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45–251 CC 1998

FDA REGULATION OF BLOOD SAFETY: NOTIFICATION, RECALL, AND ENFORCEMENT PRACTICES

HEARING

BEFORE THE

SUBCOMMITTEE ON HUMAN RESOURCES

OF THE

COMMITTEE ON GOVERNMENT 

REFORM AND OVERSIGHT 

HOUSE OF REPRESENTATIVES

ONE HUNDRED FIFTH CONGRESS

FIRST SESSION

JUNE 5, 1997

Serial No. 105–59

Printed for the use of the Committee on Government Reform and Oversight

(

(II)

COMMITTEE ON GOVERNMENT REFORM AND OVERSIGHT 

DAN BURTON, Indiana, Chairman 

BENJAMIN A. GILMAN, New York 

J. DENNIS HASTERT, Illinois 

CONSTANCE A. MORELLA, Maryland 

CHRISTOPHER SHAYS, Connecticut 

STEVEN SCHIFF, New Mexico 

CHRISTOPHER COX, California 

ILEANA ROS-LEHTINEN, Florida 

JOHN M. MCHUGH, New York 

STEPHEN HORN, California 

JOHN L. MICA, Florida 

THOMAS M. DAVIS, Virginia 

DAVID M. MCINTOSH, Indiana 

MARK E. SOUDER, Indiana 

JOE SCARBOROUGH, Florida 

JOHN B. SHADEGG, Arizona 

STEVEN C. LATOURETTE, Ohio 

MARSHALL ‘‘MARK’’ SANFORD, South 

Carolina 

JOHN E. SUNUNU, New Hampshire 

PETE SESSIONS, Texas 

MICHAEL PAPPAS, New Jersey 

VINCE SNOWBARGER, Kansas 

BOB BARR, Georgia 

ROB PORTMAN, Ohio 

HENRY A. WAXMAN, California 

TOM LANTOS, California 

ROBERT E. WISE, JR., West Virginia 

MAJOR R. OWENS, New York 

EDOLPHUS TOWNS, New York 

PAUL E. KANJORSKI, Pennsylvania 

GARY A. CONDIT, California 

CAROLYN B. MALONEY, New York 

THOMAS M. BARRETT, Wisconsin 

ELEANOR HOLMES NORTON, Washington, 

DC 

CHAKA FATTAH, Pennsylvania 

ELIJAH E. CUMMINGS, Maryland 

DENNIS J. KUCINICH, Ohio 

ROD R. BLAGOJEVICH, Illinois 

DANNY K. DAVIS, Illinois 

JOHN F. TIERNEY, Massachusetts 

JIM TURNER, Texas 

THOMAS H. ALLEN, Maine 

HAROLD E. FORD, JR., Tennessee 

———

BERNARD SANDERS, Vermont 

(Independent) 

KEVIN BINGER, Staff Director 

DANIEL R. MOLL, Deputy Staff Director 

WILLIAM MOSCHELLA, Deputy Counsel and Parliamentarian 

JUDITH MCCOY, Chief Clerk 

PHIL SCHILIRO, Minority Staff Director 

SUBCOMMITTEE ON HUMAN RESOURCES

CHRISTOPHER SHAYS, Connecticut, Chairman 

VINCE SNOWBARGER, Kansas 

BENJAMIN A. GILMAN, New York 

DAVID M. MCINTOSH, Indiana 

MARK E. SOUDER, Indiana 

MICHAEL PAPPAS, New Jersey 

STEVEN SCHIFF, New Mexico 

EDOLPHUS TOWNS, New York 

DENNIS J. KUCINICH, Ohio 

THOMAS H. ALLEN, Maine 

TOM LANTOS, California 

BERNARD SANDERS, Vermont (Ind.) 

THOMAS M. BARRETT, Wisconsin 

EX OFFICIO

DAN BURTON, Indiana HENRY A. WAXMAN, California 

LAWRENCE J. HALLORAN, Staff Director and Counsel 

ANNE MARIE FINLEY, Professional Staff Member 

R. JARED CARPENTER, Clerk 

CHERRI BRANSON, Minority Counsel 

(III)

C O N T E N T S 

Page 

Hearing held on June 5, 1997 ................................................................................. 1

Statement of: 

Friedman, Michael, lead Deputy Commissioner, Food and Drug Administration, accompanied by Kathryn C. Zoon, Director, Center for Biologics 

Evaluation and Research; Dr. Jay S. Epstein, Director, Office of Blood 

Research and Review; and Ronald G. Chesemore, Associate Commissioner for Regulatory Affairs ........................................................................ 221

Steinhardt, Bernice, Director, Health Services Quality and Public Health 

Issues, U.S. General Accounting Office, accompanied by Marcia Crosse, 

Assistant Director, Health Service Quality and Public Health Issues, 

U.S. General Accounting Office; and Thomas D. Roslewicz, Deputy 

Inspector General for Audit Services, U.S. Department of Health and 

Human Services, accompanied by Thomas J. Robertson, Region III 

Inspector General for Audit Services, U.S. Department of Health and 

Human Services ............................................................................................ 95

Letters, statements, etc., submitted for the record by: 

Chesemore, Ronald G., Associate Commissioner for Regulatory Affairs, 

information concerning 2-year statutory inspection coverage ................... 284

Friedman, Michael, lead Deputy Commissioner, Food and Drug Administration: 

Information concerning current data ....................................................... 269

Prepared statement of ............................................................................... 224

Roslewicz, Thomas D., Deputy Inspector General for Audit Services, U.S. 

Department of Health and Human Services, prepared statement of ....... 126

Shays, Hon. Christopher, a Representative in Congress from the State 

of Connecticut: 

Additional prepared statements ............................................................... 6

Prepared statement of ............................................................................... 4

Steinhardt, Bernice, Director, Health Services Quality and Public Health 

Issues, U.S. General Accounting Office, prepared statement of ............... 100

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

of New York, prepared statement of ........................................................... 211

(1)

FDA REGULATION OF BLOOD SAFETY: NOTIFICATION, RECALL, AND ENFORCEMENT 

PRACTICES 

THURSDAY, JUNE 5, 1997 

HOUSE OF REPRESENTATIVES, 

SUBCOMMITTEE ON HUMAN RESOURCES, 

COMMITTEE ON GOVERNMENT REFORM AND OVERSIGHT, 

Washington, DC. 

The subcommittee met, pursuant to notice, at 10 a.m., in room 

2247, Rayburn House Office Building, Hon. Christopher Shays 

(chairman of the subcommittee) presiding. 

Present: Representatives Shays, Pappas, Towns, and Kucinich. 

Staff present: Lawrence J. Halloran, staff director and counsel; 

Anne Marie Finley, professional staff member; R. Jared Carpenter, 

clerk; and Cherri Branson, minority counsel. 

Mr. SHAYS. I’d like to call this hearing to order. On July 25, 

1996, the House Committee on Government Reform and Oversight 

adopted a report offered by this subcommittee entitled ‘‘Protecting 

the Nation’s Blood Supply from Infectious Agents: The Need for 

New Standards to Meet New Threats.’’ Forwarded to the House 

with broad bipartisan support, the report found the U.S. blood supply safer than ever, but recommended seven specific steps to maintain and improve the safety of the blood and plasma products used 

by more than 40 million people each year. 

Two of those recommendations called for improvements in the 

Food and Drug Administration’s—FDA’s—regulatory approach to 

blood issues. Specifically we called for more rigorous inspections of 

blood banks and plasma facilities by the FDA’s Center for Biologics 

Evaluation and Research [CBER] and for the development of a 

more effective system to notify patients when unsafe blood products 

must be recalled. 

Today we ask, what has the FDA done to implement those recommendations? 

Blood and plasma products must flow through a five-tier safety 

system before reaching patients: donor screening, donor deferral, 

blood testing, blood quarantine and compliance monitoring, which 

includes inspections and recalls. 

In the inevitable event an infectious agent slips through the 

human and high-tech barriers of the first four layers, all that 

stands between a patient and potentially harmful, even fatal, therapy is vigilant, responsive regulatory inspections and recall. For 

some time, that final safety barrier against bad blood products has 

shown signs of leakage. Ten years ago FDA’s own Office of ReguVerDate Sep 04 2002 13:04 Sep 26, 2002 Jkt 010199 PO 00000 Frm 00005 Fmt 6633 Sfmt 6633 W:\DISC\45251 45251
2

latory Affairs cited lapses and inefficiencies in CBER’s inspection 

practices. 

In 1988, the Presidential Commission on the Human Immunodeficiency Virus epidemic called FDA’s dependent, 

nonconfrontational relationship with the blood industry an obstacle 

to progress toward improved safety. Before 1990, many thousands 

of people were infected with the hepatitis C virus through blood 

and blood products and never told of their exposure. 

While significant blood safety improvements have made since the 

1980’s, some of the same regulatory policies and practices that 

failed to prevent the devastating spread of AIDS to blood product 

users, particularly hemophiliacs, are still in place today. 

Then, as now, the lack of aggressive regulatory enforcement 

delays the detection of problems and delays the recall of potentially 

dangerous products, putting patients at risk. The number and 

scope of blood product recalls provides further evidence of a fraying 

regulatory safety net. 

Since January, the FDA has announced 17 recalls, withdrawals, 

or quarantines of fractionated blood products for reasons including 

inadequate viral testing, product impurities and the use of plasma 

from persons with CJD, the human form of ‘‘Mad Cow Disease.’’ Last October the FDA announced the largest blood product recall 

in U.S. history when one manufacturer of human products were 

found to be unsterile. 

The Department of Health and Human Services—HHS—report 

on that recall concluded, ‘‘If FDA had been more aggressive about 

responding to its earlier inspections and if those earlier inspections 

were more encompassing, the incident probably would not have occurred.’’ Even when a recall is not delayed by regulatory inattention, patients and their physicians still must rely on informal, voluntary, sometimes haphazard communication channels to learn 

their lifesaving therapies may be life threatening. 

The current recall notification system seems more designed to 

pass the buck down the product distribution chain than the pass 

the word about unsafe blood products. The ineffectiveness of the recall notification system is especially important to hemophiliacs and 

other patient groups who rely on regular doses of blood and plasma 

products for disease control and to maintain their quality of life. In 

this era of global telecommunications, they wait at the end of a 

fragile network manned by nonprofit groups and volunteers. They 

wait for the call or the fax identifying a product lot that may transmit hepatitis or some new infectious agent. And they hope, they 

pray, they haven’t already used it. 

They are also waiting to hear from us. The subcommittee received thousands of letters from individuals and organizations representing thousands of blood product users, encouraging us to persist in our oversight of blood safety improvements. I ask these letters be made part of this hearing record. Theirs is compelling testimony on the need for strong enforcement and effective recall notification as the central parts of the blood safety system. 

In February, the General Accounting Office—GAO—echoed our 

recommendations for strengthening blood and plasma facility inspections. At the subcommittee’s request, the Department of 

Health and Human Services—HHS—Inspector General—IG—also 

3

examined aspects of FDA’s blood safety product. Their testimony 

and that of the FDA today should tell us and these patients how 

we can keep the U.S. blood supply among the safest in the world. 

[Note.—Additional prepared statements can be found in subcommittee files.] 

[The prepared statement of Hon. Christopher Shays and the information referred to follow:]

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Mr. SHAYS. Today we have two panels. The first panel will be 

testimony from Bernice Steinhardt, Director, Health Services Quality and Public Health Issues, U.S. General Accounting Office, accompanied by Marcia Crosse and Thomas Roslewicz—— Mr. ROSLEWICZ. Roslewicz. 

Mr. SHAYS. Roslewicz? 

Mr. ROSLEWICZ. Yes, sir. 

Mr. SHAYS. Sir, it’s nice to have you here. 

Mr. ROSLEWICZ. Thank you. 

Mr. SHAYS. And accompanied by Thomas Robertson. And as is 

the practice we swear in our witnesses, even Members of Congress. 

[Witnesses sworn.] 

Mr. SHAYS. For the record, all four of our witnesses have responded in the affirmative. And we will begin, I guess, with the 

testimony from you, Ms. Steinhardt. 

Ms. STEINHARDT. Yes. Thanks very much. 

STATEMENTS OF BERNICE STEINHARDT, DIRECTOR, HEALTH 

SERVICES QUALITY AND PUBLIC HEALTH ISSUES, U.S. GENERAL ACCOUNTING OFFICE, ACCOMPANIED BY MARCIA 

CROSSE, ASSISTANT DIRECTOR, HEALTH SERVICE QUALITY 

AND PUBLIC HEALTH ISSUES, U.S. GENERAL ACCOUNTING 

OFFICE; AND THOMAS D. ROSLEWICZ, DEPUTY INSPECTOR 

GENERAL FOR AUDIT SERVICES, U.S. DEPARTMENT OF 

HEALTH AND HUMAN SERVICES, ACCOMPANIED BY THOMAS 

J. ROBERTSON, REGION III INSPECTOR GENERAL FOR 

AUDIT SERVICES, U.S. DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Ms. STEINHARDT. Before I begin I’d like also to introduce some 

other members of the team who contributed substantially to our 

blood study. I have Kurt Kroemer and Jacqui D’Alessio and Dr. 

Kwai-Cheung Chan also with me. 

Mr. SHAYS. Let me ask. Is it likely that any of those who are accompanying you might respond to testimony? 

Ms. STEINHARDT. It’s possible. Yes. 

Mr. SHAYS. OK. I would just ask—even it’s possible you won’t, 

but if it’s possible you might, I’d like you to stand now and swear 

in anyone who is accompanying. Do you have anyone that would 

be accompanying? 

Mr. ROSLEWICZ. Yes, sir, I have. 

Mr. SHAYS. If you would invite them to stand, as well. 

Mr. ROSLEWICZ. I will. It’s Carol Lessans, Steve Virbitskby, Joe 

Green, and Frank Zuraf. 

Mr. SHAYS. All right. Thank you. For the sake of our transcriber, 

if they do come and testify, we’ll make sure you have their full 

name. But if you’d raise your right hands. 

[Witnesses sworn.] 

Mr. SHAYS. For the record, all seven have responded in the affirmative. Sorry. Thank you. 

Ms. STEINHARDT. OK. Thanks very much. We appreciate the opportunity to be here today to talk about our two recent reports on 

the safety of the blood supply. Let me begin by saying, as the subcommittee did in its report last year, that the blood supply in the 

United States is safer than it has ever been. Since HIV was introVerDate Sep 04 2002 13:04 Sep 26, 2002 Jkt 010199 PO 00000 Frm 00099 Fmt 6633 Sfmt 6602 W:\DISC\45251 45251
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duced into the blood supply in the early 1980’s we’ve taken important steps to improve the way blood is collected, processed—— Mr. SHAYS. I’m just going to stop you a second. I’m sorry, Ms. 

Steinhardt. We’ve getting a little bit of an echo. And this is one of 

the fascinations that I have, is figuring out why. If you could just 

turn your mic away a bit and if you’d lower your mic and just put 

it a little away from you. Let’s see if that makes a difference. 

Ms. STEINHARDT. OK. 

Mr. SHAYS. OK. All right. 

Ms. STEINHARDT. We’ll try this. 

Mr. SHAYS. No, it’s not good. 

Ms. STEINHARDT. No. That’s worse. Let me see if—— Mr. SHAYS. OK. Yes. Why don’t we do that? 

Ms. STEINHARDT. Putting it over to the side. 

Mr. SHAYS. Do you have a way of turning it down a little bit or 

is it just one level? Yes. OK. Why don’t we try again here? 

Ms. STEINHARDT. OK. I simply wanted to turn to the graphic that 

we’ve provided which shows the five layers of safety that FDA and 

the blood industry now have in place as a quality assurance system 

to help ensure the safety of the blood supply. I want to emphasize 

that even if this quality assurance system were working perfectly 

there would still be risks associated with transfusion. Blood is a biological product—it comes from humans—not a synthetic process. 

In one of the reports we did we set out to calculate the risks associated with transfusion. And we estimate that for people receiving the average transfusion of five units of blood, the risk of receiving a contaminated unit of blood is 1 in 250, or 4 out of every 1,000 

patients. Ultimately, roughly 1,500 of the 4 million patients who 

receive transfusions each year are likely to die or develop a chronic 

disease as a direct result of a blood transfusion. 

On the other hand, as many as half of the patients receiving 

transfusions—that’s about 2 million of the 4 million—would be at 

serious risk of dying if they didn’t receive transfusions. Many of 

them, in fact, do die even after transfusion. So the risks from contaminated blood are considerably smaller than the risks of dying 

as a result of surgery or the risk of developing an infection from 

a stay in intensive care. 

Having said this, let me reiterate my earlier point. These are the 

risks that we calculate from transfusion if the quality assurance 

system—the five layers of safety—are working perfectly. The second major part of our work revealed that, in fact, the system is not 

working perfectly. I’d like to spend the remainder of my testimony 

focusing on some of the more significant problems that we found 

and the actions we think FDA can take so that it can better vouch 

for the safety of the blood supply. 

The first area I want to talk about this morning has to do with 

notification. Blood facilities have an opportunity to notify both donors and recipients of indications of infection. But these are not 

standard nor required practices. Let me speak first about donors. 

While some facilities may notify donors that they’ve tested positive 

on a viral screening test and that they are deferred from donating 

again, not all do. 

FDA recommends that facilities notify donors who test positive 

for HIV, but it doesn’t require facilities to do so nor does it even 

97

recommend this practice for other types of viral infection, like hepatitis. Although the blood in those cases wouldn’t be used for transfusion, donors can still attempt to donate at another site. And, of 

course, they don’t have the information that might prompt them to 

seek treatment or change their behavior. 

Facilities also vary in how they handle notifying recipients of infected blood. FDA now requires that patients be notified if they’ve 

been transfused with blood that came from a donor who has since 

been confirmed as HIV-infected, but the agency doesn’t require that 

patients be notified if they’ve received blood from donors who were 

later found to be infected with other viruses. We think this kind 

of notification is important both from an ethical as well as from a 

public health perspective. 

Hepatitis C, for example, can be treated, even if medical therapies aren’t yet 100 percent effective. And while the mechanisms of 

transmission are not well established, CDC has issued guidance on 

measures that people infected with hepatitis C can take to avoid 

transmitting it to others. 

I’d like to turn now to the issue of recalls and the problems we 

found in the last layer of safety. If an error or accident occurs that 

results in a potentially contaminated unit of blood being made 

available for distribution, licensed facilities have to report the incident to FDA. A reportable error or accident could involve the release of blood that was repeatedly reactive to tests or blood where 

mistakes were made in testing or that came from donors that 

should have been deferred or a number of other conditions. 

If a facility hasn’t already taken steps to recall the blood products, FDA may recommend that it be recalled. This system of required error and accident reports is by and large the basis for recalls. About two-thirds of recalls in 1994 were preceded by error 

and accident reports. Yet these reports are only required of licensed 

blood facilities. Those facilities that are not licensed are only asked 

to submit error and accident reports. 

Let me try and put this into some sort of perspective. Of the 

roughly 3,000 blood facilities in the United States, about 770 engage in interstate commerce and are therefore required to obtain 

licenses from FDA. The remaining 2,300 or so, many of them hospital-based blood banks, for example, are intrastate facilities, and 

therefore don’t require licenses to operate, although they are required to register with FDA and they are subject to many of the 

same regulations. 

