclear, whether FDA had the authority or not. This 
registration that compounding pharmacies do with the FDA is not 
the same as what a commercial manufacturer that is 
manufacturing under a new drug application and is licensed to 
manufacture under that application. I do believe it's a 
regulatory gray area that must be confirmed by Congress.
    Mr. Miller. No question, Senator. NECC was engaged in 
illegal manufacturing. They did not have a license in the State 
of Massachusetts as a manufacturer. All States oversee that, in 
addition to the FDA. They were not registered with the FDA. 
They were shipping products nationwide without prescriptions, 
without official authorized orders from prescribers. Bottom 
line, that's manufacturing.
    Senator Roberts. I appreciate that. I have no further 
questions, Mr. Chairman.
    The Chairman. Senator Alexander.
    Senator Alexander. Thanks, Mr. Chairman.
    Thank you for being here and for your testimony. You make 
the solution sound pretty simple, that you just take these 
large facilities that are in the gray area, and some of them 
are manufacturers and they're regulated by the FDA, and the 
rest of them aren't. They're filling prescriptions and they're 
regulated by State boards of pharmacy. Am I hearing you right?
    Mr. Miller. From--go ahead, Kasey.
    Mr. Thompson. I'm sorry. Yes, you are hearing me correctly 
in that respect. We do believe that traditional pharmacy 
compounding is the filling of a prescription and dispensing 
that to a patient. These entities that are preparing large 
amounts of medications and not necessarily dispensing those to 
patients but selling those to various entities, whether it's 
hospitals, physician offices or others, are manufacturing.
    Senator Alexander. There are some--let's take Tennessee. 
Maybe we've got 1,000 to 1,200 pharmacies. Let me just guess at 
it. And based upon your testimony, maybe 500 of them do 
compounding.
    Mr. Miller. That's correct.
    Senator Alexander. Now, apparently, there must be a number 
of other larger compounding pharmacy facilities in Tennessee, 
for example. Would that be true? Anybody know? I have some 
suggestions here that there may be 7,500 pharmacies that 
specialize in advanced compounding, 3,000 that provide sterile 
compounding. Are these just large drug stores that we're 
talking about, or are these large entities or companies that 
fill prescriptions, that do advanced sterile compounding and 
still fill prescriptions? How many are we talking about here?
    Mr. Miller. Senator, thank you. I can answer that. Those 
statistics actually come from the International Academy of 
Compounding Pharmacists. The 7,500 and 3,000 you've heard 
mentioned are actually our statistics.
    There are compounding pharmacies, sterile compounding 
pharmacies, in the State of Tennessee, actually, quite a few of 
them. Some are large. Some are relatively small. One of the 
things I don't want us to get too hung up on is the issue of 
size, because size does not necessarily mean that you're a 
manufacturer. It's actually what you do--Senator Harkin, to 
what I was saying before.
    Senator Alexander. There might be 40 or 50 in Tennessee, 
roughly. We're usually 2 percent of everything, so if there are 
3,000 sterile manufacturers, there might be 40, 50 or 60 of 
varying sizes. Is that right?
    Mr. Miller. Sterile compounding pharmacies, not 
manufacturers.
    Senator Alexander. Sterile compounding pharmacies.
    Mr. Miller. Yes, sir. What we have to recognize is they may 
be part of a hospital. They may be part of a home infusion 
company that specializes in outpatient, a nursing home, long-
term care, or it could be affiliated with one of our major 
chains. It could be a standalone, community-based pharmacy.
    Senator Alexander. These are the ones we're talking about 
here. We're not talking about the 1,000 pharmacies that are 
doing traditional compounding, or we're not talking about 
manufacturers who are selling in bulk. We're talking about, in 
my State, maybe 40, 50, or 60 entities of various sizes which 
are compounding pharmacies, some of them doing sterile work.
    Mr. Miller. Actually, you have more than that in terms of 
compounding, in general. That estimate for sterile compounding 
in your State--I would say that's extremely accurate. Those are 
the pharmacies we would want to make sure are identified by 
your State.
    Senator Alexander. That's where the potential trouble is, 
insofar as this incident is concerned. Is that right?
    Mr. Miller. My hesitation isn't because I don't agree. I'm 
concerned that that may be too narrow of an interpretation.
    Senator Alexander. Let me ask it this way, then. The 
trouble is the lack of clarity about who's on the flagpole.
    Mr. Miller. Yes, sir.
    Senator Alexander. If I can understand--let's just narrow 
it down to these, let's say, 50 advanced compounding facilities 
in Tennessee. That gets rid of most of the drug stores in 
Tennessee, and it gets rid of all the manufacturers. We're 
talking about 50. How do we decide who regulates those 50? Does 
the State board of pharmacy do it, or does the FDA do it?
    Mr. Miller. Right now?
    Senator Alexander. Well, no. How should it be? How should 
it be going forward?
    Mr. Miller. To identify them, I would send the State board 
of pharmacy in to inspect all of them. That State board 
inspector should be able to determine is this pharmacy a 
pharmacy, or is this pharmacy actually engaged in 
manufacturing.
    Senator Alexander. What if they're as incompetent as the 
State Board of Pharmacy of Massachusetts seemed to be over the 
last 10 years?
    Mr. Miller. Then we have a very significant problem. 
Fortunately, that doesn't seem to be the case in most States. 
One of the recommendations our organization has at the State 
level is we need to adequately fund our boards and provide them 
with inspectors who are trained and kept up-to-date so they can 
go in and review a pharmacy so that we can identify and prevent 
an NECC----
    Senator Alexander. I interrupted you. You were saying you 
would send the State board of pharmacy in to decide, first, are 
they pharmacies, or are they manufacturers?
    Mr. Miller. That's correct.
    Senator Alexander. Then what?
    Mr. Miller. If they are identified as being a manufacturer 
outside of the practice of pharmacy and the rules and 
regulations within the State, the State board has the ability 
to shut them down, discipline them, revoke their license, 
suspend it, if they believe--the State board, just as Colorado 
did with NECC--if they identify that pharmacy as a 
manufacturer, they can cross-file that complaint, specifically, 
with the FDA, who has the ability to shut down an illegal 
manufacturer.
    Senator Alexander. Yes.
    Mr. Miller. So it's a combination of both----
    Senator Alexander. Well, this is helping me. Sometimes when 
we get these large, difficult questions, getting it down to a 
quantifiable level helps. We're really talking about, in a 
State like ours, what to do about 30, 40 or 50 institutions. 
How do we identify them, and then how do we regulate them. If 
we don't trust the State in every case, or don't trust the FDA 
in every case--I would trust the Tennessee Board more than I'd 
trust the FDA to identify them, to tell you the truth, based on 
what I've heard today. But not Massachusetts.
    So there we have the dilemma. I suppose with that smaller 
number, you could allow the FDA to go in and make its own 
judgment about whether they're manufacturers or not. If they 
are, regulate them. You're saying have the State board go in 
and decide it.
    Mr. Miller. Senator, first off, the FDA can go into those 
facilities, those pharmacies, at any time. No question about 
that. If we wish to, from a policy standpoint, require that the 
FDA inspect all potentially identified sterile compounding 
pharmacies, that's a decision we could make as a policy.
    Senator Alexander. That wouldn't be so many that it would 
be an overwhelming number, would it? Or would it?
    Mr. Miller. I can't answer that for the FDA. My biggest 
concern would be----
    Senator Alexander. We're just talking about identification.
    Mr. Miller. Yes. The agency would need to not only identify 
them, but also then deal with the fact that each State has 
conflicting compounding guidelines. For example, in the State 
of Tennessee, your board of pharmacy said clearly to all 
licensees in January, ``No non-patient-specific prescriptions 
in our State.'' Other States do permit that.
    Senator Alexander. Why is that?
    Mr. Miller. Why is that? Because the individual State board 
of pharmacy makes a decision as to what is needed and how it 
needs to be regulated to protect the citizens within their 
State.
    Senator Alexander. Well, I'm running a little bit over my 
time here, Senator Harkin. It helps us, in terms of developing 
a policy to solve the problem looking forward, to narrow it 
down to the number of entities we're talking about. Perhaps we 
could agree to exclude manufacturers and people who are 
illegally manufacturing. They're just illegally manufacturing. 
And then traditional compounding, we understand, exists.
    To identify the number of entities that fall into this gray 
area, how do we identify them, and then how do we regulate 
them? One of the things I'm experimenting with in my mind is an 
idea for these areas, such as sterile compounding, that sort of 
area, where the FDA may have standards, and actually certify a 
State to handle that narrow area of compounding and be able to 
take it away.
    For example, in the case of Massachusetts, had there been 
such a structure existing, based upon what we've heard today, I 
would say if the FDA had the authority, it should jerk the 
ability of Massachusetts to deal with these sorts of entities 
at least until Massachusetts cleaned up its act. On the other 
hand, it should give Tennessee an award for working with the 
CDC to move quickly to eliminate the spread.
    Anything you could submit to the committee, to the 
chairman, Senator Enzi, Senator Roberts, those of us who are 
interested, identifying exactly the number of entities we're 
dealing with and a practical way for identifying, with the end 
result being that we have some agency clearly on the flagpole, 
so when we come up here 6 months from now, we don't have one 
saying, ``Yes, I had responsibility,'' and the other one 
saying, ``Well, I had some, too''--I want one to say, ``It was 
my fault, my job, my responsibility,'' or the other one saying, 
``No, that's my fault,'' just as the head of the CDC said when 
I asked her--I said, ``Whose job was it to let the world know 
what happened?'' She said, ``That was my job.''
    The Chairman. Thank you, Senator Alexander. We're preparing 
this letter, as I mentioned earlier, to go out to all the State 
boards of pharmacy. Please take a good look at that, and if 
you've got some suggestions for other things that you might 
want to go into that letter, please let us know. I'd like to 
get it out as soon as possible.
    Senator Alexander. Good. I'll look at it today.
    The Chairman. Some of the things you brought up may not be 
in there, and I want to have you take a look at that to see if 
we need to put----
    Senator Alexander. Thank you. Good.
    The Chairman. I appreciate that very much.
    I just wanted to ask Dr. Thompson--I read through your 
testimony yesterday, and I'll just refer to it again, just 
reviewing it. I know you're saying that hospitals and large 
entities like that can't really ensure the inspections to make 
sure that they're getting the right kind of products that are 
sterile and everything like that.
    It seems to me if hospitals are outsourcing compounding, 
can't they take steps to ensure that they're buying from 
suppliers who utilize sterile practices? It seems like--don't 
take this wrong, but it seems like in your testimony you're 
shoving it all off on the compounding pharmacies. Don't the 
hospitals also, especially large entities, have a 
responsibility? Can't they take steps to ensure who they're 
buying from and that they're meeting good manufacturing 
practices?
    Mr. Thompson. Yes, sir, and I believe that many of them do. 
They verify that they're licensed by the State board of 
pharmacy. They look to see whether or not they're registered 
with the FDA as a manufacturer, which is a regulatory gray 
area. I've spoken with many pharmacists that do go out and 
visit facilities.
    As you can imagine, Senator Harkin, a small hospital in 
Iowa with 25 beds or less----
    The Chairman. Can't do that, no.
    Mr. Thompson [continuing]. You know, flying to 
Massachusetts. That's where the challenge comes in. I think 
many do that. But, at the end of the day, they have to be able 
to count on the regulatory apparatus, whether it be the State 
or the FDA, to do their part. We don't inspect Pfizer to make 
sure that their products--so that's sort of the point I was 
trying to make.
    The Chairman. I understand a small hospital in Tennessee or 
Iowa can't do that. There are some big hospital chains, and 
they buy a lot of product. A lot of the smaller hospitals would 
rely upon their ability to make sure that from whom they're 
buying is practicing good manufacturing practices.
    Mr. Thompson. Oh, sure, absolutely. Many of them do that. 
I've spoken with many hospital pharmacists that go out and look 
at compounding pharmacies. It gets a little difficult when they 
go into these manufacturing operations, because that's sort of 
a different type of expertise--that somebody needs to inspect a 
manufacturer. But many of them do that, to your point.
    The Chairman. I also want to again say forthrightly about 
compounding products that we think a lot about it as meeting 
specific needs of individuals. It has to be prescription-based, 
rather than just producing mass products. Compounding 
pharmacies also fill a real niche in our society for meeting a 
drug shortage that might happen at some time. They can step in 
and do things right away and help us meet certain drug 
shortages. That's just another valuable service that they 
provide.
    Dr. Kainer, I didn't ask you any questions, but, again, 
more than anything, you illustrate the diligence and the 
professionalism of our public health professionals in the 
United States and the close cooperation between the State 
departments of health and the CDC. To me--and I have looked at 
different health systems around the world--our public health 
system in this country, in terms of prevention and in terms of 
immediate diagnosis--that's the wrong word--immediately finding 
things that are happening--detection and response, beats 
anything anywhere in the world.
    We have to make sure that we continue to have adequate 
funding so that we employ and hire the best possible 
epidemiologists and other professionals. You exemplify that, 
and I appreciate it very, very much.
    Mr. Miller, thank you very much. The two responses that I 
liked hearing from you today were, No. 1, on the clarification 
on 503A, and in response to Senator Roberts that your 
association will, indeed, work with us as opposed to what 
happened a few years ago.
    Mr. Miller. Absolutely, Senator.
    The Chairman. That's good news.
    Senator Alexander. Mr. Chairman.
    The Chairman. Yes.
    Senator Alexander. Mr. Chairman, something you said, might 
provide an opportunity for Dr. Kainer to respond. I thought you 
made a very good point. The hospitals and the clinics and the 
physicians, particularly after this, who buy compounded 
medicines will be on alert. Maybe there's something else that 
the CDC or its associates could do to create a warning system.
    For example, was there anything that went on over the last 
10 years that we've heard about in Massachusetts with the New 
England Compounding Center that could have been put up as a 
yellow flag that a hospital, like the Saint Thomas pain clinic 
might have known about before they bought that, just by 
checking the internet?
    Is there a system like that, Dr. Kainer? I thought Senator 
Harkin's question was a very good one.
    The Chairman. That's interesting.
    Dr. Kainer. I'm not specifically aware of such a system 
that occurs right now that is in the public, specifically on 
identifying or having a warning signal for a hospital. They 
have the 483 inspection reports that people can do. It's not 
necessarily user-friendly or easy for hospitals.
    If I may add, many of the physicians who ordered these 
medications did not realize that they were ordering from a 
compounding pharmacy. They actually thought that they were 
purchasing things from a manufacturer. Alerting clinicians as 
to what is the difference between a compounding pharmacy and a 
drug manufacturer, what's the difference between a generic 
medication versus a brand name medication, and compounded 
products are not the same.
    There's a lot of confusion among those providers. Perhaps 
there's an opportunity here to educate the providers that there 
is a difference between compounded products and manufactured 
products.
    The Chairman. That's very interesting. We should pursue 
that, too. I was just told by my staff that many of the 
documents that came out of the board in Massachusetts were not 
public. There was no way for anybody out there, a hospital or 
someone, to know that there were these indications. Maybe 
that's something else we should look at.
    Is there anything else that any of you want to impart to 
the committee at all before we close it down? No?
    Thank you all very, very much, each of you, for your 
diligence, for being here, for adding to our deliberations. You 
can sense that this is truly a bipartisan effort. This 
committee will forge ahead in developing legislation, and, 
toward that end, we again seek your input and your advice and 
work with you to develop this legislation. Hopefully, we'll 
have something soon next year that we'll be able to move ahead 
on and put this sad chapter behind us.
    Thank you all very much. I request that the record stay 
open for 10 days to allow Senators to submit statements and 
questions for the record.
    With that, the committee will stand adjourned. Thank you 
all very much.
    [Additional material follows.]

