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45–902 CC 1998

FDA OVERSIGHT: BLOOD SAFETY AND THE IMPLICATIONS OF POOL SIZES IN THE MANUFACTURE OF PLASMA DERIVATIVES

HEARING

BEFORE THE

SUBCOMMITTEE ON HUMAN RESOURCES

OF THE

COMMITTEE ON GOVERNMENT 

REFORM AND OVERSIGHT 

HOUSE OF REPRESENTATIVES

ONE HUNDRED FIFTH CONGRESS

FIRST SESSION

JULY 31, 1997

Serial No. 105–70

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 July 31, 1997 ............................................................................... 1

Statement of: 

Crooker, Dolores, R.N., parent; Glenn Pierce, M.D., Ph.D., National Hemophilia Foundation; and Charlotte Cunningham-Rundles, M.D., 

Ph.D., Immune Deficiency Foundation ....................................................... 102

Davey, Richard, M.D., chief medical officer, American Red Cross; Robert 

Reilly, executive director, International Plasma Products Industry Association; Michael Fournel, vice president, Biologicals Division, Bayer 

Corp.; Ed Gomperts, M.D., vice president, Medical Affairs & Clinical 

Development, Baxter Healthcare Corp.; Fred Feldman, Ph.D., vice 

president, Centeon Corp.; and M. Sue Preston, vice president, Quality 

& Regulatory Affairs, Alpha Therapeutic Corp. ......................................... 136

Satcher, David, M.D., Ph.D., Director, Centers for Disease Control and 

Prevention, accompanied by Mary Chamberland, Bruce Evatt, and 

Lawrence Schonberger; Paul W. Brown, M.D., senior research scientist, 

Laboratory of Central Nervous System Studies, National Institute of 

Neurological Disorders and Stroke, National Institutes of Health; and 

Kathryn Zoon, Ph.D., Director, Center for Biologics Evaluation and 

Research, Food and Drug Administration .................................................. 8

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

Brown, Paul W., M.D., senior research scientist, Laboratory of Central 

Nervous System Studies, National Institute of Neurological Disorders 

and Stroke, National Institutes of Health, prepared statement of ........... 26

Crooker, Dolores, R.N., parent, prepared statement of ................................. 105

Cunningham-Rundles, Charlotte, M.D., Ph.D., Immune Deficiency Foundation, prepared statement of ...................................................................... 125

Davey, Richard, M.D., chief medical officer, American Red Cross, prepared statement of ........................................................................................ 140

Feldman, Fred, Ph.D., vice president, Centeon Corp.: 

Information concerning recalls ................................................................. 416

Prepared statement of ............................................................................... 196

Fournel, Michael, vice president, Biologicals Division, Bayer Corp., prepared statement of ........................................................................................ 170

Gomperts, Ed, M.D., vice president, Medical Affairs & Clinical Development, Baxter Healthcare Corp., prepared statement of ............................ 181

Hall, Zach W., Ph.D., Director, further information ...................................... 100

Pierce, Glenn, M.D., Ph.D., National Hemophilia Foundation, prepared 

statement of ................................................................................................... 113

Preston, M. Sue, vice president, Quality & Regulatory Affairs, Alpha 

Therapeutic Corp., prepared statement of .................................................. 255

Reilly, Robert, executive director, International Plasma Products Industry 

Association, prepared statement of ............................................................. 148

Satcher, David, M.D., Ph.D., Director, Centers for Disease Control and 

Prevention, prepared statement of .............................................................. 11

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

of Connecticut, prepared statement of ........................................................ 3

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

of New York, prepared statement of ........................................................... 6

Zoon, Kathryn, Ph.D., Director, Center for Biologics Evaluation and Research, Food and Drug Administration, prepared statement of ............... 41

(1)

FDA OVERSIGHT: BLOOD SAFETY AND THE 

IMPLICATIONS OF POOL SIZES IN THE MANUFACTURE OF PLASMA DERIVATIVES 

THURSDAY, JULY 31, 1997 

HOUSE OF REPRESENTATIVES, 

SUBCOMMITTEE ON HUMAN RESOURCES, 

COMMITTEE ON GOVERNMENT REFORM AND OVERSIGHT, 

Washington, DC. 

The subcommittee met, pursuant to notice, at 10:05 a.m., in room 

2247, Rayburn House Office Building, Hon. Christopher Shays 

(chairman of the subcommittee) presiding. 

Present: Representatives Shays, Snowbarger, Pappas, Towns and 

Kucinich. 

Ex officio present: Representative Burton. 

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

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

clerk; Cherri Branson, minority counsel; and Ellen Rayner, minority chief clerk. 

Mr. SHAYS. I would like to call this hearing to order. 

Welcome to our witnesses and our guests. To minimize the risk 

of injury or death in the event of an emergency, the fire safety laws 

set a maximum on the number of people allowed in this room. 

This was not a good way to open. 

Surprisingly, the blood safety laws don’t contain the same type 

of common-sense safeguard. There are currently no limits on the 

number of blood plasma donations combined into the pools from 

which therapeutic proteins are extracted or fractionated. In the 

event of an emergency such as the appearance of a new blood-borne 

infectious agent, excessively large plasma pools increase the risk of 

disease transmission to the users of plasma-derived products, and 

make recalls more difficult. 

A user of a single dose of a fractionated product today may be 

exposed to plasma from as many as 400,000 donors. Pool sizes vary 

widely from company to company, product to product, lot to lot, 

dose to dose. There is no standard. 

Patients are not routinely informed of the risks associated with 

plasma pool sizes. Last year, in our oversight report on blood safety, we recommended, among other steps, that plasma fractionators 

should limit the size of plasma pools, with pool sizes determined 

as much by public health risk factors as by production economies 

of scale. 

Today, we ask Federal public health agencies, blood product consumers, and the plasma industry what progress has been made 

2

bringing safety considerations to bear and setting practical upper 

limits on plasma pool sizes. For some products, pooling is beneficial, even required, to capture a broad range of antibodies, for example, or to extract a sufficient volume of a scarce protein. For 

other products, however, there is an undeniable and direct relationship between the number of donors in the plasma pool and the risk 

of exposure to an undetected infectious agent. 

Tragedy taught us that lesson. In the early 1980’s, new hepatitis 

strains and the human immunodeficiency virus, HIV, slipped into 

the blood supply. Thousands died. Hundreds of thousands were exposed to Hepatitis C, many of whom have never been told of their 

possible infection. 

Now other viral agents, and perhaps prion diseases, pose similar 

threats to the safety of the blood supply. Yet the risks presented 

by pool sizes have not been addressed. 

Why? Because some believe pool size limits are unnecessary, 

even imprudent. Others tell virtually any production pool limits 

will have long-term negative effects on the availability and costs of 

needed medical therapies. One recent study concluded pool size reductions offer only marginal added safety for frequent and chronic 

plasma product users. This study suggests as much or more could 

be achieved by focusing on other aspects of the blood safety system—donors screening, viral inactivation, more aggressive disease 

surveillance. 

But the vigilance required to maintain a safe blood supply demands we avoid false choices between safety and supply, and pursue every reasonable risk reduction strategy. Given the known 

vulnerabilities of the donor screening and product recall process, it 

is not plausible to expect those aspects of the safety system to bear 

all the burden of excluding or retrieving the infectious agents 

present in plasma products as a function of pool size. As long as 

production pool sizes remain the only aspect of the entire process 

not in any way delimited by some safety considerations, we tolerate 

avoidable risk. This is intolerable. 

Plasma pool size limits could serve as a fire wall against the 

spread of a new infectious agent, particularly one that is not yet 

widely distributed or for which no detection or inactivation technology has been developed. However transitional or brief, the 

added safety margin afforded by practical pool size limits could last 

some plasma product users a lifetime. 

We are fortunate, and grateful, to have witnesses before us today 

who are expert in every aspect of this issue: public health, clinical 

usage, safety, efficacy, blood supply, and cost. The subcommittee 

appreciates their being here today, and we look forward to their 

testimony. 

At this time, I recognize the gentleman from New Jersey. 

[The prepared statement of Hon. Christopher Shays follows:]

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Mr. PAPPAS. Thank you, Mr. Chairman. I, too, want to thank the 

panelists for being here. I am equally as interested in this issue. 

I appreciate the chairman’s leadership in calling this matter. 

Mr. SHAYS. Thank you. 

I ask unanimous consent that all members of the subcommittee 

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

the record remain open for 3 days for that purpose. 

And without objection, so ordered. 

I ask unanimous consent that all witnesses be permitted to include their written statements in the record, and without objection, 

so ordered. 

And I will just mention that the ranking member wanted us to 

proceed, but we may interrupt your testimony to allow him to 

make a statement and to put it in the record. 

At this time, the committee calls before us panel one: David 

Satcher, Director, Centers for Disease Control and Prevention; Paul 

Brown, senior Research Scientist, Laboratory of Central Nervous 

System Studies, National Institute of Neurological Disorders and 

Stroke, National Institutes of Health; and Kathryn Zoon, Director 

of Center for Biologics Evaluation and Research, Food and Drug 

Administration. 

At this time, we are going to let our ranking member take his 

breath, sit down, and make a statement. 

Mr. TOWNS. Mr. Chairman, for the first time in all the years you 

have known me, I would just like to submit my statement for the 

record and let you move forward with the witnesses. 

Mr. SHAYS. OK. Thank you. I acknowledged that you allowed us 

to start earlier and we thank you because we have a long and very 

interesting day. 

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

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Mr. SHAYS. I have called our witnesses and they are at the table. 

As you know, we swear in everyone, including Members of Congress who come and testify. And at this time, I would ask you to 

stand and raise your right hand. 

Let me also say if there is anyone on your staffs who you think 

might want to respond to a question, we will take their names if 

they do testify. But this way we don’t have to swear them in twice 

or do it a second time. So if you all would raise your right hand. 

[Witnesses sworn.] 

Mr. SHAYS. OK. For the record, everyone standing answered in 

the affirmative. 

This is a very important issue and one in which we appreciate 

having such expert witnesses. We will proceed in the order I called 

you: Dr. Satcher, then Dr. Brown and Dr. Zoon. 

Dr. Satcher, we are going to try to stay within the bounds of 5 

to 10 minutes. I will roll the 5-minute over, it will turn red, and 

then we will roll it over. But if we can stay close to 5, but if you 

go over a little bit that is all right. 

STATEMENTS OF DAVID SATCHER, M.D., Ph.D., DIRECTOR, 

CENTERS FOR DISEASE CONTROL AND PREVENTION, ACCOMPANIED BY MARY CHAMBERLAND, BRUCE EVATT, AND 

LAWRENCE SCHONBERGER; PAUL W. BROWN, M.D., SENIOR 

RESEARCH SCIENTIST, LABORATORY OF CENTRAL NERVOUS SYSTEM STUDIES, NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE, NATIONAL INSTITUTES 

OF HEALTH; AND KATHRYN ZOON, Ph.D., DIRECTOR, CENTER 

FOR BIOLOGICS EVALUATION AND RESEARCH, FOOD AND 

DRUG ADMINISTRATION 

Dr. SATCHER. OK. Thank you very much, Congressman Shays 

and members of the subcommittee. I am David Satcher, Director 

for the Centers for Disease Control and Prevention. I’m accompanied by Drs. Mary Chamberland, Bruce Evatt, and Lawrence 

Schonberger. We’re pleased to be here this morning to discuss 

issues regarding plasma pool size and surveillance efforts related 

to Creutzfeldt-Jakob disease, CJD, and the blood supply. 

The Nation’s blood supply is safer than it’s ever been. However, 

the blood supply continues to face infectious disease challenges 

from both recognized and unrecognized threats. 

Since I last addressed the committee on this subject, in November 1995, CDC has implemented a number of steps to improve our 

ability to monitor and respond to potential threats to the blood supply. CDC has developed new and enhanced other surveillance systems. We have created a full-time position occupied by Dr. 

Chamberland to facilitate intra- and interagency coordination of 

CDC’s blood safety activities. In addition, CDC continues to participate actively in various departmental and agency committees related to blood safety. 

The risks for infectious diseases associated with plasma products 

have decreased dramatically since the introduction of donor screening and testing and effective viral inactivation procedures. Many 

viruses are efficiently inactivated. Unfailing adherence to and refinements of inactivation procedures, combined with donor screening, are our most critical safeguards for plasma products. However, 

9

blood products made from plasma do carry risks for transmission 

of bloodborne infectious agents that cannot be eliminated through 

current inactivation practices. One strategy that has been proposed 

is to limit the number of individual donors who contribute to the 

large plasma pools. The relationship between pool size and infectious disease risk is 

very complex and will not reduce infectious disease risk in certain 

situations. Nonetheless, CDC believes that setting an upper limit 

on the number of individual donors who contribute to pools used 

in the manufacturing of plasma products would be beneficial. 

Smaller pool size would provide an increased margin of safety to 

persons who receive infrequent infusions of plasma products. An industry-wide standard would have to be established. FDA is in the 

best position to work with industry to define an upper limit and determine how it can be implemented most expeditiously. It will be 

critical to ensure that our efforts to improve the safety of blood 

products do not result in interim product shortages. Now concerning CJD, regarding potential transmissibility of CJD 

by blood and blood products, as Dr. Schonberger testified in January 1997, I reiterate CDC’s assessment that the risk of transmission of CJD by blood and blood products is extremely small, if 

it exists at all.