In this case FDA requires that both licensed and unlicensed facilities maintain records of errors and accidents, but only licensed 

facilities are required to notify FDA when blood safety is affected. 

Unlicensed facilities are asked to do this on a voluntary basis. The 

resulting differences in reporting rates is quite striking. I have a 

graphic here that I would like to refer to. Looking at this in terms 

of how much blood they are collecting, the licensed facilities, which 

make up the large bar on the left, are submitting 82 error and accident reports for every 100,000 units of blood they collect. For unlicensed facilities, the comparable number is 12. 

Thus, even though unlicensed facilities account for 10 percent of 

the blood supply, they are submitting only 1 percent of the reports. 

Mr. SHAYS. So, 2,300 out of the 3,000 are 10 percent? 

98

Ms. STEINHARDT. They make up 10 percent of the blood supply. 

They make up far more in terms of the total number of facilities. 

But in terms of the volume of blood they collect they account for 

10 percent. 

Mr. SHAYS. Ten percent of the patients? 

Ms. STEINHARDT. Ten percent of the blood, of the actual volume 

of blood collected. 

Mr. SHAYS. Right. But I just wanted to have an idea of the number of patients that would be affected in either case. Can I draw 

a parallel that if it’s 10 percent of the blood supply it’s potentially 

approximately 10 percent of the patients, give or take? 

Ms. STEINHARDT. Probably. Sure. 

Mr. SHAYS. Nodding of heads behind you. Does that give you—— Ms. STEINHARDT. As long as we’re all moving in the same direction. 

Mr. SHAYS. And they’re under oath. So, my gosh, even nodding 

of heads has got to be acknowledged as—OK. 

Ms. STEINHARDT. In addition to these overall error and accident 

reports, unlicensed facilities also underreport errors that end in 

product recalls. Out of the hundreds of error and accident reports 

that preceded a recall in 1994, only six came from unlicensed facilities. And while more than 70 percent of licensed facilities submitted a report before recall, only 17 percent of the unlicensed facilities did this. 

Given that these reports are one way of alerting FDA of the need 

for an immediate recall, we feel that the underreporting by unlicensed facilities is a serious problem. We’re also concerned about 

the amount of time that’s taken in responding to error and accident 

reports leading up to a recall. The longer it takes to initiate a recall, the more likely it is that all the product will have already 

been transfused. 

But as you can see from the pie chart—and I’ll refer you to the 

sum of the green and blue wedges—we found that in 70 percent of 

the approximately 300 recall cases in 1994, FDA took more than 

7 months to confirm a recall from the time it got the error and accident report to review. The total time ranged from a little over a 

month to 21⁄2 years, with an average of nearly 91⁄2 months. And we 

couldn’t find any significant difficulties in these times based on the 

severity of the cases. That is, more serious cases were not processed any faster than less serious ones. 

Now, typically, a facility will initiate a recall without waiting for 

FDA to give the go-ahead. But 25 percent of recalls are not undertaken until the agency recommends it. So the agency’s timeliness 

can have very important safety implications. 

Finally, I want to highlight some concerns that we have about 

FDA’s standard setting and inspection processes—in point of fact, 

the underpinning of the entire safety system. FDA now communicates the requirements of this system through a complex of regulations, manuals, guidance documents and recommendations that is 

often confusing and ambiguous to those facilities who are supposed 

to implement the system. 

Many of the blood facilities we surveyed didn’t know which of 

FDA’s various statements were recommended and which were required. With regard to inspections, we found problems in several 

99

areas. FDA policy calls for inspecting facilities every 2 years, unless there have been problems, in which case they could be inspected annually. At the end of the inspection the inspector prepares a report and lists his or her observations. One of the problems we found is that the agency is not performing any sort of systematic statistical analysis of these reports or these observations to 

try to understand more about problem areas within and among facilities and to make sure that the inspection process itself is working well, that inspections have a certain consistency and rigor. 

Second, we found that inspections are not always timely. Twelve 

percent of the blood facilities nation-wide, according to our projections, may not have been inspected in the past 2 years, as FDA 

regulations require. And when inspections are conducted, it’s not 

clear that they’re complete. In looking through a sample of reports, 

we could find no indication that about a third of the areas that 

should have been covered in the inspection—like screening, deferral and testing—had, in fact, been covered at all by the inspector. 

FDA’s current policy is for inspectors to list on the reports only 

those areas that were not covered during the inspection. We think 

this policy is not reliable. 

Let me sum up and review what actions we think FDA ought to 

take in light of our findings. As I indicated at the outset, we think 

the blood supply is safe, but that it can be safer still. 

To start with, we believe that FDA ought to require blood facilities to notify all donors who are permanently deferred, not just 

those who test positive for HIV, that they have been deferred, and 

the medical reasons for their deferral. These people should not be 

attempting to continue donating blood. And they should be given 

the opportunity to seek further medical care if they choose. 

Next, we require that FDA ought to require blood facilities to notify patients when they have been transfused with blood from a 

donor whose subsequent donations were found to be positive, here 

too, not just for HIV, but for all viruses for which a confirmatory 

test is available. Likewise in these cases, we believe facilities ought 

to be conducting a look back, to identify and remove from their inventories any implicated blood units. 

FDA should also be requiring unlicensed as well as licensed facilities to report all errors and accidents. To improve its own enforcement efforts, we believe that FDA ought to clarify what facilities have to do to remain in compliance by determining which 

guidelines or recommendations are essential for ensuring blood 

safety, and publishing these in the form of regulations. 

And finally, FDA should improve its inspection processes by 

doing statistical analyses of its reports, making sure that its inspections are more timely, and having inspectors indicate in reports the activities they’ve actually observed. With that, I’ll conclude my remarks and look forward to your questions. 

[The prepared statement of Ms. Steinhardt follows:]

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Mr. SHAYS. Thank you. Mr. Roslewicz, I forgot to introduce your 

title. You’re Deputy Inspector General for Audit Services, Office of 

the Inspector General, U.S. Department of Health and Human 

Services. And it’s nice to have you here. It’s very helpful to our 

committee to have both the GAO and the Inspector General participate in these hearings. You do a lot of the work for our committee, 

and we appreciate it. You may begin. 

Mr. ROSLEWICZ. Thank you, Mr. Chairman. I also have with me 

Mr. Tom Robertson, who is the Regional Inspector General for 

Audit in our Philadelphia regional office. It was his staff that did 

the review of the audit. I’m pleased to discuss the results of our 

work which you requested concerning the Food and Drug Administration’s inspection process for the plasma fractionator industry. 

The Center for Biologics Evaluation and Research [CBER] is the 

FDA component responsible for regulating blood products, vaccines, 

serums and toxins. The Office of Regulatory Affairs [ORA] directs 

the agency’s field staff which performs inspections of FDA-regulated establishments. Our work focused on FDA’s role of regulating 

the industry that fractionates, or chemically breaks down, blood 

plasma into other useful components. 

Products made from plasma are essential in treating serious 

health conditions such as hemophilia, shock, trauma, and burns. 

The FDA has licensed 26 sites worldwide to fractionate plasma and 

manufacture plasma derivatives that are used in the United 

States. The Food and Drug Administration is responsible for inspecting licensed plasma fractionators to ensure that the products 

are safe, effective, properly labelled and contain the quality and purity that they purport to possess. 

Inspections where problems are identified can result in FDA 

issuing regulatory actions. Prior to 1992, CBER staff performed inspections of plasma fractionators and initiated regulatory action 

stemming from such inspections. From 1992 through 1996 ORA 

was phased into the inspections of fractionators, with CBER retaining the lead role in the inspections. That CBER performed these 

inspections was unique because ORA’s field staff conducted inspections of all other FDA regulated firms including manufacturers of 

drugs, devices and foods. 

Prompted by a variety of factors including the subcommittee’s 

concern about this unique inspection situation, FDA has begun to 

change how it inspects plasma fractionators. Beginning in fiscal 

year 1997, except for prelicensing inspections, ORA assumed lead 

responsibility for inspecting plasma fractionators. 

Mr. Chairman, the FDA is moving in the right direction to ensure that plasma fractionators and other biologics manufacturers 

are properly inspected and held accountable for regulatory violations. However, we do believe that the agency can do more to improve the inspection process. 

We reviewed 63 plasma fractionator inspections conducted between 1992 and 1997 which accounted for 25 of the 25 

fractionators. Of the 63 inspections, 33 were conducted by CBER 

staff only and 30 were conducted jointly by CBER and ORA staff. 

Our review revealed two key areas where ORA’s involvement appeared to bolster the plasma fractionator inspection and the enforcement processes. 

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By comparing the inspections conducted solely by CBER, the 

joint inspections resulted in, first of all, more reported problems 

being identified and, second, more enforcement actions. If I may 

call everybody’s attention to the chart on the wall here, the blue 

represents the joint inspections by ORA and CBER, the red represents the inspections that were done by CBER only. As you can 

see, the CBER only—— Mr. SHAYS. Do you have fun using that little thing? 

Mr. ROSLEWICZ. Oh, I love it. 

Mr. SHAYS. My staff moved back, thinking it was going to kill 

him here. 

Mr. ROSLEWICZ. I love it. It helps me to focus on the chart. 

Mr. SHAYS. OK. The FDA—do you regulate this? OK. It’s a safe 

product. And effective. 

Mr. ROSLEWICZ. As long as I don’t point it in somebody’s eyes it’s 

safe. 

Mr. SHAYS. I would like to be able to use that, and I could just 

point to each one as I wanted them to speak. OK. Sorry. 

Mr. ROSLEWICZ. What we’re showing on this chart is that the average problem reported where CBER only did the review was six. 

However, when they did joint review, the average problems reported on the inspection were 26. Now, of course, the more observations or problems that are reported result in more advisory actions 

and more other regulatory actions being taken. As you can see, 

again, the red bar shows that with CBER only, there were two regulatory actions taken. When the joint review started, it increased 

to 11, adding the 9 here plus the 2 over there. 

So, while CBER brings scientific expertise to the inspection process, ORA offers the following. The ORA staff are full-time inspectors, compared to the CBER staff, who are part-time inspectors. 

Further, the ORA staff have expertise in conducting good manufacturing practices. We also noted that when ORA was involved, the 

joint ORA/CBER inspections had more staff and lasted longer than 

the CBER only inspections. 

Our work also revealed continuing problems in two other areas: 

prenotification and documentation. Although CBER’s policy is not 

to prenotify plasma fractionators of upcoming inspections, we have 

found that CBER has not followed its own procedures on requiring 

production schedules. The subcommittee expressed concern that 

CBER’s practice of required production schedules resulted in de 

facto prenotification, which could permit out of compliance firms to 

clean up their facilities prior to FDA’s appearance. 

In November 1996, CBER developed new procedures designed to 

ensure that prenotification would not occur. The procedures state 

that CBER is to simultaneously request, by letter, every 6 months, 

production schedules from all licensed manufacturers of biological 

products, which number about 150. However, instead of sending 

these letters, CBER opted in making telephone calls, resulting in 

only 23 firms submitting their production information. 

Contacting all manufacturers ensures that those to be inspected 

are not tipped off to FDA’s appearance onsite. As a result of not 

following its procedures, CBER cannot provide definitive assurance 

that all manufacturers were contacted and that all manufacturers 

were contacted at the same time. A second continuing problem we 

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noted with plasma fractionator inspections is the absence of documentation in the files to show the inspection was classified. 

The classification occurs when CBER reviews the inspection report. It indicates the seriousness of the problems observed, and determines whether some form of corrective action or sanction is appropriate. Of the 63 inspection files we reviewed, 15 did not contain 

documentation to show that the inspection was classified. CBER informed us that six of these inspections were never classified. 

Without a timely classification, any appropriate corrective action 

or sanction is unlikely. We were encouraged to learn that FDA has 

plans for ORA to take the lead for all biological inspections now 

being conducted by CBER. An April 1997 draft plan proposed a 

core team of ORA and CBER investigators, and allows the agency 

to focus highly skilled resources on violative situations and to expedite their correction. 

We recommend that FDA implement this plan and ensure that 

appropriate milestones are included for transferring all biological 

inspections to ORA. 

Finally, at the subcommittee’s request, we reviewed FDA’s handling of two plasma problem cases. In the first case, involving a 

fractionator called Centeon, a plasma product recall was effectively 

communicated to the affected parties. However, FDA ineffectively 

handled the initial report of the problem related to the Centeon 

product and had not previously inspected the production of the 

plasma product, albumin. 

The second case study involved an industry-wide saline contamination problem associated with the collection of plasma. Such contamination could result in a viral test showing false negatives. We 

found that FDA’s involvement with an industry-sponsored work 

group formed to solve the problem was neither illegal or unethical. 

We noted, however, that FDA did not provide equal regulatory 

oversight to the two device manufacturers involved. They did not 

inspect the viral inactivation procedures at a manufacturers plant 

and were not aware of saline contamination problem for 5 years because they had not required the industry to report it. 

With regard to the inspection, we subsequently learned that the 

manufacturer initiated a class 3—the least serious—recall of a 

plasma product on May 24, 1997, due to the firm not maintaining 

the specified temperature for the viral inactivation process. 

Mr. Chairman, we believe that FDA’s actions to increase ORA’s 

role in the inspection and enforcement of plasma fractionators have 

improved the process, as evidenced by the increased number of 

problems identified and enforcement actions taken. Our report, 

which we submit today for the record, contains recommendations 

that should further strengthen FDA’s role in preventing, detecting 

and handling plasma related problems. 

As indicated in the report, FDA generally agrees with our recommendations and is taking action to correct them. 

Thank you, Mr. Chairman. 

[The prepared statement of Mr. Roslewicz follows:]

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Mr. SHAYS. Thank you very much. I’d like to just get a sense, to 

start, the impact of, Ms. Steinhardt, this last chart. I don’t really 

grasp the implications of it. So I want you to just walk me through 

it a little more in depth. 

Ms. STEINHARDT. OK. The chart graphs the amount of time that 

it takes FDA to review a report that is submitted by a facility. The 

facility is required to submit a report of any errors and accidents, 

including anything that may warrant a recall. 

Mr. SHAYS. Right. 

Ms. STEINHARDT. And once it gets this, this chart outlines the 

amount of time that it takes FDA to review that report, from the 

time it’s submitted to FDA until it determines whether to recall. 

Mr. SHAYS. A course of action. 

Ms. STEINHARDT. Right. And it says that in about 70 percent of 

the time it takes the agency more than 7 months to confirm a recall. That is from the time it gets the report. 

Mr. SHAYS. But the company, itself, can recall an item? 

Ms. STEINHARDT. Yes. That’s right. 

Mr. SHAYS. And, in most cases, if the company has determined 

that they have contaminated blood, an infected supply, wouldn’t 

they just intuitively and for their own, for the protection of the patients and the users and for the company’s protection, recall it? 

Ms. STEINHARDT. In three out of four cases they do. 

Mr. SHAYS. How many? 

Ms. STEINHARDT. Three out of four cases. It’s the company, themselves, that initiate the recall, 75 percent of the time. 

Mr. SHAYS. Right. 

Ms. STEINHARDT. And, in fact, it’s the companies, themselves, the 

facilities, themselves, that are responsible for carrying out a recall. 

Mr. SHAYS. Now, have you provided us statistics that tell us 

when FDA review with a particular delay how often it decides then 

to take action and have a recall? 

Ms. STEINHARDT. This chart is only for those cases where there 

was a recommendation for a recall. 

Mr. SHAYS. OK. 

Ms. STEINHARDT. This is in the subset of cases that proceeded to 

have a recall recommendation from FDA. In 70 percent of those 

cases, it took 7 months or longer. 

Mr. SHAYS. So what I’m seeing is, in 1 to 6 months it took 27 

percent of the cases—1 to 6 months—7 to 12, 25 percent—— Ms. STEINHARDT. Correct. 

Mr. SHAYS. And——

Ms. STEINHARDT. Close to half the time—47 percent—it took 

more than a year. 

Mr. SHAYS. And after a year they then decided to have a recall? 

Ms. STEINHARDT. Correct. 

Mr. SHAYS. That’s—yes, ma’am? 

Ms. CROSSE. This is to confirm the recall. This is not for the first 

step of recommendation of recall. This is to confirm the recall, to 

confirm that this recall has occurred. 

Mr. SHAYS. OK. This is the bottom line to what I want to know. 

I want to know how many cases would it have taken more than 6 

months before the FDA ordered a recall? 

Ms. STEINHARDT. 150 cases out of 300. 

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Mr. SHAYS. 150 cases out of 300, the FDA would have made a 

determination——

Ms. STEINHARDT. Confirm. 

Mr. SHAYS. Now, confirm—I need to understand what you mean 

by confirm. 

Ms. STEINHARDT. When it’s published. When the decision is made 

final and it’s published. 

Mr. SHAYS. But is it possible that it had been recalled already? 

Ms. STEINHARDT. It’s possible that it could have been recalled, 

that the product actually could have been recalled before then. 

Mr. SHAYS. Well—but I think you know where I’m going. I want 

to know when did the FDA require a recall that wasn’t taking place 

before then, and how often would we have seen a case that would 

have been more than 6 months or more than a year. 

Ms. STEINHARDT. Do we know that? 

Mr. SHAYS. Do you understand what I meant? 

Ms. STEINHARDT. Yes, I do. In 25 percent of the cases where 

there was a recall, it was FDA who initiated it. 

Mr. SHAYS. OK. 

Ms. STEINHARDT. So, three out of four cases the manufacturer or 

the facility had already taken an action. 

Mr. SHAYS. And that’s the ones I’m—now, of the 25 percent of 

the recalls that FDA initiated, how many of those took more than 

a year before they were——

Ms. STEINHARDT. Presumably 70 percent. Oh, more than a year. 

I’m sorry; 47 percent. 

Mr. SHAYS. So, more than 50 percent of the cases that the FDA 

decided to have a recall were not ordered until a year after the 

fact. 

Ms. STEINHARDT. Close to 50 percent. Right. 

Mr. SHAYS. Now, I make an assumption that the FDA made a 

recall because the blood supply was not safe, the product was not 

safe. 

Ms. STEINHARDT. Right. They made a determination. Now, let me 

be clear, it’s not FDA that makes the recall. 

Mr. SHAYS. OK. Let me just say—and someone else who wants 

to respond to this part, if someone else is more closely related to 

it, I’d just as soon—yes. Please identify yourself. And would you 

also leave a card afterwards to our—OK. 

Ms. D’ALESSIO. I’m Jacqueline D’Alessio. 

Mr. SHAYS. You can just pick it up, so you don’t have to bend 

over if you’d like. 

Ms. D’ALESSIO. That would help. 

Mr. SHAYS. Yes. 

Ms. D’ALESSIO. If in 25 percent of the cases FDA is prompting 

a facility, and there are 300 of the cases altogether, that means 

that there’s about 75 percent of the cases that FDA needs to 

prompt the facility. If you assume that in 50 percent of those cases 

it takes more than a year, that’s about 40 or so cases. 

Mr. SHAYS. Now, in those 40 or so cases then—and that may be 

a year after they’ve been notified, correct? 

Ms. D’ALESSIO. Notified? Yes, that there was an error and accident. 