                          ADDITIONAL MATERIAL

                  Prepared Statement of Senator Casey

    Chairman Harkin, Ranking Member Enzi, I would like to thank 
you for convening this investigative hearing. As members of the 
Health, Education, Labor, and Pensions Committee, many from 
States affected by this terrible tragedy, I believe we have a 
duty to exercise our investigative and oversight authority, and 
to make sure that we take every step possible to ensure that a 
tragedy like the ongoing meningitis outbreak does not happen 
again.
    Like you, I am deeply disturbed by the long history of 
problems at the New England Compounding Center, and concerned 
that it took an event of this magnitude, with over 400 people 
infected with a potentially lethal strain of meningitis and 
over 30 having succumbed to its effects, to alert us to the 
dangers of this company's practices.
    In the face of this crisis, Pennsylvania has seen only one 
case, compared to dozens of cases in the home States of some of 
my colleagues on the committee. This outbreak has alerted us 
all to the dangers to public health posed by bad actors in the 
pharmacy compounding arena.
    I know there are many good compounding pharmacists, and I 
recognize the important role they play in ensuring that 
patients have access to the drugs they need, when they need 
them, and in the right form. Something went wrong at NECC, and 
now over 30 people are dead as a result. We are here to learn 
what led to this situation, and what we need to do to ensure it 
never happens again.
    There are many questions we have yet to answer, and we are 
not sure what the best path forward will be. It is clear that 
NECC was operating outside the bounds of Federal and State law. 
Do we need greater Federal oversight of compounding pharmacies? 
Do we need to require the FDA to work more closely with State 
boards of pharmacy, and improve their communication? How have 
the split district court decisions affected the FDA's ability 
to take action with regard to compounding pharmacies?
    There appears to be a lot of confusion surrounding the 
regulation and oversight of these larger compounding pharmacies 
that operate in the middle ground between traditional, small-
scale compounding pharmacies and large manufacturers. I believe 
that everyone would benefit by reexamining current Federal law 
and reevaluating whether our existing regulatory system is 
appropriate for an industry that is changing and addressing new 
challenges in our health care system. I know that this issue 
has been contentious in the past, and I hope that all of the 
interested parties will come together in good faith to protect 
the public from future tragedies.
    I look forward to hearing from our witnesses, I thank them 
for sharing their expertise, and I thank Chairman Harkin and 
Ranking Member Enzi for their commitment to protecting the 
public from harm. I look forward to working with the other 
members of the committee to clarify the law as it pertains to 
compounding pharmacists.
                                ------                                

                                 ______
                                 
     Prepared Statement of John J. Dreyzehner, M.D., MPH, FACOEM, 
      Commissioner, Tennessee Department of Health, Nashville, TN
    Please accept my sincere appreciation for your investigation into a 
matter that has, regrettably, impacted thousands of Americans. Our 
concerns and prayers for the patients, families and loved ones affected 
by this preventable tragedy are continuing. On behalf of those who have 
died or suffered physical and mental anguish, and their families and 
friends who have also endured loss and anxiety, I thank you for your 
work and assure you the Tennessee Department of Health is firmly 
committed to working with you, our State legislators, the healthcare 
community and other stakeholders to take this clear opportunity to do 
all we can to assure this never occurs again.
    As you know, healthcare and public health professionals in 
Tennessee were the first in the Nation to detect, investigate and 
understand what had gone horribly wrong in our clinics as a result of a 
compounding pharmacy that now appears to have been acting as a 
manufacturer in another State. Our investigation began Tuesday, 
September 18, when an astute clinician provided the first indication of 
something unusual in a patient's presentation and subsequent laboratory 
evaluation. The finding of fungal meningitis launched a rapid 
investigation that soon identified contaminated methylprednisolone 
acetate (MPA) from the New England Compounding Center in Massachusetts 
as the cause of an outbreak of meningitis, stroke and death for 
patients who had received epidural steroid injections with the 
egregiously tainted product at three facilities in our State.
    I am proud of the work done in Tennessee to expeditiously identify 
the contaminated medication which within 8 days of that first report 
September 18th sparked a national recall of the three contaminated lots 
of MPA. I am equally proud of work by the Tennessee Department of 
Health, our central and local health department teams and our many 
healthcare partners to rapidly find, reach out and provide close 
assistance and regular contacts to more than 1,000 at risk individuals 
and their families. I'm also proud of the cooperation among many States 
in addressing this most serious outbreak. None the less, because this 
whole tragic episode was preventable, I am not just saddened by the 
occurrence, I am angered.
    This does not appear merely to have been an unfortunate lapse or 
error in pharmacy judgment or practice. It appears to have been a 
cascade of increasingly serious and obvious omissions and commissions 
that were persistently not addressed for reasons currently unknown. The 
people who compounded these medications knew they were being relied 
upon to be sterile by patients and clinicians--real people who trusted 
them. This was a blatant disregard for health and safety by pharmacists 
who should understand the potential consequences of the final 
catastrophic failure that ultimately occurred. This was, at root, a 
fundamental breach of an ethical duty and sacred obligation by the New 
England Compounding Center to first, do no harm.
    As a physician, my colleagues and I rely on a long-standing 
foundation of trust and confidence in the drugs we administer to 
patients, believing these materials are safe and effective and will 
help, not hurt, an individual. I've talked with doctors who unknowingly 
administered contaminated NECC products to the people they were trying 
to help, and the impact to them is devastating. The men and women in 
the medical community who trusted NECC products are among the victims 
in this tragedy. We are angered by a few who failed to uphold the 
integrity of critical processes, protocols and procedures, resulting in 
harm to those we have pledged not to harm.
    I turn now to the committee's specific questions. It is important 
to retain the ability to compound medication. Compounding pharmacies 
play a vital role in the practice of medicine. While the national 
attention has focused on major compounding operations, most family 
pharmacists across America are occasional compounding pharmacists, 
attested to by the mortar and pestle that are symbols of pharmacy 
practice. These pharmacists help patients who need smaller doses or 
different forms or formulations of medications than may be readily 
available from manufacturers. Children may need medication in a 
different form to use it. If a child cannot swallow a pill, for 
example, he or she may need a liquid. Similar considerations apply to 
hospice patients who may be unable to receive medication by its 
traditional route. Dermatologists often prescribe compounded products 
because of the unavailability of certain drug combinations; others are 
allergic to dyes and preservatives used in medications they need.
    It is vital to preserve this traditional compounding, maintaining 
the value provided to patients, but we must make sure manufacturing of 
pharmaceuticals is not done under the guise of drug compounding.
    Tennessee's laws and regulations, as do most States, provide that 
the practice of pharmacy includes compounding. In Tennessee, there is 
not a separate license for pharmacies who do drug compounding; 
therefore Tennessee regulates pharmacies under its general pharmacy 
laws and regulations. It is important to note Tennessee also has a 
similar license category that encompasses and regulates manufacturers/
wholesalers/ distributors of drugs. The same regulations apply to out-
of-state pharmacies, although we necessarily must rely upon the 
pharmacy's home State and/or Federal entities to inspect and provide 
``on the ground'' regulation. There is always room for improvement. 
Attention to both regulatory and industry standards are necessary, 
complimented by a robust and adequately resourced regulatory effort to 
achieve these improvements. We are actively reviewing our own 
processes--and in partnership with our Boards, including our Board of 
Pharmacy, professional associations and other stakeholders--we are 
considering how we can improve our own regulatory posture, efficiency 
and effectiveness in Tennessee to assure the safety of patients and the 
confidence of our public, as well of the people outside our borders who 
rely on us to regulate their suppliers.
    We understand in this situation we can be vulnerable to over-
reacting but at the same time we do not want to do too little. Clearly 
the status quo is not acceptable. While our State is also a victim of 
these bad actors in another jurisdiction, that does not relieve us of 
our responsibility to look at our own processes with a critical eye and 
make them better. When events like this contaminated medication tragedy 
occur or when we identify a ``near miss'' we must take the opportunity 
to see how we can prevent a similar event from occurring again. We are 
committed to doing just that. In my 15 months as Commissioner of Health 
in Tennessee and more than two decades in public health, the need to do 
so has never been more clear.
    As an example, we acquire information about non-resident 
compounding pharmacies from the pharmacy's home State through 
reciprocity. We could require more information be provided with respect 
to a pharmacy's operation, so we can more readily identify issues which 
require investigation or action by State regulators. We also believe 
information can be collected that will help draw a distinction between 
traditional compounding and mass-compounding pharmacies. Our review of 
these issues has led us to believe the factors which the FDA stated it 
would consider in determining when it would take enforcement action are 
generally appropriate. We believe a regulating body should:

     Determine whether the pharmacy is compounding drugs in 
response to or anticipation of receiving prescriptions for individual 
patients.
     Determine whether the pharmacy is compounding drugs that 
were withdrawn or removed from the market for safety reasons;
     Determine whether the pharmacy is compounding finished 
drugs from bulk active ingredients that are not components of FDA 
approved drugs;
     Determine whether the pharmacy is receiving, storing, or 
using drug substances without first obtaining written assurance from 
the supplier that each lot of the drug substance was made in an FDA-
registered facility; and for substances intended for sterile 
compounding, is sterile upon receipt.
     Determine whether the pharmacy is receiving, storing, or 
using drug components not guaranteed or otherwise determined to meet 
official compendia requirements;
     Determine whether the pharmacy is using commercial scale 
manufacturing or testing equipment for compounding drug products;
     Determine whether the pharmacy is compounding drugs for 
third parties who resell to individual patients or offering compounded 
drug products at wholesale to other State licensed persons or 
commercial entities for resale; and
     Determine whether the pharmacy is compounding drug 
products that are commercially available or that are essentially copies 
of commercially available FDA-approved drug products.

    We don't believe any adverse event reporting requirement that 
exists will capture every occurrence that could lead to harm. 
Additionally, some errors are not easily detected and therefore not 
likely to be identified or reported. In the subject outbreak, the 
fungal meningitis, was not a reportable disease and may have gone 
undetected as an adverse medication event had we not had robust and 
trusting relationships with healthcare professionals through our CDC 
funded healthcare associated infection team and the astute clinicians 
and scientists that identified a concerning occurrence. In this same 
case, strokes occurred that were not initially recognized as being 
linked to the injection of tainted epidural steroids.
    We believe it is important for the Federal Government to respond to 
this issue because many drugs are introduced into interstate commerce, 
and it is the proper role of the Federal oversight agencies to regulate 
these drugs and those producing the drugs. In addition to appropriate 
Federal regulation, however, the Tennessee Department of Health would 
like to take this opportunity to stress the importance of our State-
Federal partnerships. The capacity building funding for emergency 
preparedness and training has ensured our ability to marshal resources, 
particularly people and expertise, to respond correctly and rapidly and 
to be able to mount a surge of effort in an emergency situation. The 
prior existence and availability of those resources and excellent 
communication with Federal partners in this outbreak made a significant 
difference in the speed and thoroughness of our response. It is crucial 
these resources remain available to the States for any such future 
event of public health significance.
    In summation, the Tennessee Department of Health is supportive of 
strengthening the regulatory process for compounding pharmacies through 
fact-based initiatives that ensure what happened at New England 
Compounding Center will not happen again. Compounding pharmacies have 
provided safe, reliable medications for many years, and we shouldn't 
allow the aberration of a few to negate the value of many who serve 
admirably. We would also note that regulation is necessary but not 
sufficient to ensure safe and effective medications. We must also rely 
on the professionals who do the work every day to keep their sacred 
obligations to the patients and clinicians they serve in the forefront 
at all times. We encourage the committee to make sure existing laws and 
regulatory practices are rigorously enforced, and to consider any 
additional authorities deemed necessary to ensure all Americans that 
the drugs they receive through interstate commerce meet all applicable 
quality standards including safety and effectiveness.
    Thank you for your work in this critical area.
                                 ______
                                 
          State of Tennessee, Department of Health,
         Bureau Of Health Licensure and Regulation,
                 Division of Health Related Boards,
                                       Nashville, TN 37243.