The most direct reason for concern comes from experimental 

studies demonstrating the possible occasional presence of CJD 

agents in the blood of infected patients and the infectivity of blood 

when injected into animals. Some of these studies were conducted 

by Dr. Paul Brown from NIH who is on the panel today. From animal studies we cannot directly infer that there is any 

risk of transmission of CJD by blood transfusion. To help answer 

these questions it is necessary to focus on available surveillance 

and epidemiologic data. CDC conducts routine surveillance for CJD 

through review of national mortality data that demonstrate stable 

annual rates for 16 years, from 1979 to 1995, and no case of CJD 

among persons with hemophilia. CDC also has undertaken to supplement its routine surveillance of CJD with an increased focus on 

persons with hemophilia. Specifically regarding persons with hemophilia, CDC expanded 

its collaboration with hemophilia treatment centers by active solicitation for any case reports of CJD and by facilitating neuropathologic examination of brain tissue from deceased hemophilia 

patients to look for signs of CJD. Finally, CDC is assisting the American Red Cross in coordinating 

a long-term study of persons who receive blood components from 

donors who are subsequently reported to have been diagnosed with 

CJD.

So how effective are CDC’s surveillance efforts?

CDC is aware of two studies which indicate that routine mortality surveillance has good sensitivity for detecting CJD cases. 

One study found that 80 percent, another found 86 percent of confirmed CJD cases could be ascertained by review of death certificates.

Our efforts to supplement routine surveillance for CJD with focused activity in hemophilia treatment centers have had varying 

success—obtaining brain tissue from deceased hemophilia patients 

to examine for evidence of CJD is challenging. 

10

CDC has developed a number of approaches to increase the level 

of participation by treatment centers and the number of brain autopsies performed on persons with hemophilia who die with 

neurologic disorders. CDC has begun direct funding of treatment 

centers in order to implement a nationally coordinated prevention 

program to reduce complications of hemophilia. 

In these centers, we are phasing in our nationwide monitoring 

system, the Universal Data Collection System, which should capture bloodborne infections occurring in patients and improve participation in CJD surveillance activities. 

So in conclusion, Mr. Chairman, ensuring the safety of the Nation’s blood supply is an important public health priority and one 

to which CDC remains strongly committed to address. Enhanced 

surveillance can play an important role in helping to ensure the 

safety. Surveillance data have certain limitations and must be interpreted with caution; however, these data provide increasing support for CDC’s conclusion that the risk of transmission of CJD by 

blood products in humans is extremely small and, in fact, remains 

theoretical. Periodic reevaluation of data will undoubtedly provide 

a stronger scientific basis for modifying public health procedures on 

CJD and blood safety in the future. 

In regards to pool size, CDC concurs with FDA’s proposal that 

some upper limit on pool size be established. We urge careful deliberation be undertaken by public health officials, by industry and 

consumers in advance of implementing pool size limitation to ensure that the supplies of these life saving products are not generalized. 

It is a critical issue. Thank you for the opportunity to testify before the subcommittee. And I will be happy to respond to any questions. 

Mr. SHAYS. Thank you, Dr. Satcher. 

[The prepared statement of Dr. Satcher follows:]

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Mr. SHAYS. I know this room is very crowded, and I apologize for 

that. If there happen to be any people from the media, we have two 

chairs over there that I would have no problem being used. They 

may use those two chairs on that side and those two chairs there. 

I am welcome to have you do it. 

Dr. Brown. 

Dr. BROWN. Mr. Chairman, Mr. Pappas, Mr. Towns. Good morning and——

Mr. SHAYS. Thank you. 

Dr. BROWN. And good morning and thank you for the opportunity 

to testify before you. My name is Dr. Paul Brown. I’m a board certified internist. However, I have spent the bulk of my life at the 

NIH studying issues related to the transmissible spongiform 

encephalopathies, notably Creutzfeldt-Jakob disease. 

Any time that we transfer tissues or tissue extracts from one person to another, we have to be concerned lest we transfer some unwanted passengers. The recent outbreak of Creutzfeldt-Jakob disease in hypopituitary patients as a result of contaminated growth 

hormone, and the continuing occurrence of Creutzfeldt-Jakob disease in recipients of patients who have received dura mater grafts, 

warn us again to be vigilant about attending to the question of 

where risk might be preventable and trying to predict it and prevent it rather than simply cleaning up afterwards. 

With this in mind, we have to ask the question, what is the risk, 

if any, of the recipient of a blood product or blood to contract 

Creutzfeldt-Jakob disease from that administration? That is not 

the same question as asking what is the probability of a patient 

with Creutzfeldt-Jakob disease contributing to a donor pool. The 

bottom line is what is the risk to an individual. And that is a threestep process. 

And the first is: what’s the probability that a CJD patient will 

donate blood to a blood pool? 

The second step is: what is the probability that such a donation 

will in fact be contaminated? Is there going to be infectivity in the 

blood? 

And the third step is: in a recipient exposed to blood that does 

have the infectious agent in it, what is the probability that that 

person will be, in fact, infected? 

Each one of these steps is contributed to by a number of things 

which we will not have time this morning to go into. Blood pools 

and the size of blood pools contribute to the first two steps. Clearly, 

it’s a matter of common sense to say that if a disease like CJD has 

a prevalence of about one in a million, that a pool size of a million 

people will have a much greater chance of being contributed to by 

a person with CJD than if the pool size is 10,000. It’s just common 

sense. 

The numbers for a pool size of 10,000, 100,000, 500,000 are in 

the written statement. But in general, if we take the one in a million prevelance figure, a pool size of 10,000 would have a probability of a little less than 1 percent of being—of being contaminated, had being contributed to by a CJD donor and a pool size of 

100,000 about 7 percent. If you push it up to 500,000, the probability that a CJD donor is going to be amongst those contributors 

goes up to 20 to 30 percent. 

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Now you’d say that’s not good and, therefore, we should keep 

pool sizes small. However, if there are three donors out there, it 

really doesn’t matter whether they donate to one pool or five pools. 

The same number of donors are going to be contributing. And, 

therefore, it doesn’t much matter whether you’ve got 10 pools of 

10,000 contributors or 1 pool of 100,000 contributors. The same 

number will be there. 

Now, you might say, well, wouldn’t it be better if the contamination was only the three pools? We’d have at least seven pools that 

we knew were clean. And that is quite correct. But that brings us 

to the second step, which is how much infectivity is going to be 

found in the blood of a donor. And CJD is a little special in that 

regard, because unlike hepatitis or AIDS, the amount of infectivity 

in the blood of a CJD donor, although we don’t have precise measurements, is almost certainly very small. And unlike the situation 

with HIV, a single donation could not saturate the entire donor 

pool. With CJD we’re probably talking, at most about 10, 20, 30, 

40 infectious particles. And they will be fully dispersed in donor 

pool sizes as small as 10,000 donors. So that those 30 or 40 particles are still going to find their way to 30 or 40 different recipients, whether the pool has 10,000, 50,000, or 100,000 donors. 

And that brings us to the third step, which is what’s the likelihood that a patient who’s getting a product is going to be infected. 

Again, we don’t know the answer to that question with precision. 

We do know that the administration by peripheral routes, as opposed to intracerebral inoculation directly into the brain, is a very 

inefficient way of transmitting infection. This is not an easy disease 

to get. We know that the efficiency is anywhere between 10 and 

10,000fold less. So the question as to whether or not a person is 

actually going to contract CJD from contaminated blood donation 

is not at all clear. 

I think this morning, in conclusion, you will certainly have a consensus, if for no other reason than the common sense reason, that 

if you decide to recall a pool, it certainly seems to make sense to 

recall a smaller pool than a larger pool. But I would hope that the 

committee and the general public through this committee would 

recognize the equal importance of what you said in your preamble, 

which is that continuing research is needed on the questions for 

which we still have very imperfect information. How long, for example, before a CJD patient develops signs, is his blood infectious? 

How inefficient is intravenous administration of a product? Can we 

clean up the plasma in ways that would be quite simple? For example, why not spin plasma 10 times faster or 5 times longer if infectivity of this disease is associated with white cells? What a simple 

way to clean up plasma. We just sediment the infectivity. Nobody 

has done it. What if we used iodine? We have a collaboration now 

with Dr. William Drohan in the Red Cross which gives us a possibility of perhaps inactivating the virus. So these are the kinds of 

laboratory experiments that should throw some light on the problem. And I very much look forward at this sort of twilight of my 

own career to be in a position to help solve some of these problems.

25

Thank you, Mr. Shays. 

Mr. SHAYS. Thank you. I am tempted to ask you to define twilight in your career. 

Dr. BROWN. Pink scalp. 

Mr. SHAYS. That would apply to many. And I’m not offended. 

[The prepared statement of Dr. Brown follows:]

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Mr. SHAYS. Dr. Zoon. 

Ms. ZOON. Thank you. 

Mr. Chairman and members of the committee, I am Dr. Kathryn 

Zoon, Director of the Center for Biologics Evaluation and Research 

of the Food and Drug Administration. I appreciate this opportunity 

to discuss the safety of the blood supply and the safety of plasma 

derivatives. 

Mr. Chairman, you requested that we address safety implications 

of plasma pool size in the manufacture of plasma derivatives. Let 

me start by stating that the FDA believes that upper limits on 

plasma pool size will have public health benefits. It is, however, 

only one of the aspects of FDA’s commitment to blood and blood 

product safety. And I will discuss it in more detail later in my testimony. 

FDA is absolutely committed to taking every appropriate action 

to help ensure the safety of the Nation’s blood supply. In recent 

years, we have taken numerous steps in this regard. I would like 

to briefly explain some of those initiatives. 

As you will recall, Mr. Chairman, these efforts were elaborated 

on by Dr. Friedman’s testimony to this committee last month. For 

example, some of these initiatives by FDA have focused on good 

current manufacturing practices, or GMPs, and FDA expects these 

to be a primary concern to the manufacturers of blood and plasmaderived products. To ensure substantially greater attention to this 

issue, the lead responsibility for conducting inspections of plasma 

fractionators has been transferred from the Center for Biologics to 

the Office of Regulatory Affairs. 

The Center for Biologics Evaluation and Research’s internal 

emergency response procedures have been redesigned to assure a 

more effective and coordinated response to emergency situations. 

FDA has provided enhanced public access to recalls and withdrawals of plasma derivatives by providing easily accessible information through the Internet, fax, and e-mail. 

FDA now receives monthly reports from plasma derivative manufacturers on adverse experience reactions of potential infectious disease transmissions associated with their products. 

We believe that these steps are vital additions to our existing efforts to help assure the safety of the blood supply. 

As you know, our existing efforts are based on a five-layered system of overlapping safeguards, each layer contributing to blood and 

plasma derivative safety. These layers are described in detail in my 

written testimony. 

This five-layered system forms a solid basis upon which additional efforts can be built. We are committed to continually addressing all the potential areas of improvement in our blood safety 

program. Plasma pool size is one such potential issue. Recognizing 

that plasma pool size is only one of many factors that we are considering in our efforts to minimize the risks associated with the use 

of plasma derivatives, FDA continues to assess the limits of pool 

sizes and potential public health benefits. 

FDA has brought this issue of plasma pool size before the Blood 

Products Advisory Committee several times. In March 1995, FDA 

discussed with the Blood Products Advisory Committee whether reducing the size of plasma pools from which plasma derivatives are 

39

manufactured would be an effective precaution against transfusion 

transmitted diseases, and under what circumstances FDA should 

consider mandating limits to the scale which certain plasma-derived products are manufactured. The Blood Products Advisory 

Committee made no recommendation for upper limits on plasma 

pool size. 

In response to further discussions with consumer groups, and the 

recommendation of this committee in its August 1996 report, FDA 

reconsidered the issue of pool size and brought the issue to the December 1996 Blood Products Advisory Committee meeting for reconsideration. At that time, the following limits were constituted 

for implementation in the short-term: 15,000 donors per pool for 

products manufactured from source plasma, and 60,000 donors per 

pool for products manufactured from recovered plasma. 

Over the longer term, FDA proposed for discussion further reductions of pool sizes. The Blood Products Advisory Committee determined that data were not sufficient to make a recommendation on 

upper limits for pool size. The additional data, CBER requested, 

and continues to request, information from the plasma products industry to better understand the potential public health implications 

of limiting plasma pool size. CBER recently has received interim 

responses to its inquiries on plasma pool sizes used by some 

fractionators in its manufacturing of various plasma derivative 

products. 

This recent information indicates that plasma pool size, after adjustment for combination of intermediates, may result in the pooling of material from several hundred thousand donors for single 

lots of some products. 

FDA does consider there are public health benefits in limiting 

pool size, particularly for infrequent users of plasma products. The 

exposure risk for infrequent users would be reduced in instances 

where the prevalence of the infectious agent is low. 

Reduction in pool size also might lessen the impact of recalls and 

withdrawals on the supply of the products. For the full public 

health benefit of the smaller pool size to be realized by the recipients of these products, measures also must be taken to ensure that 

recipients are not simply exposed to more lots of products and 

thereby essentially the same number of donors. 

We have not fully assessed the interim estimates of pool size obtained in response to our inquiries. After more detailed information 

is collected, analyzed, and verified, we will be able to make a more 

informed proposal on limiting pool size. 

In addition to limiting pool size, we believe there are other approaches to reducing risk, including additional and more sensitive 

testing methods, improved donor screening procedures, improved 

viral clearance procedures, and improved plasma management 

practices. FDA is committed to examining all of these possibilities. 

In conclusion, FDA is facing significant changes in helping to ensure the safety of blood and plasma derivatives. We must strive for 

continued improvements in the regulation and management of 

plasma derivatives and the plasma fractionation industry. It is important to remember that pool size is only one factor which can be 

considered in ensuring the safety of plasma derivatives. Good manVerDate Jan 31 2003 09:52 Apr 14, 2003 Jkt 086131 PO 00000 Frm 00043 Fmt 6633 Sfmt 6602 W:\DISC\45902 45902
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ufacturing practices and our enforcement of those practices is also 

an important part of the system of overlapping safeguards. 

