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88–247 PDF 2003

S. Hrg. 108–110

TISSUE BANKS: THE DANGERS OF TAINTED

TISSUES AND THE NEED FOR FEDERAL

REGULATION

HEARING

BEFORE THE

COMMITTEE ON

GOVERNMENTAL AFFAIRS

UNITED STATES SENATE

ONE HUNDRED EIGHTH CONGRESS

FIRST SESSION

MAY 14, 2003

Printed for the use of the Committee on Governmental Affairs

(
(II)

COMMITTEE ON GOVERNMENTAL AFFAIRS

SUSAN M. COLLINS, Maine, Chairman

TED STEVENS, Alaska

GEORGE V. VOINOVICH, Ohio

NORM COLEMAN, Minnesota

ARLEN SPECTER, Pennsylvania

ROBERT F. BENNETT, Utah

PETER G. FITZGERALD, Illinois

JOHN E. SUNUNU, New Hampshire

RICHARD C. SHELBY, Alabama

JOSEPH I. LIEBERMAN, Connecticut

CARL LEVIN, Michigan

DANIEL K. AKAKA, Hawaii

RICHARD J. DURBIN, Illinois

THOMAS R. CARPER, Delaware

MARK DAYTON, Minnesota

FRANK LAUTENBERG, New Jersey

MARK PRYOR, Arkansas

MICHAEL D. BOPP, Staff Director and Chief Counsel

CLAIRE M. BARNARD, Professional Staff Member

JOYCE RECHTSCHAFFEN, Minority Staff Director and Chief Counsel

KATHRYN J. SEDDON, Minority Professional Staff Member

DARLA D. CASSELL, Chief Clerk
(III)

C O N T E N T S

Opening statement: Page

Senator Collins ................................................................................................. 1

Senator Coleman .............................................................................................. 4

Senator Pryor .................................................................................................... 6

Senator Carper ................................................................................................. 24

WITNESSES

Steve and Leslie Lykins, parents of Brian Lykins, accompanied by daughter

Tammy .................................................................................................................. 6

Steven L. Solomon, M.D., Acting Director, Division of Healthcare Quality

Promotion, National Center for Infectious Diseases, Centers for Disease

Control and Prevention, U.S. Department of Health and Human Services .... 15

Jeanne V. Linden, M.D., Director, Blood and Tissue Resources, Wadsworth

Center, New York State Department of Health ................................................ 17

Jesse L. Goodman, M.D., Director, Center for Biologics Evaluation and Research, Food and Drug Administration, U.S. Department of Health and

Human Services ................................................................................................... 26

ALPHABETICAL LIST OF WITNESSES

Goodman, Jesse L., M.D.:

Testimony .......................................................................................................... 26

Prepared Statement with an attachment ....................................................... 61

Linden, Jeanne V., M.D.:

Testimony .......................................................................................................... 17

Prepared Statement with an attachment ....................................................... 55

Lykins, Leslie and Steve:

Testimony .......................................................................................................... 6

Prepared Statement ......................................................................................... 39

Solomon, Steven L., M.D.:

Testimony .......................................................................................................... 15

Prepared Statement ......................................................................................... 44

EXHIBITS

1. Deposition of James C. Vander Wyk, Ph.D., taken on January 21, 2003,

on behalf of the plaintiff in the case of Steve Lykins v. CryoLife, Inc.;

Civil Action File Number 02105613–24; Superior Court of Cobb County,

State of Georgia; pages 1–4, 25–32, 69–80, and 189–192 ............................. 84

2. ‘‘Update: Allograft-Associated Bacterial Infections—United States, 2002,’’

Mortality and Morbidity Weekly Report; Centers for Disease Control and

Prevention; March 15, 2003, at http://www.cdc.gov/mmwr/preview/

mmwrhtml/mm5110a2.htm .......................................................................... 91

3. ‘‘Hepatitis C Virus Transmission from an Antibody-Negative Organ and

Tissue Donor—United States, 2000–2002,’’ Mortality and Morbidity Weekly Report; Centers for Disease Control and Prevention; April 4, 2003,

at http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5213a2.htm .... 96

4. Letter from Senator Susan M. Collins, Ranking Minority Member, Permanent Subcommittee on Investigations, to Bernard A. Schwetz, D.V.M.,

Ph.D., Acting Principal Deputy Commissioner, Food and Drug Administration (FDA), December 21, 2001, concerning the death of Brian Lykins

and the status of the FDA’s tissue action plan .............................................. 100
Page

IV

5. Letter from Senator Susan M. Collins, Ranking Minority Member, Permanent Subcommittee on Investigations, to Bernard A. Schwetz, D.V.M.,

Ph.D., Acting Principal Deputy Commissioner, Food and Drug Administration (FDA), February 11, 2002, concerning the status of the FDA’s

tissue action plan .............................................................................................. 101

6. Letter from Melinda K. Plaisier, Associate Commissioner for Legislation,

Food and Drug Administration (FDA), to Senator Susan M. Collins, Ranking Minority Member, Permanent Subcommittee on Investigations, April

3, 2002, concerning the status of the FDA’s tissue action plan .................... 103

7. Letter from Senator Susan M. Collins, Ranking Minority Member, Permanent Subcommittee on Investigations, to The Honorable Tommy G.

Thompson, Secretary of Health and Human Services, April 12, 2002,

concerning the status of the FDA’s tissue action plan .................................. 106

8. Letter from The Honorable Tommy G. Thompson, Secretary of Health

and Human Services, to Senator Susan M. Collins, Ranking Minority

Member, Permanent Subcommittee on Investigations, August 28, 2002,

concerning the status of the FDA’s tissue action plan .................................. 109

9. Responses to questions for the record, transcript of hearing on the nomination of Mark B. McClellan, to be Commissioner of the Food and Drug

Administration, Department of Health and Human Services; U.S. Senate

Committee on Health, Education, Labor, and Pensions, October 2002 ....... 110

10. FDA Notice of Inspectional Observations (Form FDA–483) from Inspection 3/25/2002–4/12/2002 (FEI #3001451326), issued to James C. Vander

Wyk, Vice-President of Quality Assurance/Regulatory Affairs, CryoLife

Inc., dated April 12, 2002 ................................................................................. 111

11. Letter from James C. Vander Wyk, Ph.D., Vice-President, Regulatory

Affairs and Quality Assurance, CryoLife, Inc., to Mr. Ballard H. Graham,

District Director, HFE–SE100, Food and Drug Administration, regarding

‘‘Initial reply to Notice of Inspectional Observations (483) from Inspection

of 3/25/2002–4/12/2002 (FEI #3001451326), dated May 15, 2002 ................. 119

12. Sample of Complaint Record, CryoLife, Inc ................................................... 121
(1)

TISSUE BANKS: THE DANGERS OF TAINTED

TISSUES AND THE NEED FOR FEDERAL

REGULATION

WEDNESDAY, MAY 14, 2003

U.S. SENATE,

COMMITTEE ON GOVERNMENTAL AFFAIRS,

Washington, DC.

The Committee met, pursuant to notice, at 9:37 a.m., in room

SD–342, Dirksen Senate Office Building, Hon. Susan M. Collins,

Chairman of the Committee, presiding.

Present: Senators Collins, Coleman, Carper, and Pryor.

OPENING STATEMENT OF CHAIRMAN COLLINS

Chairman COLLINS. The Committee will come to order.

Good morning. Today, the Committee on Governmental Affairs is

holding a hearing on the dangers of tainted human tissue and the

need for Federal regulation of the tissue bank industry.

Tissue banks procure, process, store, and distribute human tissue

for transplantation. Tissue transplants have soared in recent years

due to advances in technology that have greatly reduced the risk

of rejection. The American Association of Tissue Banks estimates

that more than 800,000 tissue products were made available for

transplantation last year in the United States. Yet despite the ever

increasing number of transplants, there are serious questions about

the safety of our Nation’s tissue supply.

Some of these concerns stem from the Food and Drug Administration’s failure to finalize much-needed regulations governing the

tissue bank industry. This is not a new problem. In fact 2 years

ago this month I chaired a hearing of the Permanent Subcommittee

on Investigations exposing the safety issues concerning the practices of some tissue banks. Yet in the intervening 2 years, the FDA

has made virtually no progress in strengthening the regulatory requirements for an industry whose products are in wide use and affect human health.

While many people are familiar with the concept of organ donation, tissue donation is not as well understood. Human tissue,

including tendons, bone, and skin is unlike an organ transplant because it is not usually transplanted as-is from the donor’s body into

that of the recipient.

Rather, donated tissue generally undergoes considerable processing before it is transplanted into a patient. Bone from a donor’s

femur, for example, may be completely reshaped into a component
2

designed to give support to a recipient’s spine. The reconfigured tissues are also known as allografts.

Once processed, donated tissue can be stored for a period of time

before it is used to enhance, improve, and even save lives. If, however, human tissue is not properly processed, it can pose dangerous

risks to the recipient.

Therefore, it is critical that the tissue come from carefully

screened donors, and that it be properly processed and stored. Otherwise, communicable diseases such as HIV and hepatitis, among

others, can be transmitted through the tissue to the recipient.

The FDA has been aware of these public health risks for years.

In 1997, the agency examined the health issues involving tissue

transplantation and concluded that the existing regulatory framework was insufficient. The agency undertook the review in response to incidents in which imported foreign tissue had tested

positive for serious diseases.

The FDA then notified the tissue bank industry that it intended

to make regulatory changes to strengthen the oversight of tissue

banks. The changes were threefold. First, all tissue banks would be

required to register with the FDA. Second, screening of potential

donors would be expanded to require testing for the human variant

of mad cow disease, syphilis, and other viruses. And third, and perhaps most important, a rule would be issued on the methods and

controls used during the processing of human tissue.

This third proposal, known as the good tissue practices rule is intended to help ensure that tissues are not contaminated as they

move from recovery to distribution.

The hearing that I held 2 years ago exposed dangerous practices

by some tissue banks as well as the inadequacy of the regulatory

framework. The testimony that we heard at that time was deeply

troubling. First of all, we learned that the Federal Government had

no idea how many tissue banks were operating in the country. The

Department had estimated that there were about 150, but approximately 350 tissue banks registered with the FDA when the registration requirement went into effect. But that indicated that

many tissue banks were operating without any Federal oversight

whatsoever.

Second, there was also considerable testimony about the unacceptable practices of some tissue banks. For example, a deputy inspector general from the Department of Health and Human Services testified about unscrupulous tissue banks that engaged in a

practice in which tissues that initially tested positive for contamination were simply tested over and over again until the technicians

achieved the negative result they wanted.

Another witness testified that a Lion’s eye bank, which also participated in tissue recovery, accepted a donor who was 82-years-old

and had a history of cancer. That is a frightening example of inadequate donor screening by a tissue bank.

Based on our findings, it was evident to the Subcommittee that

Federal oversight of tissue banks was woefully inadequate. Until

the necessary changes were made, gaping holes would remain in

the safety net that protects patients who receive transplanted tissue. Now the FDA assured us at this hearing 2 years ago that it
3

would act expeditiously to remedy this problem by implementing

the long-overdue regulations.

Since that time, I have repeatedly pressed the FDA to finalize its

regulations. I have offered help to the agency to overcome any obstacles that it might face along the way. Senator Durbin and I

asked the FDA to provide a breakdown of the costs for implementation of the proposed regulations. We never received a response. I

wrote additional letters to the FDA. I then wrote to the Department of Health and Human Services about the very troubling

delays and seeking assurance that the implementation of the regulations was a priority. In its response, the Department agreed that

the FDA needed to move as quickly as possible to finally put the

regulations in effect.

Unfortunately, the FDA still has not kept its commitment to addressing this public health risk through effective regulation. And,

as I predicted 2 years ago, the result of this bureaucratic inertia

has been tragedy.

My greatest fears were realized when Brian Lykins, a healthy

23-year-old man from Minnesota, died in November 2001 after receiving a tissue transplant in his knee during routine surgery. The

tissue was infected with a deadly bacterium, and yet it made its

way from Georgia to St. Cloud Hospital in Minnesota.

Good tissue practices appear to have been totally absent in this

case. CryoLife, the company that processed the tissue used in

Brian’s transplant, accepted a tissue donation from an individual

who had been deceased for 19 hours and his body had not been refrigerated during that time. I dare say that if Brian had been

aware of that fact alone, he would have refused to have a transplant of that donor.