Hon. Lamar Alexander,
U.S. Senate,
Washington, DC 20510.

    Senator Alexander: I wanted to thank you for the opportunity to 
submit testimony for the upcoming hearings related to compounding 
pharmacy. The magnitude of the fungal meningitis outbreak has 
reinforced the need to improve regulation of facilities performing high 
volume sterile product preparation, both pharmacies and manufacturers. 
My answers to the questions posed are delineated below.

    Question 1. What is the appropriate role of compounding pharmacies 
in providing medicines to patients?
    Answer 1. Compounding is a cornerstone of the practice of pharmacy. 
Compounding pharmacists prepare custom medicines for patients who may 
be allergic to a particular ingredient, require a smaller (or larger) 
dose, or need specialized or rare pharmaceuticals. Compounding has 
traditionally been limited to these sorts of activities. Compounding 
requires a high level of pharmacological expertise, as well as close 
coordination with other health care providers and patients. However, in 
recent years the practice of compounding has been expanded to include 
the large-scale repackaging, mixing, and fabrication of drugs. This 
practice, which under certain circumstances could be considered ``drug 
manufacturing,'' varies from the traditional practice of compounding. A 
complex set of factors has led to the rise of this practice, and it is 
therefore difficult to lay the blame at the feet of any party. While 
these sorts of organizations have played a valuable role in ensuring 
the stability of our drug supply, steps should be taken to ensure the 
continued existence of traditional pharmacy compounding.

    Question 2. What is Tennessee's experience with licensing, 
regulating, and overseeing in-state compounding pharmacies operating 
within Tennessee's borders? Out-of-state compounding pharmacies? Are 
there areas that need improvement?
    Answer 2. Tennessee law recognizes that compounding is an integral 
part of the practice of pharmacy. Compounding pharmacies in Tennessee 
are regulated under the same standards applied to retail pharmacies; 
there are not distinct licenses for each type of practice. Periodic 
inspections are carried out by pharmacist investigators to ensure 
compliance in all areas of pharmacy practice, including compounding.
    Out-of-state compounders are judged by the same standards as out-
of-state retail pharmacies. The same regulations apply to each, but we 
have to rely upon regulators in each pharmacy's home State to inspect 
and ensure that out-of-state pharmacies comply with the law. It would 
not be practical to inspect all out-of-state pharmacies that hold 
Tennessee licenses, nor would it be practical to inspect all drug 
products shipped into the State from out-of-state pharmacies.
    Specific legislation targeted at sterile compounding practices, as 
well as legislation or regulation that makes a distinction between 
traditional compounders and manufacturers are two areas to consider. 
Additional resources could also be helpful.

    Question 3. Where do you obtain information about non-resident 
compounding pharmacies? What solutions would you recommend to improve 
the availability and understanding of that information?
    Answer 3. We acquire information about non-resident compounding 
pharmacies from regulators in each pharmacy's home State. We could 
require that more information be provided with respect to a pharmacy's 
operation, so that we could readily see if there are issues which 
require investigation or action by State regulators. We could also 
increase our cooperation and information sharing with Federal entities 
such as FDA and DEA when the regulatory boundaries blend or crossover.

    Question 4. Is there a way to draw a distinction between 
traditional compounding pharmacies and mass-compounding pharmacies 
similar to what NECC was doing?
    Answer 4. The FDA uses several factors to differentiate between 
traditional compounding and NECC-type operations. These factors are 
very helpful in drawing this distinction, and are set out below:

     Determine whether the pharmacy is compounding drugs in 
anticipation of receiving prescriptions, except in limited quantities;
     Determine whether the pharmacy is compounding drugs that 
were withdrawn or removed from the market for safety reasons;
     Determine whether the pharmacy is compounding finished 
drugs from bulk active ingredients that are not components of FDA 
approved drugs;
     Determine whether the pharmacy is receiving, storing, or 
using drug substances without first obtaining written assurance from 
the supplier that each lot of the drug substance was made in an FDA-
registered facility;
     Determine whether the pharmacy is receiving, storing, or 
using drug components not guaranteed or otherwise determined to meet 
official compendia requirements;
     Determine whether the pharmacy is using commercial scale 
manufacturing or testing equipment for compounding drug products;
     Determine whether the pharmacy is compounding drugs for 
third parties who resell to individual patients or offering compounded 
drug products at wholesale to other State licensed persons or 
commercial entities for resale; and
     Determine whether the pharmacy is compounding drug 
products that are commercially available or that are essentially copies 
of commercially available FDA-approved drug products.

    Question 5. How do Tennessee providers using an out-of-state 
compounding pharmacy evaluate and determine to use that pharmacy?
    Answer 5. This aspect is part of the practice of medicine in 
Tennessee. It is the facility or provider's ultimate choice to pick a 
supplier.

    Question 6. Do you believe that existing adverse event reporting is 
adequate to capture any event that may occur as the result of a 
compounded prescription drug?
    Answer 6. It is difficult to determine what sort of adverse event 
reporting structure could have prevented this tragedy. It is hard to 
develop event reporting requirements that cover enough ground, but 
aren't overly burdensome to our health care providers. Given the 
rapidly changing nature of the healthcare and pharmaceutical 
industries, event reporting criteria would likely need to be constantly 
updated. While it is important that health care providers report 
adverse events to the appropriate bodies, it also ensures that the 
regulators have the necessary tools to work with the private sector in 
the event of an emergency.

    Question 7. Do you think there should be a Federal response to 
clarify how compounding pharmacies are regulated in light of the 
actions of NECC?
    Answer 7. Yes, clarification is highly important as it pertains to 
the differentiation between manufacturing and compounding pharmacy and 
the resulting variances in regulation. Federal leadership would also be 
beneficial to develop communication channels that will increase 
transparency and facilitate interstate and interagency information 
exchange, resulting in more informed regulation by individual States or 
regulating bodies.

    Thank you for your willingness to take on the daunting task of 
regulatory reform. With thoughtful input from a variety of sources, we 
are more likely to find a fitting solution to the challenges that we 
face.
            Sincerely,
                                  Andrew C. Holt, Pharm.D.,
                                        Executive Director,
                                       Tennessee Board of Pharmacy.
                                 ______
                                 
   Prepared Statement of Craig Becker, President, Tennessee Hospital 
                    Association (THA), Nashville, TN
    On behalf of the Tennessee Hospital Association and its member 
hospitals, I would like to thank Senator Alexander for the opportunity 
to comment on the recent meningitis outbreak in Tennessee and the 
impact on the patients we serve. It is my intention to provide the 
Health, Education, Labor, and Pensions (HELP) Committee with a 
chronological description of events, the role of THA and finally with 
lessons learned from this tragedy.
    First and foremost, THA and its members' primary concern is over 
the health of the patients impacted by this tragedy. Once the problem 
had been identified by the Tennessee Department of Health (TDH) and the 
Center for Disease Control (CDC), THA members stopped using the tainted 
product. Once the cause of the outbreak and a course of action had been 
determined, THA and its members took every appropriate action to deal 
with this unprecedented crisis.
    We hope and pray that there never will be another incident like 
this, but we feel the systems in place to notify members, pull the 
tainted product off the shelves and treat the infected patients, 
worked. We cannot thank enough the TDH, Commissioner John Dreyzehner, 
M.D., MPH, Marion Kainer, M.D., MPH, Director, Healthcare Associated 
Infections and Antimicrobial Resistance program and the rest of the TDH 
staff for its prompt actions and for its succinct directions to the 
provider community.
    THA's role in this event was primarily to act as a conduit for 
information to our members and non-members alike, as it was made 
available from the TDH and other Federal agencies. THA has a data base 
of all key administrative and clinical people in Tennessee's hospitals. 
At various times, at the direction of the TDH, THA provided hospitals, 
both members and non-members, with critical information about the 
crisis and more important, actionable directions on how to treat, or 
not treat those affected patients.
                               chronology
    I believe it would be instructional for the committee to know the 
chronology of events THA has developed from our combined notes and 
calendars. It should be understood this is based on THA material and 
not others, who may differ with our view.

    September 18, 2012--Dr. April Pettit, an infectious disease 
specialist at Vanderbilt University Medical Center, treats the first 
(index) case, realizing this type of spinal meningitis was extremely 
rare. Dr. Pettit alerted TDH to the potential problem. Dr. Kainer 
immediately implements surveillance procedures to determine if there 
were other cases.

    September 20, 2012--TDH identifies two other possible cases. Dr. 
Kainer notifies CDC.

    September 24, 2012--After surveying the clinic where the outbreak 
had occurred, TDH traces tainted product back to New England 
Compounding Center (NECC) and requests from Massachusetts Department of 
Health (MDH) a distribution list of all products shipped to Tennessee.

    September 25, 2012--Tracing records back, TDH determines ``Clinic 
A'' as the likely location for several of the patients. It should be 
noted that the provider community acted immediately, closing the 
suspected clinic and totally supported the TDH investigation. The 
clinic identified and gave all patient information to TDH and provided 
full access to clinical records.

    September 26, 2012--NECC issues a voluntary recall of steroid 
products.

    September 28, 2012--CDC declares the problem a multi-state 
outbreak.

    October 30, 2012--At the direction of Commissioner Dreyzehner, THA 
began acting as a conduit of information to get information to all key 
staff in hospitals and clinics, noting the clear connection to NECC.

    October 5, 2012--Federal Drug Administration (FDA) confirms a 
sealed vial is contaminated and issues a national recall and order to 
cease using NECC products.

    October 8-10, 2012--THA and TDH work together providing constant 
timely information to providers on findings and treatment 
recommendations.

    October 15, 2012--THA hosts a conference call with TDH and key 
hospital staff.

    October 16, 2012--THA staff follows up with personal calls to same 
key staff of all hospitals and clinics that received NECC product to be 
sure the product has been pulled from all clinical areas, including 
crash carts, ambulatory units, etc.

    October 17, 2012--THA briefs FDA on the situation and requests 
guidance on who our providers should contact, what they should say, 
what patient prioritization (surgery, topical, etc.) should providers 
use, and guidance on how to deal with the pediatric population. FDA 
took our request under advisement.

    October 18, 2012--THA, working with TDH, sends out sample 
notification letters, which includes guidance from FDA and CDC. Again, 
THA personally contacts those impacted hospitals and clinics.

    October 19, 2012--THA provides additional information received from 
TDH on media responses, patient letters. This became a burden for 
hospitals not NECC. Also, a flood of ``worried well'' patients began 
showing up in hospital ERs. Hospitals had to take critical staff away 
from patient care to staff call centers to field calls from the 
``worried well.''

    October 20, 2012--To present TDH determines 42 days is the critical 
time for incubation of the disease, and flood of patients begins to 
ease. THA and TDH continue to be in constant contact and alerts are 
sent as needed.
                            lessons learned
    As in any crisis, it is always important to review lessons learned 
to be prepared for the future disaster. The following represent the 
significant findings from THA's perspective.

    1. The Tennessee Health Alert Network, (THAN), developed after 9/11 
was invaluable. Even with THA having an extensive list of key staff, 
THAN alerted providers about the problem much faster than we could have 
otherwise.
    2. Having a transparent and open line of communication with TDH, 
THA and the provider community was the most important element of 
dealing with the crisis. Drs. Dreyzehner and Kainer are to be commended 
for keeping in constant contact and for being willing to utilize a non-
government entity such as THA to transmit accurate and timely 
information. We found it discouraging that Federal agencies weren't 
aware of the role non-governmental entities could play in such an 
emergency.
    3. There needs to be a better system of contacting smaller 
ambulatory care and physician office settings. Getting the information 
to them was mostly through the media.
    4. Better and timelier guidance from Federal agencies is critical. 
There were many questions around whether or not products such as eye 
drops should be given priority status and what providers should tell 
patients. It appeared to those of us in the field that coordination 
among agencies was lacking. One suggestion would be to designate a lead 
agency in a crisis like this and to empower the appropriate staffs to 
give out information to providers and their representatives instead of 
having to ``run it up the flag pole.''
    5. As a follow up to No. 4, a national spokesperson speaking out on 
the crisis would have been very helpful. In Tennessee, Dr. Dreyzehner 
was the very effective face of the crisis. He was transparent, open and 
didn't avoid the tough questions.
    6. This was a supplier issue, not a provider issue. Hospitals, 
doctors and nurses worked on the assumption these drugs were safe; 
however when the crisis erupted, it became their problem, not NECC's. 
It would have been helpful for a Federal agency to make it clear to the 
public that it was NECC's problem, not the provider community. In some 
ways, our doctors and nurses feel as much a victim as our patients.
                               conclusion
    This was a tragedy to our patients, to the trust in the safety of 
our drugs from both the provider and patient perspective and to the 
providers who injected what they thought was safe product. I have 
personally talked with doctors and nurses who have said they are 
devastated by what happened.
    Again, I cannot express enough appreciation to Drs. Dreyzehner and 
Kainer and the entire TDH staff for its support, quick action and 
openness, all of which no doubt saved lives. We have learned from this 
tragedy and will be better prepared for the next one. It is our 
greatest hope that hospitals, doctors and nurses can be assured we have 
safe and adequate medications, to serve the American people.
    Thank you for your time and for allowing me to thank those who 
acted so courageously in dealing with this outbreak.
                                 ______
                                 
           Tennessee Pharmacists Association (TPA),
                                       Nashville, TN 37219,
                                                 November 15, 2012.
Hon. Lamar Alexander,
U.S. Senate,
455 Dirksen Senate Office Building,
Washington, DC 20510.