As the Director of the center, I assure you that I am committed 

to the safety of the blood supply and plasma derivatives. And I will 

pursue the efforts described with utmost diligence and attention. 

Thank you for this opportunity. I’ll be glad to answer any questions. 

Mr. SHAYS. Thank you. 

[The prepared statement of Ms. Zoon follows:]

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Mr. SHAYS. Why don’t we start in—and I’ll start with you, Dr. 

Zoon. What is the largest pool size that has been reported to the 

FDA? 

Ms. ZOON. The interim information that we have received to 

date, approximately 400,000, if one includes the pooling of intermediates. 

Mr. SHAYS. And was that a surprise to you, this size? 

Ms. ZOON. I would say that that was larger than I had anticipated. 

Mr. SHAYS. What would explain why the FDA wasn’t able to tell 

us the pool size? Is it just something you hadn’t focused in on 

or——

Ms. ZOON. We had information that is available to us from a variety of sources. One initially was some information that we had received from ABRA, which is the association—let me see if I can remember—the Association of Blood Resource—American Blood Resources Association. And those estimates that we were given at 

that time were approximately 10,000, I believe. 

However, further information upon receipt of the request FDA 

issued to nine of the major plasma pools, there is clarification also 

at the BPAC advisory committee that, in fact, these reflect the primary pool sizes and did not include estimates of the intermediate 

pooling or consideration of adding excipients to the purified or the 

final product. 

Mr. SHAYS. Is it fair to say the FDA was thinking that these pool 

sizes were more like 10,000 and then learned it was 60,000? But 

wouldn’t it be pretty surprising for you all to have learned that it 

was 400,000 in one instance? I mean, was that a surprise? 

Ms. ZOON. I think the number of 400,000 was high. I think at 

the Blood Products Advisory Committee earlier, I believe a presentation was made by one of the blood associations, that it was potentially as high as 100,000. But 400,000, I think was higher than I 

would have predicted. 

Mr. SHAYS. Does that give the FDA a greater interest in trying 

to take a look at this issue? 

Ms. ZOON. Well, we are committed to putting a limit on pool size. 

Mr. SHAYS. OK. 

Ms. ZOON. And I think as we get additional information and analyze it and verify that information, we will certainly view limits on 

pool size as part of a—our recommendations. 

Mr. SHAYS. OK. 

Dr. Satcher, I got the sense from you that you were basically saying we needed to obviously be pretty cautious when we get into this 

area for a variety of reasons. And Dr. Brown, from your comments, 

I made an assumption that one individual could contaminate the 

whole lot. And the whole pool. But from your testimony, it made 

me wonder if you were saying to us that a large pool could make 

the one bad donor almost insignificant because it would be spread 

out over so many, I just want to clarify that, without it being diluted. 

Dr. BROWN. The significance, in my judgment, would be the 

same. And the concept of a fully dispersed small number of particles——

Mr. SHAYS. Right. 

86

Dr. BROWN [continuing]. Is crucial here. Already at the smallest 

pool size that’s made, probably the number of infectious particles 

are already fully dispersed and they’re in their 40 doses whether 

it’s 100,000 doses or——

Mr. SHAYS. I need to understand you in my way of thinking. 

Dr. BROWN. OK. 

Mr. SHAYS. The question I am asking, you are answering it, but 

I am not hearing you right, so let me just say it again, and maybe 

you can put it in my terms. I just want to be clear. Can one donor 

in a very large pool be so diluted that it doesn’t have significance? 

Or will there be—will some of the pool be polluted, will be contaminated, or will the whole pool be contaminated with one bad donor? 

Dr. BROWN. Some of the pool. 

Mr. SHAYS. OK. 

Dr. BROWN. And it doesn’t much matter whether it is 10,000, 

100,000, or a million. The same amount, the same number of donors will be at risk—excuse me, the same number of recipients will 

be at risk. 

Mr. SHAYS. Right. But some will not actually end up with contamination. 

Dr. BROWN. That’s correct. If you have 10,000 doses and say 5 

infectious particles, 5 people are going to be at risk and the rest 

of them will not be. 

Mr. SHAYS. I got you. 

Dr. BROWN. Yes. 

Mr. SHAYS. It would seem to me, maybe I guess we will get into 

the whole economies of it, but it would seem to me that using—

let me back up and say does that only relate to CJD or does it relate to all types of contamination? 

Dr. BROWN. It may relate to more than CJD if we’re talking 

about unknown agents. It certainly, I think, relates to CJD in a 

way that it does not relate to things like hepatitis and HIV, correct. 

Mr. SHAYS. So with HIV, if a large pool is contaminated, that entire plasma will be contaminated, or just again particles hit or 

miss? 

Dr. BROWN. My understanding is, using this analogy of a large 

number of particles versus a small number of particles, a much 

greater amount of infectivity will be distributed. And many more 

individuals would be infected than is true for CJD, which, although 

we haven’t measured it in humans, we have a pretty good idea 

from experiments that the amount of infectivity, even in an infected animal or human, is very, very small. 

Mr. SHAYS. OK. 

Dr. Satcher, do you want to respond to any of the questions I 

asked? 

Dr. SATCHER. No, except to restate the fact that we support 

FDA’s commitment to reexamine this issue and to take advantage 

of the benefits of smaller pool sizes. We realize that there are some 

other issues involved, like the pool size required for immunoglobins, for example, that we need in these pools. And also, the 

whole issue of the supply and the effect of pool size on the supply 

of available plasma products. But given that, yes, we support the 

direction of FDA. 

87

Mr. SHAYS. OK. Before this panel leaves, I am going to want us 

to just list the advantages of a large pool size and the disadvantages. But, I would like to move to Mr. Towns. 

Mr. TOWNS. Thank you very much, Mr. Chairman. So could I just 

sort of get the format, are you going to have a second round or 5 

minutes, Mr. Chairman? 

Mr. SHAYS. Pardon me? 

Mr. TOWNS. Five minutes or a second round? 

Mr. SHAYS. No, no. You have as much as you want. You just 

move along. 

Mr. TOWNS. OK. Thank you very much. 

Dr. Brown, you have conducted experiments on rodents and CJD. 

First of all, have those studies had peer review? 

Dr. BROWN. Yes, they have from one journal. 

Mr. TOWNS. And what do you believe the results mean for humans? 

Dr. BROWN. I think they put us on an alert status, which is to 

say, granted we can’t infer from rodent studies what exactly is happening in humans, but, as you know, we don’t have 500 disposable 

humans to experiment on, so rodents and primates and experimental animals are the only way to go. 

I think what we have shown is that not only is there potentially 

infectivity present in blood as a whole, but we have defined where 

in the blood we have to be most careful. And they include at least 

two plasma fractions. Therapeutic products are made from plasma. 

And plasma is processed and then made into products such as 

antihemophiliac factor and immunoglobulin. 

The first step in that is a step called Cohn fractionation. The 

plasma is made into fractions and each one of those fractions is a 

source of a specific therapeutic product. We’ve determined that, at 

least in the rodent experiments, and using inoculation of specimens 

directly into the brain, again not the same thing as transfusing an 

animal, that infectivity can be detected in white cells, in plasma, 

in cryoprecipitate, which is the source of Factor VIII, and in what 

is called Cohn fraction 1, plus 2, plus 3, which is the source of 

immunoglobulins. We have not detected infectivity in the two last 

Cohn fractions, which among other things is the source of albumin. 

Mr. TOWNS. Thank you. 

Dr. Satcher, can you tell me about the CDC’s efforts to establish 

active surveillance systems in six States and tell us what we can, 

in Congress, can do to help you establish the similar surveillance 

systems in the other 50 States? And also name the States you have 

surveillance in. I know Connecticut is one. 

Dr. SATCHER. You—I’m glad you said it. Now I know what you’re 

talking about. You’re talking about the emerging infectious disease 

centers. 

Mr. TOWNS. Yes. 

Dr. SATCHER. Let’s see if I can remember them. Connecticut is 

one. New York is one. California. 

Mr. SHAYS. New York is one. 

Dr. SATCHER. California has one. And I believe Oregon. Georgia 

now has a center. And I’m blocking—oh, Minnesota and Maryland. 

Mr. TOWNS. Minnesota. 

88

Dr. SATCHER. Those are the seven. And we do hope to fund one 

more in fiscal year 1998. And then we would like to move to maybe 

at least two more without addressing Emerging Infectious Disease 

Programs. So we have in the fiscal year 1998 budget plans for continuing to expand our Emerging Infectious Disease Programs 

throughout the country. 

And as you know, the one in Connecticut was very helpful to us 

in looking at some of the issues related to the cases you’ll probably 

be discussing later with some of the others. But it’s been very helpful in terms of surveillance in that area. 

Mr. TOWNS. Thank you. 

One of you alluded to the whole HIV thing. Let me sort of—is 

there any similarity between the growth and spread of AIDS 

throughout the population and the growth of CJD? 

Dr. SATCHER. I guess I would say very little. And let me just explain what I mean. If you look at the HIV epidemic, which we first 

identified in 1981 from epidemiologic data, we didn’t identify the 

virus until 1983 in this country, the AIDS epidemic has spread rapidly throughout the world and is now a global epidemic or a pandemic. 

It’s an epidemic that continues to spread for many reasons. No. 

1, the transmissibility of the virus. It’s possible to spread this virus 

through the transfer of body fluids and that includes sexual intercourse and other ways in which body fluids are transferred, obviously transfusion; injection drug use. And so generally the transfer 

of body fluids makes spreading of HIV possible. We don’t think 

that’s true with CJD. 

The other thing with HIV that’s made it such an epidemic, of 

course, is the prolonged period of incubation before a person becomes ill in many cases, and the fact that all during that period 

of time, that person is capable of transmitting the virus to other 

people. 

We get excited about Ebola when there’s an Ebola outbreak because it’s so dramatic. It kills 80 percent of the people it infects. 

But it cannot sustain an epidemic easily because it kills the host 

so rapidly that they don’t have time to spread it to others. But HIV 

is just the opposite. People can walk around 5 to 10 years with the 

virus spreading it to others without being ill themselves. 

Now, with CJD, we have conducted mortality surveillance since 

1979 in this country. And we have seen no evidence of any major 

change in the fact that about 1 in 1 million persons is infected with 

CJD. There’s been no significant increase. You know, that’s been 

very important with the BSE out—problem in England, bovine 

spongiform encephalopathy. The fact that we’ve seen no increase 

and no change in terms of the age of persons with CJD has given 

us some comfort that we’re not facing that problem. So CJD has 

been very stable and the preponderance of scientific evidence would 

suggest to us that it is not transmitted through blood. 

However, as Dr. Brown said, things like being able to detect the 

prion in the blood of a very small number of persons with CJD concerns us and the fact that in animals you can, in fact, transmit the 

infection from blood if injected into the brain. But there is a big 

difference from HIV. 

89

Dr. BROWN. And to Dr. Satcher, in the context of comparison between HIV and CJD, there are two things that we don’t have in 

CJD that would be awfully nice to know. The first thing is that 

people with CJD are rarely found to be donating blood. People who 

are sick don’t generally donate blood. We don’t know how long before a patient gets CJD clinically he might be infectious. And we 

have no test to detect the infectivity in blood. Major difference with 

HIV. We can’t screen for silent incubating CJD patients. And that 

would be a very useful thing to know. 

Dr. SATCHER. Very good point. 

Mr. TOWNS. All right. Let me just ask one more, and then I will 

move on. 

Mr. SHAYS. Sure. 

Mr. TOWNS. Dr. Satcher, I have read the public health system is 

in disarray. I understand that in some States and local health clinics the simple process of getting children vaccinated can become a 

long, long ordeal. 

Do you have any suggestions for the Congress in what we need 

to do to assist in rebuilding our health system? 

Dr. SATCHER. That’s a very important question. And I hope I can 

do it some justice. 

The Institute of Medicine’s report in 1988 pointed out that our 

public health system was in disarray. We have allowed our public 

health infrastructure in many cases to deteriorate. I think we’ve 

seen that most dramatically in the resurgence of tuberculosis, a 

disease that we thought we had under control. But for many reasons, not just the deterioration of our public health infrastructure, 

but new changes like HIV and increasing immunodeficiency, for 

various reasons we saw the return of tuberculosis. 

CDC has been committed now for several years to help rebuild 

the public health infrastructure by supporting State health departments, for example. And one of the things we’re doing with the 

emerging infectious disease program, in addition to the emerging 

infectious disease centers that we have in a few States, we have 

now 20 States where we have been rebuilding the public health 

laboratories so that they can play a stronger role. We have the 

Public Health Leadership Institute, and we just initiated one in the 

Northeast with New York, Pennsylvania, Maine, Vermont, New 

Jersey and Rhode Island where we’re training leaders in public 

health over a year’s period of time. So that now in almost half of 

the States in the country there are public health leadership institutes. 

We keep asking Congress for support that would allow us to rebuild a public health infrastructure so every year our budget reflects that goal. 

Mr. TOWNS. Right. 

Dr. SATCHER. And not just ours, we’re working with our partners 

in FDA and NIH and others. 

Mr. TOWNS. This question comes up, Mr. Chairman, in the question you raised you wanted additional information on. It is my understanding that although the FDA Blood Advisory Committee has 

considered pool size, it has not issued final recommendations about 

pool size. 

90

Can you tell us where the FDA is in that process? If you want 

to add that to what the chairman is saying, we can do it at that 

time. I would like that to be a part of the question. And at this 

time I would yield back. 