Brian’s parents will testify before the Committee today about the

devastating loss that their family have suffered. It is a tribute to

them and to their daughter Tammy that they have agreed to come

forward and testify publicly about this most painful and private

event. They have done so in the hope that others will not have to

endure the tragic loss that they have suffered.

I just want to thank them publicly for their willingness to speak

out and for their commitment to seeing that no other family suffers

the tragedy that they have. So I want to thank you for being with

us today. My hope is that their participation in today’s hearing will

finally be the catalyst that prompts the FDA to act.

In the wake of the tragedy of Brian’s death, 6 months later in

May 2002, an FDA official stated on national television that the

agency intended to make the regulations final within 1 year. Yet

here we are a full year after that, without any discernible progress

having been made toward issuing the regulations. I just do not understand that. That is why I am holding this hearing today.

Moreover, there is now evidence to suggest that the absence of

regulations is being used as a legal defense for questionable practices. After Brian Lykins died, his family filed suit against the tissue processor, CryoLife.

In a deposition, a CryoLife executive stated that the FDA had

not imposed final regulations regarding what industry practices

should be, but instead had issued only non-binding guidance. That

CryoLife representative is correct on that point. Under the current
4

regulations, a tissue bank is not even required to report situations

to the FDA in which an adverse event—that is bureaucratic language for what happened to Brian Lykins—has occurred. Reporting

is completely voluntary. As outrageous as that may seem, perhaps

the industry’s defense strategy will provoke the FDA into action.

Recent evidence confirms that Brian Lykins’ case was not an isolated event. Last year after his death, an investigation was undertaken by the Centers for Disease Control and Prevention along

with the New York and Minnesota State Departments of Health,

to determine what killed him. That inquiry led the CDC to examine

other cases of allograft-related infections.

In its March 2002 report, the CDC identified 26 cases of infection

in donated human tissue that had been linked to allografts used in

transplants. The CDC now reports that more than 60 cases of

transplanted tissue infections are now being investigated. We will

hear more about that from the CDC today.

It is also surely significant that New York State, which has the

most stringent tissue oversight regulations in the country, had not

experienced the same problems. Today we will hear testimony from

that State’s top tissue oversight official regarding the authority

that has allowed New York State residents to have greater confidence that the tissue transplants they received are free from infection.

It is well past time for the FDA to finish what it started more

than 6 years ago when the agency correctly identified a serious

threat to public health and the need to improve regulatory oversight of the tissue industry. The remaining safety regulations must

be completed without delay, and tissue banks that do not comply

with the regulations must be suspended from doing business and

punished for jeopardizing public health.

Last year, Senator Durbin and I introduced a bill, the Tissue

Transplant Safety Act of 2002. It would have required the FDA to

impose tougher safety standards. Later today, Senator Durbin,

Senator Coleman, and I will reintroduce that legislation which we,

with the family’s permission, are naming in honor of Brian Lykins.

This time we will require the FDA to issue the final regulations

within 90 days. It is obvious to me that without a statutory deadline, FDA will continue to delay and delay.

I look forward to hearing the testimony of our witnesses today

and at this time I would like to yield to my colleague from Minnesota, who has a special interest in this case, for his opening

statement as well as to introduce our first panel of witnesses.

OPENING STATEMENT OF SENATOR COLEMAN

Senator COLEMAN. Thank you, Madam Chairman. It will be an

honor to introduce today, Steve and Leslie Lykins, and their

daughter Tammy. I want to thank you for calling this hearing.

Twelve years ago, the FDA first studied this issue. Two years ago

almost to this day you held hearings on this issue. During those

hearings the FDA promised to issue regulations soon. A year anda-half ago Brian Lykins died, he did not die of complications stemming from the procedure. He was a healthy young man and his

death should have been prevented.
5

His death was followed by national press and CDC studies that

once again pointed to the need for national standards. The FDA

still has not acted. So today we are revisiting the issue. I suspect

we will hear roughly the same testimony we heard 2 years ago. But

this time we will also hear from the Lykins family about the death

of their son. I can only hope that 2 years from now we do not have

to revisit the issue and listen to the same testimony again perhaps

with yet another victim whose friends and family had to watch

their son or daughter die.

I suspect the problem here is a bureaucratic desire to draft the

perfect rule, regardless of the cost in time or lives. I believe in the

old 80/20 rule, about 80 percent of the problem can be dealt with

with only 20 percent of the effort. It is the last few bits that require

the most time. We all agree on certain things like the ability to

trace tissue from recipient to donor and back to other recipients,

and the need for testing for additional diseases. We could at least

get some components in place. No doubt there are more difficult

issues that do take a long time to resolve, but why are we still

waiting to do the easy stuff, the stuff we know can make a difference?

New York, as the Chairman has noted, has put a law into place

which can serve as a model. New York did not wait, nor should we.

If nothing else, we can move forward with legislation modeled on

the New York law setting up a simple system for testing and tracking. The system could be later augmented by further rules that

would allow us to avoid having to return here in 2 years to hear

from another family.

Although I will reserve final judgment until I hear from the

FDA, it appears to me that this hearing should not have had to be

held to deal with this issue. We dealt with it 2 years ago.

Madam Chairman, it is my great but sad honor to introduce today’s first witnesses, Steven and Leslie Lykins from Willmar, Minnesota, and their daughter and Brian’s sister, Tammy. I wish they

did not have to be here today. Brian’s death was especially tragic

because it occurred after an elective surgery not from medical complications stemming from the procedure itself but rather from a

cause that could have been presented if proper regulation had been

in effect.

I do not think most people can possibly understand how painful

it would be to discuss the death of your children before a roomful

of strangers. I want to thank the Lykins for their courage and their

commitment for being here today. I want to commend the Chairman for having hearings on this issue. But I also want to remind

ourselves that hearings are not always enough.

Madam Chairman, under your leadership, the Permanent Subcommittee on Investigations held a hearing on tissue banks on May

24, 2001, 6 months before Brian’s death. But again, as I noted before, the FDA did not take the required actions. It seems to me

that the Lykins are doing something we should all admire. Faced

with a personal tragedy, their first instinct was to use the painful

lessons learned to try and make the world a little bit better.

For our part, we should pledge to them that we will not need to

relearn this issue at the cost of someone else’s life. Hopefully, and

more than hopefully, the FDA will promulgate final regulations
6

1The prepared statement of Steve and Leslie Lykins appears in the Appendix on page 39.

that address the problem. If they do not then we need to, and we

will move quickly forward on legislation that the Chairman is

bringing forth. One way or another we must honor the Lykins’ experience not just by listening to their story but by acting on it.

Madam Chairman, it is, as I said, a great but sad pleasure to introduce Steven and Leslie and Tammy Lykins from Minnesota.

Chairman COLLINS. Thank you very much, Senator. Before I call

on Mr. and Mrs. Lykins for their testimony I want to see if my colleague Senator Pryor has any opening comments.

OPENING STATEMENT OF SENATOR PRYOR

Senator PRYOR. Thank you, Madam Chairman.

Thank you all for being here today. Madam Chairman, I am a

recipient of an Achilles tendon from a donor bank. I must tell you

that was about 7 years ago. I had a very rare and deadly form of

cancer in my Achilles tendon. I had great results, but one thing

that I took for granted was that the tendon I was receiving out of

a donor bank, which happened to be in New Jersey was going to

not be tainted and healthy. And it was.

But I must tell you that what I have been reading in preparation

for this hearing, I am bordering on outrage at some of the lack of

control out there and the lack of supervision. It really is troubling

to me. So I really do appreciate you all coming. It takes a lot of

courage to be here. I know it is a sad story that you are going to

tell. But we are going to do everything we can to listen and try to

make the situation better.

Thank you, Madam Chair, for allowing me to speak.

Chairman COLLINS. Thank you, Senator Pryor. I think your experience shows exactly the way most people would react. You would

never dream of getting a tissue transplant that you might be putting your life at risk.

Senator PRYOR. That is right.

Chairman COLLINS. Yet properly done and safely done, a tissue

transplant can save lives.

Senator PRYOR. Absolutely. It definitely saved my leg. Otherwise

I probably would have had to have an amputation. You have so

many other considerations at that point. Depending on why you are

having the transplant—it could be cancer, it could be any number

of ailments, any number of reasons why you are doing it. But you

are so preoccupied with that. You always know there is a chance

of some sort of tissue rejection. We all know the medical risks

there, and the medical community has gotten that risk down to a

very low level, a very manageable level. The last thing the patient

needs to be concerned about is that he may receive some tainted

tissue. Thank you.

Chairman COLLINS. Thank you. Mr. Lykins, I would ask you to

proceed with your testimony. Again, thank you so much for being

here today with your family.

TESTIMONY OF STEVEN AND LESLIE LYKINS,1 PARENTS OF

BRIAN LYKINS, ACCOMPANIED BY DAUGHTER TAMMY

Mr. LYKINS. You are welcome.
7

In September 2001, our son Brian had arthroscopic surgery to remove a bone chip in his knee. It went very well.

Afterwards, Dr. Mulawka, the surgeon, showed us pictures of

Brian’s knee which revealed a quarter-size divot in the bone. He

told us that Brian should have follow-up surgery in order to prevent future arthritis in his knee. He also explained that a piece of

bone from a cadaver would be used in the procedure and told us

about the effort and testing that went into ensuring the donated

bone tissue would be clean and safe. It was supposed to be a routine surgery, one that Brian could have lived a completely normal

life without. In other words, it was strictly a preventative and elective procedure. The recovery from the procedure was expected to

take a little longer than the previous one, but no one expected any

significant complications.

On Wednesday, November 7, Brian had the follow-up surgery

which went well. Dr. Mulawka told us that Brian would become a

little sick from the medications and possibly experience more pain

than the previous arthroscopic surgery, but otherwise the recovery

should go well.

After the operation, Brian was experiencing a lot of pain. He had

a horrible headache, upset stomach, and felt like he was burning

up. The nurses, however, said his temperature was normal. The

doctor decided to keep him overnight for observation. Leslie and I

drove home to Willmar for the night. We did not expect any complications so I left for work the next morning and was scheduled

to work in Minneapolis for the 5 days.

Ms. LYKINS. After Steve left, I drove to St. Cloud Hospital to pick

Brian up. When I got there I found out that he was sick to his

stomach and in excruciating pain. The pain pack the doctor had inserted into his knee during the operation apparently was not working. The purpose of the pain pack was to administer medication directly to the knee to help control the pain.

After Brian was released from the hospital I drove him to the St.

Cloud Orthopedic Clinic where they removed the pain pack. Brian

was originally scheduled to go to the doctor on Friday, the following day, but the doctor thought that he could wait to see Brian

until Monday morning. So instead we drove to my home in Willmar

where Brian stayed with me overnight. Throughout the evening,

Brian began to feel better. His knee was still sore and he felt warm

at times, but otherwise he felt fine.

On Friday morning, Brian woke up feeling much better. Of

course his knee was still sore, which was to be expected. That

afternoon he said he felt well enough to go home. At his home he

rested, ate and drank a bit, used the exercise machine they had

sent along, and occasionally iced his knee. His recovery was going

exactly as we thought that it would. That evening we watched a

movie together and he told me that he felt fine and if I wanted to

go home I should, which I did.

On Saturday, I had previous plans to be out of the house for

most of the day so I was up early. Brian called me, told me that

he felt fine, and asked some questions about when he was supposed

to take his medication. He said his leg was still sore, but otherwise

he felt fine. Then I went out, returned home at about 5 p.m. that

night and called Brian. He told me he had been sick to his stomach
8

for a while, which we had expected. I told him, I would come on

over to his house after I took care of a few things and he said that

was fine. I got to his house about 6 p.m. As soon as I arrived I realized that he was in worse shape than he had let on. He was throwing up, and told me he almost passed out twice walking to the sink.

He complained about feeling warm but he did not feel warm to the

touch.

I called Dr. Mulawka’s office right away and I got the answering

service. They told me that they would call the doctor and have him

call me back soon. Shortly after that someone else called from the

clinic. When I explained how Brian was feeling, he told me to

change the dosage on one of the medications which was likely the

culprit of the stomach problems. Brian told me he would like to

spend the night at our house so we packed up some of his things

and we started to drive to my house which is only two and-a-half

miles away.

On the way Brian said he would like to stop at the hospital and

have them check him out. We got to the emergency room about 8

p.m. When the nurse and the doctor on duty examined Brian they

suspected that he was simply dehydrated and they put him on IV.