Re: Response to Request for Testimony Regarding Pharmacy Compounding in 
        Tennessee

    Dear Senator Alexander: The Tennessee Pharmacists Association 
appreciates the opportunity to submit testimony for the record to the 
U.S. Senate Health, Education, Labor, and Pensions (HELP) Committee for 
your November 15, 2012, hearing entitled ``Pharmacy Compounding: 
Implications of the 2012 Meningitis Outbreak.'' We thank you for your 
service to the citizens of Tennessee and our country.
    The Tennessee Pharmacists Association (TPA) is a professional 
organization representing pharmacists, student pharmacists, pharmacy 
technicians and others interested in improving medication use and 
patient care in Tennessee. TPA members provide care in all practice 
settings, including community pharmacies, hospitals, long-term care 
facilities and other settings. TPA and its members are deeply concerned 
about the tragic situation that has occurred as a result of what 
appears to be large-scale manufacturing by a pharmacy in Massachusetts, 
and we are prepared to work with legislators and regulators to assure 
public safety and access to quality medications that meet patients' 
needs. We extend our deepest sympathy to patients and families affected 
by this tragic event.
                    responses to specific questions
    The questions you posed demonstrate a sincere desire to understand 
the complexities of the issue, and Tennessee's pharmacists appreciate 
your commitment. Our responses are provided after surveying TPA member 
pharmacists and reviewing their responses to the questions. In some 
instances, responses are provided that are specific to hospital/health-
system pharmacy practice settings and are so noted.
    To assure a clear understanding of the answers below, we are 
providing the definitions for ``compounding'' and ``manufacturer'' 
found in the Tennessee Pharmacy Practice Act, TCA 63-10-204:

    Compounding

    (4) ``Compounding'' means the preparation, mixing, assembling, 
packaging or labeling of a drug or device:
        (A) As the result of a prescription order or initiative based 
on the prescriber-patient-pharmacist relationship in the course of 
professional practice,
        (B) In anticipation of prescription orders based on routine, 
regularly observed prescribing patterns; or
        (C) For the purpose of, or as an incident to, research, 
teaching or chemical analysis and not for sale or dispensing;

    Manufacturer

    (21) ``Manufacturer'' means any person, except a pharmacist 
compounding in the normal course of professional practice, engaged in 
the commercial production, preparation, propagation, conversion or 
processing of a drug, either directly or indirectly, by extraction from 
substances of natural origin or independently by means of chemical 
synthesis, or both, and includes any packaging or repackaging of a drug 
or the labeling or relabeling of its container and the promotion and 
marketing of such drugs or devices;

    Question 1. What is the appropriate role of compounding pharmacies 
in providing medicines to patients?
    Answer 1. Compounding has been and continues to be an essential and 
integral part of the profession of pharmacy and was the major component 
of pharmacy practice for many years prior to large-scale pharmaceutical 
manufacturing. Compounding allows pharmacists to meet specific patient 
medication needs, including veterinary needs. Pharmacists are educated, 
trained and qualified to provide these services for their patients.
    Generally speaking, compounding of a pharmaceutical product occurs 
when a particular patient has a specific need and the medication dosage 
form or concentration required to treat that need is not available from 
a commercial manufacturer, or is not available due to a shortage. Many 
patient populations require medications that may not be available for a 
variety of reasons. For example:

    1. Pediatric patients, particularly neonates, may require small 
dosages or customized dosage forms that aren't manufactured by an FDA-
approved manufacturer.
    2. Geriatric patients may need a dose in an oral liquid that can be 
administered via nasogastric tubes.
    3. Patients undergoing anesthesia, such as women in labor, require 
medications that must be sterile and free of preservatives in order to 
be safely administered through an epidural injection.

    Increasingly, compounded pharmacy products are also purchased to 
fulfill patient needs for prescription drugs that are not available due 
to manufacturers' shortages or back-order situations. When certain drug 
products cannot be purchased through the routine inventory chains, the 
critical product may only be available through compounding pharmacies. 
Critical shortages continue to contribute to medication safety issues, 
and compounding pharmacies are often the only source of these agents.
    Compounding is a necessary component of the professional practice 
of all pharmacies. Many community pharmacies routinely engage in 
preparation of non-sterile pharmaceuticals. The simple mixing of two 
commercially manufactured products into a new product--such as adding a 
customized flavoring agent--is compounding, as is mixing two creams 
together. Preparing of any intravenous admixture or creating specialty 
pediatric or geriatric dose formulations is also compounding, in that a 
manufactured product is altered for specific patient needs. All 
pharmacists must have the right to compound and prepare a product for 
an individual patient need.
Additional Comments From the Health-System/Hospital Pharmacy Community
    While not every community pharmacy is equipped for sterile 
compounding, it is a necessary component in the daily routine of every 
hospital pharmacy. Compounding pharmacies provide a significant service 
to hospital patients. They formulate therapeutic and diagnostic 
products, make noncommercial formulations, customized preservative-free 
and dye-free formulations, and are essential to meet the needs created 
by national pharmaceutical shortages. Compounding pharmacies fill a 
niche with high-risk compounding, such as non-sterile to sterile IV 
admixtures like cardioplegia solutions or IV Continuous Renal 
Replacement Therapy solutions. Most inpatient hospital pharmacies in 
Tennessee do not have IV rooms that meet structural USP 797 
regulations, nor the equipment, expertise, or testing processes to 
perform this level of compounding safely. Compounding pharmacies can 
provide this service at an extremely high quality. With the critical 
shortages of sterile injectibles, especially medications that are used 
in code or emergency situations, compounding pharmacies also perform 
sterile transfer from larger size injectibles to the size and dosage 
form that is readily available. This prevents serious medication errors 
from occurring and prevents delays in emergency therapy.

    Question 2. What is Tennessee's experience with licensing, 
regulating, and overseeing in-state compounding pharmacies operating 
within Tennessee's borders? Out-of-state compounding pharmacies? Are 
there areas that need improvement?
    Answer 2. The Tennessee Board of Pharmacy has successfully 
regulated all pharmacies providing patient care services in Tennessee, 
including both hospital- and community-based pharmacies that compound. 
Additionally, the Board of Pharmacy regulates manufacturers, 
wholesalers and distributors located in Tennessee. State law requires 
all Tennessee Board of Pharmacy investigators to be pharmacists 
licensed in Tennessee. The Tennessee Board of Pharmacy routinely 
inspects all licensees located in-state to verify compliance with laws, 
rules and standards of practice.
    Tennessee law requires any pharmacy, regardless of whether located 
in-state or out-of-state, providing services to a Tennessee resident to 
be licensed by the Tennessee Board of Pharmacy. Regarding out-of-state 
pharmacies, the Tennessee Board of Pharmacy relies on the Boards of 
Pharmacy in other States for regulation of the pharmacies in their 
respective States. The Tennessee Board does not and cannot conduct on-
site inspections of out-of-state pharmacies to verify compliance with 
Tennessee law and Board regulations. Inspections by out-of-state 
agencies, if conducted at all, may vary widely from State to State, as 
do State rules and regulations. The qualifications of the inspectors in 
other States may vary as well.
    Inspections of pharmacies by qualified personnel are critical. 
Visual, on-site inspection of the premises, the culture of the pharmacy 
staff, and operations are important in assessing the appropriate 
actions of the pharmacy being inspected. We believe all States must 
have requirements for routine and thorough inspections of pharmacies. 
It is imperative that all Boards of Pharmacy be provided sufficient 
resources to employ optimal numbers of pharmacists as inspectors and to 
provide the ongoing training needed by those pharmacist inspectors.

    Question 3. Where do you obtain information about non-resident 
compounding pharmacies? What solutions would you recommend to improve 
the availability and understanding of that information?
    Answer 3. From a regulatory perspective, information on non-
resident compounding pharmacies comes from the Tennessee Board of 
Pharmacy or, if information is shared, from the Board of Pharmacy in 
the State where the pharmacy is originally licensed.
    Most information regarding sources of compounded products comes 
either from hospital pharmacy buying groups or as ``word of mouth'' or 
recommendations from colleagues. Marketing materials or advertisements 
may also be a source of information. Small hospitals would rely heavily 
on such materials, while larger institutions with greater resources at 
their disposal may conduct on-site visits at out-of-state pharmacies.

    Question 4. Is there a way to draw a distinction between 
traditional compounding pharmacies and mass-compounding pharmacies 
similar to what NECC allegedly was doing?
    Answer 4. It is very difficult to definitively differentiate 
between compounding and manufacturing in all circumstances. While it is 
easy to determine that a traditional pharmacy practice providing 
patient-specific, small-volume services as described in the definition 
of compounding is ``compounding,'' the provision of compounded 
medications may be of significant volumes and still be compounding as 
opposed to manufacturing. Manufacturing occurs when individual patient 
needs are not part of the process. Altering drug products in large 
quantities for resale that are not prepared and labeled for specific 
patient use in the final State is manufacturing. Current State and 
national laws need to be enforced to protect our citizens.
    Whatever proposals are considered, we believe it is important that 
State Boards of Pharmacy continue to license and regulate traditional 
compounding, while recognizing that large-scale production of sterile 
products that are not for specific patients may require oversight by 
the Food and Drug Administration (FDA) in cooperation with State Boards 
of Pharmacy. A process for better collaboration and cooperation between 
State Boards of Pharmacy and the FDA would be a step forward.

    Question 5. How do Tennessee providers using an out-of-state 
compounding pharmacy evaluate and determine to use that pharmacy?
    Answer 5. The Tennessee Department of Health has an on-line 
resource that allows healthcare providers to research the licensure of 
all entities through a web portal: http://health.state.tn.us/HCF/
Facilities_Listings/facilities.htm.
    Pharmacists also use an evaluation tool published by the American 
Society of Health-System Pharmacists. This tool can be located at: 
http://www.ashpfoundation
.org/sterileproductstool.
    In addition, pharmacists receive information through hospital 
buying groups and from marketing information received. Again, word of 
mouth or positive recommendations by colleagues can have a major 
influence on selection of out-of-state compounding pharmacies.
    Availability and pricing may be considered in these decisions.

    Question 6. Do you believe that existing adverse event reporting is 
adequate to capture any that may occur as the result of a compounded 
prescription drug?
    Answer 6. The Tennessee Board of Pharmacy rule 1140-03-.14(14) 
states:

          ``The designated pharmacist in charge shall report to the 
        board any situation in which a medical or prescription order 
        has caused serious personal injury or death.''

In Tennessee, reporting of adverse events that occur at this level is 
not an option but a requirement.
    The current national system of voluntary reporting adverse 
medication reactions is probably underutilized for both compounded and 
manufactured medications. While pharmacists support the concept of 
actively reporting adverse reactions to compounded and commercially 
available preparations, the existing system--FDA MedWatch program--is 
designed in such a manner as to actually impede pharmacists' 
participation. There needs to be additional collaboration between the 
FDA and compounding pharmacists, so this system can be widely and 
meaningfully used.
Additional Comments From the Health-System/Hospital Pharmacy Community
    The existing FDA adverse event reporting mechanism commonly 
referred to as MedWatch (https://www.accessdata.fda.gov/scripts/
medwatch/medwatch-online.htm) is cumbersome and time-consuming. 
Furthermore, it is an entirely voluntary process. We believe that the 
vast majority of providers/prescribers are unaware of this reporting 
process. We also believe that many reports are never made due to a fear 
of reprisal.