Mr. SHAYS. Dr.—Mr. Snowbarger. 

Mr. SNOWBARGER. Not Dr. And I am going to prove that with the 

questions I asked. And I do apologize in advance for perhaps the 

ignorance of the questions, but I need to get back to a little more 

basic information. And prior to preparation for today’s hearing I 

was not aware of CJD and don’t know much about it. So I would 

like to ask some questions there particularly as it is related to the 

blood supply. 

Am I hearing you correctly, and I am talking about you as a 

panel, that we are not certain the extent to which CJD is transmitted by blood or blood products? 

Dr. SATCHER. I think, and Dr. Schonberger testified here in January and he is certainly one of the world’s experts in this area, I 

think our conclusion would be that the preponderance of scientific 

evidence to date is that there is no evidence that CJD is transmitted in the blood. Having said that, CDC continues to look at 

this issue through retrospective studies. And to date, for example, 

there has been no evidence that persons with CJD are more likely 

to have hemophilia or sickle-cell disease or thalassemia where people receive a lot of transfusions. In fact, I don’t believe there’s been 

a report of CJD in a hemophilia patient in the world. And now of 

course we’ve initiated our prospective studies looking very critically 

in hemophilia patients and studying over a period of time to make 

sure that if there is any evidence out there that we will find it. 

So on the one hand I’m saying there’s no preponderance of evidence to date, and on the other hand I’m saying we’re still looking 

openly and critically at this issue. 

Dr. BROWN. Do you want a 33-second primer on CJD? 

Mr. SNOWBARGER. Thirty-three would be about right. That’s 

about all I can hold. 

Dr. BROWN. CJD kills about 1 in 1 million people each year, 

which translates to about 250 to 300 cases each year in the United 

States. It starts out with forgetfulness, to which is added fairly 

quickly abnormal movements, visual deterioration, rigidity, mutism, blindness, coma, death. You can think of it as Alzheimer’s disease in fast forward played out in about 7 months instead of 5 

years. 

Mr. SNOWBARGER. That is OK. 

Mr. SHAYS. It is amazing. He did that in 33 seconds. 

Mr. SNOWBARGER. You timed it. 

What age patient does it normally affect, presuming it is not 

transmitted by blood? 

Dr. BROWN. I understand. The average age is 60, right on the 

money for your present witness, and span about 15 years in either 

direction and you’ve got about 90 percent of all cases of the disease. 

So it’s a disease of, well, I used to say old age, now I say middle 

age. 

Mr. SNOWBARGER. I understand. 

Dr. SATCHER. Let me just say, that’s so important because there 

is the problem in England with BSE. The difference was, of course, 

91

that younger people were getting this disease. And so we started 

to look to see if there was any change in this country in the age 

at which people were getting CJD and there was none. So that was 

very important. 

Mr. SNOWBARGER. OK. I have heard the figures ‘‘one in a million’’ 

mentioned several times. And as it relates to the blood supply—

well, first of all, my understanding is the one in a million refers 

to the number of people that have the disease or are diagnosed 

with the disease. 

Dr. BROWN. The number of new patients that will appear each 

year so——

Mr. SNOWBARGER. OK. So we are sort of—as we talk about the 

blood supply, we are sort of transposing that figure over there and 

saying, well, if it’s one in a million patients, then it may or—well, 

it is probably one in a million units of blood or one in a million donors. 

Dr. SATCHER. No, I don’t think so. Because I think because of the 

age of CJD persons and the fact that they’re more likely to be ill, 

I don’t think they’re as likely to donate blood as an HIV patient, 

for example. 

Mr. SNOWBARGER. OK. 

Dr. SATCHER. So we don’t think it would be one in a million. 

Dr. BROWN. For your thinking in rough figures, you can stay 

with one in a million. 

Mr. SNOWBARGER. But I think this is important. I mean, we are 

spending a lot of time, effort, research dollars paying a lot of attention to pool size, et cetera, on this particular—I mean, pool size affects other diseases, I presume. And I am aware of that. But talking about CJD, you know, is it 1 in 2 million? Is it 1 in 3 million? 

Dr. BROWN. For donors? 

Mr. SNOWBARGER. Yes. I mean if we are saying that you have got 

one in a million of the general population—I guess what I am looking for is if we have got any kind of guess about what it would be 

in the donor population. 

Dr. BROWN. Well, I think the answer you’re looking for is known. 

And that is that in studies, large epidemiologic studies in Europe 

and a couple of other places in the world, as it happens, looking 

back, if you ask what proportion of patients dying of CJD have at 

any given time donated blood, it’s exactly the same proportion as 

the general population. 

Mr. SNOWBARGER. OK. And because we don’t know whether it—

it lays there dormant as a factor in the blood, we have to assume 

it is one in a million; is that what you are trying——

Dr. BROWN. That’s right. 

Mr. SNOWBARGER. I am kind of like a chairman, I have to have 

it explained in my terms or I don’t understand it. So I understand 

what you are saying. 

Now, it is my understanding that it is very, very difficult to diagnose CJD. 

Dr. BROWN. It used to be. I think it is no longer. And the diagnosis of CJD has now, as we speak, achieved an extraordinarily 

high degree of accuracy. 

Mr. SNOWBARGER. And how is it diagnosed? 

92

Dr. BROWN. You usually diagnose it clinically. There are not too 

many diseases with which it can be confused. I mentioned Alzheimer’s disease. That’s always an issue for a little while. But Alzheimer’s disease tends to stretch out for 5, 6 years; whereas CJD 

usually kills within a year and typically within 4 or 5 months, a 

much faster evolving disease. 

Mr. SNOWBARGER. So we are saying that the main method of diagnosis is how fast you die, not if you die? 

Dr. BROWN. No. 

Mr. SNOWBARGER. And you are finally diagnosed when you actually hit the end? 

Dr. BROWN. Well, pathologists will say ‘‘right on’’ because they 

always like to make the final diagnosis. But in point of fact you can 

diagnose it clinically by the kind of evolution and by the combination of symptoms. The pathology of the brain will put the stamp 

on it. And there are biologic tests which will, also. But it’s not a 

difficult disease to diagnose either clinically or at autopsy. 

Mr. SNOWBARGER. And you are still in the process of researching 

whatever factors that would allow us to begin finding the same factors in the blood supply or do we have any way to do that? 

Dr. BROWN. Well, there’s enough unknowns about this field and 

the disease that can sustain further careers, and the blood supply 

or the issue of CJD as a risk in causing CJD through the blood 

supply is one of the issues that we are discussing this morning. 

Mr. SNOWBARGER. OK. 

My last question, Mr. Chairman, because I am interested in the 

answer to your question, because I think that is the crucial question, of pool size and how we deal with that. Let me ask two questions, if I may. 

One is, it sounds to me like in terms of CJD, not looking at other 

infectious diseases, but in terms of CJD, the ideal pool sizes are either one or infinity, not somewhere in between. I mean that would 

be the best of all worlds. Because if you have it in one—I mean, 

if we do it in pools of one unit, which we are going to do, but I 

mean, if you do it in pools of one unit, then you can isolate, you 

know, one to one. And if you have an infinite supply, then what 

you are saying is that that may dilute these factors. 

Dr. BROWN. Yes. That’s a very intelligent summary, Mr. Snowbarger. You start with——

Mr. SNOWBARGER. Well, I appreciate that. It doesn’t lead us to 

any conclusions unfortunately. Nice academic question. But I 

mean——

Dr. BROWN. Yes, if you give a contaminated donation to one recipient, you can never cause more than one infection for sure. It is 

possible that your pool of infinity might dilute out infectivity to 

zero. But only if it takes two or three particles to make a single 

infection. Then as you diluted it out to infinity you would have less 

and less chance of having those three particles together. But that’s 

not a fact that is known. We don’t know how many particles it 

takes. And if it only takes one, then when you dilute out, you will 

get down to the threshold plateau minimum and that will stay the 

same until infinite. So I don’t think we can properly say that that’s 

not an important conclusion. 

93

Mr. SNOWBARGER. Well, we are going through a lot of math exercises today which may or may not help, I don’t know, but I want 

to ask a question that I understand may seem very callous. We are 

going through a period of time where we are trying to do cost-benefit analyses on things that we do and things that we get involved 

in. And the figures that I have heard today is that, No. 1, we don’t 

have any clinical evidence that CJD is passed on by blood products. 

And No. 2, the risk is at about one in a million, at best from what 

we know. 

Could you give me your observations about the cost-benefit analysis of all the effort that we are going through? And, again, I understand that is callous, particularly for those who either suffer the 

disease or have loved ones that do, but in trying to get a handle 

on priorities, there are certainly other diseases out there that have 

a much higher risk for the population as a whole than one in a million. 

Anybody care to comment on that or are you just going to leave 

me hanging out there with my——

Dr. BROWN. I won’t leave you hanging, Mr. Snowbarger. Obviously, there is what is trendily called ‘‘cost-benefit’’ to everything 

we do. And when we wake up in the morning, we’re taking a risk. 

We can minimize the risk as best we can, and that’s going to cost 

money. But I really have no feeling about where the line should be 

drawn in this particular disease. As a career research scientist 

working on the disease, I would say keep spending. 

Mr. SNOWBARGER. Sure. I understand. I didn’t expect an unbiased answer, but the reason for my question is that, as you said, 

we all take risks every day. And there are certain risks that—and 

a certain level of risks that we have all come to be willing to accept, the risk of an automobile accident, the risk of slipping and 

falling in a bathtub. You know, most folks don’t stay out of the 

bathtub because they might slip and fall, and most of us still ride 

in cars and stuff like that. And, again, it is a callous approach to 

it. Any cost-benefit analysis is a callous approach. I am not suggesting necessarily we take that approach here, but I do think that 

at some point we have to figure out how to allocate scarcer and 

scarcer resources for the things. 

Mr. SHAYS. Let me say to you it is not a callous question. I have 

been in public life for 24 years. And in the State House. I would 

continually have people say, well, if it saves one life, you should do 

it. And then you don’t even—that’s the argument. But we could 

save a lot of lives by making the speed limit 25 miles an hour. So 

we make certain decisions whether we care to acknowledge it or 

not. 

I am going to want to get an answer, not a long answer, to the 

advantages and disadvantages, just so I have it outlined. But I 

would like to call on Mr. Towns, and then we will come back to 

that. 

Mr. TOWNS. Two things. One came out of the dialog between you. 

But this is a diagnosis that is easy. So help us here because we 

need to know as much as we can, as much of a basis as we can 

get. 

As people begin to live longer, and thank God that that is happening, will the diagnosis then be harder to make? 

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Dr. BROWN. Yes, Mr. Towns. It will be a little harder, because 

a major feature of CJD is mental deterioration, senility, if you like. 

Mr. TOWNS. Right. 

Dr. BROWN. You know, and Aunt Emmy starts to forget at the 

age of 83, she might be coming down with CJD, or she might just 

be getting old. The answer is usually what physicians describe as 

the fourth dimension, which is time. If she’s getting old, she’ll probably get old fairly slowly. If she’s got CJD, she’s likely to be dead 

in 6 months. 

Mr. TOWNS. We will hear testimony about a case of a young hemophiliac who died of HIV-related causes. Because of receiving a 

letter from the FDA, his grandmother suspected CJD involvement 

at his death. After the autopsy and additional information by CDC, 

CJD was ruled out. 

This question is for the entire panel. It seems that some would 

point to this as a failure of the system, but it seems to me that 

there was notification and investigation by the Government agencies, so that is a question. I think the failure here was that the 

child died of HIV-related causes. 

Can someone here tell me what has been done about the HIV exposure, what steps were taken once it was realized that this child 

died of HIV, which presumably was contracted through the blood 

products he used? Either one of you can start. 

Dr. SATCHER. Let me just briefly comment on the HIV exposure. 

I think, as you know, early in the epidemic there was really an unfortunate situation with the number of people who were exposed to 

HIV through blood transfusions. Since that time we’ve made a lot 

of progress in terms of donor screening and viral inactivation. So 

it would be very unusual for a person with hemophilia to acquire 

HIV through routine transfusions because of what we have 

learned. But that was a very unfortunate part of our history in 

public health any way you look at it. 

And so our sensitivity and our concern in this area is very high, 

very deep. We don’t claim to understand all of the aspects of this 

one case in terms of the system of surveillance. As you pointed out, 

we have had pathologists to examine slides of tissue and the conclusion was that this was not CJD, but still the child had HIV and 

there were some neurological concerns. So it was not reported to 

CDC by the physician as a case of CJD or suspected CJD. 

Mr. TOWNS. Yes. 

Ms. ZOON. Yes. From the FDA’s perspective, the safeguards and 

the tests, donor screening testing methods, viral inactivation have 

been a focus of activities since the AIDS epidemic. And every step 

is being taken with the team of the Public Health Service, the cooperation between the research being done at the National Institutes of Health and others, and the surveillance efforts of the FDA 

to make the maximum use of the information that we get to develop and additional safeguards, if possible, for blood safety as it 

comes to HIV. 

Like Dr. Satcher, without the particulars of the case, I cannot 

comment more specifically about this unfortunate incident, but we 

are committed to working very hard to improve systems that have 

been dramatically improved, even more as the technology evolves. 

Mr. TOWNS. Mr. Chairman, I yield back. 

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Mr. SHAYS. I don’t want to spend a lot of time on this because 

I want to get to our next panel, but I want a list of the advantages 

and the disadvantages of a large pool size. 

We will first take the advantages. Dr. Zoon, why don’t you start? 