205

Mr. SHAYS. And how much time would it have been on the market before they were notified? What would the range be? 

Ms. D’ALESSIO. About 6 months, I think. We have a pie chart. 

Ms. CROSSE. On average it took 4 months from the time that the 

facility detected the error and accident until they filed the report 

with FDA. 

Mr. SHAYS. OK. 

Ms. D’ALESSIO. But we don’t know how long it was between the 

detection and the actual occurrence. 

Mr. SHAYS. OK. What I want to know from FDA when it comes 

before us is, one, why that would happen, and what is the solution. 

If I were using any of these products, I would be pretty outraged— if I had been using them—and it took a year before FDA came to 

a conclusion. 

Ms. STEINHARDT. There is one other point that I think is important to add here. 

Mr. SHAYS. Sure. 

Ms. STEINHARDT. Which is that some blood products can be 

stored for a time before they’re actually transfused, but a lot of 

whole blood products have to be used within a matter of days. And 

in my mind it raises some questions about—at least for some portion—the value of a system that takes this long to carry out. 

Ms. D’ALESSIO. May I add one more thing? 

Mr. SHAYS. Sure. 

Ms. D’ALESSIO. In the vast majority of the cases, the blood facilities are amply capable of recognizing a very serious error and accident and they will recall the blood even before they’ve notified 

FDA. It’s the cases where the blood facility does not recognize the 

seriousness of the even that we’re talking about here. And, as far 

as we know, FDA has no requirement. When they recognize the potential seriousness and are evaluating it, there is no requirement 

that they contact the facility and ask them to quarantine the blood 

until they’re done with their review. 

Mr. SHAYS. OK. Do you have any comment about this here? 

Mr. ROSLEWICZ. We did look at this issue about 2 years ago, for 

the committee, with regards to the licensed and the unlicensed facilities. We found similar results as GAO is talking about in terms 

of the length of time it takes to issue the recall. And maybe Tom 

has some of the specifics with him. 

Mr. SHAYS. Tom. 

Mr. ROBERTSON. Yes. I think when we looked at it we took a 

sample of the error and accident reports that were coming in, and 

found that, for the most part, the action was taken by the blood 

establishment before they even sent the error and accident report 

in. When you’re talking about a delay of over 1 year for a recall, 

you’re not talking about a delay in the actual recall, you’re talking 

about a delay in the recall classification. That’s where FDA classifies the recall as a class 1, class 2, or class 3. 

Long before that happens, we found that corrective action was 

taken. And we found certain problems with the process, but that 

wasn’t one of them. We didn’t find, I believe, one case where there 

was a risk to the health because of that delay. Corrective action 

was taken. And you’ll find that in most cases—in almost every 

case—and they put it right on the error and accident report—when 

206

the blood establishment prepares that they put their corrective action right on the report. 

Mr. SHAYS. But was the corrective action recall? 

Mr. ROBERTSON. Yes, sir. They don’t call it a recall. They destroy 

the blood. They get the blood if they can—and certain times they 

identify the problem after the blood has already been shipped and 

infused in a patient. Now, when we looked at it, we found problems 

with the timeliness of submitting the error and accident reports. 

They were delayed quite a bit. 

And, as a matter of fact, FDA didn’t have any specific criteria as 

to when they should be turned in. I think the term they used was 

promptly. But promptly was never defined. But we didn’t find any 

problem with the health hazard. 

Mr. SHAYS. Let me just get to other issue—— Ms. STEINHARDT. Can I just add on this point, though, that the 

information about this came—what we got came from FDA, that 25 

percent of those cases were ones where they had to take the actions 

as opposed to those facilities. 

Mr. SHAYS. Right. And I think we just need to understand the 

significance of it. But I’m just trying to put myself in the position 

of someone who uses these products. And the letters—I was tempted to take these letters and read some of them. It’s people who literally stay by the phones, have fax equipment, have children who 

are highly dependent on blood supply products and, obviously, 

would die or their health would seriously deteriorate if they didn’t 

have it. So, we’re all on the same wavelength. They need this product. But they need it safe. 

And you read through some of this and you realize, what a way 

to exist. And the focus that I have—and my interest is, we do have 

a tiered system. We do donor screening. We do donor deferral. We 

do blood testing. We do blood quarantining. And the compliance 

monitoring, which includes the inspections and recalls. And that’s 

kind of a big focus of what I’m at least interested in today. 

And on the surface this looks quite alarming. And before this 

hearing is over today we’re going to really need to get into it. Why 

don’t I let Mr. Towns have the floor. And just beforehand, if I 

could—given that we have our Members on both sides of the aisle 

here, I’d like to do a little housekeeping here. 

I ask unanimous consent that all members of the subcommittee 

be permitted to place any opening statement in the record and the 

record remain open for 3 days for that purpose. And without objection, so ordered. 

And I ask further unanimous consent that all witnesses be permitted to include their written statements in the record. And without objection, so ordered. Mr. Towns, you have the floor. 

Mr. TOWNS. Thank you very much, Mr. Chairman. Let me also 

thank you again for holding this hearing. I know we’ve had three 

hearings on this issue. And this is the fourth. And I think it’s a 

very important issue. And we cannot have enough hearings on it. 

Because as long as people are concerned, we need to see what we 

can do to address those concerns. 

Just recently I was on an airplane flight and a gentleman recognized me and he came over and took a seat. And, according to 

him—he said it’s possible to reduce the risk to the blood supply. 

207

However, such measures would cost additional money, he says, and 

we’d probably have to change procedures to a degree if we did that. 

Are there any estimates or have any studies been done to assess 

how much that cost will increase and whether the patient or customer will be willing to pay the high price if this is true? 

Ms. STEINHARDT. Well, I can say we didn’t do—at least of the actions we recommended we think should be taken, we didn’t do any 

specific cost estimates. So we don’t know how much some costs 

would increase. But I think it’s important to point out that some 

of the things that we’re talking about—donor notification, recipient 

notification—are practices that many blood facilities in the country 

are already undertaking. And what we’re talking about would just 

extend that to all blood facilities and it would extend the notification to some kinds of viral infections that are not covered under 

current practices. 

Ms. CROSSE. Could I just add? 

Mr. TOWNS. Sure. 

Ms. CROSSE. Also, we think that some of these actions would be 

offset by savings at later stages in the process. For example, if you 

notified donors that they were permanently deferred and the medical reasons for that deferral, you could eliminate them returning 

at a later date to donate blood. So you would save the costs of 

screening and possibly, if they went to a different center, the possibility of having to test that blood at a later time. So, while some 

of the actions would have costs, they might have some offsetting 

savings in terms of not having to go through as many steps of the 

process, particularly the testing of blood products, which is quite 

expensive. 

Mr. ROSLEWICZ. While we have not done any specific cost-benefit 

studies in the Inspector General’s office, there certainly on some of 

the recommendations could involve additional costs. Sometimes it 

can be just a matter of changing a regulation which doesn’t necessarily increase the cost too much. But on the other hand, for example, in the plasma fractionator industry, as ORA shifts over to 

taking the lead on doing some of those reviews, the Food and Drug 

Administration certainly has to give consideration as to whether 

there are sufficient resources to do that or do they need to reallocate the resources differently. 

But we in the Inspector General’s office have not at this point 

done any such cost-benefit analyses of these kinds of things. 

Ms. STEINHARDT. If I could just add one important point to note, 

which is, not just the costs, but the benefits. If you look at the benefits to the American people since a lot of these measures have 

been put into place—this quality assurance system—in 1984 there 

were over 700 cases of transfusion related AIDS. In the 12 years 

since then, in that whole period, there have only been 38. And I 

think that’s a considerable benefit to offset looking at the costs that 

we’re already incurring. 

Mr. TOWNS. Let me add one other point that was raised that this 

gentleman felt that to be able to do a lot to correct the problem 

when it exists, that many of the blood banks were unlicensed—but 

actually the facilities that were involved in collection and processing and distribution of blood were unlicensed. And he said, 

208

therefore, it makes it difficult to do a lot to them. Could you respond to that? 

Mr. ROSLEWICZ. The blood banks that are unlicensed—it is generally because they are intrastate only. They don’t transmit their 

products between States. And that’s why they’re unlicensed and 

they’re not required to submit error and accident reports. But they 

have been asked to volunteer to submit their error and accident reports. 

In a report that we did several years ago, one of our recommendations was that the policy be changed there to make it 

mandatory that they submit the error and accident reports just as 

the licensed facilities do. I believe that GAO supports that recommendation and FDA has a proposed regulation I think in April 

of this year, where they’re proposing to make that a regulatory 

change. 

Mr. TOWNS. I think that when you look at that, that within itself 

makes people feel uncomfortable. I think when you can think about 

being over 2,000 unlicensed facilities, about a lot of reasons, people 

would feel uncomfortable for the fact that they’re not licensed, even 

though we know that there’s regulations and all that, in terms of 

Federal regulations. And, also, I think that the key here is the confidence. 

And if people don’t have confidence this could be a real problem. 

Do you want to react? Yes? 

Ms. STEINHARDT. Well, I think the fact that they’re not licensed 

by FDA doesn’t mean that they’re operating without any oversight. 

Because they don’t engage in interstate commerce they aren’t subject to licensure by a Federal agency. But they may be, and in fact 

usually are, licensed by the State in which they are operating. So 

there is oversight there. And they are, as we indicated, subject to 

FDA requirements—to many FDA requirements, particularly for 

blood safety. Ultimately they are responsible for blood safety. 

The point that we’re making here is that one of the key features 

of this quality assurance system is error and accident reporting. 

This is a way of keeping track of what’s happening, to take any corrective actions as quickly as possible to prevent errors and accidents in the future. And this part of the system—this key piece of 

the system—is that these facilities, because FDA doesn’t require it 

of them, it’s only voluntary. And it can be fixed. It can be readily 

fixed. And FDA has indicated that it intends to do that. We think 

it’s important to the integrity of the system. 

Mr. TOWNS. Right. And it should be fixed. It is my understanding 

that there is some controversy regarding whether FDA inspectors 

should use a check list approach or a more narrative approach in 

the inspection of facilities. Can each of you tell me which approach 

you would prefer and why? 

Ms. STEINHARDT. Well, if I can start. The issue we have with 

FDA’s inspection reports is that they simply—and we really don’t 

care whether they use a checklist approach or a narrative approach. What we care about is that they indicate on their inspection reports what they’ve actually done. The policy that they have 

now with regards to inspection reports is that the reports will presume that the inspectors will have covered everything that they’re 

supposed to cover unless they indicate otherwise. And we think it’s 

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just not a very reliable system. We found some of the inspection reports are quite complete. Others only say, this facility was in compliance. They never indicated what they looked at, what areas they 

covered. And we found some examples where clearly the inspections couldn’t have covered some areas. But there’s no documentation. 

Ms. CROSSE. Right. We don’t think it’s necessarily a problem that 

they do not cover all areas at every inspection. They may need to 

focus their attention to certain areas. We don’t expect that they 

would stay there for weeks to try to do an in depth examination 

of absolutely every aspect, particularly for a facility that engages 

in a full range of activities and has a large number of donors. 

However, we think that they need to indicate for the next inspector, and for the people back in the district offices and at CBER who 

have to review the reports, exactly what was done on that inspection so that they can have a clearer understanding of what type of 

examination was conducted during that inspection. 

Mr. TOWNS. Yes. 

Mr. ROSLEWICZ. I believe the checklist approach is certainly useful in terms of making sure that you cover all the different areas 

that you’re required to inspect. But I believe that there’s also a 

need for some narrative for some of the reasons that GAO pointed 

out in terms of future inspectors coming along the previous year to 

try to understand what was looked at in the past year. Simply a 

check mark sometimes won’t tell you what problem you found or 

what recommendations you might make to fix it. So I think a combination of both would certainly be beneficial. 

Mr. ROBERTSON. Yes, I agree with that. As auditors, for every 

audit that we start, we have an audit program. We don’t necessarily put everything in the audit report itself. But in our working papers, you can tell exactly what we did do. I think this would 

be a good idea for FDA. Now, they’re coming up with a guide. And 

I think when they’re coming up with the guide, as they’re drafting 

it, this might be something they will want to take a look at. 

Mr. TOWNS. Right. Thank you. I guess this is probably for GAO. 

In fact, it is. You noted in your report that better donor screening 

has refined the volunteer blood donor pool. However, as you know, 

there is a commercial pool as well. What kinds of actions or guidelines do you believe would be effective in reducing the risk from 

people who are paid for their blood. 

Ms. STEINHARDT. Yes. That’s a very good question. Not a lot is 

known about this pool of donors. But what is known I think raises 

some questions and suggests the need for some more information. 

As you pointed out, the commercial industry—the plasma products 

industry—relies mostly on paid donors. And from some data that 

are available we know—and I’ll point—the red bars are voluntary 

blood banks, and the blue bars are plasma centers. And this is data 

tracking HIV prevalence rates among donations in California from 

1989 to 1994. 

And you can see that among plasma centers—those blue bars— the prevalence of HIV in the donor pool was considerably higher. 

Now, the good news here is that in both the blood banks and the 

plasma centers the prevalence rates began to decline. But they’re 

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plications for HIV prevalence, but it also links to other kinds of 

high risk behaviors and the possibility of other kinds of infectious 

diseases within this population. 

In the plasma industry—plasma products, themselves—there’s 

very good techniques, very effective techniques for viral inactivation of HIV. And I think there is not a lot of concern there. But 

there is some concern about other types of viruses that may be 

prevalent in this donor pool. And we just don’t know much about 

it. And they may not be caught in these same inactivation techniques. So, it’s some newly emerging kinds of infectious agents that 

we’re concerned about. 

There have also been other studies that have been done that indicate that there is higher risk among paid donors than volunteer 

donors. And, in fact, FDA a number of years ago required facilities 

to indicate whether a blood was coming from those paid donors. 

But these are—the data are sort of spotty about this. And we think 

that there are enough indications to suggest that it’s worth looking 

at in greater depth. 

Mr. TOWNS. All right. Thank you very much, Mr. Chairman. 

Thank you. I yield back. 

[The prepared statement of Hon. Edolphus Towns follows:]

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Mr. SHAYS. Thank you very much. What aspects of GAO’s report 

did the FDA oppose? Where do you have your most lines of contention? 

Ms. STEINHARDT. I would say in the area of inspections and reporting. I think by and large the agency agreed with most of our 

recommendations. But the one area that we seem still to have some 

difference is with inspection reports, and, in particular, on the way 

in which the reports are documented. I talked about this a little 

earlier in the response to Mr. Towns’ question. FDA continues to 

believe that the system they now have for requiring inspectors to 

indicate only those areas that they don’t cover in an inspection is 

sufficient, and we simply disagree. 

We think that whatever an inspector observes ought to be documented for the record. And I would just note here the fact that 

FDA, itself, in its inspection of facilities, requires facilities to keep 

documentation of their quality assurance, quality control procedures. And they would cite a facility for the absence of documentation of what they’ve done. And they ought to follow the same kinds 

of standards and principles in their inspection and procedures. 

Mr. SHAYS. I know that Mr. Towns got into this a bit. But I’d 

like you again to tell us what you think the solution is between licensed and unlicensed. And it all involves the issue of interstate. 

Ms. STEINHARDT. Right. 

Mr. SHAYS. We license those that are interstate and don’t those 

that are intrastate. But what is the solution to that? 

Ms. STEINHARDT. FDA can simply require the unlicensed facilities to report error and accident reports. They have the authority, 

we believe. And, in fact, I know that they’re proposing—they’ve announced that they’re going to propose such a regulation. 

Mr. SHAYS. Yes. There’s no logical reason not to have them report. 

Ms. STEINHARDT. And the data suggest that there’s a good reason 

to have such a requirement. 

Mr. SHAYS. Right. OK. I’m treading back into your chart again 

on the delay of time. Because it sounds like we have a disagreement between you, Mr. Robertson—the GAO and the Inspector 

General—in terms of the significance of the chart. The chart seems 

to be valid, and yet, Mr. Robertson, your point to me is, don’t 

worry, because it doesn’t say anything. 

Mr. ROBERTSON. No, sir, I’m not saying that. I guess what I’m 

saying is, the ones that we looked at—we looked at the error and 

accident reports. I think we looked at about 150 of them. They 

came in from the establishments and all had instances of what 

they did in response to the error or accident. 

The problem that I see is that when you have that delay in the 

classification, you really have to rely on what the establishment 

said. Now, when we’re adding what they said it looks like everything is perfect. But if you classify it as a recall, then the FDA is 

required to do some monitoring. So that would be the effect. And 

I think we mentioned that in our report that we issued back in 

1995 or so. 

But without the classification the action was taken. But there is 

not assurance that what the establishment said they did, they actually did—No. 1—and, No. 2, that it was effective. So, one of the 

214

purposes of making the recall classification is to do—I think FDA 

calls them audits. They go out there and they verify that the problem that was reported is now corrected. 

Mr. SHAYS. OK. 

Mr. ROBERTSON. So, it doesn’t necessarily mean that the product 

remains out on the market. 

Mr. SHAYS. Have you made a recommendation to FDA that there 

not be such a time lapse between notification and a decision? 

Mr. ROBERTSON. I think our report dealt mainly with the error 

and accident reports. And one thing we did look at—of the 100 or 

more that we looked at, there were 17 that FDA took a good look 

at and decided that there was a potential for a recall. We looked 

at those 17 in detail. We found that 5 of their 17 were not processed properly, and we made recommendations. 

Mr. SHAYS. I don’t really think you were responsive to my question. You had a point that you wanted to make. I’m happy to have 

you make that. But the question is, did the Inspector General’s office weigh in on whether or not there should be corrective action 

in shortening the time in which the FDA is notified and then 

makes an order? 

Mr. ROBERTSON. We made a recommendation to them within the 

timeframe of when they’re notified. 

Mr. SHAYS. Yes. 

Mr. ROBERTSON. That was the extent of our recommendation 

with regard to the timeframe. 

Mr. SHAYS. What happened? What about the timeframe? 

Mr. ROBERTSON. We recommended that they have a 45-day timeframe. 

Mr. SHAYS. OK. 

Mr. ROBERTSON. That when the error and accident is identified 

they have to be notified within 45 days. I don’t believe that it has 

been implemented yet. 

Mr. ROSLEWICZ. The way the regulations were written indicates 

that the error and accident report should be submitted promptly. 

But there was no definition of what is prompt. So, our recommendation was to set something to the effect like 45 days. 

Mr. SHAYS. Yes. OK. If we have some more recalls, larger recalls, 

what implication do I make from that? That the screening process 

before was bad or that we have a better process now to do recalls 

and we should have had more recalls in the past? I’d like both of 

you to respond to that. Do you understand what I’m asking? Do I 

make an inference that if we have a lot more recalls now, that 

things are more serious or better, better in the sense that we now 

can identify that we should have recall and we’re taking action 

whereas, in the past, we should have had a recall and didn’t? I’m 

just trying to understand how I interpret significant numbers of recall and know if that’s a good thing or a bad thing. 

Ms. STEINHARDT. I think it’s really hard to tell. You know, you 

can increase the number of cases, of problems that you detect because the system is working better. And you can take that as a 

sign that the system is working better, or you can take it as a sign 

that overall the problems are actually increasing. I don’t know that 

there’s any way to definitively tell. I think——

Mr. SHAYS. OK. Yes. I’m trying to find that out. 