    Question 7. Do you think there should be a Federal response to 
clarify how compounding pharmacies are regulated in light of other 
actions of NECC?
    Answer 7. We believe that if NECC had been properly categorized as 
a manufacturer (instead of a compounding pharmacy), existing 
regulations as enforced by the FDA would have been adequate to prevent 
this tragedy from taking place. We believe there is a need for more 
stringent oversight and a clearer distinction between compounding and 
manufacturing. The FDA does require clear authority, adequate funding 
and staffing in order to properly inspect and oversee manufacturers of 
pharmaceuticals.
    Unfortunately, there are no laws that will absolutely prevent 
unethical behavior or operations that fall short of recognized 
standards. Thorough and routine inspections by qualified and trained 
individuals and stringent oversight by regulatory personnel are the 
best approaches to prevent these types of situations.
    TPA remains committed to working with Congress, State legislators, 
national and State regulators, and other stakeholders to address any 
regulatory gaps that may exist and reduce the likelihood of any 
problems from compounded products in the future.
    Please contact me if you have questions or need additional 
information regarding the comments that TPA has submitted. Again, thank 
you for requesting input from pharmacists and other health care 
professionals in Tennessee.
            Sincerely,
                                  Baeteena M. Black, D.Ph.,
                                                Executive Director.
                                 ______
                                 
               Tennessee Medical Association (TMA),
                                       Nashville, TN 37212,
                                                 November 14, 2012.
Hon. Lamar Alexander,
U.S. Senate,
455 Dirksen Senate Office Building,
Washington DC 20510.
Re: Meningitis Outbreak

    Dear Senator Alexander: Thank you for the opportunity to make 
comments on the recent nationwide meningitis outbreak. First and 
foremost, our hearts go out to the thousands of patients who sought 
care from physicians for chronic back pain, only to later learn that 
the medication administered was contaminated. Whether the patients were 
diagnosed with fungal meningitis or were fortunate enough not to be 
affected, they all were placed in an unfortunate position that was 
probably preventable had there been more oversight of the Massachusetts 
compounding pharmacy.
    For background purposes, members of the Senate Health, Education, 
Labor, and Pensions Committee should be aware that chronic pain and its 
treatment has become an increasingly visible part of medical treatment 
over the last 20 years. Well-educated and appropriately trained 
physicians will almost always initiate other, less aggressive forms of 
treatment, such as pharmaceutical or physical therapy, before 
initiating spinal injections or even more invasive surgical procedures. 
A provider treating chronic back pain should be somewhat passive when 
starting spinal injections and, if the patient does not get relief, 
stop the treatment regimen.
    Compounding pharmacies, both local to the State of Tennessee and 
those that are external to the State of Tennessee doing business in our 
State, are overseen and licensed by the Tennessee Board of Pharmacy. 
Tennessee physicians believe that our Pharmacy Board performs these 
duties with great care and diligence. We have no reason to believe that 
any patient seen and cared for at any of the three centers which 
received the tainted medication here in Tennessee was provided anything 
but the appropriate standard of care. Our pain physicians in the State 
tell us that they do use compounded drugs for those hard to get drugs 
or for repackaging. Prior to this outbreak, the prevailing perception 
among the physician community in Tennessee was that compounding 
pharmacies were as regulated as manufacturing pharmacies and that 
generally the products they marketed met the necessary quality control 
standards for safety and efficacy.
    We now know differently and believe that Congress can assure the 
development of a transparent and accountable regulatory system, whether 
that be Federal or on a State level, over the production and 
distribution of compounded drugs. It is our understanding that, if the 
company had been licensed as a manufacturer, they would have come under 
the aegis of the FDA. Regulatory gaps should be filled so physicians 
can once again feel safe about the compounded drugs they order. Should 
Congress determine that the Food and Drug Administration is the proper 
entity to oversee this facet of the health care system, we would ask 
you to provide the agency with the necessary authority and resources to 
effectively regulate the industry.
    In terms of the adverse event reporting, existing mechanisms are in 
place to report adverse outcomes. The elusive component of any 
reporting system is ``recognizing'' an event as adverse and related to 
a medication, compounded or not. Fortunately, a very perceptive 
Vanderbilt physician was able to identify the cause of a very bad 
outcome and reported it immediately to State officials. Once 
recognized, capturing and reporting is reasonably straight-forward.
    Since the outbreak was publicized, we have heard from some 
individual physicians specializing in pain care that patients have 
expressed a real reluctance to undertake spinal injections. For some, 
other treatment options may be available but for many the injections 
represent the best long-term hope for relief of their pain. Although 
their reluctance is certainly understandable, such a response limits 
the options available to the treating physician and ultimately will 
mean less-than-acceptable care to the patient. Whatever Congress can do 
to assure consumers that this outbreak represents an opportunity to 
make real change that will minimize the possibility of future 
reoccurrences would be a significant step forward.
    Thank you again for the opportunity to make comments on this issue.
            Sincerely,
                                 Wiley Robinson, M.D., FHM,
                                                         President.
                                 ______
                                 
                 The Commonwealth of Massachusetts,
                                     Boston, MA 02108-4619,
                                                  January 23, 2013.
U.S. Senate,
Committee on Health, Education, Labor, and Pensions,
Attn: Pamela J. Smith, Staff Director; and
Frank J. Macchiarola, Republican Staff Director,
428 Senate Dirksen Office Building,
Washington, DC 20510-6300.

    Dear Ms. Smith and Mr. Macchiarola: Thank you for the opportunity 
to respond to your member's inquiries regarding compounding pharmacy 
oversight and the New England Compounding Center (NECC)--the company 
primarily responsible for the meningitis outbreak that has claimed 
dozens of lives across the country. As the Massachusetts Department of 
Public Health continues to take aggressive actions to protect public 
safety, our ongoing collaboration with your committee is important to 
ensure that this type of tragedy never happens again.
    In Massachusetts, we have taken significant actions to enhance our 
regulations, increase inspection schedules and hold pharmacies 
accountable following this tragic outbreak. And this month, Governor 
Patrick filed strong legislation to further increase oversight of 
pharmacies, including regulation of out-of-state pharmacies and 
reconstitution of our Board of Pharmacy. As we work to raise standards 
in Massachusetts, we urge Congress to act to strengthen Federal 
oversight to address the regulatory grey areas that exist between State 
and Federal regulation.
    The Department is committed to our continued and close 
collaboration with the committee, the Centers for Disease Control and 
Prevention (CDC), the U.S. Food and Drug Administration (FDA), and 
other States' public health officials to investigate the exact cause of 
an outbreak to take the necessary actions to enhance policies and adopt 
best practices both here and across the Nation.
    I welcome the opportunity to continue this work with you, your 
fellow committee members, and the U.S. House Energy and Commerce 
Committee to address these critical needs.
    Below you will find answers to your specific questions. Please do 
not hesitate to be in touch with me or my staff. We thank you for your 
continued leadership.
            Sincerely,
                                Lauren A. Smith, M.D., MPH,
                                              Interim Commissioner.
                                 ______
                                 
    Question 1. Why did the Massachusetts Board of Pharmacy enter into 
a weakened consent agreement with NECC, even after forwarding the 
original, stronger consent agreement (which included a public 
reprimand) to the prosecuting attorneys within the Department of Public 
Health?
    Answer 1. These actions were taken in 2006 during a previous 
Administration and are deeply troubling. An extensive file-by-file and 
e-mail review conducted by staff has yet to uncover any documentation, 
information or communications that clearly describe what transpired 
between the initial consent decree in 2004 and the final actions taken 
by the Board in 2006.
    While NECC bears the primary responsibility for this tragic 
outbreak, it is apparent that Board staff displayed poor judgment, 
missed opportunities and failed to take appropriate action to hold NECC 
accountable. Those individuals who were responsible have been removed 
from their jobs.

    Question 2. Did the Department of Public Health ever consider legal 
action as an alternative to either of the consent agreements?
    Answer 2. As stated above, the lack of documentation related to 
these decisions is troubling. In the absence of such information, we 
cannot clearly establish the array of options that may have been 
considered.

    Question 3. What steps are you currently undertaking to improve 
oversight of compounding pharmacies in Massachusetts?
    Answer 3. Following my testimony before the committee on November 
15, 2012, the Commonwealth has taken significant actions to this 
effect, which I am happy to share with you.
    We advanced emergency regulations that went into effect immediately 
on November 1, 2012, to enhance our ability to monitor the sterile 
compounding industry. The new regulations require sterile compounding 
pharmacies in Massachusetts to report, for the first time, volume and 
distribution figures to the State, which will alert the Board of any 
pharmacy that is acting like a manufacturer, which requires an FDA 
license.
    The regulations also require all licensed pharmacies and 
pharmacists to report to the Board when they are the subject of any 
disciplinary action by any State or Federal agency. This will allow the 
Board to know when other entities have identified issues with 
Massachusetts-licensed pharmacies.\1\
---------------------------------------------------------------------------
    \1\ Please note that the Massachusetts Board of Pharmacy voted on 
final regulations as described on January 8, 2013. These regulations 
will become final once published within the Massachusetts Register on 
February 1, 2013.
---------------------------------------------------------------------------
    Nearly 40 pharmacies have been inspected since Governor Patrick 
directed the Board of Pharmacy to begin checks of compounding 
pharmacies that produce sterile injectable medications. These 
inspections identified problems in several pharmacies for which new 
cease and desist orders have been issued and corrective plans have been 
put into place.
    Other pharmacies that have been inspected have come back with minor 
deficiencies that have since been corrected, or are currently being 
addressed. Unannounced inspections of compounding pharmacies that 
produce sterile injectable medications will continue until all have 
been inspected.
    We also announced changes at the Massachusetts Board of Pharmacy, 
with three new members who work across diverse health care settings 
filling seats on the Board.
    In October 2012, the Governor established a Special Commission on 
Pharmacy Compounding as part of the Administration's comprehensive 
response to the outbreak. The Commission met regularly, looking at best 
practices in other States and exploring changes to the law to help 
address the regulatory gray area surrounding compounding pharmacies. A 
final report was issued on January 4, 2013.
    Building on the recommendations identified by the Commission, on 
January 4, 2013 Governor Patrick also announced the filing of 
legislation to reform the Board of Pharmacy and strengthen the 
Commonwealth's oversight of the compounding pharmacy industry in 
Massachusetts. Specifically, the legislation:

    1. Requires a special license for sterile compounding that will 
enable regulators to better track and hold pharmacies accountable for 
their practices;
    2. For the first time, authorizes the Board to assess fines against 
Massachusetts-licensed pharmacies that violate Board of Pharmacy 
policies, regulations, or statute; and establishes whistleblower 
protections for pharmacists and pharmacy staff;
    3. Requires licensure for out-of-state pharmacies that deliver and 
dispense medications in the Commonwealth;
    4. Establishes a clear process to restructure and reorganize the 
composition of the Board of Pharmacy, ensuring more balanced 
representation of background of Board members to improve oversight of 
the industry. The Board will include more members not practicing in the 
industry they are responsible for regulating. Under the legislation, 
the eleven (11) member Board would be comprised of four pharmacists, 
one pharmacy technician, one nurse, one physician, one quality 
improvement expert, and three public members who have experience in 
healthcare delivery or consumer advocacy.

    Question 4. FDA inspectors released recently a report last week 
from their recent investigation of Ameridose--a company owned and 
managed by the same families as the New England Compounding Center. 
This report included the following description of the conditions they 
found--I quote:

          `` . . . insects were observed to be located in the 
        unclassified area where finished sterile product is packaged 
        and stored. The insects were also located within approximately 
        3 to 10 feet of the controlled area where sterile products are 
        manufactured. At least one bird was observed flying in the 
        unclassified area where sterile finished product is packaged 
        and stored.''

    How do you explain the fact that Ameridose was shipping products 
all over the country that had been manufactured under these 
circumstances, given the years of complaints about both the New England 
Compounding Center and Ameridose?
    Answer 4. In the course of its licensure in Massachusetts, 
Ameridose had been subject to one complaint, pertaining to potential 
patent infringement. This issue was settled between Ameridose and the 
complainant.
    During previous licensure inspections, Board staff did not identify 
any findings similar as those witnessed during the joint inspection 
with the FDA. As soon as we learned of these issues, we took action to 
suspend operations at Ameridose and NECC's other sister companies. The 
FDA secured a recall of all Ameridose products and the company remains 
closed.
    These events have clearly indicated that the complaints-driven 
inspection policies that were used by Massachusetts and continue to be 
used by many States are insufficient to provide comprehensive oversight 
to compounding pharmacies. It is important to know how a pharmacy is 
operating when they are not scheduled for an inspection. That is why 
Massachusetts now has unannounced inspections of all pharmacies 
compounding sterile injectable substances and we have advanced new 
regulations to enhance our inspection schedules.

    Question 5. Many State Boards of Pharmacy rely on the Board of 
Pharmacy in the State where a pharmacy is physically located to conduct 
inspections, since most Boards of Pharmacy do not have the capacity to 
inspect pharmacies across the country. Given the current crisis, how do 
you think Minnesota's Board of Pharmacy can make sure that a pharmacy 
in Massachusetts is shipping safe products into Minnesota? Does the 
current system work?
    Answer 5. As you have pointed out, limited, geographic-bound 
resources require greater, more consistent and streamlined 
communications between States, as well as our Federal partners. 
Although we have taken great strides to increase oversight in 
Massachusetts, similar progress is needed at the Federal level. The 
Federal Government's role in oversight of interstate commerce is 
essential to our shared success. Likewise, the FDA must fulfill its 
obligation to ensure that manufacturers declare themselves as such and 
abide by all Federal laws and regulations. In Massachusetts, our Board 
of Pharmacy has adopted emergency regulations that require every 
pharmacy to report within 7 business days all adverse events relating 
to the preparation of medications in that pharmacy. Additionally, 
pharmacies in Massachusetts are now required to share all disciplinary 
actions taken by other States and the FDA on receipt. While this does 
not substitute for clear, regular and streamlined communications 
between all parties, I believe these to be important steps forward to 
ensure this never is allowed to happen again.
    As outlined in the Department's response to Question 3, through the 
Governor's filed legislative reform, the Board will now have the 
authority to regulate out-of-state compounding pharmacies that ship 
medications into Massachusetts through the development of an out-of-
state oversight process. The Board will also gain the authority to 
create an alternate licensure category for pharmacies that pose a 
higher risk to the public, and to levy fines against these licensees 
where appropriate. Additionally, Massachusetts is working with our 
Commission on compounding pharmacies as well as the National 
Association of Boards of Pharmacy (NABP) to further address these 
issues and make enhancements where necessary.