Ms. ZOON. I will start and give Dr. Satcher a break. He has been 

starting all of the questions. 

I would like to start—what I will do is I will list advantages and 

disadvantages that I see for larger pool sizes. 

The disadvantages that I see are the spread of infectious risks 

over more recipients for a single lot with a larger pool size. Second, 

large single lots will cause bigger recalls or withdrawals, depending 

on the size. 

Mr. SHAYS. These are disadvantages? 

Ms. ZOON. Disadvantages. I think there is an increased exposure 

risk to infrequent recipients with larger pool sizes. 

Mr. SHAYS. Explain that one? 

Ms. ZOON. An increased exposure risk to infrequent recipients. 

That means if you are getting just a product once, versus someone 

who is taking product daily or frequently for management of a disease. If I were in a car accident and it was a one-time recipient, 

that would be an infrequent exposure. 

Mr. SHAYS. Right. I understand that part. I don’t understand 

how it relates to the disadvantage. What is the disadvantage here? 

You have given me one, the spread; you have given me the recall. 

Ms. ZOON. I said, with larger pool sizes, there is an increased exposure risk. So it is a disadvantage because you have a greater 

probability of being exposed. 

Mr. SHAYS. I understand that. OK. What is the next one? 

Ms. ZOON. OK, the next one would be it could accelerate in the 

case of a new emerging infectious agent the spread of an epidemic. 

Mr. SHAYS. That I would think would be one of the most alarming ones, obviously. In other words, basically an infection we have 

never even considered in a large pool size. 

Any other disadvantages? 

Ms. ZOON. Those are the major ones. 

Mr. SHAYS. What would be the advantages? 

First off, would we add any other disadvantages, Dr. Brown or 

Dr. Satcher? You have given us four. 

Dr. BROWN. You are going to get this, I am sure, from the industry tomorrow. Obviously——

Mr. SHAYS. Tonight. Sorry, this afternoon—not tonight. 

Dr. BROWN [continuing]. It is the cost-benefit argument again. I 

am sure you will hear economic arguments, and I would suppose 

if we were making a list——

Mr. SHAYS. We are talking disadvantages. 

Dr. BROWN. OK. 

Mr. SHAYS. The larger the pool, the disadvantages. I think we accept those disadvantages. 

Let me talk about the advantages. What are the advantages? Dr. 

Zoon, since you started? 

Ms. ZOON. Sure. One advantage, potentially, could be manufacturing efficiencies. Another could be possible neutralization of an 

agent. Often there are antibodies present, and having more donors 

in a larger pool size could have some neutralizing agents in them. 

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Mr. SHAYS. Could the opposite happen? 

Ms. ZOON. Could the——

Mr. SHAYS. Opposite of neutralization happen. 

Ms. ZOON. You mean enhancement? 

Mr. SHAYS. Yes, enhancement. You didn’t mention that in your 

four. I am wondering if we could add that to No. 4. 

Ms. ZOON. It is theoretically possible. 

Mr. SHAYS. OK. 

Ms. ZOON. Possible dilution below the——

Mr. SHAYS. Let me say, if we are going to use the same judgment, is it theoretically possible of neutralization? Or is that more 

established that there is a concept? 

Ms. ZOON. There is more established data. 

Mr. SHAYS. Neutralization is more established than enhancement. 

Ms. ZOON. Correct. 

Mr. SHAYS. OK. 

Ms. ZOON. Possible dilution to extinction. This refers to the situation that Dr. Brown——

Mr. SHAYS. I am with you. 

Ms. ZOON [continuing]. Referred to. Enhancing genetic diversity 

in the product. This would be particularly important, perhaps in 

the area of immunoglobulins. 

Mr. SHAYS. OK. That is helpful. 

I am going to ask this question just because we need it for our 

record and our report. This would be addressed to both of you, Dr. 

Satcher and Dr. Zoon. Is the FDA position on withdrawal of products manufactured with plasma of donors infected with, or at risk 

of infection with, CJD still prudent public health policy in light of 

current research on CJD? 

Dr. Zoon. 

Ms. ZOON. As Dr. Satcher mentioned, at this time there is no evidence of a body of data suggesting that transfusion of blood products to humans results in a case of CJD. 

As Dr. Brown has discussed, there are experiments under way 

helping us to further evaluate in a variety of animal models the 

risks associated with fractionated products using these animal 

models to have a sense of what that is. 

At this time, the agency believes that we should be looking at 

this very carefully and very closely and be ready to act more aggressively as data is generated. I think this is a case where the 

Public Health Service has discussed this very frequently. We have 

brought it to several of our advisory teams. 

Mr. SHAYS. You remind me of the State Department here. I need 

to get the answer. 

Ms. ZOON. Oh. I think at this time we believe it is still considered a withdrawal. However, we are constantly poised to re-evaluate that situation. 

Mr. SHAYS. Fair enough. Dr. Satcher. 

Dr. SATCHER. I agree. The only thing I would add is I think the 

action of this committee, I believe, established the blood safety 

committee of our Department, and now we have established the 

Advisory Committee to the Department. I think some of these 

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mittee. The perspective has to be broader than those of us who 

work in public health that on a day-to-day basis. There are some 

values involved. Some of these things will be taken to the advisory 

committee. 

Mr. SHAYS. Before we go to the next panel, a very active member 

of the committee, Dennis Kucinich, is here and has a question to 

ask. Then we will go to the next panel. 

Mr. KUCINICH. This is to Dr. Brown. Thank you very much, Mr. 

Chairman. 

In reviewing your testimony, Dr. Brown, I am impressed by your 

comments relating to the situation with respect to a donor pool 

which contains a large number of infectious particles and also to 

your, if I may say, tentative conclusion that the chance of contracting CJD from a pooled blood product in which a patient with 

CJD has contributed is extremely small, no matter the size of the 

donor pool. 

That, of course, assumes, for the sake of the study, that the only 

pathway you are looking at is the pooled blood supply with respect 

to this study. 

In looking at this overall issue, Mr. Chairman, it occurs to me 

that what we are talking here about CJD is synonymous, is it not, 

with the bovine spongiform encephalopathy, popularly known as 

‘‘mad cow disease,’’ which has resulted in a pathway of transition 

being consumption of food products? 

Would it not then be true that the consumption of food products 

in a given population that would be contaminated with the BSC, 

bovine spongiform encephalopathy, CJD, whatever you want to call 

it, does that increase the possibility of contamination of the blood 

supply? And then is it not true that protocols for prevention of such 

contamination to the blood pool would necessarily include contact 

with those agents which transmit the disease through the food supply? 

And the final part of the question, a small question——

Mr. SHAYS. He said he had one question. It is going to take an 

hour to answer this. That is cheating. 

Mr. KUCINICH. In line with your question, have you had contact 

with the State Department and the U.S. Department of Agriculture 

about these things? 

Mr. SHAYS. I am going to give you each a minute. 

Mr. KUCINICH. What are you doing for lunch? 

Mr. SHAYS. I am sorry to interrupt you. 

Mr. KUCINICH. Thank you. That is fine. 

Dr. BROWN. Your analysis is absolutely correct. 

Mr. SHAYS. He was just showing off. We can really go on to the 

next question. 

Dr. BROWN. It is one of the things that the United Kingdom is 

currently concerned about. 

Let us suppose that instead of 20 cases of the new variant, which 

they now have, and let us further suppose that the new variant is 

the result of consumption of tissues from animals with the ‘‘mad 

cow disease,’’ instead of 20 cases, suppose in the next year they 

have 2,000 or 20,000 cases? Nobody knows whether that is going 

to happen yet. If that happens, you have augmented the potential 

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er it be blood, dura mater, kidneys or any other tissue, by 100 

times. 

So, again, that is a correct analysis; and it is something that is 

very worrisome to the United Kingdom and also which we are 

studying at the NIH. Because, again, we would like to prevent 

things and not just say, ‘‘oops, we didn’t see it in time.’’

Mr. SHAYS. I am going to just make sure I have this on the 

record. Is the gentleman done? 

Mr. KUCINICH. Yes. 

Mr. SHAYS. Do you all agree that a lot size of 400,000 is far larger than it needs to be? I don’t want to put words in anyone’s 

mouths here, so I don’t want you to say ‘‘yes’’ if you don’t think 

that. We were surprised with a lot size of 400,000. 

Let me put it this way, since I didn’t get a quick answer to that. 

Do we agree that there are benefits in having some standard sizes? 

Dr. Satcher. 

Dr. SATCHER. Yes, we think there are benefits to looking at this 

issue and trying to arrive at some limits in terms of size. 

Mr. SHAYS. Not just limits but also that there would be—we 

could learn things from having standard sizes when we encounter 

certain problems and then can maybe compare, as opposed to having them all over the lot. 

So I am asking specifically, No. 1, should there be an upward 

limit; and, No. 2, should there be some standard sizes? Is there an 

advantage in having some standard sizes? 

If you don’t know——

Dr. BROWN. No, really, we have standards for everything else in 

the world. I suppose we could have standards for lot sizes. I am not 

trying to be facetious, but I can’t at the moment think of any advantage to having a standard lot size. 

Mr. SHAYS. OK. Let me ask you—fine, I don’t mean to stretch 

this out, but—yes, Dr. Zoon? 

Ms. ZOON. Yes. I think that the considerations will need to be on 

a product-by-product basis, and that is the analysis we are hoping 

to do. Clearly, for products like immunoglobulins, you would like 

to have diversity in the pool; and, actually, there is a regulation of 

a minimum donors per pool for that particular type of product. 

So I think the answer to your question is twofold: One is, should 

there be an upper limit to the primary pool; and then looking at 

the fractionation of each of the separate products that would need 

to be analyzed and looked at very carefully, and we are in the process of collecting the data and evaluating that data. 

Mr. SHAYS. OK. I am just going to say, for the record, this committee is not about to try to push the FDA, the CDC or any part 

of the National Institute of Health in a direction that doesn’t make 

sense. As we look at it, though, we do see there has got to be some 

ultimate limit, unless it can be proved that there is a reason to do 

it. I mean, that is where this committee is headed. We will be interested in testimony from others as it relates to that. 

You have been a wonderful panel. I am going to do this at risk. 

There were about eight people who stood up behind you who were 

sworn in. But if any of you just felt there is something we really 

need to put on the record and you are willing to show courage and 

risk offending your bosses for the good of humanity, I would love 

99

you to just feel free to come forward. I sometimes have been in 

your position and say, why the heck didn’t they say that? 

Is there anyone who just wants to make a point? I am being serious. We would welcome it. 

OK. Thank you. Thank you very much. 

[The information referred to follows:]

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Mr. SHAYS. We are going to call our next panel. This is Dolores 

Crooker, a parent, a registered nurse and a grandparent; Dr. Glenn 

Pierce, National Hemophilia Foundation; and Charlotte Cunningham-Rundles, Immune Deficiency Foundation. If they would come 

forward. 

I am going to say for the record that Mr. Snowbarger just wants 

to kind of contradict something I said. I really would like it part 

of the record just because I think it is important to see diversity 

on this committee. 

Mr. SNOWBARGER. Well, I noticed that the chairman asked those 

who were sitting behind their bosses if they cared to contradict or 

say anything that their bosses might not appreciate, but he didn’t 

ask me if I wanted to contradict what the chairman had said. 

At the risk of offending my chairman—and I know he will take 

it in the right way—I was a little concerned about the comment 

that the chairman said about the committee’s direction. It left me 

with the impression that the committee is attempting to say that 

there needs to be—we need to find the optimum pool size and, once 

we find it, we need to make sure everyone is adhering to that. 

When what I heard from the witnesses sort of led me to the indication that there may not be an optimum pool size. 

If there is not an optimum pool size, then why do we care? And 

maybe in this era of deregulation it might be a time to think about 

maybe it is something we don’t need to get into, as opposed to trying to find every little place where we can do what we think is 

best, where the industry, particularly if the regulators don’t see 

any particular need for it, we don’t need to push them into regulation. 

That was my comment. 

Mr. SHAYS. I appreciate your putting that on the record. 

What I really should say is that that was the position of the committee last year; and, obviously, there is no reason why we 

shouldn’t revisit it. It was in a report recommending there be a 

limit. But this is why we have hearings. So I am happy you are 

putting that on the record. 

Mr. SNOWBARGER. Thank you, Mr. Chairman. 

Mr. SHAYS. I am going to ask the witnesses to stand up and raise 

your right hands. 

[Witnesses sworn.] 

Mr. SHAYS. All three have responded in the affirmative. 

STATEMENTS OF DOLORES CROOKER, R.N., PARENT; GLENN 

PIERCE, M.D., Ph.D., NATIONAL HEMOPHILIA FOUNDATION; 

AND CHARLOTTE CUNNINGHAM-RUNDLES, M.D., Ph.D., IMMUNE DEFICIENCY FOUNDATION 

Mr. SHAYS. We will just go right down the row, starting with 

you, Ms. Crooker. 

Ms. CROOKER. Good morning, Mr. Chairman. 

Mr. SHAYS. I am sorry. I should tell you to move the microphone. 

I know it is hard for you to put papers in front of you and do that, 

but that is not going to be close enough, Ms. Crooker. Then you can 

turn it sideways a little bit. Turn that a little sideways a little bit. 

I am going to have you lower it down a little bit. 

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Ms. CROOKER. OK. Good morning, Mr. Chairman and committee 

members. 

My name is Dolores Crooker. I am a grandmother and was the 

caregiver of Roger. I had taken care of him since he was 18 months 

old and diagnosed with severe hemophilia in 1984. 

Roger died on June 21, 1995, of AIDS complications at the age 

of 11, 1 month short of his 12th birthday. In fact, yesterday would 

have been his 14th birthday. He became HIV infected from contaminated blood products he used to control his bleeding problems. 