I think they also gave him something in the IV to help settle his

stomach. He still complained about burning up, and he stripped off

his shirt and his blankets but he still did not register a fever.

Brian also complained about his knee hurting, but the nurse could

not find any unusual swelling, redness, or hot spots. A couple of

times he doubled over with an upset stomach before the medications seemed to kick in and help him.

The nurse and the doctor thought he would feel better once he

was more hydrated from the IV. His vital signs seemed to be OK.

The doctor also ordered chest x-rays and had blood drawn. After

that was done, Brian was back in his room and he was resting better. No one seemed alarmed about anything at that time and they

told us that he would be going home soon. Brian finally appeared

to be dozing off to sleep. I was tired and told the nurse that I would

go out into the emergency room to get some rest. At that point it

was about 1 a.m. in the morning.

I was in the waiting room for about 15 maybe 20 minutes when

someone came in and told me to come right away. Brian had suddenly taken a turn for the worse. He had been moved to a larger

room in the ER where several people were anxiously working

around him. He was awake at that time. After a few minutes, the

doctor told me that Brian’s vital signs had changed all of a sudden

and that they were trying to find out what was wrong. Then the

doctor asked me if there was anyone in town who I wanted to call

to be with me. I began to worry.

He told me that I should call my husband who, thankfully, was

in Minneapolis and not on a trip as he is a pilot. I called Steve and

the doctor explained to him that he should come to the hospital immediately, that things did not look good for Brian. I had not expected any of this when I brought Brian to the hospital. We

thought he was just dehydrated and nauseous from the strong

medicine. The doctors were now planning to move him to the intensive care unit.
9

I made my way to the ICU when Brian was being wheeled into

a room. The doctor was trying to ask Brian questions and he answered them in short little statements. He had not been in the

room long when Brian had a convulsion. He sat straight up, gave

a loud, long groan. I think that was the point that he went into

a coma. The doctors and nurses got me out of the room, attended

to Brian, and some time passed. A nurse came and got me and

brought me back to Brian’s room. I was not in there for long before

he had another convulsion. It appeared as though he stopped

breathing until the doctor put some sort of respirator on him. I was

then led back into the waiting room.

Steven got to the hospital about 4 a.m. The doctor filled him in

on Brian’s condition and told him they were not exactly sure what

was happening but that it was life-threatening.

Mr. LYKINS. Brian was in a coma when I got to the hospital. His

blood pressure had been at zero for several hours. All the organs

in Brian’s body were failing. His heart was the last organ to fail

and at 6:21 a.m. our son died.

Shortly after Brian’s death we learned that the tissue put into

his knee was infected with a deadly bacteria. This infected tissue

was allowed to be implanted in Brian’s knee due to several industry and government failures.

First, there were no Federal guidelines for the automatic rejection of high-risk cadavers. The cadaver that supplied the tissue for

Brian’s operation should have been rejected for at least two reasons. First, he died due to suicide so the time of death was uncertain. Second, the body was allowed to remain unrefrigerated for at

least 19 hours before tissue harvesting began.

Second, CryoLife procedures for testing and preparing the tissue

to make it clean and safe were flawed.

The Centers for Disease Control began an investigation into the

cause of Brian’s death because two other men from the same area

died within about 1 week of each other after having routine knee

surgery. One of the men had his surgery in the same hospital as

Brian. The CDC found that the other two men died from blood

clots. They did not have cadaver tissue put into their bodies. Their

knee operations were completely different from Brian’s.

However, due to the presence of the deadly bacteria found in

Brian’s body, the CDC continued with a lengthy investigation into

the cause of our son’s death. Over the next 6 months I talked on

a regular basis with Dr. Kainer from the CDC who was running

the investigation. I could not believe the things that I was hearing

about the tissue industry as a whole and CryoLife in particular.

How could a medical industry in the United States of America be

allowed to operate like this? A medical industry allowed to operate

with little or no State and/or Federal regulation, how could this be?

The FDA had known about the problems in this industry for

years and for some reason was dragging its feet in bringing about

the necessary regulations. The CDC had clearly defined the problems in this industry and the FDA would do nothing about it.

It became very clear at that point that the CDC had no power

to bring about change in this industry and the FDA was not going

to do its job. CryoLife was going to continue to operate in the unsafe manner that caused the death of our son. So at that time we
10

decided to bring a lawsuit against CryoLife. The purpose of our suit

was to bring about change in this company and this industry.

Money was never the motivation for the suit. It was only the vehicle that would get people to pay attention.

We did not sue Dr. Mulawka and we did not sue the hospital.

We only sued the people responsible for Brian’s death because they

would not fix the problems on their own. All we ever wanted was

for the people involved in Brian’s death to learn from what happened and fix the problems. It became clear that CryoLife and the

FDA would not fix the problem without the lawsuit. Less than 30

days after we filed the suit, the FDA shut CryoLife down due to

their unsafe practices. Unfortunately, there are still no Federal

regulations to prevent companies like CryoLife from operating in

unsafe ways.

One and a half years after Brian’s death, the FDA is still only

proposing regulations for the tissue industry. Nothing has changed.

The tissue industry can still operate any way they want with little

or no Federal regulations. What is taking the FDA so long? In our

lawsuit, we listed seven areas of meaningful reforms that are needed in this industry. First is rejection of high-risk cadavers such as

diseased cadavers that have cancer, meningitis; cadavers that are

over 70-years-old; cadavers unrefrigerated for over 10 hours; suicide cadavers.

Second, testing of tissue when cadaver is received.

Third, sterilize tissue before distribution.

Fourth, discard cadaver if any contamination is found.

Fifth, mandatory reporting of contamination to Federal agencies

and the end-user doctor.

Sixth, certification of cadaver harvesting personnel, uniform

basic qualifications and uniform training.

And seventh, mandatory annual procedure and inventory audit.

Had these reforms been in place at the time of Brian’s operation,

our son would not be dead and many other people would not be

dealing with some very serious medical conditions. How much

longer is it going to take the FDA to do its job and bring the tissue

industry into the 21st Century? This industry has been allowed to

operate like something out of the Wild West for too long. Too many

people have had their lives ruined and too many people have died.

We need reforms and regulations in this industry now, not some

day. There is no question that the tissue industry is necessary and

important for the advancement of quality of life. However, there is

no need for it to operate in such a dangerous manner.

Chairman COLLINS. I want to thank you both for your very eloquent testimony. I know I speak for everyone in this room when

I say that I am so sorry for your loss. My hope is that by your coming forward that we have put a human face on this problem, and

that it will prompt the FDA to act. I just want to pledge to you that

I am going to ensure that they act. We have given them too long

already and I believe that your experience and your moving testimony will help convince our colleagues that far too long an amount

of time has passed already and that we do need prompt action.

You mentioned that prior to Brian’s surgery that there was a discussion with his physician about the transplanted tissue. Now I

know that anyone undergoing any kind of surgery signs a standard
11

informed consent form, but was there any discussion of possible

risks of the tissue itself, Mr. Lykins?

Mr. LYKINS. Dr. Mulawka sat with my wife and I and Brian and

we talked about that and he explained over—it was quite a lengthy

explanation of all of the safety standards that went into ensuring

that the tissue was safe. After he finished explaining that to us,

we were very confident that the tissue was going to be clean, that

there would be no problems. It was never even a consideration that

the tissue may not be safe to be put in Brian’s body.

Chairman COLLINS. Did you assume at that time that as with

organ transplants, as with medical devices, that there was Federal

regulation of the tissue industry so that you really did not need to

worry about the safety, Mrs. Lykins?

Ms. LYKINS. Yes, we did, at that time. We just assumed, which

now from hindsight we know better, but that just like any—like

the organs and such, that these things were already handled

through the medical field and knew them to be safe.

Chairman COLLINS. I think that is a very logical assumption for

you to have made. It is one that I think most health care professionals made, including the physician. The surgeon who treated

your son obviously assumed that there was a process in place to

ensure the safety of the transplanted tissue.

How did you learn of the cause of Brian’s death, Mr. Lykins?

Mr. LYKINS. When Brian died, the doctor in the ICU, even when

he died they said, we do not know what happened. So we talked

with him and we ordered that they do an autopsy on Brian to find

out the cause of what killed him. That is where we started the

learning process was from that autopsy.

Chairman COLLINS. When did you learn that the cadaver from

which the tissue had been taken had been left unrefrigerated for

at least 19 hours, clearly raising the risk of infection and other

problems?

Mr. LYKINS. During that next 6 months after Brian’s death when

we were in contact with—first it started with the Minnesota Department of Health and then it went to the CDC, that is when we

started learning things like that. It was sometime during that investigation that the fact that it had been unrefrigerated for 19

hours came up.

Chairman COLLINS. During the course of your lawsuit against

the tissue bank that procured and processed the tissue for Brian,

which is CryoLife, did you learn of any previous complaints against

the company or other problems that CryoLife had experienced?

Mr. LYKINS. Yes, there were at least two of them that we were

familiar with. One, and I cannot remember the gentleman’s name

but he is out in the San Francisco area that a couple of years before Brian’s death he had a knee operation where he received tainted tissue which caused him some real severe medical problems.

Chairman COLLINS. Is there anything that you have learned from

this experience that particularly concerned you?

Ms. LYKINS. I think it probably would be in the medical field in

dealing with this is that we did not have the information and that

our doctors did not have this vital information that was so needed.

Mr. LYKINS. Of course we have done a lot of talking with friends

and family and even acquaintance at work about it and the thing
12

that I really struggle with is if they had given us a document when

we went in for this operation that said that the tissue that your

son will be receiving is not regulated, in fact we do not know where

it is coming from, we have no standards for how it is produced, we

cannot guarantee it is going to be safe, and there is a risk of death

or serious infection from this we would, of course, have said, no,

we were not going to do that operation. We were not given that option because nobody knew that at the time.

So the fact that we were not given that option, but we assumed,

like every other part of the medical industry, that it is regulated,

when it is a public safety thing—that companies just cannot operate like that where they can pose a serious health risk. I cannot

think of any industry—I am a pilot and you look at the high regulation in the airline industry and you look at all the other areas

where we have such good safety standards in place and then to see

this one with none, I think that is the part that has bothered us

the most.

Chairman COLLINS. I am going to yield to Senator Coleman at

this point because I know he is on a very tight schedule.

Senator COLEMAN. Thank you, Madam Chairman. I am not going

to ask any questions. I hope to have an opportunity to visit with

the family a little later. My daughter and her class are in my office

and I am going to go down there and see them in a couple of minutes.

But I do want to note, in their testimony the Lykins said their

purpose here was not to sue people for money. It is to fix the problem. I will say to them publicly what I said privately, that the

Chairman is very serious about this issue, and that something will

come from this testimony today. So your purposes will be achieved

and I just want to again thank you for your courage and your commitment.

Thank you, Madam Chairman.

Chairman COLLINS. Thank you, Senator. I just have one more

question before I yield to my colleague and one comment. When we

met yesterday, just to expand on your last response, you told us

that if there were a sign up in the operating room or a form given

to a patient saying, warning, the transplant you are about to receive has no safety guarantee it all. The Federal Government does

not really regulate it. Unless you are living in one of three States

there is no State regulation. Proceed at your own risk. That your

son would not have proceeded with this operation. Indeed, it would

be the end of the tissue bank industry, which is unfortunate because there is a lot of good that comes from tissue transplants.

But I think that you are absolutely right and that only makes

the case for effective regulation even stronger, because we want to

make sure that transplanted tissue which literally can save lives,

does not take lives. That is what this is all about.

My final question for you is, we will have a representative from

the FDA testifying before us today. In his defense, he has only been

on the job for a few months. He is new to his position. But this is

an indictment of the agency for failure to act. I just want to ask

you if there is any question that you want me to pose to the FDA

representative today? Mrs. Lykins.
13

Mrs. LYKINS. I think what we have put in here is, how can the

American public, the people, the patients that are needing this

help, how can they turn their back and oppose some safety that

these people can rely on and know that they will indeed be getting

tissue that will be helping them in their life?

Chairman COLLINS. Thank you. Mr. Lykins, do you have anything to add?

Mr. LYKINS. I guess I really do not. In our statement we have

said it. We just do not understand why this is taking so long. We

have heard at least two or three times since Brian died, and statements before that, just one more year, just one more year and we

will have it done. We just heard that again recently, just one more

year. It does not seem like it is that hard to get some kind of, like

Senator Coleman was saying, let us get the basic framework in

place. New York has it right now. If nothing else, let us adopt New

York’s and get it started. But there are people that are at serious

risk today having these operations that do not even know about it.