    Question 6a. In addition to the report from the FDA of infestations 
of insects, vermin, and even a bird in Ameridose's facility, according 
to the FDA's inspection report, Ameridose did not adequately test 
sterility or log complaints from patients and reports of adverse 
events. Can you clarify the requirements of a compounding pharmacy in 
the Commonwealth of Massachusetts regarding sterility testing and the 
reporting of complaints and adverse health events?
    Answer 6a. The Massachusetts Board of Pharmacy regulation 247 CMR 
9.01(3) requires that ``a pharmacist shall observe the standards of the 
current United States Pharmacopoeia.'' Briefly, United States 
Pharmacopoeia (``USP'') requires the following testing:

     Viable particle testing must be done every 6 months at a 
minimum and when certifying new equipment, following any servicing of 
facilities or equipment, and in response to issues of compounded 
sterile preparations (CSPs).
     Sampling of compounding personnel glove fingertips, at 
least annually.
     Media fill test, at least annually.
     All high-risk level CSPs that are prepared in groups of 
more than 25 identical single dose packages or multi-dose vials must 
meet sterility tests before they are dispensed/administered. (They also 
have to be tested for bacterial; endotoxins (pyrogens)).

    Additionally, the emergency regulation, 247 CMR 6.15(5), adopted on 
November 1, 2012 requires pharmacies to attest to compliance with USP 
<797>. In the Spring of 2012, the Board began requiring new pharmacies 
that engage in sterile compounding to complete a USP <797> Gap 
Analysis. Presently, inspections of pharmacies engaged in sterile 
compounding focus on compliance with USP <797>.
    The emergency regulation, 247 CMR 6.15(6), adopted on November 1, 
2012, requires every pharmacy to report within 7 business days all 
errors that occur during the preparation of medications in that 
pharmacy, building on previously established reporting requirements for 
medication errors that led to patient harm.

    Question 6b.  Had these requirements been fully implemented, would 
they have been sufficient? Does the State have the capacity to enforce 
these requirements?
    Answer 6b. Massachusetts has the authority to enforce its 
regulations, which require compliance with USP <797> and reporting of 
adverse events, and to impose disciplinary action for any violation of 
its regulations. 247 CMR 6.15(5);247 CMR 9.01(3); 247 CMR 10.03.

    Question 6c. Does the State have the capacity to enforce these 
requirements for compounding pharmacies located in other States that 
are shipping into Massachusetts--for example, the statewide requirement 
that Minnesota also has on the books that sterile products be 
compounded according to the United States Pharmacopea?
    Answer 6c. The Governor's proposed legislation introduces an out-
of-state licensure category, currently not in existence in 
Massachusetts. Through comprehensive requirements on all pharmacies 
that seek to ship medications to the Commonwealth, we will gain the 
authority to enforce requirements in the quality and safety of 
compounding processes.

    Question 7. After reviewing the documents and looking at the 
timeline, it is clear that NECC had multiple violations of 
Massachusetts pharmacy law. What, in addition to the multiple 
violations and inspection reports, would prompt the Board to suspend or 
revoke a pharmacy license?
    Answer 7. Under my leadership, the Board and DPH will continue to 
act swiftly to hold pharmacies and pharmacists sufficiently responsible 
for their actions. While I was not at the Department during the 
deliberations around NECC's 2006 consent agreement, it is my position 
that the action was insufficient given the severity and volume of 
deficiencies from their initial licensure in 1998 through 2004. Since 
we learned of this crisis, we secured suspension of operations at NECC 
and its sister companies and launched unannounced inspections of all 
pharmacies compounding sterile injectible substances, which have also 
resulted in additional cease and desist orders and corrective plans.

    Question 8. How often do you suspend or revoke licenses, and what 
factors are considered when deciding between different disciplinary 
actions? What is the process to suspend or revoke a license, both when 
you have the consent of the company and you do not?
    Answer 8. Inspections and resulting disciplinary actions by the 
Board, including but not limited to suspensions and revocations of a 
pharmacy's retail license, constitute a complaint-driven process. As 
defined with the Board of Pharmacy, a ``complaint'' is a formal 
proceeding and does not refer to the colloquial use of the word. The 
Board receives approximately 300 complaints per year. The Board opens a 
``complaint'' after receiving information about issues with a licensee, 
and establishing that an investigation is warranted.
    Complaints that warrant disciplinary action are often a result of 
identified deficiencies found in the course of an inspection. 
Historical data is readily available for the 6 years of the Patrick-
Murray Administration (January 2007 through December 2012). During this 
time period, the Board identified deficiencies during its inspections 
of the self-identified sterile compounding pharmacies on eight 
occasions. In seven of these instances, the deficiencies were resolved 
without the need for further Board action; however, Board action was 
required in one case. (See CIVAS complaint history, appended and 
referenced as Attachment A.) While Attachment A provides a thorough 
summary of the history, below are examples of types of deficiencies 
noted:

     Failures to maintain required documentation (e.g., 
perpetual inventory for controlled substances);
     Unregistered technician observed working in control room;
     Failure to maintain appropriate supervisory ratios;
     Equipment lacking and having outdated seals and/or 
certification (e.g., balance);
     Broken equipment (e.g., thermometer in ante room);
     General concerns regarding cleanliness;
     Refrigeration concerns (e.g., refrigeration logs with 
temperature readings below recommended level);
     Expired drugs on shelves; and
     Inadequate security (e.g., door left ajar).

    Should a complaint warrant Board action, the Board can choose to 
take either a disciplinary or non-disciplinary action. The 
Massachusetts General Laws grant the Board the authority to take 
various disciplinary and non-disciplinary actions. Disciplinary actions 
are intended for those described in our regulations that result in a 
permanent mark on a licensee's record that is publicly reported and 
available to consumers on our Web site. Disciplinary actions may 
include: suspension, revocation of personal registration, pharmacy 
permit, license or controlled substance registration, reprimand or 
censure of the registrant or licensee, cease and desist notice, consent 
agreement or probation. Non-disciplinary actions may include a non-
disciplinary warning letter, advisory letter, a consent agreement with 
non-disciplinary actions, or dismissal of the complaint. The actions 
available to the Board are summarized with the corresponding statutory 
authority (See Attachment B). It should be noted that Governor 
Patrick's recently filed legislation authorizes the Board to assess 
fines against Massachusetts-licensed pharmacies that violate Board of 
Pharmacy policies, regulations, or statute.
    From 2002-12, the Board recorded sixty-eight (68) disciplinary 
actions taken against Massachusetts retail pharmacies:

    Year 2002--No. of Disciplinary Actions: 1
    Year 2003--No. of Disciplinary Actions: 4
    Year 2004--No. of Disciplinary Actions: 2
    Year 2005--No. of Disciplinary Actions: 4
    Year 2006--No. of Disciplinary Actions: 2
    Year 2007--No. of Disciplinary Actions: 4
    Year 2008--No. of Disciplinary Actions: 9
    Year 2009--No. of Disciplinary Actions: 9
    Year 2010--No. of Disciplinary Actions: 11
    Year 2011--No. of Disciplinary Actions: 17
    Year 2012--No. of Disciplinary Actions: 5

    Question 9. Please briefly discuss past situations in which the 
Board has revoked a license. What violations were evident in those 
facilities? Was the revocation communicated to other State boards or 
the FDA?
    Specifically, were any revoked for violations of the patient-
specific prescription rule? What were the circumstances?
    Answer 9. Since January 1, 2000, the Massachusetts Board of 
Pharmacy has taken action against 14 pharmacies, to revoke, suspend, or 
summarily suspend licensure, or enter into a consent agreement for 
surrender of licensure. None of the 14 instances involved violation of 
the patient-specific prescription rule. The circumstances varied, and 
include: Medicaid fraud (false claims to MassHealth), improper storage 
or handling of drugs; failure to maintain proper sanitation; 
repackaging and redispensing medications that had been returned; issues 
involving sample medications; sale of drugs to an unlicensed entity; 
and failing to keep medications properly labeled leading to dispensing 
errors.
    Staff formerly employed to support the Board of Pharmacy did not 
maintain sufficient records to clearly delineate when actions were 
shared with either the FDA or other relevant State Boards. Going 
forward, the Department is conducting an extensive audit of all 
operational policies and procedures in all nine (9) health professions 
licensure boards supported by DPH staff. These efforts will facilitate 
alignment of these entities, ensuring uniformity and enhanced quality 
control of these critical functions.

    Question 10. Please describe any standard operating procedures that 
were put in place since September 25 to facilitate communication and 
coordination with other boards of pharmacy. How is any disagreement 
with another board of pharmacy resolved?
    Answer 10. See response to Questions 3 and 5.
    Question 11. How often do you contact other State boards of 
pharmacy? Do you know which of your pharmacies ship out-of-state, and 
do you ever get requests to inspect those facilities? How do you 
respond to such requests?
    Answer 11. On November 1, 2012, the Massachusetts Board of 
Registration in Pharmacy adopted emergency regulations that include the 
following provision:

          ``Every pharmacy licensed pursuant to M.G.L. c. 112, 39, 
        that performs central intravenous admixture services (CIVAS), 
        or engages in sterile compounding, shall report to the Board 
        every 6 months, or upon request by the Board, at a minimum, the 
        following information:

          (a) total number of prescriptions dispensed, distribution 
        data identifying the States in which the prescriptions were 
        distributed, status of any non-resident licenses issued by 
        other States, hood certifications required by 247 CMR 
        6.01(5)(c) 5, status of CIVAS approval is) where applicable, 
        and any other information required by the Board.
          (b) All such report shall be accurate and comply with the 
        Board's reporting requirements.
          (c) All reports shall be accompanied by an affidavit 
        attesting compliance with all laws and regulations pertinent to 
        sterile compounding. This attestation shall be made under pains 
        and penalties of perjury, and include attestation to the 
        following: ``this registrant/licensee only prepares and 
        dispenses medication pursuant to a valid prescription as 
        defined in M.G.L.
          c. 94C for a single patient, regardless of whether the 
        medication is prepared for a Massachusetts or out-of-state 
        patient.''--247 CMR 6.15(5).

    Prior to enactment of these regulations, there was no formal 
mechanism for designating which pharmacies shipped their products to 
other States.

    Question 12. I am concerned that if a State board wants to know the 
history of a facility, not all the information is reported and it is 
hard to know the full compliance history. I understand the National 
Association of the Boards of Pharmacy keeps a database with this 
information. Could you describe which of the numerous actions against 
NECC in the past 14 years were reported to NABP, or how the actions 
were made known to other State boards of pharmacy?
    Answer 12. All of the dispositions taken against NECC were non-
disciplinary. As a result, none of the Board actions would have likely 
been reported to the Healthcare Integrity Protection Data Bank (HIPDB) 
and the National Practitioner Data Bank (NDBP). These actions included 
the 1999 informal reprimand (against both NECC and Barry Cadden, the 
co-owner and head pharmacist of NECC, as an individual), the September 
30, 2004 advisory letters to NECC, the January 2006 consent agreement 
(specifically agreed not to report), and the 2010 Ameridose complaints.
    This highlights what I have said before: that poor judgment, missed 
opportunities and a lack of appropriate action allowed NECC to continue 
on this troubling path.
    The Division of Health Professional Licensure (DHPL) reports 
disciplinary actions against its licensees in several ways. First, the 
Board reports disciplinary actions with respect to pharmacists and 
pharmacy technicians to the HIPDB. The Board also reports disciplinary 
actions with respect to pharmacies to the NPDB. In both instances, 
Board staff prepares an internal report that Division staff use to 
enter into the Federal databases within a day of action. The reported 
disciplinary actions include not only the initial discipline imposed 
(e.g., suspension of license), but also subsequent changes (e.g., 
reinstatement of licensure, with probationary status).
    In addition to the foregoing, the Board maintains a spreadsheet, 
listing the disciplinary licensing actions reported to HIPDB and NPDB. 
As I mentioned before, under previous Board policy, non-disciplinary 
actions were not reported publicly, something both the Board and the 
Commission are actively reexamining. This spreadsheet is cumulative for 
the period beginning in calendar year 2005 (fiscal year 2006) to the 
present. During the first week of each month, Board staff updates this 
spreadsheet with the NPDB and HIPDB reports made during the preceding 
months. The spreadsheet is then emailed to individuals or entities on a 
distribution list. The distribution list includes the National 
Association of Boards of Pharmacy (NABP), specifically, 
[email protected]. DPH cannot comment on NABP policy as to how 
this information is then reviewed and shared more broadly.