In 1993, Roger received a Factor VIII infusion in a local emergency room for an injury he received. This was recalled in 1994 for 

possible contamination with CJD. One year from product dispensing to community notification. 

In late summer 1994, Roger came down with a severe neurological motor coordination problem. He improved for a short time 

and then continued to deteriorate until his death in 1995. No one 

could definitely identify the specific reason for his neurological deterioration, which included muscle spasms, seizures, blindness. It 

was 5 months before his death when I received notification that he 

had received this recall factor. This is 2 years after he received the 

factor. 

Roger died at home on June 21, and an autopsy was performed. 

The first autopsy results showed spongiosis cells, and a second 

opinion was requested. In that report, it was suggested that a special protein stain be used. After a letter from me, the slides were 

then sent to the CDC for evaluation. 

I know that Roger died of HIV infection he contracted from the 

blood product he used since his diagnosis of HIV in 1984, but was 

CJD present? Were these spongy cells caused by HIV or CJD? I 

had to know. It was about 2 years before I knew he had received 

the recall factor and now 2 years after his death I finally got the 

answer that CJD was not present. 

I am not aware of what reporting methods were used by the various medical/scientific communities to study this unusual autopsy 

report. I do feel, however, that a final answer to myself for closure 

and peace of mind—that took too long. 

As a member of the hemophilia community, I should not have to 

tell you how important it is to explore and analyze matters such 

as this in a very timely fashion. In the 1980’s, we waited long periods of time and lost precious years waiting for the final answer on 

the question of HIV and AIDS and blood products transference. As 

we are aware, the answer then was positive; and the devastating 

epidemic took more than 50 percent of our community. 

We cannot afford to waste more years at a tragic cost and more 

lives on finding out answers regarding CJD and other transference. 

It took over 2 years since my grandson’s death to get a definite 

answer on his disturbing autopsy. My anxiety and my concern are 

not for my peace of mind only. This community, including the new 

generation so far untouched by HIV and hepatitis, needs to be completely informed about the hidden perils lurking in an FDA-approved product they continually use. Product recall notification 

must be faster than 2 years. It was 2 years to find out he received 

recall product and 2 years to find out the autopsy results. 

104

Faster recall notifications have occurred within the past few 

years because of collaboration with community organizations, the 

treatment centers and Government regulations—and some Government regulations. 

In closing, I feel that it is imperative that all departments of the 

medical community—clinics, hospitals and labs—should have a 

common goal: find answers quickly and relay this information accurately to the waiting family members. Unfortunately, delay may 

cost additional lives. 

In my case, 2 years is 2 years too long. If the Government is 

going to approve a Federal product through the FDA, then it 

should also take the responsibility to regulate procedures for recall 

and withdrawal of that product, because contamination and even 

potential hazards can cost human lives. 

Thank you. 

Mr. SHAYS. Ms. Crooker, it is so important that you provide a 

human face to what we are talking about. We can just talk about 

statistics and numbers and so on, and it is just very welcome that 

you would express your concern. You cared for your wonderful 

grandson for 11 years of his life, and so we just really appreciate 

your being here. 

Ms. CROOKER. Thank you. 

Mr. SHAYS. Are you accompanied by Roger’s sister? 

Ms. CROOKER. His sister is over here. 

Mr. SHAYS. It is nice you are as well. 

Ms. CROOKER. His younger sister. 

[The prepared statement of Ms. Crooker follows:]

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Mr. SHAYS. Dr. Pierce. 

Dr. PIERCE. Thank you for this opportunity to present testimony 

today on behalf of the National Hemophilia Foundation. 

The NHF is a voluntary health organization dedicated to improving the health and welfare of people with hemophilia, von 

Willebrand’s disease, and other coagulation disorders. I am a 

former president of the Foundation and currently serve as the 

chair of its Blood Safety Working Group. I am a person with hemophilia and, as a result, have been exposed and infected by many 

viruses and other agents through my use of blood clotting factor. 

In my professional life, I manage research projects for a biotechnology company. 

The NHF appreciates the continued efforts of Chairman Shays 

and this subcommittee in bringing greater attention to the critical 

need for safer blood products and a safer blood supply. 

The Government Reform and Oversight Committee’s 1996 report 

included two critically important recommendations which I will discuss today: reductions in plasma pool size and prompt patient notification. 

The NHF has issued 12 medical bulletins in 1996 regarding 

products investigations or recalls and already has issued 12 bulletins this year, including 4 alone in July. In addition to the withdrawal or recall of products related to evidence of infectious agents, 

we are alarmed by the number of recalls this year that have resulted from violations in the FDA’s good manufacturing practices 

where sterility was not maintained, vials were mishandled or viral 

inactivation did not occur as specified. Even recombinant DNA produced/non-blood based products have been recalled. Although these 

products are highly unlikely to contain human viruses, potential 

mold contamination during manufacturing resulted in a recall just 

last week. 

Historically, the hemophilia community has been impacted by a 

number of viruses through the blood supply. While HIV has been 

the most devastating, a number of other viruses continue to plague 

the hemophilia community through their sequela, including Hepatitis A, B, and C and Parovirus B19. 

Strong evidence of the need for a more responsible and responsive blood safety system accumulates as new announcements of 

blood product recalls are issued, often weeks after the seriousness 

of the problem has been detected. Too frequently, individuals in our 

community find out too late that they just infused themselves or 

their child with a recalled product which has been stored in their 

home refrigerators. 

It is important, as we consider plasma pool size, to be more precise in defining the term. That has been a part of the problem, I 

believe. Plasma pool refers to the plasma donations that are mixed 

together for subsequent manufacture into purified coagulation 

products and immunoglobulins, albumin and other products. 

During the manufacturing process, multiple batches of plasma 

may be mixed together, as we have heard this morning. The purified product is packaged and distributed in what is referred to as 

a lot. For some, but not all products, each lot is given a unique 

number to facilitate tracking. Thus, multiple pools make a lot. It 

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110

munity as lot size represents the total donors to which blood recipients are exposed. 

We were both surprised and troubled to recently learn that there 

are no upper limits on the number of donors contributing to plasma 

lots. While manufacturing practices differ, we had been led to believe by FDA and manufacturers that manufacturers were observing limits of around 15,000 donors per lot for paid plasma and 

60,000 donors per lot for volunteer plasma. 

We now know from testimony this morning that some manufacturers place well over 100,000 separate donations in a single lot of 

products. The absence of any upper limit on lot size places our community at significant risk for emerging infections. 

There have been attempts over the past year that have been 

made to pit the Immune Deficiency Foundation against the NHF 

on this issue. I will tell you categorically that will not work. 

Immunoglobulin and coagulation products are separated early in 

the manufacturing process. Thus, the needs of both groups in terms 

of final lot size do not impact on one another. This has been a 

smoke screen, and there has been deliberate obfuscation by industry on this issue. 

In its own analysis of the issue, the FDA has published an article 

last year that made the case that larger plasma pools do increase 

the risk of exposure to and thus the risk of transmission of infectious agents, especially to highly susceptible populations, such as 

persons with hemophilia. Past experience with hepatitis and HIV 

in our community has demonstrated that not everyone who received a contaminated lot of product becomes infected as is assumed in the transfusion article. 

We need only look at the spread of HIV to realize that patients 

received multiple exposures of HIV before becoming infected. Exposure to fewer donors would have allowed some individuals to escape infection. 

We have communicated to FDA our requests for limits on the 

maximum number of donors that can be pooled together in the 

manufacture of blood products for the following reasons. 

First, increased safety. As future emerging infectious agents 

threaten the blood supply, reductions in pool size can delay the 

possibility of widespread transmission. 

Second, reduction of exposures. By reducing the total number of 

donors that a person is exposed to over a period of time, the likelihood of transmission of an infectious disease is minimized. As we 

heard this morning, this point is especially important for individuals who take product infrequently, who don’t take it once every 

2 or 3 days, but who may use it once a month or once every 2 

months. 

Finally, preservation of the product supply. Under the current 

situation, identification of a single blood donor with a disease can 

result in the recall of thousands of vials of clotting factor concentrate. Smaller pool sizes and placing donations from a single individual into a single lot, multiple donations from a single individual into a single lot, would do a lot to alleviate the amount of 

product that is withdrawn. 

With regard to CJD, we have recently had numerous recalls due 

to possible CJD contamination. As this committee knows from its 

111

previous consideration of the issue, we don’t know if CJD can be 

transmitted by blood products, although the experimental evidence 

in animals suggests there is something to be concerned about 

there. 

The number of recalls that have occurred because a donor was 

later identified as having CJD or at risk for CJD is staggering and 

has affected the supply of coagulation products in the marketplace. 

Clearly, if pool size limits were in place, substantially less product 

would be recalled. 

With regard to patient notification, we know that recalls occur 

when the system of donor deferral, donor screening, viral inactivation, coupled with good manufacturing practices, is broken down. 

Frequent occurrence of these events at 1 to 2 per month on average 

continues to shake the confidence of consumers and providers within our community. 

As a result of the events of the 1980’s, where nearly half of our 

members were infected with HIV, we are committed to ensuring 

that consumers have information about the products they are using 

in order to make informed and educated decisions about their 

treatment. We believe this is only possible when they are provided 

with crucial and possibly life-saving information as soon as possible 

after an FDA investigation of an adverse event begins. 

Since the announcement last year that notification should go 

down to the level of consumers by the FDA, the FDA has requested 

that companies with products in question contact consumer organizations such as the NHF; and we have issued medical bulletins to 

chapters, treatment centers and volunteer leaders and placed information on our web site. This is only an interim system which 

wrongly places the burden of notification upon a consumer organization like the NHF, and it highlights the urgent need for the FDA 

to establish a prompt patient notification system clearly defining 

the responsibilities of the manufacturer in communicating directly 

with the consumers and their providers when an adverse event occurs. 

In conclusion, more than 2 years after this committee first began 

to examine blood safety issues, many of the recommendations for 

a safer blood supply that were part of this committee’s blood safety 

report, the 1995 Institute of Medicine report, and this year’s U.S. 

General Accounting Office report have not been implemented. As a 

community that has been irreparably harmed by contaminated 

pooled plasma products and that has been advocating for improvements in collection, testing, manufacturing, viral inactivation, product tracking and recipient notification, we are at a loss to understand why the FDA and manufacturers continue to be reluctant to 

implement meaningful measures to ensure a safer blood supply. 

The bleeding disorder community and others who rely on blood 

products remain vulnerable to infectious agents entering the U.S. 

blood supply, but we have no sense that a lesson has been learned 

from the past.

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Thank you, Mr. Chairman. 

Mr. SHAYS. Thank you, Mr. Pierce. As you can imagine, we will 

be following up on some of those recommendations; and, actually, 

we will be examining some of our own to see if we are still on target. 

[The prepared statement of Dr. Pierce follows:]

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Mr. SHAYS. Dr. Cunningham. 

Dr. CUNNINGHAM-RUNDLES. First, I would like to thank the subcommittee for inviting me to participate in this session on the topic 

of safety implications of plasma pool sizes in the manufacture of 

blood products. 

My name is Dr. Charlotte Cunningham-Rundles. I am professor 

of medicine, pediatrics and biochemistry at the Mount Sinai School 

of Medicine in New York City. I am a member of the Immune Deficiency Foundation’s Medical Advisory Committee, and my work for 

the last 23 years has been in the laboratory study and clinical 

treatment of primary immunodeficiency diseases. 

There are about 50 or more of these diseases and many of these 

result in frequent and life-threatening infections. Due to these genetic defects, there is an estimated group of more than 20,000 people in the United States—infants, children and an enlarging population of adults—who are not able to make antibodies and who receive regular infusions of a plasma derivative, intravenous 

gammaglobulin. 

The antibodies are complex proteins found in the serum portion 

of blood, and these proteins are vital for protection against bacterial and viral infections. Since the early 1950’s, the standard 

treatment for immunodeficient patients has been the regular administration of gammaglobulin obtained always from the blood of 

normal donors. Originally, this was given by intramuscular injection, but since the early 1980’s the preferred route of administration has been by intravenous infusion. 

Gammaglobulin pools from human blood contain antibodies of a 

tremendous variety, representing the immune experience of thousands of donors. Patients who don’t make their own antibodies are 

completely dependent upon these infusions which they receive 

every 3 or 4 weeks, with the expectation of doing so for the remainder of their lives. 

I first started to use intravenous formulations of gammaglobulin 

about 17 years ago, and I think I was one of the first investigators 

in the United States to use this kind of treatment. Since that time, 

I have used all of the existing formulations; and I have published 

a number of articles on the clinical benefits, the biological and 

immunological effects, and the occasional adverse reactions which 

might result when using these products. 

All the manufacturers fractionate intravenous immunoglobulin 

from large pools of plasma, using their own proprietary methods 

and pools of varying sizes. These antibodies, currently at least, cannot be synthesized in the laboratory; and there is very little expectation that molecular techniques will produce any other alternative 

source of gammaglobulin. 

The very reason that the gammaglobulin pools protect our patients is that they contain antibody molecules that protect against 

the widest possible spectrum of bacteria and viruses. Limiting 

blood pool donor size will at some point diminish the value of these 

pools to our patients since the variety of antibodies would necessarily be restricted. 

We don’t know how small these pools can be and still provide 

broad antibody protection to these immunodeficient patients. Our 

point is, before we stipulate donor pool size, we really need to have 

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this information; and this is the major point that I would like to 

make today. 