We have got to get something going here.

Chairman COLLINS. Thank you. Senator Pryor.

Senator PRYOR. Thank you. Again thank you all for being here.

I have a factual question about your case and that is, CryoLife, is

that a private company? Is that an association? Is that a for-profit

company? Is that a lab? What is that or what was that?

Mr. LYKINS. It is a for-profit corporation and they do a lot of different things and part of the things that they do is they supply this

tissue.

Senator PRYOR. Did I understand what you said a few moments

ago that they are no longer in business?

Mr. LYKINS. No. Just shortly after we filed this suit the FDA

went in and stopped, shut down their tissue processing part of

their business. They were stopped from doing that except in lifethreatening circumstances until they got their house in order. I forget exactly how long but they eventually did comply with the FDA’s

request so they are back operating now.

Senator PRYOR. Tell me about your contacts with the FDA. It

sounds like you had some litigation going and you have also had

some contacts with the Food and Drug Administration. I would like

to zero in on your contacts with the FDA. Give me a feel for how

you have communicated with them. Is it by letter, by phone call,

by personal visit? How have you communicated with FDA?

Mr. LYKINS. We have not personally communicated with the FDA

at all. Our attorneys, during the lawsuit there was communication

there, but we have never personally communicated with them.

Senator PRYOR. Has the FDA taken steps to keep either you or

your attorneys advised about the status of the process within the

agency?

Mr. LYKINS. Not that I am aware of.

Senator PRYOR. Have they ever been proactive in any way with

you to try to give you any kind of assurance that they are working

on this problem as quickly as they can? Are they going to try to

move things out as quickly as they can to prevent this from happening in the future?

Mr. LYKINS. No.

Senator PRYOR. This incident occurred in 2001?
14

Mr. LYKINS. Yes.

Senator PRYOR. How old was your son?

Mr. LYKINS. He was 23.

Senator PRYOR. You made a statement about this industry, that

it is analogous to the Wild West. When you say that, do you mean

that your concern is it is totally unregulated and there is no government supervision about what is going on out there, or at least

it is very limited?

Mr. LYKINS. The symbolism behind that statement was, I see this

industry as operating like a bunch of Wild West gunslingers that

are just shooting from the hip, doing it any way they want to do

it, and with no laws or regulations they are just making it up as

they go. That was the thinking behind that statement.

Senator PRYOR. Have you been in contact with other families

who have had similar experiences?

Mr. LYKINS. We have had several families that have called us

and talked to us, yes. Yes, we have.

Senator PRYOR. One last question on the nature of the bacterial

infection. What was the origin of that bacterial infection? Was it

because the tissue was not handled properly? Or was it pre-existing

in the cadaver? Do you know?

Mr. LYKINS. The bacteria is called Clostridium sordellii. My understanding of it is it is a spore-based bacteria, which to me means

it is in a little, kind of like an egg shell. It is a normal part of a

decomposing body. It starts in the intestines and then moves out

into the body over time. That is where the time issue is such a big

deal. So it was not a pre-existing. It was allowed to——

Senator PRYOR. It is naturally occurring if proper steps are not

taken to prevent it?

Mr. LYKINS. That is right.

Senator PRYOR. Madam Chair, that is all I have.

Chairman COLLINS. Thank you very much, Senator Pryor.

I want to thank you so much for your very courageous and moving testimony. I want to thank Tammy for being here as well. If

you have anything that you feel that your parents forgot to say

today or that you would like to add I just wanted to give you the

opportunity. If you feel it has been covered, that is fine too.

Ms. TAMMY LYKINS. I think they covered it.

Chairman COLLINS. Thank you. Again, thank you so much for

sharing your story with us. All of us simply cannot imagine the

pain and anger you must have endured. But I want to tell you that

we are committed to working with you to make sure that no other

family goes through what you have gone through. That is our goal

and I know it is yours as well. So thank you so much for being with

us today.

Mr. LYKINS. Thank you.

Chairman COLLINS. I would now like to call forward our second

panel. Our first witness on the second panel will be Dr. Steven Solomon. Dr. Solomon is the acting director of the Division of Health

Care Quality Promotion at the National Center for Infectious Diseases which is part of the Centers for Disease Control and Prevention. We also will be hearing from Dr. Jeanne Linden, the director

of Blood and Tissue Resources for the New York State Department
15

1The prepared statement of Dr. Solomon appears in the Appendix on page 44.

of Health. We want to thank both of you for your willingness to

participate today and, Dr. Solomon, I would ask that you go first.

TESTIMONY OF STEVEN L. SOLOMON, M.D.,1 ACTING DIRECTOR, DIVISION OF HEALTHCARE QUALITY PROMOTION, NATIONAL CENTER FOR INFECTIOUS DISEASES, CENTERS FOR

DISEASE CONTROL AND PREVENTION, U.S. DEPARTMENT OF

HEALTH AND HUMAN SERVICES

Dr. SOLOMON. Thank you. Good morning. I am Dr. Steven L. Solomon, acting director of the Division of Healthcare Quality Promotion in the Centers for Disease Control and Prevention’s National Center for Infectious Diseases. Thank you for the opportunity to report to you on CDC’s activities with regard to the problem of infections occurring in association with the surgical implantation of human tissue. As a physician and as a parent, I want to

express my sympathies to the Lykins family for their tragic loss.

An allograft is human tissue which is recovered from cadavers

and processed before being transplanted into another person. The

most common type of allograft is bone. Tendons, skin, heart valves,

and corneas are other common types of human tissue allografts.

Allografts may be lifesaving and can substantially improve the

quality of life for many patients, reducing disability and restoring

mobility or sight. The use of allografts has increased dramatically

in recent years.

As with any surgical procedure, the implantation of human tissue allografts may be associated with complications, including infections at the surgical site. Although rare, some of these infections

are associated with bacterial contamination of the implanted

allografts, a complication that can result in serious morbidity and

death. In collaboration with the Food and Drug Administration, the

Health Resources and Services Administration, and other partners,

CDC continues to investigate reports of infections and assess the

need for possible changes in the processing and quality control

methods for allografts as a means of preventing allograft associated

infections.

As indicated, transplanted tissue is commonly obtained from

cadaveric material. After recovery from the cadaver, allografts may

be either sterilized or undergo aseptic processing without sterilization. In aseptic processing, careful handling ensures that no new

organisms are introduced during the recovery of tissues from the

cadavers. Tissues may be treated with chemicals or antibiotics to

minimize intrinsic contamination, that is, bacteria that contaminate these tissues following death and prior to, or during recovery

of, the tissues. Thus, the tissue is not sterilized. The processing is

intended only to reduce intrinsic contamination and prevent further contamination of the tissue.

In November 2001, CDC began an investigation after receiving

a report from the Minnesota Department of Health of a fatal case

of infection with Clostridium sordellii bacteria in a young man who

had recently received a bone cartilage allograft. Clostridium

sordellii bacteria were identified in cultures of this young man’s

blood obtained prior to his death. Investigators at CDC contacted
16

the tissue bank from which the transplanted allograft had been obtained and the tissue bank provided CDC with samples of non-implanted tissues from the same cadaveric donor. CDC laboratories

identified C. sordellii bacteria in some of these tissues. As a result

of this investigation, CDC concluded that this young man’s infection had resulted from intrinsic bacterial contamination of the

transplanted cartilage tissue.

CDC subsequently contacted the health care providers of all patients who had already received transplanted allografts from this

same donor to determine if other infections had occurred. CDC

found that tissues had been transplanted into nine patients located

in eight States. One of these patients developed an infection following the surgical procedure. This patient’s infection was successfully treated with antibiotic therapy and the patient recovered.

To follow up this investigation, CDC, in collaboration with FDA,

requested that cases of allograft-associated infections be reported to

CDC through State and local health departments in addition to the

reporting of such cases to FDA. Cases reported to FDA were shared

with investigators at CDC and State health departments. As of

March 2003, 62 reports of allograft-associated infections had been

reported to CDC. Ninety-three percent of these infections were associated with musculoskeletal tissues. Cases of infection were reported from 20 States and involved tissues that had been treated

at 12 different tissue processors. These surveillance findings have

been shared with FDA, the American Association of Tissue Banks

and others.

In addition to investigating infections associated with bacterial

contamination of allografts, CDC has investigated reports of infections caused by fungi, parasites, and viruses following transplantation of organs and tissues. Examples include the transmission of

hepatitis C from a bone allograft, and transmissions of West Nile

virus and Chagas disease, a parasitic infection, following solid

organ transplantation.

CDC believes that the best way to reduce the risk of infectious

agents associated with tissue transplants is to develop new methods of sterilizing tissue that do not adversely affect the functioning

of the tissue when transplanted into patients. Every effort should

be made to use suitable sterilization methods. However, if that is

not possible, every effort should be made to minimize the risk of

intrinsic bacterial infection. Recovered tissue should be cultured before suspension in anti-microbial solutions, and if bacteria commonly found in the human bowel are isolated, all tissue from that

donor that cannot be sterilized should be discarded.

Other public health interventions that will greatly facilitate the

prevention and control of infections associated with tissue and

organ transplantation are enhanced surveillance and enhanced

communication with clinicians. Addressing the problem of infections associated with tissue and organ transplantation is part of

the larger problem of patient safety requiring significant changes

through all parts of the health care industry.

Organizations involved in organ and tissue procurement, and

suppliers and processors of tissues must put in place assiduouslyfollowed procedures to assure that any risks associated with tissue

transplantation are greatly minimized, if not completely elimi-
17

1The prepared statement of Dr. Linden with an attachment appears in the Appendix on page

55.

nated. State and Federal public health authorities must continue

to enhance their ability to collect, analyze, interpret, and disseminate information about potential patient safety hazards due to biological products, medical devices, and medical procedures

Clinicians and medical professionals must, with our help, increase their awareness of specific patient safety problems and fulfill their role in reporting such problems promptly to the appropriate authorities so that necessary public health action can be

taken. CDC, FDA and other partners, as noted earlier, are actively

engaged in ensuring that biological products, including tissue

allografts are as safe as possible.

Thank you so much for the opportunity to present this information to you today. I am happy to answer any questions that you

may have.

Chairman COLLINS. Thank you, Dr. Solomon. Dr. Linden, welcome.

TESTIMONY OF JEANNE V. LINDEN, M.D.,1 DIRECTOR, BLOOD

AND TISSUE RESOURCES, WADSWORTH CENTER, NEW YORK

STATE DEPARTMENT OF HEALTH

Dr. LINDEN. Thank you. Good morning Members of the Committee. My name is Jeanne Linden. I direct the New York State

Department of Health’s Blood and Tissue Resources Program. New

York State has spearheaded development of many innovative programs and maintains an active regulatory oversight in many important areas of public health. Since infected tissue poses the risk

of pathogen transmission to recipients, oversight of tissue banking

activities is an essential component, we feel, of any comprehensive

public health regulatory program.

In addition to the well-known risks associated with viral and

prion-associated diseases, bacterial infections in recipients of

aseptically processed cadaveric tissues, and infections with emerging agents such as West Nile virus, possibly SARS, are also of

grave concern.

In New York State regulation of tissue banks began with adoption of standards for hematopoietic stem cell banks in 1988, for

semen banks in 1989, and for human milk banks in 1990. In 1991,

a successful comprehensive tissue bank oversight program was developed and instituted in New York. Comprehensive rules set

standards for donor medical history assessment, and evaluation of

risk factors for disease transmission, laboratory testing, and recordkeeping to ensure the ability to track disposition of donated tissue

from donor to recipient and vice versa. These standards were formulated based on the medical literature, consensus of experts in

the field, and existing standards of professional organizations such

as the American Association of Tissue Banks, the Eye Banks Association of America, and the American Society for Reproductive

Medicine, which at that time was known as the American Fertility

Society.

Technical requirements are in place for all human tissues intended for transplantation, also for research or education, including
18

cardiovascular tissue, musculoskeletal tissue, skin tissue and eye

tissue. Licensure requirements for tissue banks apply to all facilities that collect, process, store, or distribute, or transplant tissue

in New York State. At present, 736 tissue banks are licensed to

operate in the State, including more than 130 facilities located outside the State. The table included with my written statement enumerates the various types of tissue banks that are licensed to operate in New York.