215

Ms. STEINHARDT. How you can tell. I think this is an area—— Mr. SHAYS. Let me just preface my comment again and say, 

there can be almost a temptation to say, this is terrible, we have 

another recall, the whole system is falling apart. Or we can say, 

at least this last line, we’re more on top of it. And then I’d want 

the time span to be real quick. But I’d say maybe that’s good. 

So I’d like to know—and you have no opinion—I don’t want you 

to have an opinion if you don’t. You don’t know how to read that 

yet? 

Ms. STEINHARDT. No. And the other thing I don’t know is whether the right approach here is to try and figure out how to make 

this system more efficient just by cutting down the number of days 

or if maybe there’s a whole other way to go about this. 

Mr. SHAYS. Well, one thing I know we’re going to do, we’re going 

to make the system more efficient. Even if the Inspector General 

makes the conclusion that action had already been taken, it 

shouldn’t take more than a year if people’s lives are threatened. 

And then we just need to find out what the FDA needs to do to 

make sure that doesn’t happen. I’d like you to take a pass at this. 

If we hear more recalls, larger blocks of recalls, should I view that 

as proof that the system is breaking down or that, at least in that 

final stage, we’re doing a better job of catching things we should 

have caught in the past? 

Mr. ROSLEWICZ. OK. Our audits certainly didn’t move in that direction. That was not one of our objectives. 

Mr. SHAYS. OK. 

Mr. ROSLEWICZ. But it seems to me that if you’re having more 

recalls, for example, the plasma fractionator—the chart I’m showing here. As ORA became involved we started to see more regulatory actions being taken as a result of more in depth inspections 

being conducted. 

Mr. SHAYS. Right. 

Mr. ROSLEWICZ. They’ve increased tremendously. When CBER 

was doing the inspections, there was an average of six observations 

per inspection. As they began to include ORA in these inspections, 

the number rose to 22 on the average. Now that ORA is doing them 

themselves, the number of observations being filed on an inspection 

is up to 49 on an average. So what you see is there’s more potential 

there for identifying problems as you do more in depth inspections. 

I don’t know if that’s exactly getting to your point. 

Mr. SHAYS. OK. Do you want to make another pass? 

Ms. STEINHARDT. Yes. I think we’re getting to something very important here. There needs to be—and it’s an issue that we did raise 

in the report. There needs to be some way of analyzing the information. Obviously, if it’s reached a stage where a recall is indicated, it means that something wasn’t working earlier in the 

screening process. There’s several layers of this quality assurance 

system that the blood had to go through to get to this point. And 

it didn’t get screened out before this point. So, something wasn’t 

working before then. 

There should be a kind of feedback mechanism here. FDA should 

be looking—and the facility, itself—should be looking at what’s 

going on beforehand in the earlier layers to make sure that it 

doesn’t reach that point. And that’s one of the concerns we have—

216

that there isn’t necessarily that kind of rigorous analysis of data 

coming out of the system that would allow us to tell. 

Mr. SHAYS. Can you outline, again, when you analyze the recalls, 

what was the primary reasons we’re having recalls? Was there any 

one area? 

Ms. STEINHARDT. Excuse me while I check. 

Mr. SHAYS. No. Why don’t you just step right up and get in that 

seat. And if you just identify yourself. 

Ms. D’ALESSIO. Thank you. Jacqueline D’Alessio. I must say a lot 

of them were post-donation information, so the blood center did not 

know the information from the donor at the time of the donation. 

It may be that the donor came back subsequently and made an admission regarding some risk behavior. Or perhaps called on the 

telephone to say that they had come down with some other disease, 

something like that. 

We can tell you about the proportions for error and accidents, but 

I don’t believe we have the information regarding the types of problems for the recalls necessarily. But they really ran the gamut, 

from bacterial contamination to releasing units that were repeat 

reactive for various diseases to more minor problems. 

Mr. SHAYS. Say the last thing again. It was muffled a bit. 

Ms. D’ALESSIO. To more minor problems. Oh, to releasing units 

that were repeatedly reactive on their screening test and should 

have been discarded instead of distributed. 

Mr. SHAYS. Is that bad management? 

Ms. D’ALESSIO. That particular case is. But if I could make a 

comment about your original question regarding whether this 

means the process is working better or worse. One point that’s very 

important to remember is that we now have a large number of new 

tests that we never had before. And we were unknowingly releasing a large amount of blood that was positive for hepatitis and 

other diseases. So, in that sense, the recall process is really working very well if we can get the blood back before it’s been transfused. 

Mr. SHAYS. OK. With the Inspector General, is the bottom line 

of the chart——

Mr. TOWNS. Would the gentleman yield? 

Mr. SHAYS. Yes, sir. 

Mr. TOWNS. Could we get her title. 

Mr. SHAYS. Your title? Everybody has a title. You can even make 

it up. 

Ms. D’ALESSIO. Senior analyst, Ph.D. 

Mr. SHAYS. Thank you. Does the IG believe that the FDA’s enforcement policies for the blood industry are better implemented by 

the Office of Regulatory Affairs, which is really a field force, rather 

than the Center for Biologics? Is that the bottom line—determination—I should make from you in that chart? 

Mr. ROSLEWICZ. The bottom line in that chart—what we’re showing is that as ORA became more involved with CBER doing joint 

inspections, it was a transition between 1992 and——

Mr. SHAYS. You’re giving me the long answer. I want the short 

answer. Do you agree with the statement I made that this chart 

would lead us to believe that enforcement policies for the blood inVerDate Sep 04 2002 13:04 Sep 26, 2002 Jkt 010199 PO 00000 Frm 00220 Fmt 6633 Sfmt 6602 W:\DISC\45251 45251
217

dustry are better implemented by the Office of Regulatory Affairs 

than by the Center of Biologics? 

Mr. ROSLEWICZ. Yes. 

Mr. SHAYS. OK. 

Mr. ROSLEWICZ. Also, on the other issue we were talking about, 

the MedWatch system that FDA asked—— Mr. SHAYS. On the what? 

Mr. ROSLEWICZ. The MedWatch system, which reports adverse 

events, like a hospital if they have a problem with their produce 

they can just call that system and put in the data. One of the recommendations that we made to FDA was to try to better use that 

system, to take advantage of the information that is put into that 

system in terms of coming up with quicker recalls. 

Mr. SHAYS. I have one last question that Anne Marie is insistent 

that I ask. What percentage of the current inspections of plasma 

fractionators are resulting in regulatory actions? 

Mr. ROSLEWICZ. What percentage? 

Mr. SHAYS. Yes. What percentage of the current inspections of 

plasma fractionators are resulting in regulatory actions? Fifty percent of the plasma inspections scheduled by the FDA in an accelerated timeframe following the Centeon incident in the fall of 1996 

have resulted in regulatory actions. Is that right? 

Mr. ROSLEWICZ. That is correct. The inspections that are being 

conducted with ORA as the lead—I believe there are 19 of them in 

1997 that we have data on so far—50 percent of those have resulted in regulatory action. That’s what we were told by—— Mr. SHAYS. Why don’t you followup on this question? 

Ms. FINLEY. Thank you, Mr. Chairman. In the IG’s testimony, 

you state that there are 19 ORA lead inspections of plasma 

fractionators and that 10 of them have resulted in enforcement actions, including one injunction. Is it also true that there has been 

one notice of intent to revoke, one consent decree and seven warning letters as a result of those inspections? 

Mr. ROSLEWICZ. Those figures are correct, I believe. But Tom, 

you wanted to say something? 

Mr. ROBERTSON. Yes. Our audit was basically the 63 inspections. 

And of the 30 where ORA was involved, there were 11 enforcement 

actions—11 out of 30—and there was one more that they were 

working on. So let’s say 12 out of 30. We ended our review as of 

the end of March 1997. Since then we were told by FDA that additional inspections took place, and that’s where they’re getting the 

50 percent. 

Mr. SHAYS. Now what’s the significance of the question and the 

answer? 

Mr. ROBERTSON. We didn’t audit the 50 percent. We were recently told that 50 percent of the inspections that were performed 

with ORA now taking the lead are resulting in enforcement actions. 

Ms. FINLEY. If 50 percent of the inspections are resulting in enforcement actions, is it fair to assume that 50 percent of plasma 

fractionators are not in compliance with FDA’s GMPs—good manufacturing practices? 

Mr. ROBERTSON. Yes. 

Ms. FINLEY. Thank you. 

218

Mr. SHAYS. That’s the significance. OK. Ed. 

Mr. TOWNS. Thank you very much, Mr. Chairman. There seems 

to be some confusion or a controversy about the FDA’s presentation 

of inspection findings to directors or owners of facilities. What does 

FDA do with the inspection results and what does it require or expect of the facility directors in response to adverse findings? Would 

you help clear that up? 

Mr. ROSLEWICZ. When the inspection is done there is a form 483 

where they document all the findings that they’re coming up with. 

These are certainly shared with the facility. And it is turned over 

to CBER for classification as to what one of the three classifications should be applied based on the results of that inspection. 

CBER then makes a determination as to whether there is no action 

indicated, whether there should be a regulatory action taken, injunction or license suspension or warning letters or whatever the 

situation would be in that particular inspection. So, the process is 

there. It’s shared with the facility. And it’s also CBER’s responsibility to make that determination. 

Ms. STEINHARDT. We surveyed 45 blood facilities. And this was 

a real problem that they perceive. It’s really not clear what actually 

is required of them. Many of them feel that they’re not kept wellinformed about what’s expected of them by the inspections. This is 

not true across the board. But it was true for a significant number. 

And I don’t know if you want to elaborate. 

Ms. CROSSE. Well, we found that many of the facilities felt that 

they were not getting good explanations in all cases of what the 

problems were that the inspections were identifying. However, it is 

FDA’s policy that the facility be presented only at the close of the 

inspection with the form 483 observations of any conditions that 

might warrant correction if the inspector has identified such conditions. At the time period that we reviewed in our study, they were 

not being presented with a full copy of the inspection report that 

was written up after the inspectors returned to their office. 

And, in fact, they were having to file a Freedom of Information 

request to receive a copy of the inspection report that was performed on their facility. And we understand from FDA that that 

policy has been changed, that they are now being sent copies of the 

full inspection reports. But at the time in which we surveyed the 

facilities, they didn’t feel that they were getting the full information about what the inspectors were discovering when they came 

and did the inspection in their facility. 

Mr. TOWNS. Shouldn’t they routinely get a report? 

Ms. CROSSE. Well, that was not the case at the time, but we understand that that policy has been changed by FDA subsequent to 

the time in which we did our work. To us it made sense that they 

be able to get that information without having to go through a 

Freedom of Information request. 

Ms. STEINHARDT. And it certainly explained why—at the time we 

did our survey—it explained why a number of companies felt sort 

of baffled or uninformed about how they were being inspected. 

Mr. TOWNS. That’s the reason why, Mr. Chairman, I think the 

checklist really plays a very important role. Because at least 

there’s some indication as to what the person actually saw or 

looked for. I think that becomes even more important to have it. 

219

So, thank you very, very much, Mr. Chairman. And I also hope 

that we can continue to push in this direction, because there still 

seems to be some real problems out there. 

And I think we need to sort of keep working to make certain that 

our blood supply is really safe. And inasmuch as you hear of maybe 

one incident—and I know we say that it is the safest. But the point 

is that there is some problems. And I think that we all have to acknowledge that fact and continue to work toward it. And in some 

instances it might require some resources. In other instances it 

might just require some changing of policy. So thank you very 

much, Mr. Chairman. 

Mr. SHAYS. Thank you very much. I just want to, unfortunately, 

open one door again. And that is the whole issue of the unlicensed. 

Because I’m really wrestling with this. We basically have 3,000 facilities give or take? 

Ms. STEINHARDT. Right. 

Mr. SHAYS. You say that 700 are licensed, but they represent 90 

percent of the blood supply activity. 

Ms. STEINHARDT. Right. 

Mr. SHAYS. You have 2,300 that have about 10 percent of the 

blood supply. Am I to infer that because they are not licensed, they 

may—and we know that the unlicensed facilities don’t have as 

many recalls. It would be logical to me that they should have it 

proportionately the same. That would seem logical to me. And so 

I have the sense that they should have some recalls from the unlicensed intrastate facilities that aren’t taking place. And I’m going 

to be asking FDA to deal with that. But I want to know, are there 

other way that these unlicensed facilities may simply not be up to 

the standard that we would want or does FDA, in other ways, ensure that these facilities are up to standard? 

Ms. STEINHARDT. Well, the key here is the error and accident report. That’s the information on what’s going on other than the inspection itself. It’s the information mechanism that FDA relies on 

to let them know what’s going on within the facilities. And that’s 

why—the statistic here is that they account for 10 percent of the 

blood supply but only 1 percent of the error and accident reports. 

That’s a significant difference. 

And that’s why we think it’s a really good starting point that at 

least if you can require them to submit the error and accident reports, then at least you can keep better track of whether there are 

other kinds of problems going on within those facilities that FDA 

ought to know about. 

Mr. SHAYS. So, bottom line: it’s an area for a good look. Now, is 

the GAO or IG looking at the unlicensed facilities? Are you taking 

a special look at these facilities? Do you have anything planned to 

do? 

Ms. STEINHARDT. Well, we looked at them as we did all the other 

facilities in this. And that’s, I think, of all the area that we observed, that’s the one that we think is the most important—just 

getting them. 

Mr. SHAYS. No. I’ve asked another question. I’ve asked the question of whether—you said the reporting—they only report 1 percent. They’re 10 percent of the blood supply, but they’re only 1 percent of the accident reports or recall. And I’m asking, does that 

220

lead us to believe there may be other problems as well with the unlicensed facilities in terms of other practices? 

Ms. CROSSE. Could I respond to that? 

Mr. SHAYS. Yes. 

Ms. CROSSE. There’s a distinction here between the filing of the 

error and accident reports, where there is a great disparity in 

terms of the percentage of the reports that are coming from the facilities that are underreporting. 

Mr. SHAYS. Right. 

Ms. CROSSE. However, of those reports that are filed, almost 

equivalent proportions go on to have an investigation of potential 

recall by FDA. About 5 percent of reports filed by licensed whole 

blood facilities are investigated as potential recalls. About 7 percent of those error and accident reports that are filed by the unlicensed facilities are investigated as potential recall situations. So 

that’s very close. 

The plasma facilities. Of the reports that they’ve filed, about 39 

percent are investigated as potential recalls. So we’re not seeing a 

great disparity in terms of the reports that are filed. 

Mr. SHAYS. Let me ask you this. What is the significance of being 

licensed or unlicensed? 

Ms. CROSSE. In terms of the primary safeguards in the system, 

they are required to comply with the same—donor screening requirements, testing requirements, deferral register requirements. 

Mr. SHAYS. OK. 

Ms. CROSSE. So—— Mr. SHAYS. What aren’t they required to do? 

Ms. CROSSE. They aren’t required to report to FDA. 

Mr. SHAYS. That’s the only thing? 

Ms. CROSSE. If they have errors and accidents. 

Mr. SHAYS. Is that the only difference? 

Ms. STEINHARDT. But that’s significant because that’s the system. 

Mr. SHAYS. No. First off. It is significant. So I don’t want to belittle it. But I just want it to be clear. Is that the only difference? 

Ms. CROSSE. No. There are some other differences in terms of the 

requirements they have to comply with if they’re making modifications in their own facility, if they’re moving equipment around. Licensed facilities have greater requirements placed upon them in 

dealing with FDA for that. An unlicensed facility does not have the 

same requirements in those regards. But the primary safeguards 

that are in place for the collection and processing of blood products 

are the same. 

Mr. SHAYS. OK. Would you like to respond. And let me just conclude this panel by saying—first off, would you like to respond to 

anything that——

Mr. ROBERTSON. No, sir. 

Mr. SHAYS. OK. 

Mr. ROSLEWICZ. The only other thing I would add to that—I 

think your question, if I understand it originally was, have we actually perhaps gone to an unlicensed facility to determine if there 

are any error and accident reports that they haven’t——

Mr. SHAYS. Right. 

Mr. ROSLEWICZ [continuing]. Or even if how many or what the 

extent is at these facilities. 

221

Mr. SHAYS. Or just looked at these facilities and said, are there 

differences between licensed and unlicensed that Congress needs to 

be aware of? 

Mr. ROSLEWICZ. We have not done that as part of our audits that 

we’ve done so far. 

Mr. SHAYS. OK. Is there any question that you wish that we had 

asked you that you feel needs to be part of the public record? This 

is really my out so later you don’t say, if you’d asked this we would 

have told you and it was significant. I am asking you to tell me— to ask yourself any question I should have asked that you would 

later on say I should have asked. 

Ms. STEINHARDT. I think almost everything—well, I would say 

everything we want to say we included in our testimony and our 

reports. 

Mr. SHAYS. OK. 

Ms. STEINHARDT. And ask that they be part of the record. 

Mr. SHAYS. They will be part of the record. 

Mr. ROSLEWICZ. Yes. I think our audit report is very detailed. It’s 

quite lengthy, as a matter of fact, with facts and figures. And the 

written testimony, itself, also carries our key points that we wanted to make. 

Mr. SHAYS. Any question that you wish we had asked? Any area 

that you wish we would have gotten into? 

Mr. ROBERTSON. No, sir. 

Mr. SHAYS. OK. We’re done. Thank you very much. We appreciate both the GAO and Inspector General being here. 

Mr. ROSLEWICZ. Thank you. 

Mr. SHAYS. Our final panel is Dr. Michael Friedman, Deputy 

Commissioner of Food and Drug Administration. I call him the Acting Commissioner. Accompanying him are Kathryn Zoon, Director, 

Center for Biologics Evaluation and Research; Jay Epstein, Director, Office of Blood Research and Review; and, Ronald Chesemore, 

Associate Commissioner for Regulatory Affairs. I’m going to ask 

you to stay standing. We’re going to swear you in, and we’re really 

happy you’re here. Do we have anyone else who might be responding? 

[Witnesses sworn.] 

Mr. SHAYS. And everyone has responded in the affirmative. Dr. 

Friedman, great to have you here and good to have your staff. And 

I’m looking forward to your testimony and asking questions. Thank 

you. 

STATEMENTS OF MICHAEL FRIEDMAN, LEAD DEPUTY COMMISSIONER, FOOD AND DRUG ADMINISTRATION, ACCOMPANIED BY KATHRYN C. ZOON, DIRECTOR, CENTER FOR BIOLOGICS EVALUATION AND RESEARCH; DR. JAY S. EPSTEIN, 

DIRECTOR, OFFICE OF BLOOD RESEARCH AND REVIEW; AND 

RONALD G. CHESEMORE, ASSOCIATE COMMISSIONER FOR 

REGULATORY AFFAIRS 

Dr. FRIEDMAN. Thank you very much. 

Mr. SHAYS. And I just note that we are joined by a former mayor 

of Cleveland, Mr. Kucinich. Thank you. 