    Question 13. In general, what actions do you report to NABP 
regarding pharmacies in Massachusetts? Could you describe the line 
between what you must report, and what is not reported?
    Answer 13. These tragic events have made one thing clear: timely 
information and communication, acted on swiftly is critical in ensuring 
public health and safety. As I have described in answering Question 12, 
there are clear policies in place for Board staff to report these 
incidents to NPDB and HIPDB.
                              ATTACHMENTS




















                                 ______
                                 
      Response of Marion Kainer to Question of Senator Whitehouse
    Question. Dr. Kainer, your testimony notes that electronic health 
records allowed ``tremendous'' savings in time and resources. How were 
electronic health records used by health care providers and the 
Tennessee Department of Health? Are there best practices you would 
recommend for other State health departments regarding the use of 
electronic health records during a public health crisis?
    Answer. All of the hospital systems caring for patients in 
Tennessee used an electronic health record to record most of their 
health information when they were inpatients. At the beginning of our 
investigation and response, as in past responses to other outbreaks, we 
sent staff to the facilities to review key records on site and 
requested faxed copies of other records. This approach provides access 
to the needed records, but it is slow and involves many staff to 
process all the requests. In general, these are the same hospital staff 
who are needed at the healthcare facility as part of their response, so 
their availability is limited.
    In the context of an evolving outbreak, when the number of cases is 
increasing rapidly and our understanding is evolving quickly, the 
questions being asked are also rapidly changing. This leads to repeated 
requests for additional records on both old and new patients. The 
process of obtaining vital information can become very slow.
    Early in this outbreak response, the Tennessee Department of Health 
worked with all five hospital facilities caring for case patients to 
obtain remote electronic access to inpatient medical records from 
Health Department computers. This allowed our staff to quickly gather 
additional information on existing patients and to initially review new 
patient records, without having to visit the facilities or take the 
time of medical staff to assist with access. This provided more 
immediate and complete access to information than ever before.
    As a result, we reduced the time to completing our analyses 
substantially, leading to better information for patients and 
clinicians in Tennessee, and the CDC. Rapid access to source data also 
allowed us to quickly compose a detailed summary of our findings, which 
was published in the New England Journal of Medicine * much more 
quickly than if we had not had access to electronic records. This 
allowed a broader audience to receive detailed information about the 
outbreak they could use to guide patient evaluation and care.
---------------------------------------------------------------------------
    * A summary of the findings mentioned may be found at www.nejm.org/
doi/full/10.1056/NEJMoa1212972.
---------------------------------------------------------------------------
   Response of David G. Miller, R.Ph., to Questions of Senator Enzi, 
                   Senator Casey, and Senator Franken
                              senator enzi
    Question 1. How do you define traditional compounding? What, if 
any, additional regulations should be placed on pharmacies that ship 
large quantities of products interstate? Is there a larger Federal 
role?
    Answer 1. IACP does not have a definition of ``traditional'' 
compounding nor does one exist within our profession. We are very 
concerned that this term has been referenced by numerous individuals, 
organizations, and agencies and is both broad and subject to 
significantly variable interpretation depending upon who is referencing 
``traditional.''
    We believe the focus should not be on the creation of a definition 
of traditional vs. non-traditional but a more close examination of what 
constitutes compounding--the preparation and issuance of a medication 
upon receipt of a valid prescription from an authorized prescriber--and 
what constitutes manufacturing--the preparation, promotion, selling and 
distribution of a medication when no authorized prescriber is involved.
    The manufacture of a medication cannot be judged, therefore, on the 
basis of quantity. It is not the amount or even the process of 
compounded medicine that is produced. Rather, it is an examination of 
the transaction in and of itself. A very busy, very large pharmacy can 
legitimately and appropriately compound and dispense medications intra- 
or interstate based upon the receipt of valid prescriptions from 
authorized prescriber and still remain a pharmacy. On the other hand, a 
small pharmacy can be engaged in manufacturing if the preparation and 
issuance of a compounded medication is done without a prescription or 
medical order from an authorized prescriber.
    We believe that an immediate area to be addressed is the 
communication link between the State Boards of Pharmacy and the Food 
and Drug Administration. State Boards are in the best position to 
determine whether their license or permit holding pharmacies are 
exceeding the scope of pharmacy practice and engaging in manufacturing-
like activities. In those instances, the State Board should have a 
liaison or communication channel to the FDA for followup inspection and 
action as the Federal agency has jurisdictional authority over 
manufacturing including illegal manufacturing by pharmacies or other 
entities.

    Question 2. Are there basic standards that all sterile compounding 
facilities should be held to, such as USP 797? How would that be 
enforced?
    Answer 2. IACP supports enactment of legislation or regulations 
which mandates the compliance with USP <797> standards by any 
practitioner or practice site involved in the preparation of sterile 
compounds. That includes all pharmacists as well as physicians, 
veterinarians or any other health care practitioner who compounds 
sterile preparations. Additionally, all settings including hospitals, 
home infusion companies, long-term care facilities, hospices, etc., 
should be held to the same accountability of adherence to these 
industry-wide standards.
    IACP also supports enactment of legislation or regulations which 
mandates compliance with USP <795> standards by any practitioner or 
practice site involved in the preparation of non-sterile compounds as 
well.
    Since States issue the licenses and permit for operation to a 
pharmacy, they are the first enforcement agency that should be 
responsible for conducting regular, unannounced inspections of all 
sterile compounding facilities.
    Should you have any further questions or wish clarification on our 
responses, please do not hesitate to contact us. In the meantime, 
please accept our best wishes for a wonderful holiday season.
                             senator casey
    Question 1. How many prescriptions are filled annually by 
compounding pharmacists, and of those, how many are filled in a non-
hospital/outpatient setting?
    Answer 1. Unfortunately, no database exists which tracks all 
prescriptions filled in the United States--compounded preparations 
included. It has been estimated by the International Journal of 
Pharmaceutical Compounding that 1-3 percent of all outpatient 
prescriptions are compounded on an annual basis.

    Question 2. When a compounding pharmacist ships drugs interstate in 
response to a valid prescription, are the products shipped directly to 
the patient or to the patient's provider? Does it depend on the type of 
product?
    Answer 2. It depends upon the prescription itself (the actual order 
from the authorized prescriber), the type of medication ordered, the 
directions given by the prescriber, and the express request of the 
patient.
    Some patient-specific medications can be delivered directly to the 
patient or, if requested to do so by either the patient or the 
prescriber, be delivered to the prescriber. In the latter case, that is 
often done when the administration of the medication is done by the 
prescriber him/herself. An example of that would be intrathecally 
administered medicines. Because those drugs are infusions, the 
integrity and stability of the medicine must be maintained. Minimizing 
steps in transport (e.g., pharmacy to patient then patient to 
physician) and controlling such things as temperature or security is 
one means of assuring that integrity.

    Question 3. How many of your members are accredited by the Pharmacy 
Compounding Accreditation Board? Have these numbers been increasing?
    Answer 3. As a professional society, IACP's membership is comprised 
of individuals: pharmacists, pharmacy technicians, student pharmacists 
and others involved in the specialty practice of compounding. The 
Pharmacy Compounding Accreditation Board accredits pharmacies--the 
physical business in which pharmacists practice. PCAB does not accredit 
individual practitioners; therefore, no IACP member is accredited by 
PCAB. As of December 1, 2012, PCAB currently accredits 168 pharmacies. 
According to their staff, there are approximately 40 additional 
pharmacies in various stages of the accreditation process. Since the 
NECC crisis, PCAB has seen a 400 percent increase in applications by 
pharmacies to begin the accreditation process.

    Question 4. What is IACP doing to encourage its membership to 
pursue accreditation and take other steps to ensure their compounded 
products are safe?
    Answer 4. IACP is a founding member of the Pharmacy Compounding 
Accreditation Board (PCAB) and has many members serving on its standing 
committees as well as providing a representative to its eight-person 
board of directors. IACP provides PCAB with complimentary exhibits at 
its national meetings and advertising space in its publications to 
raise awareness of the Board. All new members of IACP also receive PCAB 
information upon joining the Academy. Our most recent issue of our 
electronic magazine--Custom Rx Connection--featured an extensive 
article for the PCAB executive director. Additionally, our bi-weekly 
electronic newsletter also announces all newly accredited and re-
accredited PCAB pharmacies as part of our efforts to promote 
accreditation.
    IACP conducts both live and web-based accredited continuing 
education programs for its members and non-members on compounding 
standards and safety. The Academy began a collaboration with the United 
States Pharmacopeia (USP) earlier in 2012 which brings their seminars 
on standards and safety to all pharmacists through our educational 
portal.

    Question 5. Dr. Hamburg discussed a possible risk-based framework 
for the regulation of compounding, recognizing that certain compounded 
products inherently pose a greater potential risk to patients should 
they be handled improperly. Could you share your comments on FDA's 
proposed framework?
    Answer 5. Neither IACP nor its colleague professional associations 
have been provided sufficient details to determine whether or not the 
FDA's concept of a ``risk-based framework'' will lead to a meaningful 
change in their enforcement of regulatory authority. We continue to 
have a dialog with the agency to find solutions that will prevent a 
future NECC-like catastrophe; however, as outlined by Commissioner 
Hamburg, the proposed framework raises significant questions about 
scope and intent.

    Question 6. Do you feel that taking risk into account is 
inappropriate? If so, what alternatives would you suggest?
    Answer 6. IACP does not believe that the proposed framework from 
the FDA fully defines the concept of ``risk'' as it is understood in 
the professional practice community. Healthcare professionals are 
trained to assess risk of therapy but the agency's definition is not 
consistent with that commonly understood definition. Some medicines are 
technically difficult to compound because of the nature of the drug 
chemical or procedures necessary to obtain a finished preparation while 
others are clinically risky and inappropriate because they are known to 
have significant side effects and may cause harm to patients. Our 
Academy believes that developing a consensus-based definition between 
the pharmacy and medical practice communities in conjunction with State 
and Federal regulatory authorities must be undertaken before any 
framework can be addressed.

    Question 7. How do you propose drawing a clear line between 
traditional compounding for individual patients and large-scale 
compounding that much more closely resembles manufacturing? Clearly, 
there is confusion as to where this line is currently and where it 
should be.
    Answer 7. IACP's position is that there is a clear demarcation 
between compounding and manufacturing. The issue is not whether a 
pharmacy is compounding in ``large-scale'' amounts--a term that is 
nearly indefinable--but whether they are compounding pursuant to a 
valid prescription or medical order from an authorized prescriber. 
Pharmacists dispense prescription drugs only when instructed to do so 
through the form of a prescription or medical order. Manufacturing is 
substantially different. A manufacturer is permitted to sell 
medications to a facility, hospital, wholesaler, pharmacy or directly 
to a prescriber without a prescription or medical order. Compounding 
and dispensing is driven by prescriber decisionmaking. Manufacturing is 
a purchase decision made without any prescriber input. All States 
define what constitutes a ``valid prescription'' and also designate 
which persons are considered ``authorized prescribers.'' IACP believes 
that existing Federal statutory and regulatory language defines what 
constitutes a manufacturer and that the Food and Drug Administration 
has clear oversight authority in that arena.
                            senator franken
    Question 1. In a report on meningitis in 2002, the Centers for 
Disease Control and Prevention reported that ``some health-system 
pharmacists might not realize that they are purchasing injectables 
prepared through compounding.'' The CDC report continues by stating 
that ``purchasers of pharmaceuticals should determine if supplies are 
provided from a compounding pharmacy that is licensed in their State 
and that follows appropriate measures to ensure that injectable 
products are free of contamination.'' What responsibility do you 
believe that purchasers of compounded products should have to make sure 
that the products they're giving to their patients are safe?
    Answer 1. IACP believes that all purchasers of compounded 
preparations are as equally responsible for assuring the quality and 
safety of the medications they obtain as they are for products 
purchased from pharmaceutical manufacturers. That is a responsibility 
which all pharmacists in the medication supply chain have been trained 
to do and should do.
    When it comes to compounded preparations, the responsibility is 
even greater. Last year and in light of the ongoing drug shortage 
situation, IACP developed a tool to assist physicians and pharmacists 
in making informed decisions about professional partnerships with 
compounding pharmacies. This tool includes a step-wise checklist that 
includes such things as verification of licensure status, accreditation 
status, standards and processes for regular testing and validation, as 
well as recommendations to conduct an on-site interview and inspection. 
Called the Compounding Pharmacy Assessment Questionnaire 
(CPAQTM), IACP distributed that tool to State and national 
medical, hospital, and pharmacy associations upon its release in 
October 2011. A copy of the CPAQTM is included for your 
review and is also available for download at the Academy's Web site 
http://www.iacprx.org.
                                 ______
                                 
                              ATTACHMENTS

[International Academy of Compounding Pharmacists (IACPTM), 
                            October 5, 2011]

IACP Provides Meaningful Solution With Compounding Pharmacy Assessment 
                             Questionnaire
rising medication shortages affect patient health--new iacp tool helps 
     evaluate pharmacies for needed compounded medication services
    Houston.--As hospital medication shortages continue to increase by 
the day within the North American healthcare system, the International 
Academy of Compounding Pharmacists (IACP) has developed a new 
assessment questionnaire to assist hospitals, practitioners and non-
compounding pharmacies identify and evaluate compounding pharmacies as 
they seek alternative sources for medications that currently are in 
limited to complete shortage status.
    IACP's Compounding Pharmacy Assessment Questionnaire 
(CPAQTM) provides a comprehensive checklist of what to look 
for in a compounding pharmacy practice and is based upon United States 
Pharmacopeia (USP) standards which compounding pharmacists are 
obligated to follow according to State board of pharmacy regulations or 
standards of practice. Collaboration between licensed compounding 
pharmacists and their colleagues in hospitals and institutions is a 
long-standing solution to back-orders and shortages but the current 
shortage situation is at a crisis point for many health-systems. The 
expertise of a compounder with access to APIs (Active Pharmaceutical 
Ingredients--the pure, raw drug ingredient) can mean the difference 
between continued or initiation of much-needed medicines or an 
unnecessary delay in patient care.
    IACP's Compounding Pharmacy Assessment Questionnaire 
(CPAQTM) includes evaluation points in the following areas:

     Regulatory compliance
     Licensing--permits
     Internal controls and quality assurance
     Testing & verification
     Site visits

    Linda F. McElhiney, PharmD, R.Ph., FIACP, FASHP, compounding 
pharmacy operations coordinator, Indiana University Health, says,

          ``Drug shortages have been an ongoing problem for healthcare 
        facilities and the number of drug products that are unavailable 
        due to manufacturer backorders and discontinuation is on the 
        rise. These facilities are often trying to find substitutions 
        for the drug products or alternative treatments and there is 
        often a delay in the patients' treatment. Compounding 
        pharmacies may be able to prepare these medications using bulk 
        active pharmaceutical ingredients; however, it may be difficult 
        for the healthcare pharmacy administrators to know if the 
        compounding pharmacy can provide quality compounded medications 
        to meet their facilities' needs because they are unfamiliar 
        with the USP standards for compounding sterile and non-sterile 
        preparations. The International Academy of Compounding 
        Pharmacists (IACP) has developed a checklist of standards and 
        criteria to assist the administrators in finding a suitable 
        compounding pharmacy to meet these needs.''