Comprehensive tissue banks include cardiovascular, musculoskeletal tissue banks, skin banks, eye banks, semen banks, oocyte

donation programs, bone marrow collection centers, umbilical cord

blood banks, human milk banks, and non-transplant tissue banks,

which is what we call tissue for education and research purposes.

In New York State, facilities that use tissues clinically, including

hospitals, ambulatory surgery centers, and even physician’s offices

are subject to tissue bank licensure as well as the specific administrative recordkeeping and quality assurance requirements. Errors

and accidents detected after distribution of tissue as well as adverse events must be reported to the Wadsworth Center of the

State Health Department within 7 days of discovery, affording another mechanism for effective oversight. Licensed tissue transplantation facilities must report any adverse events and patients that

might be linked to the tissue.

From the very inception of the New York licensure program staff

identified unacceptable practices going on in tissue banks. In one

case, two semen bank operators were using only themselves as donors but through the use of fictitious names led physicians and recipients to believe that more than a dozen donors were available

through the program. Testing and recordkeeping at this bank were

virtually non-existent. We actually needed to wind up following the

money and subpoena bank records to track that case.

Another reported incident concerned a hematopoietic stem cell

bank that transmitted the wrong component, that is the ABO incompatible red cells that had been removed from the bone marrow

rather than the marrow itself. Had the marrow not been retrievable, the patient, who had already undergone ablative therapy,

could have died as a result of a severely impaired immune system.

One surgical bone bank lost the skull flap of an autologous donor.

These cases demonstrate the crucial importance of thoroughly identifying tissues used for transplantation.

The death of Brian Lykins in November 2001 brought the inherent risk of using aseptically processed allografts to national attention. This tragic event spurred an immediate investigation that has

been described by my colleague. In cooperation with State health

departments, the CDC was able to locate non-transplanted tissues

from the same donor and identify the bacterium. A second recipient

from the implicated donor also developed an infection but cultures

had not been done. I apologize, my written statement is incorrect

in that regard. They were not done. They were not negative. This

patient, fortunately, responded to antibiotic treatment.

The CDC investigation determined that CryoLife, the tissue bank

involved, at that time routinely cultured allograft tissues following

suspension in an anti-microbial solution, which was not acceptable.

Such a culturing protocol can lead to false negative results because
19

of the bacteriostatic nature of certain bacteria, particularly sporeforming anaerobes like Clostridium.

In February 2002, absent its own jurisdiction or assistance from

any other Federal agencies, CDC asked the New York State Department of Health’s assistance in obtaining records and seeking

additional tissue samples from the donor implicated in the Lykins

case that remained in CryoLife’s inventory, as well as records and

tissues from donors implicated in other allograft-associated infection cases. The enforcement authority of the New York State Commissioner of Health enabled the Blood and Tissue Resources Program surveyors to conduct an on-site inspection of the tissue bank

where several deficiencies were noted, including the failure to perform recovery culture testing. The Wadsworth Center, the department’s public health laboratory, isolated Clostridium septicum in

tissues from two donors implicated in allograft-associated Clostridium infections. No remaining tissues associated with the

Lykins case donor were found.

The department also assisted CDC in identifying potential additional cases of post-transplant allograft infections by contacting

physicians who had used tissue from implicated donors for transplantation. Since confidentiality requirements prohibited us from

sharing the patient names with CDC, we needed to contact these

physicians directly.

The number of allograft-associated Clostridium infections per one

million population was found to be statistically significantly lower

in New York State compared to the remainder of the country; 0 vs.

0.06 per million with a highly significant p-value of 0.0009—highly

significant.

CryoLife maintained two inventories of tissue for release; one

suitable for New York State patients and a second one for patients

in other States. Tissues from only two of the implicated donors

would have met the requirements for tissue in the New York inventory. Tissue from six of the donors, including the donor in the

Lykins case, would have been disqualified for distribution to New

York. This likely contributed to explaining why there were no

known cases of allograft-associated Clostridium infections in New

York. We believe that New York State regulations have played a

significant role in protecting the State’s patients from such adverse

transplant-related outcomes.

Based on our experience, we believe that a mechanism to ensure

documentation of disposition of all tissues must be established and

enforced so that donors may be traced in cases of adverse events,

and all recipient outcomes must be reviewed and followed up as

necessary. The 1985 LifeNet incident, which was discovered and reported in 1991 in which numerous tissues were distributed from a

donor in the window period of HIV infection, illustrates the need

for accurate accounting for all allografts distributed by a tissue

bank and issued for transplant by the hospital. In this case, 6 of

54 distributed tissues could not be accounted for by the transplanting hospitals.

New York State’s rigorous requirements for licensure and recordkeeping by transplantation facilities are aimed at ensuring accurate tracking to each recipient. States that operate tissue bank

oversight programs complement Federal efforts in this most impor-
20

tant public health area. New York State has established a partnership agreement in place with the FDA’s New York District to share

inspection documents, and other reports and documents, and minimize duplicated effort.

We commend your endeavors to address this critical public

health concern. While tissue banking is clearly in need of Federal

oversight and uniform minimum standards, any potentially deleterious effects of imposing overly restrictive standards on the tissue

supply, we believe must be balanced against the proven benefits of

such standards to the public health. Specifically, it is unrealistic to

expect tissue banks to be able to guarantee the absence of contamination in a donor when tissues are processed aseptically. It must

be acknowledged that since some tissues are in short supply, patients’ health could be adversely affected if potentially draconian

regulations further diminish the tissue supply.

The FDA’s existing rules for tissue banks and progression toward

good tissue practices represent a valuable step toward enhancing

tissue bank oversight nationwide. The established benefits of such

standards in this area are abundantly clear. The New York State

program has identified several cases in which unsuitable donors

have been rejected and recipients thus protected by adherence to

the State’s rigorous standards. However, we do remind you that

any regulatory scheme must remain flexible enough to quickly

adapt to the rapidly escalating changes in this field.

Thank you very much for the opportunity to comment.

Chairman COLLINS. Thank you, Dr. Linden. Your testimony is

very helpful to us and I want to congratulate New York State for

coming up with a regulatory framework that has helped protect patients in your State.

There are two points in your testimony that I want to explore a

little further with you. First, I find it astonishing that CryoLife actually kept different batches of processed tissue in its supply; those

that were suitable for New York State and those that could be used

elsewhere. That may not be illegal but it certainly is questionable

that different batches of tissues are sent to a State with a good regulatory scheme than are made available to States, and that is the

vast majority of States that do not have a regulatory framework in

place.

Do you think that this is an isolated example or do you think

that other tissue banks may also have separate procedures that are

followed if the tissue is going to New York State?

Dr. LINDEN. The majority of tissue banks, the 130 licensed outside New York, use the same standards for everybody. They do not

have separate inventories. I cannot say whether CryoLife was the

only one. There may be a small number of others, but the majority

just meet our standards for everyone. But from a legal standpoint

we need to allow that because our jurisdiction is protecting the people of the State of New York.

Chairman COLLINS. But in the case at least of CryoLife, CryoLife

was doing different procedures to meet your stricter standards and

thus, I would argue that the patients in New York State were at

less risk of getting contaminated tissue, as the complicated study,

which I am not sure I followed on p-values, seems to indicate. Is

that a fair statement?
21

Dr. LINDEN. We believe that is the case and we believe that everyone in the United States should benefit from the same standards. We do not encourage facilities that have two different inventories, but we do allow it.

Chairman COLLINS. The second point that I want to follow up

with you on to make sure that the Committee fully appreciates

what you said is, you said in your statement that absent its own

jurisdiction or assistance from other Federal agencies, that the

CDC had to come to New York State public health officials in order

to conduct the investigation into Brian Lykins’ death; is that correct?

Dr. LINDEN. For Brian Lykins’ case, no, they were able to handle

that with the Minnesota and Georgia State health departments,

and it is my understanding the facility cooperated fully in the

Lykins case. It is when they got into looking into other reported infections, which exceeded 25 eventually, at that point the facility

was no longer willing to voluntarily cooperate, so an agency with

authority was needed, and we in fact did have to use our subpoena

power.

Chairman COLLINS. But I think your point is, and I am reading

from your testimony on page 3 and it actually refers to the Lykins

case as well, that in order to get the additional samples that the

Federal Government did not have adequate authority; is that accurate?

Dr. LINDEN. You probably should be asking my colleague.

Chairman COLLINS. Actually, why don’t I ask Dr. Solomon that.

Is it difficult for the CDC in a case like this where the tissue bank

is under no legal obligation to report adverse events and to cooperate with you, to do the kind of tracing and careful investigation

that needs to be done?

Dr. SOLOMON. Yes. Throughout this investigation there was an

obvious sense of urgency to identify any risks to health and safety.

From the outset, CDC was working closely with a number of partner public health organizations, including the State health departments as mentioned by Dr. Linden and the FDA. At each stage of

the investigation we had the opportunity to call on the resources

of these public health partners who do have the authority, the legal

authority to obtain information and materials.

We were very fortunate that Dr. Linden and her staff have a

very experienced and very proactive program so that at one point,

obtaining some documents and specimens through the resources

and capabilities of the New York State Department of Health was

the most expeditious and the quickest way of obtaining that material. We are very appreciative of her efforts, as we are of the efforts

of the other partners, including the Minnesota and Georgia health

departments and the FDA. That kind of close collaboration is critical for all of our investigations.

Chairman COLLINS. Dr. Solomon, you mentioned in your testimony that in the course of the investigation that you discovered

that there had been tissue donation from this one cadaver that

went to nine patients in eight States; is that correct?

Dr. SOLOMON. That is correct, yes.

Chairman COLLINS. Indeed, in just the Brian Lykins case there

are three States involved. The tissue came from a donor in Utah.
22

It was processed in Georgia, and the surgery was in Minnesota. Is

that accurate?

Dr. SOLOMON. Yes, it is.

Chairman COLLINS. Does this not make a strong case for uniform

Federal regulations?

Dr. SOLOMON. We are eager to see any kind of regulation or

other type of activity which will help reduce the risks to patients.

We are very grateful that New York State has that type of regulation in place.

Chairman COLLINS. One more question, Dr. Solomon, before I

yield to my colleagues. I have a list that our Committee obtained

from CryoLife of some 20 cases involving tainted tissues or allegations of tainted tissues. Eighteen of these 20 ended up in some sort

of court case in lawsuits. Under the existing regulations, it is my

understanding that CryoLife has no obligation to report these 20

cases to the CDC or the FDA. Do you believe that there should be

a Federal requirement for adverse events to be reported? Should

there be mandatory reporting of adverse events by tissue banks?

Dr. SOLOMON. We have dealt with the issue of mandatory reporting more broadly on the patient safety front for sometime. CDC

gets most of its surveillance and other reporting through State

health departments and directly from health care providers or patients as well as health care facilities. Manufacturers and other

processors more routinely do their reporting to FDA. I think it

would be more appropriate for FDA to comment on their relationship with manufacturers and tissue processors.

Chairman COLLINS. Senator Pryor.

Senator PRYOR. Thank you. Dr. Solomon, if I can follow up on

something you said a few moments ago about New York. You mentioned you are grateful that New York has standards in place. Are

you pretty familiar with those standards?

Dr. SOLOMON. I am not intimately familiar with New York

State’s standards specifically.

Senator PRYOR. Do you think that the New York standards

should be adopted as the national standard?

Dr. SOLOMON. My familiarity with the New York standards specifically are not sufficient for me to comment on whether all of

those should be adapted as national standards. Clearly, as Dr. Linden testified, the New York standards do protect patients in New

York State. Specifically, whether those standards would be applicable point by point federally is something that I just do not have information on at this time.

Senator PRYOR. Dr. Solomon, I know you are not completely familiar with them, but is there anything in the New York standards

which you would change, or you think is unnecessary, or that you

would strengthen? Are you aware of anything, given your limited

knowledge of them, that you would change about the New York

standards?

Dr. SOLOMON. I am not aware of them sufficiently to be able to

say specifically if there are elements that would not be adaptable.

But from what I understand from Dr. Linden, many of those standards are consistent with what both CDC has proposed and FDA

has proposed throughout this investigation.
23

Senator PRYOR. That is fair. I know that you are not holding

yourself out to be extremely knowledgeable of those standards. I

understand that.

Dr. Linden, let me ask you about New York’s standards. Do you

consider them the most stringent and the most thorough in the

country?

Dr. LINDEN. We like to think so.

Senator PRYOR. Do you think they should be adopted as the national standard?