Dr. FRIEDMAN. Thank you, sir. Mr. Chairman and members of 

the subcommittee, I’m Michael Friedman and I serve as the lead 

222

Deputy Commissioner of the Food and Drug Administration. With 

me today, as you’ve mentioned, Mr. Chairman, are Mr. Chesemore, 

the Associate Commissioner of Regulatory Affairs, Dr. Zoon, Director of the Center for Biologics Evaluation and Research—the center 

primarily responsible within the agency for the scientific and regulatory activities for blood and blood products—and Dr. Jay Epstein, 

Director of the Office of Blood Research and Review. 

This committee has demonstrated a keen interest in blood issues 

in the past. And so I appreciate this opportunity to discuss FDA’s 

role in regulating and protecting the Nation’s blood supply. Each 

year in this country about 14 million units of whole blood are 

drawn from about 8 million donors. The products made from this 

blood are transfused into 3.5 million Americans. Some of this 

blood—an additional 12 million units of source plasma—are further 

processed into products such as clotting factors and immunoglobulin. 

Blood and blood products are vitally important to our health care 

system and are often used to keep the most ill and the most severely injured of our citizens alive. Let me begin, sir, by reiterating 

clearly that blood products have never been safer and that the 

American blood supply is among the safest in the world. But having said this, because of the biologic nature of blood itself, there exists risks to anyone who receives a blood product. 

Nonetheless, we are absolutely committed to taking appropriate 

steps to making these products as safe as we possibly can. We 

must acknowledge that there have been weaknesses and inconsistencies in our regulatory oversight of blood and blood products in 

the past. Based on constructive criticism and advice received from 

this committee, from GAO, from OIG and IOM, and, of course, 

based on our own on-going commitment to improve what we do, we 

have implemented a number of substantial improvements in our 

blood program. 

And if I may, I’d like to highlight some of the recent changes we 

have made. As you know, sir, since 1993 the Office of Regulatory 

Affairs has been primarily responsible for blood bank inspections. 

And as you’ve just heard, as of the fall of 1996, the Office of Regulatory Affairs has taken the lead responsibility for the inspection 

of plasma fractionators. CBER’s staff cooperate in this endeavor. 

Their scientific input is valuable and useful. But ORA has the lead. 

Second, since this time—since the fall of 1996—we’ve conducted 

a thorough reinspection of all plasma manufacturers producing 

products for citizens in the United States. As you have seen, we 

found significantly more violations than had been noted in the 

past. And these observations are being acted upon in a much more 

timely manner. 

These efforts are aimed at preventing problems. Nonetheless, we 

know that there is more that needs to be done. The Center for Biologics Evaluation and Research is in the process of restructuring 

exactly how it handles reports of blood and blood products emergencies, and is now reacting much more appropriately and much 

more promptly. We also have changed how we communicate with 

the public, patient groups and others affected by recalls and withdrawals of blood products. And, moreover, we are reaching out to 

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able input helps increase the quality of our decisionmaking. This 

is especially true for the hemophilia community who participate in 

this way. 

We also are restructuring how blood issues are managed within 

the Center for Biologics Evaluation and Research. We’ve recently 

named a new medical deputy director for this center. And this individual will be in charge of all the CBER components dealing with 

blood and blood products. And he will continue to increase the pace 

of our efforts to markedly improve how we manage this very important portfolio. 

These are just some brief comments, an overview, if you will, of 

the steps that we are taking. We are not satisfied. We clearly recognize that a good deal more needs to be done. We are committed 

to reviewing and revising as necessary all regulations and guidance 

that we provide to industry to assure that they are complete, that 

they are current, that they are appropriate and that they are clear, 

so that industry understands its responsibilities. 

We also are committed to identifying areas where new advice 

may be needed. And we’re addressing new scientific problems as 

they are identified. Among the areas that still require additional 

consideration, we know that one of great interest to this committee 

has been the issuance of look back notification involving individuals who may have been infected with hepatitis C through blood 

products. 

The Public Health Service Advisory Committee established by 

Secretary Shalala, as was promised to you, Mr. Chairman, has 

taken several notification options under consideration. We expect 

much more precise guidance on these options at their next meeting 

coming up later this summer. 

FDA has worked with its sister agencies, especially CDC, to address the public health concerns of the approximately 4 million individuals thought to be infected with hepatitis C virus, some of 

whom may well have been infected through blood transfusion. 

I am personally committed to blood safety. Shortly after coming 

to the Food and Drug Administration in the fall of 1995, I began 

holding meetings on a regular basis with senior FDA managers, especially those from the Center for Biologics Evaluation and Research, to begin to discuss aspects of our blood safety program. 

These meetings continue. And we will get the job done. I am holding specific FDA staff responsible for the success of this effort, just 

as I expect you, Mr. Chairman, to hold me publicly and personally 

accountable for this. 

America’s blood safety program must provide the finest public 

health protection that is possible. FDA must be vigilant in ensuring 

that the blood supply is as safe as it can be. We appreciate the 

chance to be here to answer questions raised by the previous panel 

and other issues that you’d like us to address. Thank you, sir. 

[The prepared statement of Dr. Friedman follows:]

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Mr. SHAYS. Thank you. Why don’t you start by just responding 

to some of the dialog that took place earlier with the charts and 

so on. 

Dr. FRIEDMAN. I’d be happy to. 

Mr. SHAYS. Well, the charts disappeared on us. 

Dr. FRIEDMAN. That’s OK. 

Mr. SHAYS. You’ve got them in front of you. 

Dr. FRIEDMAN. And you have them as well. 

Mr. SHAYS. Right. 

Dr. FRIEDMAN. It would help, sir—focus me on—— Mr. SHAYS. Why don’t we take on license first? 

Dr. FRIEDMAN. All right, sir. 

Mr. SHAYS. Tell me what that chart says to you. We’ve accepted 

the assumption that 10 percent of the blood supply is done by unlicensed organizations and that only 1 percent of the recalls. 

Dr. FRIEDMAN. We can’t give you better estimates of what actually may be occurring in those unlicensed facilities in terms of 

numbers of error and accident reports. Our commitment is to bring 

these unlicensed centers under the same reporting requirements as 

the licensed facilities, because we think that that inconsistency is 

neither sensible nor appropriate. And so, regulations are in the 

process of being finalized for issuance—a proposal for those regulations is being prepared for issuance, because it’s my intention to 

have those centers treated the same way as the licensed centers. 

Mr. SHAYS. And how long will that process take? You’re smiling. 

Dr. FRIEDMAN. Well, Mr. Chairman, that’s the one question that 

I know you always ask, and it’s the one if I can give the very best 

answer on that I can. These proposals are in a near final form now. 

We hope within the next few weeks to have them out of the agency 

to the department and OMB. I am really asking for this because 

I believe our recommendations that have been made now for, I believe, more than a year, perhaps closer to 2 years. I very much 

want to get these out and done. And it’s my intention to focus on 

these very intently. 

Mr. SHAYS. You didn’t design the process of which regulations go 

through FDA, OMB and so on. But I just need to know—the bottom line would be at best, when would the earliest? 

Dr. FRIEDMAN. If OMB were to take a full 90 days, which is their 

prerogative—— Mr. SHAYS. Right. 

Dr. FRIEDMAN [continuing]. Then it’s my intention to have them 

to OMB and to the department by the first of next month, which 

would be July. 

Mr. SHAYS. Right. 

Dr. FRIEDMAN. That would be—it could be as late as October——

Mr. SHAYS. OK. That what? 

Dr. FRIEDMAN [continuing]. That those proposals would be 

issued. There then would be a comment period. 

Mr. SHAYS. Right. Of how many days? 

Dr. FRIEDMAN. I always ask for the shortest possible comment 

period consistent with getting good comments. 

Mr. SHAYS. Does OMB decide that? 

Dr. FRIEDMAN. No. There’s some flexibility in that. Typically 

there’s a 2-month comment period—60 days. 

266

Mr. SHAYS. All right. 

Dr. FRIEDMAN. But I commit to you, sir, that we’re going to try 

and speed that process along at every point. 

Mr. SHAYS. Right. Well, what we’d like to do is followup and encourage that process to move along. 

Dr. FRIEDMAN. And we do have a history of interacting with your 

staff on these things as they go through. And we’d be happy to continue that. 

Mr. SHAYS. But we’ll also try to encourage OMB to try to move 

forward as well. 

Dr. FRIEDMAN. Thank you, sir. 

Mr. SHAYS. Can I infer that there are other differences between 

a licensed and an unlicensed facility that are significant? 

Dr. FRIEDMAN. There are—that’s what I was going to say. I’m not 

sure that many of these distinctions are important from this committee’s point of view. I’ll ask those with me to please elaborate on 

this. The agency has some additional leverage in terms of dealing 

with licensed facilities. We have certain powers over those facilities 

that others do not. The reporting requirements you already know. 

I would ask those with me to please offer other information. 

Mr. SHAYS. Sure. 

Dr. FRIEDMAN. Please, Dr. Zoon. 

Ms. ZOON. I’d be happy to start and perhaps others might add. 

With unlicensed blood banks there are a number of controls and 

points of oversight that we do have. 

Mr. SHAYS. Now, you get the ability to do that not through interstate commerce. How do you get the ability to regulate them? 

Ms. ZOON. Well, they have to comply with the regulations that 

the FDA issues. 

Mr. SHAYS. I guess the issue is—— Ms. ZOON. What authorities? 

Mr. SHAYS. No. Why is the recall the one area that you don’t 

seem to regulate? And maybe that’s meaningless history. It’s logical to me that an unlicensed facility is unlicensed given that it’s 

intrastate. But yet you’re allowed to have tremendous impact over 

these facilities in other ways. You have oversight over them except 

in this one area. And I was just curious how you get your oversight 

over an intrastate facility? 

Ms. ZOON. We have oversight by the Food, Drug and Cosmetic 

Act. 

Mr. SHAYS. OK. 

Ms. ZOON. And we also have control under the Public Health 

Service Act as it applies to communicable diseases. 

Mr. SHAYS. OK. But you do have the authority to require these 

unlicensed facilities to provide reports and recall and so on? 

Ms. ZOON. Through regulations, yes. 

Mr. SHAYS. But you don’t have the ability to license them? 

Ms. ZOON. That is correct. 

Mr. SHAYS. OK. All right. Did you have anything else that you 

wanted to say? Any other comment? 

Ms. ZOON. Well, you had asked me what types of controls we 

have, and I was just going to say that they needed to comply with 

regulations. They needed to be inspected. There are also State controls independent of Federal controls. And the last two were that 

267

they’re subject to the FD&C Act and the Public Health Service Act 

under the communicable diseases provision. 

Mr. SHAYS. OK. Any other comment? Now, the Inspector General, through this chart, responded to my question by saying, yes. 

And I said, does the IG believe that the FDA’s enforcement policies 

are better implemented by the Office of Regulatory Affairs where 

you have field offices, rather than the Center for Biologics? And we 

had both represented here. And I’m not looking for an internal battle, but I would like a candid response to what you think about 

that. 

Dr. FRIEDMAN. Let me say that if one accepts the model that 

there needs to be participation by both centers—and that will be 

my thesis here—having the Office of Regulatory Affairs take the 

lead for that activity brings this component of the products that we 

regulate into coherence with all the other things that we do. There 

are real economies of scale. There are real organizational values in 

having more uniform procedures for how certain kinds of inspections are made. 

I absolutely underscore the value of having CBER’s scientists involved in these inspectional activities. But I think that we’ve demonstrated that there’s a great deal to be gained by having ORA as 

the lead organization. Our testimony has some of the documentation of that. The number of findings that are expressed. 

Mr. SHAYS. Right. 

Dr. FRIEDMAN. The days involved in doing the inspections. And 

the timeliness—an issue that you were focusing on earlier—how 

quickly—what is the interval between the completion of the inspection and the generation of written documents and so forth. In all 

three of those areas there has been an improvement since the involvement of ORA as the lead in these inspections. 

Mr. SHAYS. So, it’s the policy that ORA should be taking the 

lead? 

Dr. FRIEDMAN. They are taking the lead, sir. Since roughly November 1996 they have been the lead for the plasma fractionators. 

For whole blood they have been the lead—it’s varied depending on 

the different facilities——

Mr. SHAYS. Right. 

Dr. FRIEDMAN [continuing]. For a longer period of time. We are 

moving to having ORA be the primary lead for all biologics. That’s 

vaccines, allergenics, so on and so forth. But for the purposes of our 

discussion here today, ORA is in the lead for plasma fractionators, 

for whole blood, components and so forth. 

Mr. SHAYS. OK. Let me go to this chart here and have you respond to that. 

Dr. FRIEDMAN. Yes. 

Mr. SHAYS. The time for errors and accident reports submission 

to recall confirmation. I first need to know what this tells you and 

then I want to know the implications. 

Dr. FRIEDMAN. Let me begin by saying I’m not sure what this 

tells me. And the reason is—and I don’t mean this to be critical. 

I was a little confused by the presentation. 

Mr. SHAYS. No. I understand. 

268

Dr. FRIEDMAN. And after our discussions here today, we will be 

touching base with them to go through this in more detail. What 

I would first point out to you, sir——

Mr. SHAYS. Let me just ask you this. 

Dr. FRIEDMAN. Yes. 

Mr. SHAYS. One, confused in what it’s saying or the implications? 

In other words, whether this is——

Dr. FRIEDMAN. Confused in what it’s saying. 

Mr. SHAYS. Whether it’s factually correct or whether, even 

though it’s factually correct, whether it’s significant. 

Dr. FRIEDMAN. In all of those areas. 

Mr. SHAYS. So you question whether it’s factually correct? 

Dr. FRIEDMAN. Well, or relevant. 

Mr. SHAYS. OK. 

Dr. FRIEDMAN. If I interpret this correctly, these data come from 

October 1992 to April 1993. And if that’s true then we’re talking 

about 4 years ago. And this may be true for then. 

Mr. SHAYS. OK. 

Dr. FRIEDMAN. What’s more relevant to me now, and the question that I don’t have an answer for you today, sir—I’m sorry——

Mr. SHAYS. That’s OK. 

Dr. FRIEDMAN [continuing]. Is what are the numbers that we 

have in a more current year. I do not have those. And I would find 

that a great deal more valuable to me. Because, to be entirely candid, we have criticisms of the timeliness with which we processed 

things in 1992, 1993——

Mr. SHAYS. OK. 

Dr. FRIEDMAN. And I’m not trying to say that everything is fixed. 

But that’s a long time ago. 

Mr. SHAYS. But one of the beautiful things is that we can followup. And we will followup. And can we make it part of the 

record, as well? And we’ll make it part of the record. I would like 

to hold the record open to just see if you can provide us some more 

current data. 

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Dr. FRIEDMAN. And I’m interested in that, as well. 

Mr. SHAYS. OK. But walk me through the process of an accident 

report being submitted and how you respond. 

Dr. FRIEDMAN. OK. I will begin with that, and then, again, I’ll 

ask others to please——

Mr. SHAYS. Someone else can respond. You don’t have to if you 

don’t want to. 

Dr. FRIEDMAN. No. There are a couple of general things that I’d 

like to say and then I’d like others to——

Mr. SHAYS. You want to take the easy stuff and have the hard 

stuff done by staff. I can relate to that. 

Dr. FRIEDMAN. My staff calls me the warm up band for the 

real——

Mr. SHAYS. For the real stuff. 

Dr. FRIEDMAN. Yes. That’s exactly right. 

Mr. SHAYS. OK. 

Dr. FRIEDMAN. I’m told that there are approximately 12,000 error 

and accident reports that we receive each year and that these are 

a variety of different sorts of reports. As you recognize, there are 

the most serious kinds of life threatening reports, and then there 

are others which are technically noted but don’t have any health 

significance either for the individual or for all people who might receive a product. 

And we have mixtures of those sorts of things here. As I understand what is being described in this pie chart, there is a period 

of time that is being counted until we close our file or we show that 

there has been a complete audit of some activity. And so there are 

two important components here that I’d like to distinguish. One is: 

are we recognizing and acting in an appropriate and timely way 

when there is a health concern for an individual patient, the sort 

of individuals that you are talking about—a patient who wants to 

know whether he or she can inject yourself from material that’s in 

her refrigerator or his refrigerator. Are we acting promptly on that? 

There is a second concern which is—are we acting promptly 

there? And I think that’s what the Inspector General was saying 

was their review of things. But there’s a second component, which 

is, are we completing all the necessary classifications, and audits 

checks that are appropriate to be done—are we completing those 

in a timely and complete fashion. And I’m distinguishing between 

those two things. 

This chart doesn’t tell me either one. I can’t be quite sure what 

it means. But what I am told—because we were—as this was being 

presented—furiously whispering questions back and forth—that in 

the most recent year and perhaps longer, there have not been class 

1—those are the most life threatening or potentially life threatening kinds of recalls—there have been none of those kinds of 

events that have taken the length of time that is portrayed here, 

that those are being handled in a much more rapid timeframe. 

As you pointed out earlier, in the Centeon situation, there was 

an unacceptable delay in a recognition of a problem. That, we believe, we’ve looked very hard at and have fixed. But those are the 

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tients. And we will become more efficient in terms of dealing with 

the paperwork that is required afterward. 

Those are my general remarks. I would ask other people to 

please make specific comments, sir. 

Ms. ZOON. Yes. The center does have standard operating procedures for handling error and accident reports. And if you would 

like, I could briefly summarize. 

Mr. SHAYS. I’d like you to just walk me through. When a complaint comes in tell me how you deal with it. 

Ms. ZOON. All right. The error and accident reports are received 

by the division of inspections and surveillance in our office of compliance. Once the action reports come in, they are reviewed and 

evaluated by a consumer safety officer and the error and accident 

coordinator within the division. 

Mr. SHAYS. Are these just mailed in? Are they FedExed in? Are 

they sent in weeks and weeks after the event? From the moment 

a facility realizes that they need to send a report, do they send it 

in within 12 hours? Give me a sense of the kind of feeling of urgency that they might have? 

Ms. ZOON. Right. May I ask Mr. Jim Simmons, head of the Office 

of Compliance to address that? 

Mr. SHAYS. Yes. Were you sworn in, sir? Good. You can just sit 

over there. And just identify your name again. I’m assuming our 

transcriber has the names. And if not, you have a card that you’ll 

be able to give him? 

Mr. SIMMONS. I think that my name was provided to the party 

already. 

Mr. SHAYS. Great. Thank you. 

Mr. SIMMONS. You were asking about the manner in which they 

were submitted? 

Mr. SHAYS. Right. I have no sense of how people deal with these 

and the sense of urgency or not. The one thing I do is I have people 

who know what it’s like when they’re taking the blood product and 

they hear many weeks after the fact that maybe what they took 

will be harmful to them. So they have a sense of urgency. I want 

to know how the urgency is felt within the Department. 

Mr. SIMMONS. The situation is certainly variable from company 

to company. And I think you may recall the representative from 

the General Accounting Office indicate that the time lapse in average is in excess—or the time of their audit—was in excess of 4 

months. And it ranges from a few days to longer than a year. And 

part of that was attributed to our regulation that currently says, 

promptly. And in the proposed revisions we will define promptly, 

and have used the recommendation from that audit of 45 days. I 

think in terms of—— Mr. SHAYS. Wait. The facility itself realizes that a—maybe I don’t 

even have an appreciation of what we’re talking about in terms of 

an accident. Maybe I need to have——

Dr. FRIEDMAN. May I just? Because I had the same question you 

do. There are several ways in which information is provided to the 

agency. Through the MedWatch system as you’ve heard, through 

adverse events, which may be phoned in by a company or by a facility where they see something very serious. 