    Scott Karolchyk, R.Ph., FIACP, IACP president-elect, says,

          ``IACP leadership recently participated in FDA's conference 
        on prescription drug shortages. While there were many good 
        intentions expressed during the conference, there were no real 
        solutions for now. Each day, pharmacists and physicians are 
        grappling with making sure our patients get the medicines they 
        need. What was clearly overlooked was how compounding 
        pharmacists are providing solutions today as they work with 
        U.S. hospitals, surgery centers, and practitioners to make 
        those medicines available.''

    John Herr, R.Ph., IACP president, asked, ``What better solution to 
this problem than pharmacists working intraprofessionally to take care 
of patients?''

          ``The CPAQ tool is compounding pharmacy's way of stimulating 
        that relationship. Given that compounders have an outstanding 
        track record for preparing quality medications on a per-
        prescription basis, we know that working together will lessen 
        the need to use the so-called `gray market' of suppliers, 
        distributors and others which are taking advantage of people in 
        need.''
                               about iacp
    The International Academy of Compounding Pharmacists (IACP) is a 
professional association founded in 1991 to protect, promote and 
advance personalized medication solutions. The association represents 
more than 2,100 pharmacists and pharmacist technicians licensed and 
regulated by their individual State boards of pharmacy and located 
throughout North America, South America, Europe, Australia and Asia. In 
addition, IACP represents more than 154,800 patients, physicians, nurse 
practitioners and veterinarians through its ally grassroots 
organization, Patients & Professionals for Customized Care (P2C2). IACP 
is committed to ensuring the rights of physicians to prescribe, of 
pharmacists to prepare, and of patients to take personalized medication 
solutions that meet their unique, individual health needs.
    IACP offers a free Compounding Pharmacy Locator Service which can 
be accessed toll free at (800) 927-4227 or via IACP's Web site at 
www.iacprx.org.











      Response by Kasey K. Thompson to Questions of Senator Enzi, 
                   Senator Casey and Senator Franken
                              senator enzi
    Question 1. USP updated their standards for sterile compounding 5-
10 years ago. Since then, have you seen an increase in outsourcing of 
sterile compounding?
    Answer 1. USP 797 became official in 2004 and underwent a major 
revision in 2008 that included additional requirements.
    Below are results from ASHP's May 2011 survey demonstrating 
increased outsourcing:

     In 2011, 70.9 percent of hospitals reported partially or 
completely outsourcing some drug preparation activities. A greater 
percentage of larger hospitals outsource some preparation activities 
compared with smaller hospitals. For example, 96.9 percent of hospitals 
with 600 or more staffed beds out-sourced some part of preparation 
activities, compared with 49 percent of hospitals with fewer than 50 
staffed beds. The outsourcing of some preparation activities has 
increased over time, from 21 percent of hospitals in 2002 to 31 percent 
in 2005 and 42 percent in 2008.
     Of hospitals that out-sourced some part of preparation 
activities, 73 percent out-sourced patient-controlled analgesia (PCA) 
and epidural analgesia preparations, 65 percent out-sourced oxytocin 
preparations, and 38 percent out-sourced some i.v. admixtures and 
minibags (Table 10). About 25 percent of hospitals out-sourced syringe-
based anesthesia medications, total parenteral nutrition (TPN) 
preparations, and flushes. Hospitals less frequently out-sourced 
cardioplegia preparations, unit dose drug repackaging, and unit dose 
repackaging for bar coding. The percentages of hospitals outsourcing 
PCA and epidural analgesia preparations, i.v. admixtures or minibags, 
and flushes have increased during the past 9 years, while the 
outsourcing of TPN preparations has declined.

 Table 10.--Preparation Activities That Are Either Partially or Completely Outsourced, Excluding Services Through a Contract Pharmacy Services Provider
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                           Patient-
                                          controlled                I.V.
                                           analgesia             Admixtures    Syringe-      Total                               Unit dose    Unit dose
         Characteristic             n         and      Oxytocin   and small-    based      parenteral   Flushes   Cardioplegia  repackaging  repackaging
                                           epidural                 volume    anesthesia    nutrient                solutions   (drug only)    for bar
                                           analgesia                I.V.     medications   solutions                                            coding
                                         preparations             solutions
--------------------------------------------------------------------------------------------------------------------------------------------------------
No. Staffed Beds:...............
  <50...........................     51          70.6      52.9        27.5         11.8         21.6       25.5          3.9         11.8          3.9
  50-99.........................     56          73.2      60.7        42.9         16.1         16.1       21.4          3.6         16.1         10.7
  100-199.......................     63          68.3      66.7        42.9         23.8         17.5       22.2         15.9         12.7          6.3
  200-299.......................     69          76.8      76.8        39.1         30.4         29.0       21.7         23.2         15.9         11.6
  300-399.......................     54          77.8      63.0        40.7         38.9         31.5       16.7         37.0         22.2         24.1
  400-599.......................     86          79.1      81.4        44.2         38.4         32.6       18.6         41.9         20.9         19.8
  600...........................     62          88.7      72.6        40.3         41.9         45.2       25.8         64.5         40.3         22.6
All hospitals--2011.............    441          73.3   65.2\1\        38.3      24.1\2\         23.6       22.2      18.3\3\         16.0      10.4\4\
All hospitals--2008\3\..........    270          64.0       \5\        37.3                      32.8       13.9                      13.4         14.6
All hospitals--2005\6\..........    186          40.2                  31.4                      39.8       12.8                      11.6          9.6
All hospitals--2002\9\..........    137          16.7                  15.7                      52.4        9.1                      12.1          8.9
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ Uncorrected x\2\ = 16.4578, df = 6, designed-based F(4.17, 1810.24) = 3.0517, p = 0.0147.
\2\ Uncorrected x\2\ = 24.0577, df = 6, designed-based F(4.19, 1817.03) = 4.2945, p = 0.0015.
\3\ Uncorrected x\2\ = 71.3848, df = 6, designed-based F(4.21, 1825.56) = 12.4305, p = 0.0001.
\4\ Uncorrected x\2\ = 20.8045, df = 6, designed-based F(4.20, 1824.14) = 3.5927, p = 0.0055.
\5\ Not surveyed.

    In April 2012, Pharmacy Purchasing and Products published its own 
survey.
    In general these results demonstrate a gradual increase (from 56 
percent to 65 percent) in outsourcing since the establishment of USP 
797 standards for compounding sterile products in 2008. While 76 
percent of respondents reported outsourcing in response to a drug 
shortage, safety and the ability to provide a ready to administer 
dosing form were equally significant reasons as demonstrated by out-
sourced patient controlled analgesia (67 percent), epidural injections 
(48 percent), controlled substances (35 percent) and pre-filled OR 
medications (34 percent). (See graphs below.)


                             senator casey
    Question 1. Do you believe that hospitals and health systems that 
outsource their compounding to external compounding pharmacies are 
sufficiently able to determine whether those pharmacies are producing 
safe products?
    Answer 1. Pharmacists have the expertise to help evaluate if 
compounding is being conducted in accordance with Federal and State 
definitions and standards established by the U.S. Pharmacopeia in 
Chapter 797. However, the ability of hospitals to conduct routine 
inspections of compounding entities is limited by resources, which is 
why it is important to have a Federal and State oversight system that 
ensures that these entities are capable of producing safe products in 
accordance with Federal and State laws. The American Society of Health-
System Pharmacists also has guidelines and assessment tools available 
to help hospitals evaluate outside entities that provide compounded 
formulations. ASHP Guidelines on Outsourcing Sterile Compounding 
Services http://www.ashp.org/DocLibrary/Bestpractices/Mgmt
GdlOutsourcingSterileComp.aspx; ASHP Foundation: Outsourcing Sterile 
Products Preparation Contractor Assessment Tool http://
www.ashpfoundation.org/Main
MenuCategories/PracticeTools/SterileProductsTool/
SterileProductsAssessmentTool.
aspx.
    Most pharmacists are not trained to evaluate manufacturing-level 
facilities where Current Good Manufacturing Practices (cGMPs) are 
applicable. Examples are bulk compounding of sterile preparations from 
(1) nonsterile ingredients or (2) from sterile ingredients using 
aseptic processing * and storing these medications for periods beyond 
those associated with compounding.
---------------------------------------------------------------------------
    *Aseptic processing uses sterile components to make a sterile final 
product. Sterility must be maintained through multiple manipulations 
which introduces more variables than formulation of products that are 
terminally sterilized.

    Question 2. Do you think that the compounded products typically 
used in a hospital or in-patient setting are different from other 
products typically used in outpatient settings, and if so, do you think 
that they should be subject to additional or different regulation?
    Answer 2. The environment in which these medications are used is 
less important than the environment in which they must be prepared. The 
difference is whether the compounded product is a sterile preparation, 
such as an injectable, or ophthalmic medication. The preparation area 
is highly controlled to prevent contamination using methods that 
include in-process and final product quality assurance procedures. The 
applicable standards, USP 797, are adequate for compounding sterile 
preparations in hospitals.

    Question 3. Under the current patchwork system of State and Federal 
regulation, do you think products compounded in a hospital pharmacy are 
safer or less safe than products compounded at freestanding compounding 
pharmacies?
    Answer 3. Compounded sterile products from pharmacies that are made 
pursuant to or in anticipation of a medication order or prescription 
and according to USP 797 standards are equally safe, whether the 
pharmacy is in a hospital or community setting.
    However, a sterile compounding business entity that does not fill 
prescriptions for individual patients is not a pharmacy. Regulatory 
oversight of these entities should be dependent on the scope and scale 
of their operations, which may range from patient-specific small 
batches to large-scale production of commonly used drugs or dose forms 
based on historical demand. The beyond use date (BUD) or shelf life 
these entities assign to final products as well as the risk level (low, 
medium, high) of the compounding activity are also factors.
    These entities are neither a pharmacy nor a manufacturer, but fall 
somewhere in between into a regulatory gray area. An intermediate 
category of drug establishment with criteria for inclusion and 
clarification of regulatory oversight should be developed.
                            senator franken
    Question 1. In a report on meningitis in 2002, the Centers for 
Disease Control and Prevention reported that ``some health-system 
pharmacists might not realize that they are purchasing injectables 
prepared through compounding.'' In your experience, is this sometimes 
the case? If so, what responsibility do you believe that purchasers--
including health systems--have to ensure that they are providing their 
patients with safe medicines?
    Answer 1. Lack of clarity regarding the nature of drug 
establishments that register with the FDA may in fact mislead 
pharmacists to believing they are purchasing products from a legitimate 
manufacturer, rather than a compounding pharmacy. Compounding 
businesses advertise that they are ``registered with FDA,'' and are 
listed on FDA's Web site, however, their registration categories are 
not disclosed. Thus, pharmacists may not be aware they are contracting 
with a retail pharmacy, a regional admixture pharmacy, or a 
manufacturing pharmacy, rather than an entity with FDA oversight.
    Pharmacists are accountable for the safety and quality of the 
products they dispense, including those obtained from contracted 
services. It should be recognized, however, that pharmacists have 
little control over how these businesses are operated. Regardless of 
State or Federal oversight, a licensed business subject to statutory 
and regulatory requirements and offering products or services for sale 
should not be allowed to shift liability for its products to the end 
users.

    Question 2. In your written testimony, you state, ``Previous court 
rulings have made FDA's authority to inspect these facilities unclear 
and subject to legal action.'' Would you expand on this statement?
    In order to determine whether a pharmacy is acting like a 
manufacturer, should FDA have the authority to inspect the records and 
processes of pharmacies that they believe may be acting improperly?
    Answer 2. It is our understanding that FDA has limited authority to 
inspect large scale compounding entities since most are essentially 
operating as pharmacies. We believe that FDA's authority needs to be 
clarified or new authorities given to FDA to regulate compounding 
businesses that produce large amounts of compounded products, and sell 
those products to entities other than the end user. We believe that FDA 
and State boards of pharmacy will need to work together more closely to 
determine when a compounding pharmacy should be placed into a new or 
clarified category of FDA oversight.

    [Whereupon, at 12:51 p.m., the hearing was adjourned.]