Dr. LINDEN. They certainly could not be adopted—the statutory

authority the FDA has is completely different from ours, so the format needs to be different. I think that certainly to the extent that

our standards capture the accepted practice in the community, justified in the medical literature, that many of those elements would

be important to be included with the FDA’s approach, and indeed

they are.

Senator PRYOR. Are you aware of any holes in the New York

standards that you think the State of New York should fix?

Dr. LINDEN. Certainly, we are always looking to improve our regulations. We, in fact, have been actively working with the associated medical schools in New York to strengthen considerably the

technical standards for the use of whole bodies in medical education where we have had few standards in the past.

On the transplant side, certainly we continue to watch for improvements in technology, possible availability this summer of testing for West Nile virus. We are always looking to improve. I cannot

think offhand of a specific hole, with the exception of making the

comment that we really regulate services, the people who collect

and process and distribute the tissue, and the users, which we feel

is a critical part of our program which I believe FDA might not

even be able to reach under their authority. FDA regulates products.

So as I said, the approach is different and they have emphasis

on certain issues like validation that is a little bit different from

our approach.

Senator PRYOR. Now walk us through that here for just a moment. Explain the point you are making about the critical nature

of this.

Dr. LINDEN. We have found that the users, that is the transplant

sites——

Senator PRYOR. Now when you say users, do you mean the doctors who are performing the transplant?

Dr. LINDEN. Yes, the hospitals, the ambulatory surgery centers,

and physicians’ offices that are actually transplanting or using

these tissues, to make sure that they do not get them mixed up,

which has happened, that they go to the right person, that there

is adequate informed consent. I made the point that some of these

tissues, including the type of femoral condyle used in Mr. Lykins’

surgery, cannot withstand, at the present time, the types of viral

and bacterial inactivation methods that are available, such as

gamma radiation. Maybe there will be other processes in the future.

But some of these tissues are very valuable. If we simply eliminated them, orthopedic surgeons would be very upset, and patients
24

would not be able to get the type of life-enhancing surgeries they

have. But we feel that the informed consent, so that the recipient

knows the risks and in consultation with the physician can weight

those is very important. So that is one of the emphasis of our program.

Senator PRYOR. On a typical tissue—and I know that this may

be an unfair question because there are lots of different kinds of

tissue. But how many tests are done, say on a bone that is going

to be transplanted? How many tests are done on that? Is that an

easy thing to do? Is that an expensive thing to do? What are we

talking about here?

Dr. LINDEN. Are you talking about testing of the bone itself or

of the donor?

Senator PRYOR. That is a good question. Both of those. How do

you do that?

Dr. LINDEN. The donor’s blood, and a pre-mortem specimen is

preferable, is tested for a lot of the same things that blood donors

are tested for, plus a few more, particularly depending on what the

tissue is. A particular concern today since we are talking about

bacterial contamination, a culture of a sample taken at the time of

recovery of the tissue and before the tissue is subjected to antimicrobial solutions is something that we require and was absent in

some of the cases that we have talked about here today. So that

would be testing of the tissue itself.

In the case of eye tissue, for example, there needs to be an analysis using a slit lamp to determine whether it is suitable for transplant and that sort of thing. These are tissue-specific tests that are

done to heart valves. There are slightly different things.

Senator PRYOR. Thank you, Madam Chairman.

Chairman COLLINS. Thank you. Senator Carper.

OPENING STATEMENT OF SENATOR CARPER

Senator CARPER. Welcome. How are you? Thanks for joining us

today.

Dr. Solomon, that is a nice-looking uniform you have got on. I almost saluted when I came in. Are you a captain as well?

Dr. SOLOMON. Yes, sir.

Senator CARPER. I used to be a captain in the Navy. Whenever

I see your folks walking around in uniforms it brings back some

good memories. But I was never a doctor.

I missed your testimony. I was involved in another meeting right

out in the anteroom with other doctors from Delaware who are

here. We talked about an issue, actually an issue involving medical

malpractice. The question is whether or not that is something that

States should deal with or we should deal with it at the Federal

level. It sounds to me, Dr. Linden, you have decided in New York

to deal with the issue of handling of tissue and the safe use thereof, try to deal with it on a State level instead of waiting for us in

Washington to come up with regulations. Is that correct?

Dr. LINDEN. Yes. We really got started in the tissue in the mid

1980’s, I think largely as a result of the HIV crisis which was particularly acute in New York and there was really recognition that

tissues are yet another way that infectious diseases could be

spread.
25

Senator CARPER. Are there other States who have followed suit

or preceded you with development of some of the kinds of regulations?

Dr. LINDEN. I believe we were the first, but Florida——

Senator CARPER. It is good being first. That is a motto in Delaware, it is good being first.

Dr. LINDEN. Yes, it is good to be first. Florida also has a comprehensive program, although it does not cover reproductive tissues

is my understanding. California also has a law, but last I heard

their technical standards had not been adopted yet. There were

some issues there. Other States such as New Jersey do certain of

the tissues. I believe ours is the most comprehensive and it was the

first.

Senator CARPER. In my old job as Governor of Delaware I was

the chairman of the National Governors Association and I always

used to say that States ought to be laboratories of democracy, and

in some cases States will come up with a particular approach, could

be welfare reform, could be education, that might serve as a role

model for us on a national level. Is there any reason to believe that

what you have developed in New York or in some other State could

be a role model for us, or a model for us to try to replicate at a

national level?

Dr. LINDEN. I do not think it can be replicated as is, but certainly

many of the components can be and in fact have been. We have

shared our regulations with FDA, and I have served on some of

their advisory committees. We have worked with them closely. As

I mentioned, we have a partnership agreement with the district office. I believe that they have in fact considered some of our suggestions and incorporated them into their existing regulations and proposed regulations.

Senator CARPER. Given what you have learned in the development and implementation of your regulations, what lessons are

there for us at the Federal level, major lessons for us at the Federal level that you would like to leave me with today?

Dr. LINDEN. Certainly checking everything and not making assumptions is very important. You cannot just adopt the standards

and just think that everybody is going to follow them. They might

not know about them, particularly when you are getting into regulating physicians, which is actually an area we are getting into. So

that everything really needs to be verified. We think the on-site inspection process is very important.

Senator CARPER. How does your enforcement mechanism work?

Or do you have enforcement mechanism?

Dr. LINDEN. Yes, absolutely. Routinely, following a survey we

will cite deficiencies and usually they are correct. For egregious situations such as one that I described in my testimony of two young

men operating a semen bank using only themselves as donors, we

filed charges. We have filed charges in some cases where there are

improprieties or very severe deficiencies that are not corrected.

Senator CARPER. Thanks. Dr. Solomon, I missed your testimony,

as I said earlier, and I would appreciate it if you would just take

maybe a minute or so and just recap for me the most important

things that you would want us to garner from your contributions.
26

1The prepared statement of Dr. Goodman with an attachment appears in the Appendix on

page 61.

Dr. SOLOMON. Certainly. Thank you. The main issues have to do

with both our ability to conduct investigations, to follow up on investigations, and to encourage the implementation of the types of

prevention measures that are in place in New York and that have

been proposed by the FDA.

Another element is the surveillance capability and the prevention

capability that goes with the public health function and with the

prevention research function that allows us to gather the kind of

information and that is so useful in following up on these kinds of

problems and implementing very rapid responses to protect public

health.

Senator CARPER. Do I understand that the FDA has developed

regulations of its own for our country; is that correct?

Dr. SOLOMON. Certainly FDA has proposed a set of regulations

and guidelines and I think we will be hearing about that later.

Senator CARPER. What is the timeline at FDA, do you know, in

terms of accepting public comment, modifying the regs?

Dr. SOLOMON. I am not familiar with that. I am sorry.

Senator CARPER. Maybe we will find out later. Again, our thanks

to both of you for being here. Thanks for your contributions.

Chairman COLLINS. I want to thank you both for your testimony

and we will now turn to our third and final panel today. We have

one witness, Dr. Jesse Goodman, who will be testifying on behalf

of the Federal Food and Drug Administration. Dr. Goodman is the

director of the FDA’s Center for Biologics Evaluation and Research.

He is also, I am told, a specialist in infectious disease and a practicing physician.

Dr. Goodman, before I have you give your testimony today I so

want to acknowledge the fact that I believe you have only been in

your current position since January, so obviously this is a problem

that you inherited as opposed to created. But nevertheless, I hope

you understand how frustrating it is for me personally and for

those of us who have worked on this issue for years now, to find

that we are no closer to final regulations, or virtually no closer

than we were when I held a hearing on this issue 2 years ago. To

hear the tragedy endured by the Lykins family I know moved you

as well. So with that introduction, I would ask that you proceed

with your statement.

TESTIMONY OF JESSE L. GOODMAN, M.D.,1 DIRECTOR, CENTER

FOR BIOLOGICS EVALUATION AND RESEARCH, FOOD AND

DRUG ADMINISTRATION, U.S. DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Dr. GOODMAN. Thanks very much, Madam Chairman, and Members of the Committee. Thank you for the opportunity to be here

today on this important matter.

You really introduced me but just as you said, since January I

have been director of the Center for Biologics at FDA, and I am

also an infectious disease physician. So I am familiar with these

problems and in fact have been involved in treatment of individuals

who get infections after tissue transplants.
27

CBER, the Center for Biologics, is the FDA center that is responsible for regulating many types of human tissues and cells transplanted during medical procedures. We also have some other very

important public health responsibilities in terms of blood, vaccines,

and other novel therapies. I really do appreciate and share the concern of the Chairman and the Committee Members that we do everything we can in this area. Let me assure you that Commissioner

McClellan and I are very committed, while new in our roles at

FDA, to doing what we can to advance the field of tissue safety.

Also I really want to convey to the family and friends of Brian

Lykins how sorry I certainly am for their loss. As a father, I can

only begin to imagine how this has affected them. Again, while

there is nothing that I can say here that will take that away, I do

want them to understand the high level of commitment we have to

do what we can to prevent problems like this in the future.

In my testimony I am going to briefly provide some background

on human tissues and their use, discuss some of the safety concerns and their evolution, and in fairness, describe some actions

that we have already taken under existing regulations as well as

the actions we plan to take to enhance tissue safety.

Transplanted human tissue products have the potential to treat

or cure a wide variety of health conditions. Over the past decade,

advancing technology has expanded the therapeutic uses of tissuebased products. As we heard from Senator Collins, it is estimated

that over 800,000 tissue transplants will be performed this year

and, fortunately, the vast majority of these have very positive outcomes. In fact these products have dramatically increased patients’

quality of life in ways that were previously unheard of. Senator

Pryor’s experience is a positive example and we would like to see

everyone have that experience and certainly that is what we are

working towards.

Cells and tissue have new uses. They can also be used in combinations with drugs or devices for doing things like delivering

gene therapies. So there is a lot of promise here, and there is a potential to provide treatment for diseases as diverse as cancer, Parkinson’s disease, even diabetes and other serious conditions.

However, with the increased uses of human tissues has come a

heightened public awareness of the need for appropriate regulations. During the 1980’s there were reports of multiple incidents of

transmission of the chronic neurologic disease, Creutzfeld-Jakob

disease by brain-covering allografts. A 1992 report documented

seven HIV infections occurring from a single donor. And in the

1990’s, possible transmission of Creutzfeld-Jakob disease through

corneas and eye tissues was reported.

Now most recently, and this is very relevant to the tragic case

we are hearing about today, it has become increasingly apparent

that tissues are also subject to contamination from other agents

like bacteria and fungi. These are unlike the viruses like hepatitis

and HIV which come from donors who were not aware, or from a

system that was not aware they carried a disease. These risks may

have little to do with the donor. Rather, they may relate largely to

how the tissue is handled, processed, and then tested.

As part of the FDA’s efforts to address tissue safety, in December

1993 the agency published an interim rule for human tissue in-
28

tended for transplantation. This rule provided specific donor suitability and testing requirements for relevant human tissues. Like

actions we had taken to improve blood safety, FDA was acting primarily to counter the transmission of HIV, hepatitis B, and hepatitis C. This rule also provided for the inspection of tissue banks

and the recall and possible destruction of unsafe human tissue. In

fact events that later occurred with CryoLife, as we will hear.

These efforts were part of our risk-based regulatory approach to

tissues, recognizing the importance of these tissues and maximizing benefits while minimizing risks with the whole goal in the

end being promoting public health.

Now I would like to report on eight areas of agency activities

since the Committee’s last hearing 2 years ago on this subject.