Mr. SHAYS. Right. 

277

Dr. FRIEDMAN. That’s a phone system that has 24-hour a day 

coverage 7 days a week. But there are also error and accident reports which can include things from—and I’ll give you a couple of 

examples so you’ll understand that it’s not the sort of significance 

that you’re speaking of. If a patient in a facility receives a unit of 

platelates—which is a portion of the blood—has an infectious disease—passes away, the question comes up whether there was any 

relationship between that unit of material and death. 

Mr. SHAYS. Yes. 

Dr. FRIEDMAN. It turns out that the unit was cultured, that the 

patient’s blood was cultured, the urine was cultured and so forth. 

There wasn’t a relationship between that unit. But it was reported 

as a perfectly plausible, possible thing that then required some followup. But the followup was that you had to wait for all those 

blood cultures and all those cultures to be competed, all the information to be assembled and so forth. It could be that a patient received the wrong unit in certain facilities. 

I’m saying this—because many of these would not be reported in 

this way. But it can be something important for the individual patient, but from your point of view, not related to a systemic problem with how a product is made or processed or drawn. And there’s 

this whole range of things. It could be a systems failure in an organization to an individual patient problem. And it encompasses a 

large number of different sorts of things, sir. 

Mr. SHAYS. OK. 

Ms. ZOON. If——

Dr. FRIEDMAN. Go ahead. 

Ms. ZOON. Would you like me to continue to tell you how we deal 

with error and accident reports? 

Mr. SHAYS. Sure. You can stay there. You need to speak clearly, 

though. Have you completed the point that you wanted to make to 

the committee? 

Mr. SIMMONS. The point that you had asked I think I did. 

Mr. SHAYS. Yes. 

Mr. SIMMONS. I will respond further if you like. 

Mr. SHAYS. The word ‘‘prompt’’ is going to be redefined to be 45 

days? You are considering that? 

Mr. SIMMONS. We have defined ‘‘prompt’’ in terms of numbers of 

days. 

Mr. SHAYS. OK. Yes. 

Ms. ZOON. Following the receipt of the error and accident report 

a determination is made—one, in terms of the completeness of the 

report. If there is insufficient information, it’s followed up and the 

further information is obtained from the filer. And that’s generally—can be—depending on the nature of the situation, direct 

contact by phone, or it could be in other forms of communication. 

The data is entered into an error and accident reporting system. 

And this data can then be accessed by the field offices by the 

CBER’s error and accident reporting system that we refer to as 

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ated or on-going regarding significant adverse event reports were 

filed. 

Then for error and accidents representing possible recall situations a copy of the error and accident report is forwarded to the 

district office as an alert to a possible recall. There also are quarterly and annual reports prepared by the division director. And 

these reports and trends are looked at with respect to those types 

of errors that are found. 

Mr. SHAYS. What I’m going to do is I’m going to have both majority and minority staff ask some questions and I’m going to just respond to some of your responses. 

Ms. FINLEY. Thank you, Mr. Chairman. Dr. Friedman, why didn’t 

the FDA require patient labeling on the factor 8 product manufactured with the transferrin produced from the plasma of a CJD patient? 

Mr. SHAYS. You’ve got to slow down a little bit. I’m going to have 

you start over again. 

Ms. FINLEY. OK. 

Mr. SHAYS. That’s why I didn’t ask this question. 

Ms. FINLEY. Could you describe the procedures for biohazard labeling of products manufactured from the plasma of CJD patients? 

It’s my understanding that you require it for CJD-derived products 

intended for research use only and the agency didn’t require it for 

patient labeling on the factor 8 product manufactured—that was 

put on hold—I think—of January of this year? 

Dr. FRIEDMAN. I’ll ask Dr. Epstein or others to embellish my answer. 

Mr. SHAYS. OK. 

Dr. FRIEDMAN. I guess there are two important things to note 

about CJD which you appreciate. One is how little we understand 

about certain aspects of the biology of the diseases and how we 

don’t have a really appropriate test for identifying potentially infectious material in either an organ or in a plasma or derived component. The second point is that although this has been looked for 

very vigorously—cases in which a human may have gotten CJD 

from a blood or blood product, it’s been difficult, some say impossible to detect such a thing. 

Nonetheless, we feel that there is reason to be cautious—because 

of the first point I made which is how large our ignorance is in certain important areas. And the policy, the guidance which has gone 

forward, tries to rank potential risks in a logical way so that if one 

has something that’s directly derived from a donor who ultimately 

turns out to have CJD that might represent one sort of risk. If you 

have that unit of which one tiny fraction is removed, purified and 

then is further removed, purified, the risk begins as remote and 

progresses to exceedingly remote. 

And that’s the sort of general framework of risk that we try and 

utilize. The question you ask is a provocative one, and I’d like Dr. 

Epstein or others to please add more. 

Dr. EPSTEIN. Yes. Thank you, Dr. Friedman. And thank you, Ms. 

Finley and Mr. Shays. In the case that you’re describing the final 

product, which was a Factor 8 product, had been manufactured 

using a purification system that depended on a synthetic antibody—a monoclonal antibody. That monoclonal antibody had been 

279

generated from an invitro culture in which the medium had been 

supplemented with a blood product. And it was that blood product 

which had been withdrawn on account of a contribution by a donor 

who later got CJD. 

So we have a fairly indirect situation in which there was some 

exposure during manufacturing many, many steps removed from 

the final product. Now, the issue, of course, was whether the policy 

on withdrawal of plasma derivatives based on subsequent knowledge of a contribution by a donor who got CJD, or was later 

learned to even have risk factors for CJD, should be applied in this 

case. But it is distinct in that you’re not dealing with potential contamination directly of the derivative due to the pool, you’re dealing 

with potential contamination due to exposure to a reagent many, 

many steps removed from the final product. 

What was done in this case is that first we charged the company, 

which did duly report this as an error or accident. We would view 

it as accident—it’s all learned post hoc—to the FDA. We charge 

them with doing a risk analysis. The company provided the risk 

analysis to the FDA. FDA performed its own risk analysis and FDA 

requested that the CDC perform a risk analysis. 

The bottom line of the risk analyses was, that the risk for any 

persistence of CJD infectivity in the final product was extremely 

remote based on effective removal of the additive—so-called 

transferrin—due to the many purification steps. Now, what we did 

in the face of that was have a dialog with the hemophilia community over the risk assessment. 

We requested and the industry voluntarily complied with informing the hemophilia community fully of the events surrounding the 

incident and the analysis and the basis for the conclusion of a safe 

product. Therefore, as a result of the investigation, a determination 

was made that there was no significant added risk. And I’m sure 

you understand—and, indeed, your question suggests—that there 

always is some risk. And we appreciate that. But the conclusion of 

the analysis was no significant added risk due to the remote exposure to a reagent at an early stage of manufacturing. Therefore, 

the product did not require special labeling and it was permitted 

to remain on the market. 

Let me just remark at a more general level that I believe you are 

aware that there has been an initiative since 1995 to work with the 

industry to develop more specific warning labels regarding viral 

risks or risks of unconventional agents in plasma derivatives. Let 

me stop there. 

Ms. FINLEY. OK. Thank you, Dr. Epstein. Dr. Friedman, the 

blood safety committee report of December 1996 analyzed the 

FDA’s management of the Centeon recall in the fall of 1996. They 

determined that the FDA had not inspected the albumin line at the 

Centeon plant in over 50 years since the license was approved for. 

I guess would have then been the Armour Co.—now Centeon—in 

1947. Could you explain why when the Inspector General determined that albumin was listed in the top five of plasma products 

which help professionals report patient adverse reactions, why the 

FDA did not determine in the course of 50 years that it was necessary to inspect that line? 

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Dr. FRIEDMAN. Again, I’ll ask Dr. Epstein to embellish on my answer. The individuals—patients who receive albumin are amongst 

the most ill, most fragile individuals who receive any blood product. 

These are often individuals who have suffered important trauma, 

major infection, and other overwhelmingly life threatening episodes. These individuals fall prey to a large number of concurrent 

infections or concurrent other physiologic problems. And they’re the 

most fragile individuals. So the fact that these people have a great 

rate of illness, of morbidity and a high mortality rate indicates just 

how ill they are in the fact that they need this product. 

I certainly cannot—because I don’t know the answer to this—construct a coherent explanation for why this product was not inspected during that period of time. There has been—the number of 

cases in which this product has been poorly manufactured has been 

historically low. But I won’t try and construct a defense of that. 

What I will say is, not only would I question the frequency of the 

inspections, I would question the quality of the inspections. And it’s 

exactly concerns about that that led us to reinspect all of the plasma derived products over the last 6 or 7 or 8 months. 

Because my concern was that we had not looked at those products either intensively enough or—in a situation like this—with 

sufficient frequency. Again, I cannot explain to you what the thinking was 30 or 40 years ago. I can tell you what our current interests and our current expectations are. Let me just ask if Dr. Epstein would like to add. 

Ms. FINLEY. And then I have a followup question. 

Dr. FRIEDMAN. Please. 

Dr. EPSTEIN. Yes. Thank you. You really have asked two questions, one regarding prior inspections at Centeon for albumin. The 

other: what is our reaction to the fact that adverse event reports 

for albumin are among the top five reported for plasma-derived 

products. On the first question—FDA, as you know, inspected 

Centeon in June 1995 prior to the recall of albumin, and did examine general GMP including air and water handling systems, environmental controls, and related matters that would be applicable 

to all the products and would include the albumin as well as clotting factors. 

In that sense—and that’s limited—aspects of albumin production 

were inspected. However, there was no focused inspection on albumin. The basic reason that there was not an in-depth review of 

processed validation related to albumin was because of its extensive record of product safety of approximately 50 years. 

I believe that it will be made clear that the new approach to 

plasma fractionator inspections does involve a more comprehensive 

review of process validation. And that is a shift of focus. And we 

acknowledge that had that been in place, there might have been a 

more effective inspection. 

Ms. FINLEY. May I assume from both of your statements and 

from the report that the blood safety committee produced for Dr. 

Lee that FDA states that its position is to inspect plasma 

fractionators every 2 years? But in this particular case, it clearly 

didn’t meet that goal. 

Dr. FRIEDMAN. I’m not sure that’s exactly accurate. I think the 

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spected every 2 years. I don’t know the answer to that. Will we inspect each facility at no less frequency than every 2 years? That 

is correct. And for cause or as a followup, it will be more frequent 

absolutely. 

Ms. FINLEY. Bottom line: What assurance can you give the American people that you will not let a product line go for another 50 

years without an inspection? What things have you put into place 

to ensure that you catch that situation? 

Mr. SHAYS. And I’m going to just add: what kind of requirements 

are on FDA for inspection? Is there an every so many years or is 

there just a—— Dr. FRIEDMAN. May I ask Mr. Chesemore to please deal with 

the——

Mr. SHAYS. Sure. 

Mr. CHESEMORE. The requirements, Mr. Chairman, are that for 

a drug or a biologic manufacturer, that we do a general GMP inspection at least once every 2 years. That’s what the law states. 

Mr. SHAYS. OK. And it gets around a problem I had with HCFA 

in terms of timeframes on HCFA and just rewriting rules. And also 

with the FDA on your licensing of products and your deciding that 

you were going to do it—you had this backlog and you were going 

to bring this backlog down and you did a sensible requirement of 

how you would get the backlog down, but it was not in conformance 

with the law. So we need to either change the law or get you to 

conform to the law. Let me ask this, and then I do want to make 

sure we—is it feasible for you to abide by the law of inspecting 

every 2 years? Is that a wish list on the part of Congress and the 

White House? 

Mr. CHESEMORE. It’s becoming much more difficult, Mr. Chairman. And the situation that Ms. Finely raised is, do we have the 

ability to cover every product that a firm manufactures once every 

2 years. And the answer to that is clearly ‘‘no.’’ Mr. SHAYS. OK. 

Mr. CHESEMORE. What we try to do is, at least try to inspect the 

process, whether it’s biological or a tablet or an injectable. And we 

try to take a look at the firm’s inspectional history. And all those 

things go into consideration in determining which firms we do need 

to inspect. 

Mr. SHAYS. Now, the law requires you to do it every 2 years. 

What is your—— Dr. FRIEDMAN. Sir, it’s very important to state—as far as I know, 

we’re in conformance with that. We are doing inspections that frequently. 

Mr. CHESEMORE. In the plasma fractionator industry. 

Dr. FRIEDMAN. So that there’s no misunderstanding about that. 

Mr. SHAYS. No. You weren’t doing it in the case of this. 

Dr. FRIEDMAN. Yes, sir. That was the point I was trying to make, 

which is, this facility was actually inspected more frequently than 

every 2 years. But this particular product line had not been inspected as a particular product line. 

Mr. SHAYS. Right. OK. Why don’t you followup? 

Dr. FRIEDMAN. Please. 

Ms. FINLEY. I still believe the question that I’m asking—and perhaps I didn’t phrase it properly—is what assurance can you give 

282

us that another Centeon situation will not occur? In other words, 

how do you structure your inspections to ensure that you’re not letting a product line like that slip by for 50 years? And the reason 

I’m concerned about this is that—according to your staff, Dr. Friedman—that is the largest plasma product recall in the history of the 

United States. For that not to have been caught at any point in 50 

years is a very serious problem, as I’m sure you’ll agree. 

Dr. FRIEDMAN. I’m sorry. I don’t mean to disagree. I think that 

it is a very important observation. I don’t minimize it for a moment. I do think, though, there are two ways in which one would 

help to ensure the American public that these sorts of problems 

would be caught at the earliest possible time. On the one hand, 

there had been previous inspections at this facility that indicated 

certain kinds of problems that had occurred, certain concerns that 

had been raised, which we do not believe were adequately followed 

up on. 

And had those been adequately followed up on, this problem potentially would not have occurred. I’m assuming the best case situation. The fact that we are much more rigorous, much more consistent and much more timely in how we do our inspections and 

how we followup on those inspections should give the American 

public some additional confidence in the quality of the product. The 

fact that there was a period of time—not when this manufacturing 

site wasn’t inspected, but when these problems were not followed 

up on—is what I am concerned about and what I think needs further attention. I believe it’s entirely credible that had we done 

more careful assessment of whether the recommendations that 

were being made were followed up on, that this particular occurrence might not have happened. 

Mr. SHAYS. Let me do this, let me ask our minority staff, Cherri 

Branson, if she has some questions. 

Dr. FRIEDMAN. Please. 

Mr. SHAYS. But I just want to be clear as someone who is not 

the expert in this group up here—and I want the record to be 

clear—there is inspection of facilities and there’s examination of 

product lines, and two separate issues? Am I’m mixing the two up? 

Is that what’s happening here? 

Dr. FRIEDMAN. Well, think of it this way, sir. If, for example, a 

drug manufacturing facility might make 10 or 20 products at different times of the year or different parts of the factory—— Mr. SHAYS. Right. 

Dr. FRIEDMAN [continuing]. That factory will be inspected. And 

if it’s a new product, before that new product is approved for use, 

that particular line will be inspected. But at subsequent visits, the 

air and the water and the general cleanliness—so there will be 

some general features of the facility that will be looked at. And 

then there will be specifics of specific manufacturing areas will be 

focused on. But not every product line in each facility will be looked 

at. 

Mr. SHAYS. Now, Mr. Chesemore, I do want to make sure that 

we’re clear on this, though, because this is under oath. Is it your 

testimony that every facility is inspected within the law, which I 

believe is a 2-year requirement? 

Mr. CHESEMORE. Every plasma fractionator facility. 

283

Mr. SHAYS. OK. And that’s what the legal requirement is? 

Mr. CHESEMORE. That is the legal requirement. 

Mr. SHAYS. Now, other facilities, do you still have a 2-year requirement or do you have another? 

Mr. CHESEMORE. We have a 2-year requirement on all human 

pharmaceuticals, all veterinary pharmaceuticals, many medical device manufacturers. There is a requirement within the Food, Drug 

and Cosmetic Act of a biennial or once every 2 years inspection. 

Mr. SHAYS. OK. 

Mr. CHESEMORE. There is no requirement, for example, for the 

majority of food firms that we regularly——

Mr. SHAYS. OK. 

Mr. CHESEMORE. And that’s where I’m coming from. 

Mr. SHAYS. I’m frankly surprised that you can keep up with that. 

Are you able to do that every 2 years? 

Mr. CHESEMORE. In all those product lines the answer is ‘‘no.’’

Mr. SHAYS. The answer is ‘‘no,’’ not ‘‘yes?’’

Mr. CHESEMORE. The answer is ‘‘no.’’ We are unable to make an 

inspection once every 2 years in all areas that we’re required to. 

Mr. SHAYS. OK. If you were to figure out the average. In other 

words, I can relate it to roads. We figured out when we were in 

the State house that we should do a road every 7 years—repave 

it—and if we didn’t, the roads would deteriorate. And the average 

was, we did every road every 50 years. What’s the average for inspections? 

Mr. CHESEMORE. It’s going to the vary, sir, by commodity. 

Mr. SHAYS. OK. 

Mr. CHESEMORE. And I’m not sure that the once every 2 years 

is the most important thing. As a matter of fact, in our thinking, 

we think the risk is much more——

Mr. SHAYS. No, I understand that. But now we get into the evaluation and then we also get into law. 

Mr. CHESEMORE. Right. 

Mr. SHAYS. And the one thing you’re not going to get from this 

committee on either side of the aisle, we’re not going to throw 

bricks at you because you can’t do something and we didn’t appropriate the money for the people to do the inspections. But we are 

going to have the public record be clear. And then we’re going to 

have an open dialog about it. 

Mr. CHESEMORE. Sure. 

Mr. SHAYS. And we can get into debate whether it should be 

every 2 years. Well, what is the average? 

Mr. CHESEMORE. Well, if I could, I’d like to submit that for the 

record. 

Mr. SHAYS. Yes. 

[The information referred to follows:]

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Mr. CHESEMORE. But I can give you an approximation. 

Mr. SHAYS. Approximate will do now. 

Mr. CHESEMORE. In drugs and devices it’s about once every 3 

years. 

Mr. SHAYS. OK. 

Mr. CHESEMORE. In foods it’s more like once every 5 to 10 years. 

Mr. SHAYS. OK. 

Mr. CHESEMORE. In veterinary products it’s a little over once 

every 2 years as well. 

Mr. SHAYS. Yes. But the once, once every 5 to 10 years, which 

is a big spread——

Mr. CHESEMORE. There is no requirement in the act for food 

firms. 

Mr. SHAYS. There’s no legal requirement. 

Mr. CHESEMORE. So, we’re close, but we’re over. 

Mr. SHAYS. OK. 

Mr. CHESEMORE. With the exception of we have concentrated, 

really, in the last 5 to 7 years, in the biologics area, since the mid 

1980’s to make sure that that’s where we at least did the biennial 

if not sooner inspections. 

Mr. SHAYS. You’re going to have to make choices given limited 

resources. 

Mr. CHESEMORE. That’s right. 

Mr. SHAYS. Now we just have to know what the law requires and 

whether the law needs to be amended. 