An additional point to consider is that patients with immunodeficiency receive immunoglobulin concentrates 12 to 16 times 

every single year. In our infusion room, where we infuse approximately 100 patients a month, our patients are currently exposed to 

10 to 12 lots of intravenous immunoglobulin of their prescribed variety. If the pools are smaller, it is theoretically possible that each 

of our patients will be exposed to a proportionately larger number 

of pools. This may reduce or perhaps eliminate the benefits of reducing the pool size. 

These patients are frequent and lifelong users, and we believe it 

becomes imperative that they have representation on the Health 

and Human Services Advisory Committee on Blood Safety and 

Availability and the FDA’s Blood Product Advisory Committee. Decisions made regarding manufacturing processes, safety and availability must incorporate the unique concerns of the immune-deficient patient population. 

Since the introduction of intravenous immunoglobulin, our patients can look forward to a normal life span. However, adverse reactions have occurred with the administration of immunoglobulin; 

and in some cases these have forever changed and in a few instances ended the lives of our patients. 

Most recently, our patients have experienced an outbreak of hepatitis C due to the use of intravenous immunoglobulin products. 

People with genetic immunodeficiency appear more likely to develop fulminant viral hepatitis and liver failure for reasons that we 

don’t understand. 

As far as I am aware, there is no information available on the 

total number of cases which have occurred; we think that a national registry compiling the natural history of this disease in this 

patient group is needed. Some information about the patient’s response to interferon, if used, results of liver transplantation, if performed, would be a very valuable resource for physicians who are 

still dealing with the aftermath of this outbreak. 

The third issue I would like to touch upon is the means of notification of product withdrawal and notification. I have received a 

number of notices of recalled or withdrawn products of gammaglobulin in the past year or so. These notices have come from a 

number of different sources, including the Immune Deficiency 

Foundation, manufacturers, the National Organization of Rare Diseases and, in some cases, home care companies. 

On the other hand, I have never had a notification from my own 

hospital pharmacy, and I have never had one from the wholesale 

distributors that I use. There may have been recalls or withdrawals 

for which I have received no notification. 

Since mine is a very large clinical practice dealing specifically 

with primary immunodeficiency, I can only imagine the difficulty 

amongst internists and pediatricians who only see a few patients 

in their practice annually. 

Because of the lack of an organized notification process, it is really likely that primary immunodeficient patients will receive an intravenous immunoglobulin infusion this week from recently withdrawn lots. 

124

As a final note on the issues of notification, the Immune Deficiency Foundation, for whom I serve as a voluntary medical advisor, reports that it is common practice for some manufacturers to 

advise them of recalls or withdrawals, but other manufacturers do 

not do that. It is also my understanding that the FDA does not routinely inform the IDF of recalls or withdrawals either. Keep in 

mind that, at the present time, the IDF organization and treating 

physicians like myself are the only direct links to patients. 

To summarize, I would like to leave the subcommittee with the 

following recommendations or suggestions. 

No. 1, the FDA, NIH or CDC should initiate a systematic study 

into the relationship of plasma pool sizes and the antibody content 

of intravenous immunoglobulin preparations. I think industry could 

be a very active collaborator in such a study. 

No. 2, the FDA, NIH and CDC should establish sufficient lookback and health surveillance programs within the immunodeficient 

population who do use intravenous immunoglobulin to assess past 

exposures and current and future risks. I am talking especially 

about hepatitis C. 

The FDA and industry must rapidly address the issue of effective 

physician and patient notification of recalls and withdrawals. The 

Immune Deficiency Foundation will assist or advise in any way 

possible. 

We think it absolutely imperative that representatives of the primary immunodeficient patient population, whether they are medical professionals or patients, be appointed to the existing blood advisory panels so that they may assist regulators and industry in 

avoiding mistakes. 

Thank you very much for the opportunity to present this information. 

[The prepared statement of Dr. Cunningham-Rundles follows:]

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Mr. SHAYS. I thank all three of you. 

Your testimony is confirmation why I like the consumers basically to go first. There is a kind of policy that has been there so 

long that the department heads get to address Congress first; and 

if we don’t allow that to happen, it is considered a slight of the legislative on the executive branch. But you have raised some questions that I wish I had asked our first panel. 

Mr. Towns, do you want to begin? 

Mr. TOWNS. Thank you, Mr. Chairman. 

Dr. Pierce, can you tell us about your group’s feelings about the 

CDC’s involvement in funding of hemophiliac treatment centers? 

Dr. PIERCE. Yes. For a number of years now, probably close to 

8 or 10, the CDC has been actively funding a number of risk reduction programs in the hemophilia community, both at the level of 

consumer-based chapters as well as at our hemophilia treatment 

centers. 

Initially, they were designed to decrease the risk of transmission 

of HIV, which came via the plasma pool, to uninfected spouses and 

sexual partners and children. So that was the initial impetus, was 

to prevent the subsequent transmission of additional infections. 

The emphasis has changed in more recent years with an emphasis on the prevention of other complications of hemophilia as well, 

including joint disease, other infectious diseases such as hepatitis 

C, which, if HIV were not in the community, hepatitis C would be 

recognized as a major killer of individuals with bleeding disorders. 

So the CDC has taken a more active role in looking at those complications as well. 

Mr. TOWNS. Thank you very much. I was getting ready to say 

that light did not give me 5 minutes. 

We talked about notification. CDC has conducted a public service 

campaign to notify people of possible exposure to hepatitis C. 

Would any of the witnesses like to comment on that campaign? 

Any of you? 

Dr. PIERCE. I am not sure, from our perspective, we can comment 

on it. In the hemophilia community, they have worked closely with 

our treatment centers, so virtually everybody in our community has 

been tested for hepatitis C infection; and it is being followed medically at this point. 

Mr. TOWNS. So you would not be. 

Dr. CUNNINGHAM-RUNDLES. In the immune-deficient patient population, many studies were done regarding the incidence of that infection. I think everyone was feeling quite complacent until approximately 1993 and early 1994, when it was discovered that 

many patients were suddenly becoming infected with a product 

they had considered safe for some 10 years prior to that. 

After that, a rather intensive sort of surveillance has been undertaken by most physicians dealing with patients who have received 

this form of gammaglobulin using the PCR tests. So I think we now 

have a pretty good means of knowing who is infected and who is 

not. 

The only difficulty is I think that not all patients know exactly 

which gammaglobulin they may have received. They don’t know 

that they are at risk; and, in fact, the infection could perhaps be 

dormant and not tested for. 

130

Mr. TOWNS. I am looking for an answer on notification and withdrawal: what can we do on this side? Just change roles for a moment. What can we do on this side to enhance that in terms of 

that? I am concerned about the fact that if there is a problem and 

then there is no real recall or if nobody pays any attention to it 

or they put it in small print and nobody reads it, what can we do 

on this side to make certain that, when something like this occurs, 

that there is vigorous action taken on the part of the manufacturers and everybody involved? What can we do? 

Dr. PIERCE. Well, in your role of oversight of the FDA, I think 

the FDA needs to make sure that the manufacturers are accountable for getting notification out about product recalls rapidly, with 

direct consumer and physician notification. That is the subject of 

interpretation in the Code of Federal Regulations. 

Industry has suggested that there may be new laws that are required. The FDA, at least as far as I had heard in the past, has 

suggested that is not the case. They believe they have the ability 

to enforce that. You would have to ask them for more specifics. 

But we seem to be at a stalemate here, where nothing is occurring that really will officially get that information out to people. 

Mr. TOWNS. I think what I am saying is that maybe we should 

look at some legislation that might bring about some specifics with 

some penalties and all that involved? I don’t know. I think this is 

why we have these hearings, to try to get information. I see there 

is a problem, and I think something needs to be done, but I am not 

sure what. 

Dr. PIERCE. Well, someone needs to figure out if the FDA already 

has the authority to do it; and, if they do, then it needs to be enforced. If they don’t, then we need legislation that gives them that 

authority. 

Mr. TOWNS. It is my understanding to some extent—and I could 

be wrong—that the size of the plasma pool is a business decision 

which is guided by economics and necessity. I understand in order 

to produce some plasma products the producer needs a certain pool 

size. I understand that. 

Would any of the witnesses care to comment on the economics 

versus the public health concerns? I get the feeling there are some 

economics tied into this. I could be wrong. 

Dr. PIERCE. You know, the economics work both ways. On the 

one hand, if you have a smaller manufacturing process or smaller 

number of pools put together to form a lot, yes, that will cost more, 

that may decrease the amount of product; and we will probably 

hear about that from industry this afternoon. 

On the other hand, the number of recalls that are occurring has 

already had a significant economic impact as well as a significant 

impact on supply. So there is a balance there. 

When you are talking about pool sizes or lot sizes, however we 

want to define it, that are in the hundreds of thousands, I will go 

back to the first panel and say, common sense tells you that is just 

way too high from a public health perspective, for all the reasons 

that have been outlined earlier today. 

Mr. TOWNS. Any other comments on that? 

Dr. CUNNINGHAM-RUNDLES. Well, I think we don’t know how 

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died around from place to place. I don’t know where that number 

1,000 came from. I don’t even know if it is accurate. So even the 

lower limit I think is something which is subject to challenge at 

this point. 

I know that for the immune-deficient patient population, there is 

a rare central nervous system disease called echo virus; and there 

have been situations, especially I would say in the last 10 years—

not commonly, but it will occur—where physicians are having to 

test various lots of gammaglobulin to make sure that they have 

enough antibody present in a given preparation to treat their patient. That says to me that perhaps those lots don’t contain enough 

broad spectrum of antibody. 

So the lower limit I think is another issue that we don’t talk 

about very much, but I suspect that may be as important. 

Mr. TOWNS. That is a good point. 

Let me just sort of ask a last question here. There are a few bills 

in the House that would establish a compensation fund for people 

who have contracted HIV as a result of exposure to blood or blood 

products. I must admit I am a cosponsor of one of them. 

I would like to know the thoughts of anyone on the panel who 

would care to comment on the compensation idea. Give me your 

views and feelings around this whole compensation concept. 

Ms. CROOKER. Compensation—basically, the hemophiliacs have 

been the watchdogs, they have been the canaries or whatever you 

want to call us, for the blood supply here in the United States and 

in the world. Anything that goes wrong in the blood supply, they 

come down with it first. So, you know, if there is no problems with 

the hemophiliacs, then the blood supply is fairly safe. 

You pay your guards, you pay—you even pay for your canary, 

those that they take down into the mines. We should get some compensation in this sense if for no other reason. Besides, it was an 

FDA-approved product. 

Dr. CUNNINGHAM-RUNDLES. I suppose I feel similarly. 

With regards to the patients with hepatitis C, with primary immune-deficiency disease, the situation is no different. That virus, in 

fact, was in certain preparations for reasons that we don’t completely understand, but the patients certainly weren’t at fault. 

Dr. PIERCE. The hemophilia community, as Ms. Crooker said, has 

been on the front lines. There has been a failure of the system in 

the 1980’s that resulted in this devastating infection, and we are 

working very hard to see that the Ricky Ray bill is passed because 

of that. 

Mr. TOWNS. I thank all the members of the panel. 

Mr. Chairman, let me thank you. It is so important that we are 

able to spend the time to get information, because it is a very serious issue, and we need to know as much about it as possible. 

Thank you for your generosity. 

Mr. SHAYS. I thank you. 

Mr. Pierce was thanking me for being involved in this effort. Mr. 

Pierce, I think you know that Mr. Towns has really been an equal 

partner in this effort, as have some of the other members—Dr. 

Pierce, I am sorry. 

Dr. Pierce, I am taught to think of the hemophiliac community 

as kind of the canary in the coal mine, so I know you are right in 

132

the front lines in this whole issue. I really do wish that we had 

gone with this panel first, because we didn’t deal with any of the 

recall issue. 

I would like each of you to tell me in your mind how the system 

works. Ms. Crooker, you lost your precious grandson, and then 2 

years after his death you were notified that one of the pools that 

he had used had a contaminated source. 

Ms. CROOKER. No. It was 5 months before his death. 

Mr. SHAYS. I am sorry. 

Ms. CROOKER. I had got information that 2 years before that he 

had received a lot of factor contaminated with possible CJD, but it 

was 2 years after his death to get the results that he had not died 

of CJD or CJD was not present in his system. 

Mr. SHAYS. They determined later it was not. 

Ms. CROOKER. It was not. 

Mr. SHAYS. So what would be your general point? What should 

I learn from your experience? 

Ms. CROOKER. Well, I know the treatment center in New Jersey 

is very fast, when they get recalls, of notifying the families of the 

community about recalls, but it seems like that there is such a 

delay between their notification from industry. So I think the industry has to be within a certain time limit or the time limit must 

be shortened between their notification of the general public. 

Mr. SHAYS. In the course of the 12 years with your grandson, had 

you experienced recalls, notices of recalls and so on? 

Ms. CROOKER. There was a lot of recall notices when he was 

younger with the HIV, and they came very slow also. In fact, a lot 

of times my recall notices came well after I had used up all the 

product. 

Mr. SHAYS. So when that happened, for instance in HIV notification, would you go and have your grandson tested for HIV? How 

does someone respond when you get a notice like that? 

Ms. CROOKER. Roger was at a time where he just received heattreated factor——

Mr. SHAYS. Right. 

Ms. CROOKER [continuing]. So it was not until some time around 

1987 where he received a recall factor from Armor; and at that 

time they said there was no need because this was not his lot numbers, because he had only received heat treated. It came to be that, 

because of the second recall factor, that he received about a year 

later, I believe it was, it was a group that he again had received; 

and shortly after that they finally did the testing. 

Mr. SHAYS. When you get a notice, is it something that you just 

kind of are blase about? 