These include many actions taken in response to the need to help

better prevent the types of problems that led to Mr. Lykins’ very

tragic outcome.

First, the death of Brian Lykins and other reports of infections

in recipients prompted collaborative investigations by FDA and

CDC, as you have heard, and in some cases involving the State of

New York. Extensive testing at CDC implicated CryoLife tissue in

the fatal infection and other reported infections. This led to a comprehensive inspection of CryoLife, the tissue bank that processed

the implanted tissue.

As an urgent response to these investigations, FDA also decided

it was critical to take additional steps now, not to wait for regulations necessarily, to control the threat of bacterial and fungal contamination during manufacturing. In March 2002, we issued a

guidance for immediate implementation concerning requirements

for validating procedures for processing human tissues under existing regulations. This guidance and the accompanying outreach to

industry and professionals emphasized important steps believed

necessary to reduce the risk of contamination.

Second, our CryoLife inspection uncovered numerous and significant violations of FDA regulations. You have heard some of these

today. When CryoLife failed to respond adequately to these deficiencies, FDA issued an order for retention, recall, and destruction

of tissue in August 2002. This resulted in a recall of 7,913 tissue

products. Further actions by FDA and CDC resulted in the firm

committing to take appropriate steps necessary to ensure the safety

of the tissues it supplies.

Third, the FDA, which had conducted—if we go back to the year

2000—we conducted 93 tissue establishment inspections then. We

conducted 132 in 2001, increased that to 165 in 2002, and in fiscal

year 2003 plans call for conducting over 200 inspections. I am

pleased to be able to report that as a result of this activity, FDA

has now inspected approximately 95 percent of the 162 registered

tissue processors. By the end of fiscal year 2003, our Office of Regulatory Affairs plans to have completed inspections of 487 of the 512

registered tissue establishments. This includes not just processors

but establishments that may test or ship or distribute or store tissue. Again, this is about 95 percent.

These increasing activities in recent years resulted in 2001 to

2002, for example, 99 investigator reports noting compliance deficiencies that warranted attention. We believe that these inspec-
29

tions and reports are already helping to increase awareness, correct

deficiencies, and ensure that better practices are followed, including proper practices to prevent contamination such as we have

heard about today.

Fourth, in October 2002, we created a new office, an Office of

Cells, Tissues and Gene Therapies which coordinates regulatory

and review activities for tissue products.

Fifth, the emerging challenges of chronic degenerative neurologic

diseases such as CJD and variant CJD, or mad cow disease,

prompted us to issue a draft guidance regarding appropriate donor

deferral for donors.

Sixth, very related to this, on October 22, 2002 FDA issued a

rule to classify human dura, which is brain lining, as a Class II device in order to establish controls to assure safety.

Seventh, In order to achieve a more robust surveillance system,

FDA is continuing to work with CDC to stimulate adverse event reporting and to investigate reported events. CDC, as you have

heard, has unique capabilities to conduct such surveillance. And we

are working on our own and with CDC to obtain adverse event information, including from health care databases.

Eighth, working collaboratively with tissue manufacturers and

trade and professional associations to identify new safety issues

and improve tissue practices is also an important component. With

this goal in mind, FDA has dramatically increased outreach activities in recent years in an effort to anticipate and avoid safety problems.

I should mention that this includes highly productive interactions with some of the professional associations, including the

one Senator Collins mentioned, the American Association of Tissue

Banks, as well as the eye banks and reproductive medicine associations. These associations have gone a long way through their voluntary programs to improving standards in their industry. Many

companies, but not CryoLife, participate in those standards.

In addition to these activities, as you have alluded to, FDA advanced three regulatory proposals. The first rule established suitability determinations for donors of human cells and tissues. The

second rule regards good manufacturing practices. And the third

rule, which became final in January 2001 required the registration

and listing of the tissue establishment. In fact this rule has already

provided important information to direct and manage our riskbased inspection activities. It is a success, I think, of the publication of this rule that we have been able to really enhance the inspections and reach the 95 percent of targeted folks.

Under FDA’s proposed regulations we would maintain this complete database of tissue products and establishments. We would

provide more comprehensive detailed requirements designed under

good tissue practices to help assure high quality during manufacturing, to further helping to prevent bacterial and fungal contamination.

We would require establishments to maintain complaint files and

investigate complaints, and to report adverse events and product

deviations to the FDA; issues that have been identified here. The

proposed rules would establish tracking requirements to allow the

agency to find recipients of implicated tissues if needed. The pro-
30

posed rule would also augment existing requirements for screening

and testing of donors for relevant communicable diseases. This

would also help us to rapidly respond to new infectious disease

threats such as West Nile virus which is something we have been

devoting a lot of energy to in our center.

While we have made substantial progress in this effort, the donor

suitability and good tissue practice rules, as alluded to here, are

continuing under review and discussion. Given that these regulations will create significant change, we want to be sure both that

they are effective and that we achieve the proper balance of enhancing safety and quality while not causing undue burden or complexity that would inhibit the development or availability of products that benefit Americans. In fact we want these rules also to be

flexible enough to permit the use of new and better technologies to

do things like sterilize tissues or improve safety.

As you heard from some of the testimony, we want to be sure

that as we do these rules we do not create a situation of shortages

or non-availability of certain tissues that actually could hurt people

if they needed the tissues. So we do want to get the right balance

here.

We do believe that the extensive process of comment and input

that has taken place will help us achieve these objectives. We are

not sitting on this. We are actively engaged in moving forward. We

have taken significant steps to make tissues safer than they were

2 years ago.

However, and even though they are rare, tragic adverse events

like that of Brian Lykins—and as you said, it is not just an adverse

event. This is something that really affects human beings. That is

why I do this. Tragic events like this are devastating, and we are

committed to doing what we can to prevent them. When a patient

has a procedure involving a tissue product, we want to do our part

to help make sure that patient can be as confident as possible that

the product will be safe and free from any preventable risk of contamination.

I have been very active working to resolve remaining issues and

I am committed to doing everything I can to help in this effort. I

would be glad to answer any questions.

Chairman COLLINS. Thank you very much, Dr. Goodman. I guess

what I was hoping to hear from you today was that the previous

FDA officials blew it and that you were going to promise me that

within a time certain we would have the regulations. I understand

you might not want to comment on the actions of your predecessors, but I want to go through a bit of a timeline with you just

so you can better understand the frustration that many of us are

feeling on this issue.

The FDA’s first regulation of tissue banks actually goes back to

1993. But it was in 1997 that the FDA started looking at the very

issues that we are talking about today. In May 2001, 2 years ago

almost to the day, I chaired the hearing at which your predecessor

Dr. Zoon testified. She told me the FDA was committed to completing the regulations. I thought it was imminent at that point.

There was testimony at that hearing that clearly said that the adequacy of tissue supply was not a concern, and indeed when you

look at the number of transplants which has soared, some more
31

than 800,000 last year alone made available in the marketplace, I

am not sympathetic to the argument that somehow the FDA regulations are going to cause shortages.

When I had the hearing, as I said, 2 years ago, I got a commitment from Dr. Zoon that the regulations would be issued. After repeated phone calls throughout the remainder of that year when

nothing happened, I wrote in February 2002 to the FDA. I expressed my frustration, the agency was taking such an inordinate

amount time to complete its work, because its work was good. It

knew what to do. It had come up with a reasonable protocol. All

we were asking was that it be made final, that it be made effective.

I asked when the regulations would be completed. The answer—

actually, I wrote again. That was in December 2001, I wrote to the

acting principal deputy commissioner. I did not even receive a reply

to that letter. In February 2002, I again wrote to FDA. This time

I received a reply 2 months later in April and the answer was, we

do not know. We do not have a date for publication and implementation of the final rules. Again, this is 5 years later at that point.

In March 2002, we had a report from the CDC after Brian

Lykins’ death in November 2001 in which the CDC said, the findings in this report have important implications for patient safety

and indicate that Federal regulations and industry standards on

processing and quality control methods need to be enhanced and

implemented. So here we have the CDC calling for implementation.

In October 2002, I asked Commissioner McClellan at his nomination hearing about this issue. Over and over again I have asked.

I have written everyone I can think of. I have a stack of correspondence. We have called. When is this going to happen? The

evidence is overwhelming that the FDA has come up with a good

approach. We have examples in three States of effective regulation.

So if there are some issues remaining, could we not look to the experience of those three States? When are we going to finalize these

regulations?

Dr. GOODMAN. I share your concern and some of your frustration

and I do appreciate it. When I started as center director, I know

that within those first few weeks I said to staff, and when I was

able to share it with Dr. McClellan, that I thought this issue and

moving forward should be a very high priority. It is on my list of

high priorities. It is not through lack of attention right now. I do

not see a problem there.

There is a new commissioner. They are complex rules. We want

to do it right. I personally feel that the framework which has

evolved with a lot of outside input and discussion with folks like

the tissue banks, with our colleagues at CDC and the States, with

a lot of comments and input I think it is a good direction and deals

with appropriate issues in a number of areas that I would like to

see us deal with. So I am very committed to doing that. We are

working, the new commissioner and I are working actively on that

now and hope to resolve some of those issues.

For some of the reasons you have said and some of the past experience, I do not control the exact timeline and also would not want

to give you one that is inaccurate. Also, I think that we want to

come up with the right product, as I said here, to meet our common
32

goals, the goals to deal with some of these areas where we could

have improved standards and regulation.

Chairman COLLINS. Dr. Goodman, I do not doubt your personal

commitment and I do not doubt your sincerity, and I do not doubt

your expertise at all. But we have to act. I cannot allow more Brian

Lykins to die because we did not have regulations in place. Every

expert with whom I have consulted has told me that they believe

that had those regulations been in place and had CryoLife followed

them, we would not have had the death of Brian Lykins. That is

just so troubling to me.

Dr. GOODMAN. Right. I would like to respond to that because

those are very important points. One is that we too want to do everything we can to prevent bad outcomes from medicines, medical

procedures, and in this case from tissues. I agree with that totally.

What I do want to emphasize is that we are in agreement that

there are areas where what can be done through regulation can be

improved, and that some of those would help prevent problems like

Brian Lykins’ death. That is particularly what drives me and

makes it important. I do not want to see more of that.

But what I also want to point out is that FDA’s actions at

CryoLife and in response to the investigation conducted in collaboration with CDC where under existing regulation we did show that

in fact CryoLife was violating existing standards and rules. Our

view is not just a guidance but they were violating principles that

are there in our regulations and those are the basis of our activities.

Now, that said, there are ways in which elements of the proposed

rules provide additional layers of protection and augment that existing authority in substantive and real ways that I think could

add value to the public health process. Those are the things that

I am committed to trying to move forward.

Chairman COLLINS. My time on this round has expired so I am

going to yield to my colleague, Senator Pryor. But when we come

back, I am going to direct to the deposition of CryoLife in which

it said it did not have to report to the FDA of adverse events. It

did not have to follow the regulations because they were just guidance and they were not effective, they were not in effect. I think

that is very troubling and should be to you as well.

Dr. GOODMAN. I agree. We can discuss that, for sure.

Chairman COLLINS. Senator Pryor.

Senator PRYOR. Thank you, Madam Chairman. I must tell you,

Dr. Goodman, I am not really satisfied with most of your answers

today. The reason I am not is because, by and large, you have

given us answers related to process, not action. I want to know

what you are going to do to get these regs out.

Dr. GOODMAN. Again, I appreciate your concern. I am not somebody—sometimes we have processes that we need to assure we

take the right action and to assure we get the action done.

Senator PRYOR. This has been pending at your agency for a long

time.

Dr. GOODMAN. Right. I appreciate the frustration over that. As

I said, in answer to your second question, I have engaged the commissioner and his office, I am working very diligently and deliberatively to resolve any issues so that we can move forward on the key
33

things here. So I agree with you on that. Without in any way diluting the importance of that work we need to do, I also would like

to say that it has been very important to me looking at this issue

even in the time since I have been center director to assure also

and to let you know that under our existing authority we have not

been doing nothing. We have dramatically gone out there and increased inspections.

The inspectors we have out there have been trained in procedures and issues related to exactly the kind of problems that led

to this tragic outcome. As a result we are seeing, for instance, more

voluntary recalls, more actions, and we believe that even our ongoing actions, which are contributing to improving quality and helping prevent such events.

Do they achieve all the things that would have been achieved

under the proposed rules if they were finalized? No. For that reason your comment is very important and I acknowledge and share

your interest in moving forward.