Mr. CHESEMORE. We’d be delighted to provide that information 

for the record. 

Mr. SHAYS. Yes. Sure. 

Dr. FRIEDMAN. That’s very——

Mr. SHAYS. Ms. Branson? 

Ms. BRANSON. On the issue of inspections, it’s my understanding 

that the FDA has a Memorandum of Understanding with HCFA 

that allows coordination of certain inspections of facilities. Can you 

give me your impression on the advisability of that sort of coordination, whether an expansion of coordination would assist you with 

some of the inspection problems that have been noted? And basically tell me your thoughts on the agreement between FDA and 

HCFA. 

Dr. FRIEDMAN. Mr. Chesemore, please. 

Mr. CHESEMORE. We’ve had a Memorandum of Understanding 

with HCFA, I think, since the early 1980’s. The HCFA inspections 

are primarily of the laboratory operations or the transfusion part 

of a hospital. It really doesn’t go into—if you would—the blood and 

blood products area that the Food and Drug Administration does. 

Some of those inspections are done by HCFA employees. And it’s 

my understanding that HCFA might contract some of those inspections as well. To the best of my knowledge, I’m unaware of any difficulties that we have with our coordination with HCFA. If there’s 

others who know differently——

Ms. BRANSON. I think what I’m trying to ask you is whether or 

not that sort of coordination and MOU agreement would be possible with other agencies in order to ease some of the burden of the 

inspections that you just described? 

286

Mr. CHESEMORE. What we’re talking about here is making sure 

that whomever does the inspection is adequately trained and will 

conduct the same type of inspection the Food and Drug Administration does. At the present time I’m not sure that we could say that 

the HFCA inspection that is now currently done under the Clinical 

Laboratory Improvement Act is the same inspection that the Food 

and Drug Administration makes of manufacturers of blood and 

blood products. 

So it’s going to be very difficult for us, I think, to transition to 

someone else doing those inspections. And right now, I think, too, 

it continues to be a critical time that we make sure the agency continues to do those inspections. And we’ve started this team approach with the Center for Biologics Evaluation and Research. Dr. 

Epstein, you might have something. 

Dr. EPSTEIN. Yes. I just wanted to make one point clear. If a 

blood establishment collects blood or plasma or processes blood or 

plasma, it must register with FDA and FDA inspects it. What we 

are talking about with the HCFA registered and HCFA inspected 

establishments are transfusion services which are engaged in storing blood, doing donor cross matching so you don’t get a mismatched unit, and distribution. But they do not collect and they do 

not process. FDA regulates all collection facilities involved at that 

level. 

Ms. BRANSON. It’s my understanding that FDA has classified certain computer software that’s used in blood facilities as medical devices. Can you tell me how this classification assists in the oversight process and whether or not the facilities we had talked about 

earlier as unlicensed facilities are required to use that same type 

of software? 

Dr. FRIEDMAN. Please. 

Dr. EPSTEIN. Yes. You are correct that FDA has promulgated a 

policy which requires pre-market approval as a device of software 

systems used in the blood bank. We believe that this step became 

necessary because of findings dating back to the early 1990’s of 

failures of performance and failures of design validation involving 

the systems which play a critical role in the operation of blood centers. We have reviewed since approximately April 1996—approximately 40 or a few more applications—these are major systems 

used throughout the country—and have approved 7 of these at this 

time including some of the largest ones. 

The problems that are encountered have mainly to do with design issues. Up until very recently there was not a regulation requiring validation of software design for software as a device, and, 

therefore, it was felt necessary to do pre-market approvals rather 

than review them simply under GMP. The policy at the FDA would 

encompass software used both in transfusion services as well as in 

establishments which collect and process. 

However, it was recognized that the original policy was unclear 

regarding the obligations of the transfusion services and, therefore, 

there was a need for a clarification and a slightly different timeframe. However, it remains our intention to assure that all blood 

bank software is properly developed, properly documented, and 

meets its functional specifications. We continue to do this under 

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ware have been promulgated by the FDA there is the question 

whether we can shift some of that effort toward review of GMP at 

the time of inspection as opposed to pre-market. But that change 

has not yet occurred. 

Ms. BRANSON. Can you just tell me whether the intrastate facilities—just ‘‘yes’’ or ‘‘no’’—whether the intrastate facilities are required to use that same software? 

Mr. CHESEMORE. If they use it, they are required to meet the 

same as the licensed facilities. 

Ms. BRANSON. But they’re not required to use it? 

Ms. ZOON. If they develop their own software and they use it 

within the intrastate blood bank, then they are not subject to submitting a 510K. It is for those commercial software or those software that are being used in a large cohort of blood banks maybe 

perhaps under a single license but crossing State lines, that then 

would be subject to this filing. 

Ms. BRANSON. And if they do develop and use their own software, 

is there any review on all of that? 

Ms. ZOON. They would be covered under GMP inspections. 

Mr. CHESEMORE. Right. 

Ms. BRANSON. Mr. Chairman, I think that’s all we have. 

Mr. SHAYS. Let me just get to one last question. And I don’t want 

to throw a curve ball here, but the Inspector General is concerned 

as well as we are on an issue dealing with the plasma industry and 

the fact that for 5 years the industry may have been aware that 

they were not properly testing saline contamination. And they notified FDA. I want to know how FDA responded to this. 

Dr. FRIEDMAN. Yes. If I could ask Dr. Epstein to please deal with 

that specifically if he would? 

Dr. EPSTEIN. Yes. The FDA became aware through a whistle 

blower complaint of the fact that at a particular fractionator—their 

testing laboratory—which dealt with the marker testing of donations intended for further use to make fractionated products, that 

some samples had been identified as improperly diluted with saline. In other words, a sample should be diluted with anti-coagulant if it’s a plasma sample, but it should not have further dilution 

with saline. This implied that it would not be a valid sample for 

testing. 

Mr. SHAYS. So it would distort all your testing? 

Dr. EPSTEIN. Pardon? 

Mr. SHAYS. It would distort the testing? 

Dr. EPSTEIN. Yes, it would. If the sample were sufficiently diluted, such as more than 50 percent, then testing might become 

false negative. 

Mr. SHAYS. And when was the FDA notified about this by the 

whistle blower? 

Dr. EPSTEIN. I can get that in one moment. 

Mr. SHAYS. Take your time. 

Ms. ZOON. 1995. 

Dr. EPSTEIN. Yes. It was February 7, 1995. 

Mr. SHAYS. And so this whistle blower came forward. And was 

the whistle blower’s complaint valid? 

Dr. EPSTEIN. Yes. The FDA did a focused inspection to determine 

whether the allegation had merit, and determined that, in fact, 

288

there was a documentary record supporting the allegation that 

some small number of samples submitted to the testing laboratory 

for infectious disease and other marker testing were saline contaminated and would not be valid. 

Mr. SHAYS. Was this with one company? 

Dr. EPSTEIN. Yes. The observation was made at only one company. 

Mr. SHAYS. What was that company? 

Dr. EPSTEIN. Am I permitted to disclose this? 

Mr. SHAYS. Why not? 

Dr. EPSTEIN. Yes. OK. This was Baxter Corp. And the laboratory 

was their Roundlake testing facility. 

Mr. SHAYS. And then what was the response? Were they fined? 

Or how long did they know that this was taking place? Was this 

a 5-year problem that they weren’t dealing with? 

Dr. EPSTEIN. Well, there was evidence in their records that management was aware of this issue for a period of as much as 5 years. 

However, it was the conclusion of the FDA investigation that this 

was in fact a systemic problem which was due to a limitation—— Mr. SHAYS. Systemic throughout the industry? 

Dr. EPSTEIN. Yes. 

Mr. SHAYS. So, the problem didn’t just exist there, it existed everywhere? 

Dr. EPSTEIN. Yes. Although we have no documentary evidence 

from our own inspections, we do have statements from industry to 

the effect that other fractionators had made similar observations. 

And the underlying causes suggest to us that it must be a widespread problem because it has to do with use of the equipment by 

which the source plasma is made in the first place and a particular 

vulnerability related to that use, that equipment. 

Mr. SHAYS. So, you have one company where you had a whistle 

blower come forward. You had other companies that were probably 

aware of the problem and didn’t step forward. That invalidates 

some testing. 

Dr. EPSTEIN. Well, let me say that when an improperly prepared 

sample was identified the unit to which it referred would not be 

used. The companies viewed their monitoring of the sample quality 

as an added quality control measure above and beyond standard 

requirements. In cases where they found diluted samples, the units 

were not used. And, therefore, there was no sense that final product had been compromised. However, the issue was failure to correct the problem at its source. 

Mr. SHAYS. Let me ask you, what was their legal requirement if 

they knew there was a problem? Were they legally required to notify the FDA? 

Dr. EPSTEIN. Well, the error and accident requirement is actually 

written to refer to reporting related to units which have issued. 

There is not obligatory reporting to the agency if a unit which was 

subject to an error and accident was never entered into distribution. That’s not to say that they lack a requirement to investigate 

and correct error or to maintain a record of such an investigation. 

But they do not actually have a requirement to report to the agency in the event that an error and accident was for an undistributed 

unit or product. 

289

Mr. SHAYS. So it’s your testimony that this company—I’m a little 

confused. 

Dr. EPSTEIN. Well, let me say it another way. We believe that 

they ought to have reported it as a matter of good sense. 

Mr. SHAYS. Right. 

Dr. EPSTEIN. However, their formal requirement since they never 

used an identified improperly tested unit, would not have been 

there. 

Mr. SHAYS. Wouldn’t it have been exactly helpful for them to report it to see if this was an industry-wide problem? 

Dr. EPSTEIN. Yes. 

Dr. FRIEDMAN. Yes. 

Dr. EPSTEIN. I think that had we learned about it sooner, we 

would have acted sooner. 

Dr. FRIEDMAN. That’s right. 

Mr. SHAYS. I’m unclear as to how FDA responded. How did FDA 

respond? You investigated, and what did you do? 

Dr. EPSTEIN. First, we made a determination that the problem 

really lived at three levels. You had the devices that make the plasma. These are called apheresis separation machines. The problem 

that causes the saline dilution is a backflow of saline, intended to 

replenish volume in the patient from whom plasma was just withdrawn, instead entering not only the patient but the collection container. 

Mr. SHAYS. Yes. 

Dr. EPSTEIN. Now, that problem arises for two reasons. First, a 

lack of a safeguard in the device design. In other words, its software programming, its monitors, its alerts, its warning lights, et 

cetera. Second, it arises because the users of that equipment—

namely the centers that collect the source plasma—may have been 

deficient in training of the operators so that the operators would 

know to adequately clamp off the tubing so that saline could not 

backwash into the collection. 

Mr. SHAYS. OK. Did this company not know why the problem 

was being caused or they just didn’t care about it? 

Dr. EPSTEIN. They had understanding. They made efforts to inform the providers of the source plasma. However, they were inconsistent in that effort. They did not notify the providers in all cases, 

nor did they document any corrections. They simply continued to 

make these occasional observations of a diluted sample. And that, 

of course, is the third level involved, which is, why didn’t the laboratory—which in this case was part of the fractionator licensee—

but it isn’t always—but why didn’t the laboratory seek effective 

correction. And we see that as the failure at the third level. 

But yes. They did attempt correction. They did notify many of 

their source plasma providers that they were finding this. But they 

did not demand correction or show evidence that correction was 

achieved. They simply continued to monitor and occasionally report 

dilution. 

Mr. SHAYS. If the whistle blower hadn’t stepped forward, what 

would still be happening? 

Dr. EPSTEIN. Well, that’s hypothetical, so I can’t say. Could we 

have learned through some other route? Yes. 

290

Mr. SHAYS. No. That’s not what I’m asking. Let me ask you this: 

What was the effect over these 5 years of your not knowing about 

it and their continuing to tolerate this? I don’t know. What was the 

impact on the public? 

Dr. EPSTEIN. Well, we believe that there was no health impact 

on the public. 

Mr. SHAYS. Let me ask you this: is this still happening? 

Dr. EPSTEIN. Measures are in place that should have mitigated 

the problem. I think that perhaps Mr. Simmons would like to comment. I think that we have not completed the phase of auditing all 

corrections. 

Mr. SHAYS. That’s too long an answer for me. 

Dr. EPSTEIN. We’re not certain that all correction is in place. We 

know that steps have been taken to correct. 

Mr. SHAYS. OK. Now, what I’m trying to understand is what is 

the impact to the public? 

Dr. EPSTEIN. It has been our assessment that there is not health 

impact to the public because of the adequacy of viral inactivation 

of the plasma derivatives. 

Dr. FRIEDMAN. Mr. Chairman, may I try and—— Mr. SHAYS. Can I ask you something before you try? I’m getting 

a little uneasy by this dialog. 

Dr. FRIEDMAN. Please. 

Mr. SHAYS. Because I feel there’s something more significant 

here. And I—— Dr. FRIEDMAN. Please. 

Mr. SHAYS. When the FDA finally inspected this Baxter plant— and that was on May 12, right? There was a class 3 recall that resulted in 26 million units of hemophilia products. Is that correct? 

Dr. FRIEDMAN. Are you talking about just recently, Mr. Chairman? 

Mr. SHAYS. Yes. I just don’t know how we can say that there’s 

not impact? 

Dr. FRIEDMAN. Sir, I’m sorry, let me——

Mr. SHAYS. I don’t want to blow this out of portion, but—— Dr. FRIEDMAN. I know you don’t—— Mr. SHAYS. I just want to say. I don’t want to blow it out of proportion, but I don’t want to end this dialog until we have a full disclosure on the record. 

Dr. FRIEDMAN. Right. Let me go through a couple of things, if I 

may, with you, sir? 

Mr. SHAYS. Yes. 

Dr. FRIEDMAN. The first thing that you’re talking about has to 

do with how viral tests are performed on plasma samples. And Dr. 

Epstein has just said that it’s our assessment that there was not 

a health hazard under those circumstances. Let me explain at least 

three reasons why that’s the case. The first is that, the best estimates we can make, is that this occurred extremely rarely. And so 

there were relatively few collections where this was a problem. 

The second is that even when it was a problem, there are those 

samples where testing was still appropriate and accurate because 

the samples were not sufficiently diluted. The third is, that even 

when there was an inappropriate false negative test—that is, there 

was too much dilution, the test wasn’t accurate—those units were 

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subjected to the same viral inactivation that would have been successful under any circumstances. 

So when he says he believes there is not a health hazard, I want 

you to understand what the levels are that document and provide 

confidence from that. The point that you’re just making, sir, is 

something which is different, if I may just talk about that for a moment. 

We have taken recent class 3 action—and, as you recall, class 3 

is the lowest health risk class—at this Baxter facility because there 

was inadequate documentation that the plasma units or the material that was derived from the plasma had been maintained at the 

proper temperature for the proper period of time. And, therefore, 

there was a recall based upon that. 

Now, when we went back and looked at other systems that were 

in place, such as a detergent system for inactivating virus—killing 

virus—those things all seemed to be perfectly appropriate. And so 

there wasn’t a health risk to an individual. But the point you made 

earlier, sir, is that if you have a multi-layer system, the power in 

the system comes from having all the layers intact. 

If you start to lose some of those layers, you start to lose not just 

the integrity of the system, but the confidence in the system. And 

so even though a particular lapse might not be associated with a 

health risk, I don’t think we should tolerate that. Because each gap 

subjects the whole system to some risks. Therefore, we took this 

class 3 action because, even though there was not a health risk by 

any assessment that we could identify, we should not have those 

lapses. I don’t know if that helps or not, sir. 

Mr. SHAYS. It does. But let me read the testimony. One of the 

problems when we ask people to summarize their testimony is that 

they don’t put it out on the public record verbally. ‘‘First, the ORA 

recommendation’’—this is the IG’s testimony to the subcommittee. 

‘‘First, the ORA recommendation to conduct a followup inspection 

of viral inactivation procedures at Baxter’s manufacturing plant 

was rejected by CBER. A regularly scheduled inspection conducted 

subsequently gave no indication that the viral inactivation procedures were reviewed. The FDA informed us that as of May 12, 

1997, it had underway an inspection of Baxter’s manufacturing 

plant and included examining the viral inactivation procedures. We 

subsequently learned that Baxter initiated a class 3, the least serious, recall of plasma product on May 24, 1997 due to the firm not 

maintaining specific temperature for the viral inactivation process.’’

Dr. FRIEDMAN. Yes, sir. 

Mr. SHAYS. OK. Now, what’s the significance of the last sentence—the temperature for the viral inactivation process? 

Dr. FRIEDMAN. As I explained, when these units are treated to 

inactivate the virus, the operating procedures say that they should 

be held in a certain temperature for a certain period of time in 

order to most effectively kill the virus. That standard operating 

procedure can be breached in a couple of ways. Either you don’t 

have the temperature documented or you don’t have the time documented. And we were concerned that there was inadequate recordkeeping to assure us that all these systems had been done exactly 

as they should be done. 

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You asked a question earlier, sir, that’s really important. And I 

know you’re going to ask me at the end, what questions you wanted to ask us. 

Mr. SHAYS. Yes. 

Dr. FRIEDMAN. The question I want to put a marker down on is, 

the fact that we are seeing more recalls, more product withdrawals, 

is this something that should give us confidence or not? I’d like to 

speak to that later because I think this is actually relevant in that 

regard. 

Mr. SHAYS. OK. 

Dr. FRIEDMAN. I’m sorry. Others may want to add. 

Ms. ZOON. I just wanted to let you know, some of the observations on the inspection were actually that the temperature range 

was 1 or 2 degrees below what the range was listed in their SOP. 

Dr. FRIEDMAN. Standard operating procedure. 

Ms. ZOON. I’m sorry. Standard operating procedure. And that 

was because it was outside of its operating procedures, that was a 

GMP deficiency. And that—— Dr. FRIEDMAN. They were cited and things—— Ms. ZOON. And an evaluation was made as to the impact of that 

deviation. 

Mr. SHAYS. But was that related to the flawed testing? 

Ms. ZOON. That was the viral inactivation procedure that was 

done at Baxter. 

Dr. FRIEDMAN. Sir, that inspection was going on anyway. The Inspector General asked that we make sure that the evaluation of the 

adequacy of viral inactivation be conducted. That had been an intention of ours at the time, and we were happy to assure the Inspectors General that in fact we were in the process of doing that 

and that we did care about that as well. 

Mr. SHAYS. Now, what I’m hearing from your testimony—and 

this is the laymen speaking—I’m hearing that this one line of defense that broke down, but the other lines of defense caught the 

problem. That’s what I’m hearing. But is that an accurate first? 

Dr. FRIEDMAN. Yes, sir. I just want to make sure I’m not misstating that. 

Mr. SHAYS. But that says to me, OK, public, we think we caught 

the problem. But what it doesn’t say to me is, that if I had five armies out there and all five were to protect me, and one army was 

asleep—one unit was asleep—then I’d say, not to worry, the other 

four protected me. I expect all five to work. And all hell is going 

to break loose if one of those parts breaks down. So I’m willing to 

have the public record reflect the fact that it’s the comfort level of 

the FDA that the public was not threatened, but one of our lines 

of defense was broke and had been broke for a long time. And one 

company knew about it. 

When you looked at that one company, because, thank God, a 

whistle blower stepped forward, your response was to look at it and 

realize that this same process was occurring throughout the industry, so this line of defense was broken down throughout the plasma 

industry. Where is my logic breaking down so far? 

Dr. FRIEDMAN. Your logic is not breaking down. It’s the association of these two things that isn’t as accurate as you want it to be. 

Let me point out. 

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Mr. SHAYS. OK. 

Dr. FRIEDMAN. There was a problem with this company. 

Mr. SHAYS. Right. 

Dr. FRIEDMAN. And the dilution and, hence, possible inaccuracy 

of the viral testing. 

Mr. SHAYS. And the company knew about it for 5 years? 

Dr. FRIEDMAN. The company knew about it for a considerable period of time and should have taken action and should have informed us. 

Mr. SHAYS. For at least 5 years. 

Dr. FRIEDMAN. Should have informed us. Should have taken action. 

Mr. SHAYS. But for at least 5 years that knew about it? 

Dr. FRIEDMAN. I don’t know that. But that’s what others are saying. And, yes. 

Mr. SHAYS. But that’s the idea. 

Dr. EPSTEIN. Alleged. 

Mr. SHAYS. It’s alleged. OK. I’ll accept that. 

Dr. FRIEDMAN. But I want to be accurate about what we say. 

That’s one problem. What we’re talking about with the temperature is a different problem in a different situation. 

Mr. SHAYS. OK. Let’s leave the temperature aside. Let’s talk 

about the problem—why the whistle blower contacted and——

Dr. FRIEDMAN. That’s not so related to this recent withdrawal. 

Mr. SHAYS. OK. I accept that. In the process of being in the plant 

you realized about the temperature problem, and that was——

Dr. FRIEDMAN. Yes, sir. 

Mr. SHAYS. The withdrawal was related to that and not this 

problem? 

Dr. FRIEDMAN. That is correct, sir. 

Mr. SHAYS. OK. And that’s important for the record to reflect. 

And so I’m sorry that I brought that up right now. Because I don’t 

want to lose—I want to understand this issue. 

Dr. FRIEDMAN. Your point is, that if viral testing is one of crucial 

components of our confidence in the safety of the blood supply and 

we identify something that compromises that, should it be tolerated. 

Mr. SHAYS. Right. 

Dr. FRIEDMAN. The answer is ‘‘no.’’

Mr. SHAYS. No. And that’s one thing. Well, there we agree. But 

that should have happened. But it is alleged that this company 

knew for many years, whether it’s 5 years or——

Dr. FRIEDMAN. That’s right, sir. 

Mr. SHAYS. And didn’t choose to tell you. And you have stated 

for the record that, in the process of looking at it, you realize that 

it is an industry-wide problem? 

Dr. FRIEDMAN. Yes. 

Mr. SHAYS. Which raises questions in my mind, which this committee will look at, and bring these companies forward. Maybe not 

in a hearing but before—to answer some questions for the committee staff at the minimal—that other companies knew about this 

problem, as well. Correct? All the other companies did not know? 

Or did some other companies know they had a problem as well? 

294

Dr. FRIEDMAN. I think a more accurate way to say it was that 

it was a kind of a machine and that this was a problem with the 

machine so that any company that used this machine might experience that problem. 

Mr. SHAYS. Would have, not might. 

Dr. EPSTEIN. We did inquire with the industry what it’s level of 

knowledge was of problems of this sort. And we did receive a letter 

from the industry trade organization documenting awareness of a 

low frequency of saline contamination of samples for testing. 

Mr. SHAYS. OK. And their point is, low frequency, not a serious 

problem. Low frequency—occurring infrequently or when it occurred, not to any major degree. 

Dr. EPSTEIN. No. Occurring infrequently. I forget the exact numbers. But it’s fractions of a tenth of a percent. You know, like 0.003 

percent. 

Mr. SHAYS. I’ve been here 10 years and I still don’t know what 

six lights means. Would you find out? It scares the hell out of me. 

Something serious is happening. I don’t want to be talking with 

you while I’m missing a vote, with all due respect. 

Dr. FRIEDMAN. Nor do we want you to, Mr. Chairman. Thank 

you. 

Mr. SHAYS. OK. I’m going to just end this, though. But I don’t 

think I’m going to like the answer to this last question. What did 

you do about it? 

Dr. EPSTEIN. The FDA did several things. First, we have ensured 

that the apheresis devices have been modified to prevent this problem. And there are several corrections that have been put in place 

for the two devices affected by the problem. Second, we have 

worked with the industry—and this was subject to the review in 

the OIG report—to assure that an information campaign would be 

developed to emphasize the adequacy of the training of the operators who use this equipment and to assure that the industry will 

be more responsive in reporting any further observed instances of 

saline contamination to the agency. 

Mr. SHAYS. OK. If I had a staff member and a staff member 

didn’t tell me that they had made a mistake, and a few weeks later 

I was confronted with that mistake by someone else, and the next 

time I interacted with that staff member I wouldn’t have the same 

confidence level. It sounds to me like you just turned this over back 

to the trade association to deal with. Is that what you basically 

did? You just put it back on their laps? 

Dr. FRIEDMAN. No. 

Dr. EPSTEIN. No. I would say that the effort is to engage the assistance of the industry in getting the word out. However, FDA 

does not leave to the industry its monitoring of correction. FDA is 

examining on inspections whether there are further incidents of saline contamination, whether there is monitoring for it, whether 

centers that have had it documented are making correction, et 

cetera. 

Mr. SHAYS. Yes. I would also have said to my staff, how can I 

trust you on something else if I couldn’t trust you in telling me 

this. No, I don’t think I have staff members that do that. In fact, 

I know I don’t. Or if I did, we’d straighten it out. 

295

Dr. FRIEDMAN. Mr. Chairman, may I just add one or two other 

things, because I understand the point that you’re making? 

Mr. SHAYS. Yes. 

Dr. FRIEDMAN. This was not something that was left entirely to 

that particular industry. I understand your skepticism there. Some 

of the changes that needed to be made had to do with the equipment—software changes so that there wouldn’t be this backup of 

saline into that part of the system. That’s a different set of industries. Those are companies who have committed to fixing the software changes for that. 

Mr. SHAYS. I’m really talking about fixing the problem which you 

feel you’re addressing. 

Dr. FRIEDMAN. You’re talking about in general levels of confidence. 

Mr. SHAYS. I’m talking about levels of confidence and I’m talking 

about integrity. I’m talking about a person who probably risked his 

or her job. And sees the FDA responded, it appears to me, in a 

pretty casual way, frankly. And the casual way is: any fines? Any 

penalties? And any riot act? Any letters to the individuals? Any 

public disclosure? You know, all those things that I’d like to think 

would take place. Did any of those things happen? 

Dr. FRIEDMAN. The question that’s been asked is, are there fines, 

are there other sorts of penalties that have been posed? 

Mr. SIMMONS. Certainly, there have been no fines or no penalties. If I could try to address some of your concerns. This was 

deemed to be an industry-wide problem. Assessing fines or penalties against one company when you have an industry-wide problem while the other problems persisted would have little effect on 

public health. And our assessment of the situation was that the 

public was better served by working with the total industry to try 

to remedy the problem. And that’s the approach we took to it. 

Mr. SHAYS. Why would you have been encumbered from dealing 

with this problem? Why are they mutually exclusive? Why wouldn’t 

someone have to pay a penalty when they are not honest and 

straightforward and come recognize it? That’s what I’m missing. 

Dr. FRIEDMAN. Sir, two things. One is that, to the best of our 

knowledge, none of these units were released to the public. 

Mr. SHAYS. That’s irrelevant to me. 

Dr. FRIEDMAN. I’m sorry? 

Mr. SHAYS. No. That’s not irrelevant. 

Dr. FRIEDMAN. No. 

Mr. SHAYS. Thank God. 

Dr. FRIEDMAN. No. I think that’s the most important thing. 

Mr. SHAYS. But it’s irrelevant to the issue. 

Dr. FRIEDMAN. I think the second thing is, in terms of—and I 

would ask our legal counsel to say what was—not what was the 

violation of trust or good sense, we’ve already spoken to that, and 

I think we’ve spoken clearly to that. The question you’re asking is 

what’s the violation in law. 

Mr. SHAYS. Well, no. There’s law. There’s a lot of things here. 

First off, this was a problem that existed for years, not a few 

weeks, not a few months. And so they knew the system wasn’t 

working properly. This one company was aware of it. It evidently 

is a problem based on equipment that therefore was an industryVerDate Sep 04 2002 13:04 Sep 26, 2002 Jkt 010199 PO 00000 Frm 00299 Fmt 6633 Sfmt 6602 W:\DISC\45251 45251
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wide problem. It meant that one of our lines of defense was faulty 

and unreliable. And yet you had every reason to believe that it 

wasn’t faulty or unreliable. But you were notified. The FDA was 

notified by a whistle blower. 

If I was the whistle blower, I would feel that I had done my job, 

but I would say, I could lose my job over this if the company knew 

and yet nothing happened to the individuals involved in this. No 

one seems to have been held personally accountable or the company appears to be accountable. 

Dr. FRIEDMAN. Well—— Mr. SHAYS. And so that just raised the question—— Dr. FRIEDMAN. Well, yes. 

Mr. SHAYS. And I just want to say, and the fact that that 

wouldn’t have helped necessarily solve the problem is another 

issue. 

Dr. FRIEDMAN. As you know, sir, this is the subject of on-going 

litigation. I think that we’ve been told that there’s only a certain 

amount that we can say publicly about this. Obviously, we’re prepared in a private venue to answer other questions about this. This 

is an actively litigated matter. If I just may—— Mr. SHAYS. Does the litigation involve the FDA? 

Ms. ZOON. Justice. 

Mr. SHAYS. What? 

Ms. ZOON. Government. 

Dr. FRIEDMAN. The Department of Justice, I understand, sir. 

Ms. ZOON. Justice is doing the case. 

Mr. SHAYS. OK. You know what I’m going to say to you, this is— I feel like we’re getting deeper into a hole and I’m getting more uncomfortable with your responses and more disheartened by your responses. I’m just going to suggest that maybe we’ll just have a special hearing on this kind of issue. The IG is looking into this issue, 

correct? 

Ms. FINLEY. That’s the subject of their testimony. 

Mr. SHAYS. Right. OK. What we’re going to do—I am not comforted that because it’s an industry-wide problem we’re not holding 

a particular company accountable. That implies to me that because 

everyone is involved we’ll hold no one accountable. You know, it 

does say that to me. And rather than make more statements that 

I may regret, I think we’ll just leave on unfortunately a negative 

note. 

Dr. FRIEDMAN. If I may, I’d like to change the tenor of that note? 

Mr. SHAYS. Sure. OK. 

Dr. FRIEDMAN. I would just point out a couple of things, sir. One 

is that lest you think there is some inherent inability or reluctance 

on the part of the agency to take strong action when we identify 

something that threatens the overall integrity of the safeguards. 

The matter that you were just discussing—the recent identification 

of inadequate recordkeeping and temperature control for these 

products, even though there was nobody that we could identify 

would be harmed by it, we imposed a restriction. We imposed a requirement on the company that is going to have a substantial financial impact on that company. 

And the purpose of that is not to be punitive. The purpose of that 

is to demonstrate——

297

Mr. SHAYS. That was another issue. 

Dr. FRIEDMAN. Right. But I’m pointing out—lest you think that 

we aren’t interested in doing this or we have some reluctance in 

doing this, that is not a message that I would like to——

Mr. SHAYS. In the Civil War, if a sentry fell asleep they shot him. 

And they couldn’t say, well, no one happened to break through out 

lines that evening. That sentry was there for a purpose. And, obviously, we wouldn’t shoot someone today, but they would be held 

very strongly accountable. 

Dr. FRIEDMAN. Right. 

Mr. SHAYS. And if someone knew for years that sentry had been 

asleep and we said, well, no harm came because nobody ever attacked us. So that’s why I’m feeling very uneasy. 

Dr. FRIEDMAN. I understand. And what I’m saying is that the 

sentry——

Mr. SHAYS. And I don’t want to get you deeply in a hole here. 

Dr. FRIEDMAN. The sentry was dealt with in this latest episode 

in a manner that you’ve just identified, and that we would be very 

pleased to go over with you——

Mr. SHAYS. Can I ask you something? I just don’t want to back 

you in a corner. Are you fully versed on this issue? Or is this an 

issue you need to take a look at? 

Dr. FRIEDMAN. This is something that I have taken some look at, 

but I am not fully versed. 

Mr. SHAYS. OK. I would like to leave it on that note. 

Dr. FRIEDMAN. OK. 

Mr. SHAYS. And I would like to hear how the FDA feels it should 

respond to this issue after you have—you may come up with the 

same answer. But I’m not looking to have you take an opinion as 

the person in charge without a full and——

Dr. FRIEDMAN. Thank you. 

Mr. SHAYS. OK. 

Dr. FRIEDMAN. I appreciate that. 

Mr. SHAYS. OK. And I did hear you ask, had any penalties been 

levied. And, so, since you asked that question, I’m assuming you 

didn’t know. 

Dr. FRIEDMAN. That is correct. 

Mr. SHAYS. And I would like you to. Do you have a point you 

want to make here? And just identify yourself. 

Ms. MALONEY. My name is Diane Maloney. I’m in the Office of 

the Chief Counsel. 

Mr. SHAYS. Yes. 

Ms. MALONEY. With regard to the company’s failure to report to 

the agency the fact that some units—there was this issue of saline 

contamination. If the company found it and did not made those 

products available for release, their system is working. That’s what 

quality control is all about—quality assurance. 

Mr. SHAYS. No. Another system caught it. 

Ms. MALONEY. I’m sorry? 

Mr. SHAYS. Another part of the defense system caught it. One 

part of the defense system broke down. Correct? 

Ms. MALONEY. Right. 

Dr. FRIEDMAN. No, sir. I’m not sure that’s right. 

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Mr. SHAYS. OK. Well, I want to be corrected. That’s why I’m stating it. 

Dr. FRIEDMAN. What she’s saying is that the company had what 

they said were other effective systems for identifying when a unit 

had too much saline in it, and that those units were put aside and 

never released. Those units were destroyed. 

Mr. SHAYS. OK. 

Dr. FRIEDMAN. And so she’s saying the company had an additional built-in mechanism. And because those units weren’t released the company—well, I don’t want to make the point. Go 

ahead. 

Mr. SHAYS. OK. 

Ms. MALONEY. Well, I was just trying to make the point when 

you asked the question of whether or not fines or penalties were 

imposed. 

Mr. SHAYS. Right. 

Ms. MALONEY. There was not a violation to the extent the 

units—regarding the saline contamination—were caught before 

they were made available. I am referring to units not made available for distribution. 

Mr. SHAYS. Right. 

Ms. MALONEY. It is not a violation to not report that to the agency. So there could be no penalties imposed in that situation. 

Mr. SHAYS. OK. For the record, what I’m hearing you saying is 

that no contaminated plasma blood supply came onto the market 

because they were able to catch it when there was—they were able 

to catch it. 

Ms. MALONEY. No. I’m not saying that, because I don’t know all 

the facts. And whether they absolutely caught every single unit I 

can’t—and I’m not sure anybody could tell you that. 

Mr. SHAYS. OK. Yes. 

Ms. MALONEY. But I’m just saying, with regard to your specific 

question, why were penalties not imposed for failing to report this 

to the agency—what I’m saying, if they catch a problem before a 

unit is made available for release, and they do not make that unit 

available for release, then it is not a violation to fail to report it 

to the agency. 

Mr. SHAYS. OK. And I would respond—and I feel like I’m beating 

a dead horse—I would respond by saying that one line of our defense was not working properly and couldn’t be trusted. And this 

company seemed to know about it for a number of years. They felt 

they could catch it through another process, and chose not to notify 

the FDA. In the words of the chairman who preceded me in this 

subcommittee, that boggles my mind. And it’s something that we’ll 

just take a better look at. 

Ms. MALONEY. Yes. 

Mr. SHAYS. And I will say to you, if I were the FDA, I would say, 

well, what other areas of the plasma industry are there circumstances like this where you also haven’t come forward? How 

can I trust you? How can I feel confident since you’ve known this 

for years? And I would also say, isn’t it dumb that you didn’t come 

forward, because if you’d come forward we could have solved this 

problem years ago. And you chose not to. 

299

And, so, you’re making a point, legally you may not be empowered to levy a fine. That’s your point. Yes? 

Ms. MALONEY. If I could just add to something Dr. Epstein said 

earlier. On the other hand, the company does have an obligation 

to investigate problems and come up with fixes. So that is something that I think we’ve been continuing to look at, and I’m not 

sure that the matter is closed at this point. 

Mr. SHAYS. No. It can’t be closed. But one of the things that the 

subcommittee will look at is to see why you can’t penalize someone. 

Is there a need to make sure that there are requirements for companies to do logical things like notify you and to share it with other 

people in the industry. I have a high respect for the FDA. I have 

high respect for you, Dr. Friedman, and the rest of the people on 

your staff. And I’m sure there are some answers that will not make 

this look as bad as it looks. And I’m sure there are some things 

that will make me feel that more action or better action needs to 

be taken. So we’ll split the difference and try to end on a medium 

note. 

Dr. FRIEDMAN. And if I may, I beg your indulgence just for 60 

more seconds, sir. 

Mr. SHAYS. Sure. 

Dr. FRIEDMAN. One is that I think that please look again at the 

number of inspectional findings that we are making with this more 

intensive, more aggressive, and, I think, more fine system of scrutiny that we’re subjecting these individuals to. I take your point 

very seriously. How can one assume that every other part of the 

system is working well? We don’t assume that. 

You’ll see the documentation. The inspections are longer. The 

number of findings is way up. We’re taking action on these. So I 

don’t want you to leave this room thinking that we think that 

there’s no problem and you perceive a problem. 

Mr. SHAYS. OK. 

Dr. FRIEDMAN. That’s No. 1. No. 2 is let me just quickly deal 

with your question to the other panel for this day’s committee hearing. It’s my view that several things have happened that contribute 

to the number of recalls or findings that are being made. One is 

the point that was made earlier. Scientifically, we’re much more sophisticated. We’re able to detect problems that were unheard of 

and unknown previously. I take great comfort in that. That’s No. 

1. 

No. 2 is: the public is simply not tolerant of risks and problems. 

They deserve and they wish to know about these. And, therefore, 

that is making the system scrutinize all aspects of this industry 

much more carefully. I think that’s a very positive thing. I really 

do. 

The third is an area of personal responsibility, which we have 

not always given consistent, clear, uniform guidance and regulation 

to industry in this regard. Our expectations have not always been 

articulated as clearly as they should have been. And that is a responsibility that we have to the extent that we make our inspections and our regulations and our requirements and our guidances 

more clear and more comprehensive, we will, at first, have more 

adverse findings. Ultimately, things will get a lot better. 

300

But I think that we share some of the responsibility there. I see 

that as a very positive thing because it means that we are bringing 

a greater discipline, a greater focus, a greater seriousness to how 

we perform our job. That’s my quick answer, sir. 

Mr. SHAYS. That’s a nice way to end. The hearing is closed. 

[Whereupon, at 1 p.m., the subcommittee was adjourned.]

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