Senator PRYOR. What issues are left to be resolved at the agency

before you get these out?

Dr. GOODMAN. Again, we have just recently briefed and engaged

Dr. McClellan and staff, and the commissioner, who is new, and his

staff in the commissioner’s office, on these issues. There are quite

a number of elements of these rules. It is not one single thing or

another. We want to be sure we are placing the priorities in the

right place, the things that will enhance patient safety while not

causing undue burden, get the right balance here and move forward.

Senator PRYOR. But specifically, what obstacles are left within

the agency to do that?

Dr. GOODMAN. I think the only obstacles are identifying issues

where those kinds of concerns are and then resolving them in a

way that can get us to the satisfactory end point. I think I do not

have a specific list here. This process has been moving forward and

quite a number of unresolved issues I think people have come up

with solutions for them.

Senator PRYOR. Is there any reason why these regulations cannot

be released in the next 90 days?

Dr. GOODMAN. I think that we at FDA—again, I understood Senator Collins’ point of view too in terms of moving these forward. I

think we do have some work to do on them. Again, I am going to

work on those, and work with the commissioner on those within

the next 90 days and try to do everything we can to move forward

in a constructive way.

We are not, also, the only parties to this obviously. Everything

we do is reviewed legally within the agency and the Department,

and at a policy level in the Department. Now we are trying, and

we plan to engage collaboratively in that process to make this more

effective and move it forward. But I agree with you. We are going

to do everything we can during the next 90 days to move things

forward.

Senator PRYOR. Do you need any additional statutory authority

to move forward?

Dr. GOODMAN. I am not aware at this time that statutory authority is at issue here. We feel under the Public Health Service Act,
34

in terms of protecting people from communicable diseases that we

have authorities, and that the proposed rules largely build on those

authorities. So we do feel we have the authority.

Senator PRYOR. I am interested in Senator Collins’ questions

here in a few moments about the deposition relating to CryoLife

and I would really like to hear and delve into that and know what

is said. But one question I have for you is, given the violations that

CryoLife was engaged in, and I guess has admitted to at this point

I guess, why are they still in business?

Dr. GOODMAN. I think that is a good question. What I would say

is that FDA has taken a number of actions with respect to CryoLife. Included in those actions in terms of permitting them to continue to release tissue were a number of steps in an agreement

reached with them. First of all, just let me say that as I mentioned,

they were required by our action to recall a large number of their

tissues and they entered into agreement with us to take the needed

steps to assure better safety in their tissue processing.

Also during the interim period while they were taking these

steps, a number of extra safeguards were put into place through

this agreement including many of the things that CDC and Dr.

Linden from the New York State Health Department alluded to.

This includes the things we wanted to see valid, I say valid preprocessing culture of these materials, appropriate disposition of

materials which failed, valid culturing of materials after processing, and again, appropriate disposition of material that failed,

and a commitment to create and validate their own procedures to

do this.

So there was quite a significant discussion and a substantive

agreement reached in order to, what we felt was to ensure needed

elements that a safety program was in place there and that overcame what we felt were, as I said, quite serious violations even of

the existing standards.

Senator PRYOR. I am out of time. Thank you, Madam Chair.

Chairman COLLINS. If you need additional time, feel free to proceed.

Senator PRYOR. I was just going to ask with regard to CryoLife,

as part of the agreement that the agency reached with this company, is there an ongoing monitoring to assure that the FDA has

assurance that they are complying?

Dr. GOODMAN. Yes, there are ongoing inspections, there are

meetings. So the answer is yes. We are still concerned. They have

steps in the right direction, but these interim procedures are still

in place in terms of the additional culturing and other procedures

with their materials. But they have taken steps. Those steps are

not finished, and we are going to watch this carefully as this goes

forward. We are quite concerned about this.

Just getting back to the availability issue, this is one area where

we did hear from a number of surgeons and others who use certain

of their products for what they felt were essential and lifesaving

issues. Part of what we did with CryoLife was make sure—this

again addresses Senator Collins and the Lykins family comments.

Part of what we did in CryoLife was work with them to be sure

that users were also informed about some of these issues with their
35

products and could themselves help make an informed risk-benefit

situation in the situation they are in.

Again, I think we have taken substantive action in this case. But

again, as I said, I think some of the components of the proposed

rules will, we hope, prevent and better deal with future situations

like this.

Senator PRYOR. Madam Chairman, I will make this the last

question. You mentioned a minute ago that you still have some

concerns about CryoLife. They are taking some steps. They are not

completely there yet. Yet the agency is allowing them to still be engaged in the business. Why not force them to clean it up first before they re-enter the business?

Dr. GOODMAN. There are two components to that. One is, because

they have not completely finished all their progress on the various

things in their agreement with the agency, they are taking additional steps that would not normally be required in terms of these

outside cultures and oversight and agreements of what they will do

in response to these cultures with us. So there are additional measures in place to provide assurance that these kinds of problems are

dealt with. So that is the first component of that.

The second is just to state—and I do not want to equate these

problems with all problems observed in all FDA inspections or

whatever, but in most cases there are different kinds of levels of

concerns and observations in different kinds of inspections, and

very frequently when FDA makes observations of concerns like this

a company will move quickly to correct those in a manner that

gives us assurance that the product is safe and will remain safe.

In this case some of those steps have been taken but not all, so

there is a need to have additional steps in place.

Senator PRYOR. Thank you.

Chairman COLLINS. Thank you very much, Senator Pryor.

Dr. Goodman, CryoLife was well aware of problems related to infections of some of the tissue that it was providing long before Mr.

Lykins died in November 2001. The corporation’s internal reports

reflect that in May 1998 the company received a report from a surgeon indicating that a patient had a problem with an allograft.

Cultures indicated the growth of Clostridium bacterium. The patient then required the removal of the allograft due to continued

problems with infection. In the year 2000 there were at least six

complaints to CryoLife regarding bacterial infections. In 2001 there

were 10 complaints at least regarding bacterial infection, and one

of hepatitis C transmission from an allograft. I mentioned earlier

that I have a list of 18 lawsuits that have been filed against the

company as a result—each case involving tainted tissues.

Now the details of each of these complaints vary but there is

clearly a pattern indicating a problem. There is one common notation made by a CryoLife employee on each of the complaint reports.

I want to quote it to you. It says, ‘‘orthopedic allografts are not

classified as medical devices as defined by FDA regulations and

therefore are not reportable.’’ So CryoLife was all too aware that

the serious problems that had been reported by surgeons, and other

health care providers to the company did not have to be reported

under current FDA regulations.
36

Should it not be mandatory for tissue banks to report adverse

events such as these to the FDA?

Dr. GOODMAN. I would like to see reporting of adverse events

that the tissue banks and processors are aware of to the FDA. I

think it could be helpful, as you allude to, in identifying problems

ahead of time, and it is an element of the proposed rules. I agree

with you.

I cannot comment on the motivation or anything like that, but

you are right. And not just adverse events. It is important that another component of what has been proposed is that complaints are

investigated and records kept of those complaints. So even if something is felt not by a company or a surgeon even not to be due to

a graft or some other medical procedure, it is information that can

be helpful to FDA who may have information from other companies, other sectors of industry to identifying a problem. It might not

even be a problem at one company. It might be a problem with

something being done elsewhere.

So we do feel this is information that is helpful. It has been helpful in helping make other kinds of medical products safe. So I

share your desire that we have such information and that we get

it in an effective way.

Chairman COLLINS. Again, I think that proposed requirement for

mandatory reporting just makes good sense and needs to be put

into effect. That is not a complicated requirement to put into effect.

Dr. GOODMAN. Frankly, I think a lot of the issues about complaints, etc., these are good quality practices that irregardless of

the FDA any good company should be following. But I agree with

you, we cannot always count on that.

Chairman COLLINS. After Brian Lykins died his family filed a

lawsuit against CryoLife and during that process, as I alluded to

earlier, an executive of the company was deposed. During his deposition he made reference to the fact that the FDA had not imposed

final regulations regarding what industry practices should be, but

instead had issued what he called only non-binding guidance. Does

it trouble you to learn that a tissue bank like CryoLife, which

clearly does not follow ideal practices, is citing the FDA’s failure to

issue regulations as a defense?

Dr. GOODMAN. Of course it troubles me. One comment I would

make is it is not infrequent for firms under FDA investigation or

with whom actions have been taken that a firm might not like, it

is not uncommon for them to question those actions or question the

authority for those actions. Everybody loves us.

Irrespective of those kinds of comments I would say that we believe or we would not have taken the recall action, that we have

clear and strong legal authority to do that irregardless of their

comments. I am disturbed by their comments and I want to do everything we can to be sure that people do not believe that and to,

in the ways we need to, enhance our activities, but I do not buy

that.

Chairman COLLINS. When FDA did its inspection and issued a

form 483, FDA inspectors noted 12 objectionable conditions identified at CryoLife. CryoLife’s written response to the FDA does challenge FDA’s authority. When questioned about that in the deposition the executive said, ‘‘there was a guidance document issued.
37

They were not formal regulations. They were opinions, and they

were not in effect at the time.’’

One of my frustrations is I do not want there to be any doubt

about your authority. I do not want a bad actor to be able to tie

the FDA up in court because you have not gone through the final

steps of issuing all the regulations. We need to clear this up. We

need to end any doubt about your authority. We need to have clear

regulations in place, and I believe the FDA has the right approach.

It is interesting that in the 6 years that these proposals have

been pending, it is not as if FDA has proposed changing them in

any formal way. In fact the American Association of Tissue Banks,

the American Red Cross have endorsed the regulations. We need

to get on with the job.

Dr. GOODMAN. I hear you and I appreciate those comments. I appreciate all of them and I understand your concerns. I do want to

emphasize that while CryoLife may have questioned our authority

in this case, this authority is the interpretation of the chief counsel

of the FDA and the actions of the FDA, and we do not think there

is question about authority in this case. That does not in any way

mean that many of the proposals in the proposed rules are not

helpful, will not help industry do a better job, will not help FDA

do a better job. That is what we want to aim for, Dr. McClellan

and I, helping industry and the FDA do a better job to help make

tissues safer. I agree with that.

Chairman COLLINS. Dr. Goodman, I do want to thank you for

coming today. I appreciate the fact that you sat through the entire

hearing so that you heard firsthand the Lykins family testimony

which I am sure you will agree that the death of their son is such

a tragedy. If by acting to implement these regulations the FDA can

prevent future cases like Brian Lykins, or future cases of disease

and infection, we need to help you get that job done. If there are

obstacles I ask again for FDA to come to us. That was a request

that Senator Durbin and I made 2 years ago. If there is some new

statutory authority that you need, as Senator Pryor asked you

about, or if there are more resources, come to us. But let us get

the job done.

I hope I have from you today, or else I will not let you go, a commitment, a personal commitment to work with us to get these regulations, which I view as absolutely vital to public health, implemented without further delay.

Dr. GOODMAN. First of all, thank you. I am personally committed

and will make a commitment to you to do everything that I can

and is within my power, which is not, as you know, everything in

the world. But I will do everything I can that is within my power

to move this forward. This is a high priority to me.

I think as we look at the proposed rules and as I work with Dr.

McClellan and the commissioner’s office we really do want to identify for sure what are the key things that we can do and we need

to do to help improve safety here and move those forward. So I am

giving you my commitment that I am going to do everything I can

to try to do that.

Chairman COLLINS. I thank you for that commitment and you

can be assured that I am going to hold you to it. I know again that

you have only been on the job for a short time, but working to-
38

gether I am convinced that we can make a difference in this area.

Again, thank you for being with us this morning.

Dr. GOODMAN. Thank you.

Chairman COLLINS. Before adjourning the hearing, I also want

to say a special thank you to the Lykins family. Steve, Leslie, and

Tammy spent time with me in my office yesterday as well as having talked to the staff. I am so impressed and moved by their courage and their determination to make something good out of the

very worst tragedy that any family could suffer through. I just

want to publicly again thank them for their courage and for their

commitment, and to assure them that we will continue to work on

this important issue.

I also want to thank my staff for its hard work. I am optimistic

today that we are going to move forward, but I felt that way exactly 2 years ago, so this is an issue we will continue to follow.

The hearing record will remain open for 15 days for the submission of questions or any additional materials. I want to thank my

colleague, Senator Pryor for sharing his personal experience and

for being here for this hearing. The Committee hearing is now adjourned.

[Whereupon, at 11:56 a.m., the Committee was adjourned.]
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