Ms. CROOKER. No. We are very aware of the notice. We check the 

lot numbers we have on record. 

Mr. SHAYS. I see. Dr. Pierce. 

Dr. PIERCE. I would like to make three points regarding recall 

and notification. 

The first is the sheer number of recalls that have occurred as a 

result of a failure of good manufacturing practices. I am not 

aware—there may be some, but I am not aware of any other FDAapproved drugs that have had this kind of history over the past 

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munity, because we have got these products at home, we use them 

at home in our refrigerators, and we are completely dependent. 

Mr. SHAYS. So when you get notification like that and you are 

looking at a lot size, you are going down, you are going to get this 

lot, this medicine, the plasma and so on, looking at it and holding 

your breath to determine if this is one that is recalled? 

Dr. PIERCE. Yes, to a large degree. You wonder, when you use 

the material, has this been recalled, and I’m just not aware of it 

yet; is this product under investigation, and I’m not aware of that 

yet. 

Mr. SHAYS. When you get a recall—I’m just trying to anticipate—

when you get a recall, you immediately check? 

Dr. PIERCE. Yes. There is no question. But if you’ve—if you get 

a recall notice for a particular product, you look at the lot numbers 

on that product and make sure you don’t have that product. 

Mr. SHAYS. OK. 

Dr. PIERCE. The other point to make on the notification is that 

it is a very haphazard. It doesn’t by—industry is not accountable 

to take notification down to the end user, which the FDA has now 

specified is the consumer of the product, the person who is infusing 

that product into their veins. And without that, then you are left 

uncertain as to whether or not the end user in all cases has gotten 

the information. 

Mr. SHAYS. I wonder if the economics would require them to try 

to contact the end user. I don’t know how feasible it is, if there 

would be an added incentive to have a smaller lot size. 

Dr. PIERCE. Well, if you’re able to go up the system by writing 

a prescription, sending that in, getting product from the manufacturer, you should be able to go down the system following that 

same pathway and make sure that you contact the person for 

whom that prescription was written for if there’s a problem. 

Mr. SHAYS. Dr. Cunningham, do you want to explain how the recall system works from your standpoint? 

Dr. CUNNINGHAM-RUNDLES. From my standpoint, we buy very 

large amounts of gammaglobulin at a time, and we stock it in our 

infusion area, and when we get a recall, we check to see whether 

we have any cases that match that lot. In most cases, the recall 

comes quite a bit after the lots have already been used, and that’s 

partly because CJD recalls, for example, often happen retrospectively. The donor was later found to have come from a family in 

which a case was reported, so it’s far too late. It might have been 

even several years previously. So that’s the first issue. 

The second thing is, since we buy it from large distributors, they 

have no idea which lot which patient got. So it becomes, I think, 

equally impossible for a manufacturer to know what lot an individual patient got given. 

The other issue is that I think a good number of physicians in 

the United States don’t write down lot numbers at all, and so that’s 

another issue that I think is important. The only way I can think 

of to do it is to put a box top into the bag of gammaglobulin and 

have it returned to the manufacturer, and that’s obviously incredibly labor-intensive. It’s almost like a coupon in a box of Cheerios. 

And that would be very impractical perhaps. 

134

But the net—the end user is the only one who really ends up 

needing the information, but that turns out to be filtered with a 

good number of layers between that individual and the manufacturer. 

Mr. SHAYS. Is the—I want each of you to tell me your position 

on lot size and why. You’ve done it in your testimony, you in particular, Dr. Pierce, but I want you to say what you would like to 

see as a consumer. It is clear from our committee’s standpoint that 

we have thought that the general lot size was in the tens of thousands, not in the hundred thousands, the pool size—I don’t mean 

the lot size, I’m sorry, in the pool size was in the tens of thousands, 

not in the hundred thousands. Does it make a difference to you? 

And if so, explain to me why it makes a difference. 

Ms. CROOKER. Lot size to me is important just from the standpoint in the sense that the more there is, the more chances of contamination. But I think a standard has to be made. This way, in 

a standard all across, you would know that in that standard there 

was a high present and there was a low present. If there was a 

variation in that, then you know there was something wrong in 

that lot size. 

Mr. SHAYS. So you want standardization and limit——

Ms. CROOKER. Limitation of size, less exposure. 

Mr. SHAYS. OK. Dr. Pierce. 

Dr. PIERCE. I think the manufacturers have been allowing us to 

confuse pool sizes and lot sizes for the last couple of years. And 

we’ve been led to believe that the pool size, which we’ve translated 

into the lot size, is about 15,000 donors for source plasma. They 

have allowed that to occur. They have told us that, knowing full 

well that they mix these pools together, which we weren’t aware 

of, and that their lot sizes are, in fact, much, much higher. So I’m 

coming at this from the perspective of feeling like I’ve been deceived by a number of individuals on this issue. 

Mr. SHAYS. I mean—and you follow this issue very closely. You’re 

not a casual participant in this process, you’re someone who has 

spent a lot of time and—and when did you become aware of the difference between pool size and lot size? 

Dr. PIERCE. I first became aware of it November 1996 when I 

was told by an individual at the FDA that there was a very real 

distinction and that pools were mixed together to form lots. I later 

queried industry by sending a letter to all of the manufacturers, 

asking them what the maximum number of units were, maximum 

number of donors were in their lots over the past 3 years and what 

the average number was. That was when I first got information 

from most of the manufacturers telling me that they were in the 

high, high—well they were in the hundred thousand range, up to 

the hundred thousand range. 

Mr. SHAYS. Well, it’s just like when this committee had a hearing 

on Gulf war illnesses, and we asked about chemical exposure, and 

we were told there was no offensive use of chemicals, therefore 

there was no chemical exposure when there was defensive exposure 

to chemicals; in other words, we blew up the depots and so on. It’s 

just—you feel like you’re in a war game. 

135

Dr. PIERCE. Exactly. You are playing 64 questions, and you just 

have to figure out what the right question is to ask. And it’s an 

iterative process. 

Mr. SHAYS. OK. Dr. Cunningham. 

Dr. CUNNINGHAM-RUNDLES. I don’t think I would be able to 

say——

Mr. SHAYS. The question is——

Dr. CUNNINGHAM-RUNDLES [continuing]. With any scientific certainty how big or how small the pool size would be. I know that 

the major impact right now for large pool size for us is a chronic 

shortage of individual products of gammaglobulin. So the patient 

doesn’t know if they’re going to be able to get their infusion. The 

home care company will cancel repeatedly. 

Mr. SHAYS. Is the larger the pool size——

Dr. CUNNINGHAM-RUNDLES. It’s more likely the recall will affect 

greater numbers of bottles, and therefore we’ll be temporarily 

short-stocked on many different products. And that, to me, is the 

single daily most annoying headache about the large pool size. 

Mr. SHAYS. OK. 

Dr. CUNNINGHAM-RUNDLES. Yes, there is the very strong issue of 

infectivity, and we cannot look past that. It’s also very important 

to say that we also think there’s a lower limit that should be adopted, although the scientific evidence for that is not in. I think we 

should gather it. 

Mr. SHAYS. OK. Is there anything else that the three of you 

would like to say before we get to our next panel? 

Dr. CUNNINGHAM-RUNDLES. There’s one more point I would like 

to make. It hasn’t been brought up in this particular committee, 

but this has to do with the growing use of intravenous 

immunoglobulin for autoimmune diseases. It’s not something which 

is part of my role at the Immune Deficiency Foundation, but as a 

clinical immunologist. You should be aware that the major use 

right now is for these diseases, and not the ones that I’ve discussed 

or we’ve discussed today. We don’t know why it works in those ailments. Many people have suspected that it might be due to the 

presence of illusive secondary antibodies called anti-idiotypic antibodies. If this is the case, then it could be that we would be reducing pool size and eliminating value which we inadvertently got by 

large pool size. So we must somewhere in our thinking process recall that is another usage and perhaps should be thought about as 

well. 

Mr. SHAYS. Thank you very much. I appreciate all three of you 

being here. Thank you. 

Dr. PIERCE. Thank you. 

Mr. SHAYS. We’re going to go to our third and final panel and 

ask for Dr. Richard Davey, Mr. Robert Reilly, Mr. Michael Fournel, 

Dr. Ed Gomperts, Dr. Fred Feldman and Ms. Sue Preston. 

I thank all of our six witnesses for being here. And as you know, 

we need to swear you in, so if I could ask you to stand and raise 

your right hands. 

[Witnesses sworn.] 

Mr. SHAYS. Thank you very much. I appreciate all of you being 

here. This is a very important hearing, very important issue, and 

we don’t pretend to have the answers. We’re wrestling with this 

136

issue, obviously, as you can imagine, and want to make constructive contribution. So it’s nice to have you here. 

I think you can imagine, with six witnesses, I’m going to be a little stricter with time. And I’m making an assumption that you 

have some—in some cases will coordinate your testimony to some 

measure that—OK. I’m looking at some question marks here. The 

bottom line is, if you feel that the issue has been covered by someone else, you can just kind of say, ‘‘ditto.’’ But I am going to be 

strict on the 5 minutes given that we have six witnesses. 

And we’ll start with Dr. Davey, and we’ll go as I called you. Let 

me just say you’re actually sitting the way I called you. 

May I just ask beforehand, it just helps me sort out—we have 

three manufacturers—we have four manufacturers plus the industry representative, and that’s you, Mr. Reilly. 

Is it fair to say that the testimony—have you all shared your testimony? I mean, do you all know what the others are saying? This 

isn’t antitrust. 

Dr. DAVEY. No, we haven’t. 

Mr. SHAYS. But I’m making an assumption that your testimony, 

Mr. Davey, will be slightly different than the other testimony. I’m 

going to give you a little more flexibility with the 5-minute rule. 

I’m just going to say that. 

And, Dr. Reilly, I’ll give you a little more—Mr. Reilly, I’m sorry—

a little more flexibility with the 5 minute rule, giving you’re representing the entire group. But I will be strict with the four of you, 

if that’s all right. That’s the way I will proceed. OK. 

So, if you didn’t get to cover it in your testimony, we’ll try to get 

it in your questions. 

So we’ll start with you, Dr. Davey. 

STATEMENTS OF RICHARD DAVEY, M.D., CHIEF MEDICAL OFFICER, AMERICAN RED CROSS; ROBERT REILLY, EXECUTIVE 

DIRECTOR, INTERNATIONAL PLASMA PRODUCTS INDUSTRY 

ASSOCIATION; MICHAEL FOURNEL, VICE PRESIDENT, 

BIOLOGICALS DIVISION, BAYER CORP.; ED GOMPERTS, M.D., 

VICE PRESIDENT, MEDICAL AFFAIRS & CLINICAL DEVELOPMENT, BAXTER HEALTHCARE CORP.; FRED FELDMAN, Ph.D., 

VICE PRESIDENT, CENTEON CORP.; AND M. SUE PRESTON, 

VICE PRESIDENT, QUALITY & REGULATORY AFFAIRS, ALPHA 

THERAPEUTIC CORP. 

Dr. DAVEY. Thank you very much, Mr. Chairman, Representative 

Towns, and members of the subcommittee for inviting me to speak 

about this important issue of plasma derivative safety. I’m Dr. 

Richard J. Davey. I’m a board certified hematologist, and I’m the 

chief medical officer of the American Red Cross Biomedical Services, and Alternate Responsible Head for FDA License 190 under 

which our blood services program operates. 

The American Red Cross is the largest not-for-profit provider of 

blood services in the United States, collecting almost 6 million 

units of whole blood from volunteer donors annually, or about 45 

percent of the Nation’s blood supply. Blood collected for transfusion 

is made into specific components such as red blood cells, platelets, 

and plasma, which Red Cross distributes to over 3,000 hospitals in 

the United States. 

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In addition to those components, approximately 1 million liters 

of plasma recovered from our volunteer blood donor units are annually processed or fractionated into plasma derivatives. Approximately 800,000 liters are fractionated at Baxter Healthcare’s 

Hyland Division under that company’s FDA license, and approximately 200,000 liters are fractionated by the Swiss Red Cross 

under its FDA license. These plasma derivative products are distributed under the Red Cross label to hospitals, hemophilia treatment centers, and other intermediaries. The Red Cross itself does 

not fractionate plasma. 

Plasma derivatives manufactured from Red Cross include Factor 

VIII Concentrate, albumin, and immune globulins. Red Cross plasma derivatives account for approximately 15 to 20 percent of the 

Nation’s supply and are produced solely from voluntary nonremunerated donations. 

I’ve been asked to comment on the role of plasma pool size in relation to plasma derivative safety and to outline new safety initiatives which will ensure that Red Cross plasma products will continue to be manufactured by state-of-the-art methods. 

Before doing so, it is necessary to distinguish between recovered 

and source plasma. Red Cross plasma derivatives are made from 

voluntary whole blood donations. Plasma obtained when whole 

blood is divided into components is called recovered plasma. In contrast, plasma derivatives made by commercial companies are manufactured principally from plasma obtained by a procedure called 

plasmapheresis. And plasma obtained by plasmapheresis is called 

source plasma. 

The amount of recovered plasma from a unit of whole blood averages 250 milliliters. The amount of source plasma obtained by plasmapheresis averages about 700 milliliters. Therefore, an initial 

pool of recovered plasma contains plasma from more than two to 

three times the number of donations as the same size pool made 

exclusively from source plasma. 

The Red Cross has taken several steps to reduce the number of 

donations in pools of recovered plasma. In early 1996, we directed 

Baxter to initiate and validate processes to ensure that Red Cross, 

AHF-M and IVIg, or Polygam S/D, are derived from pools containing approximately 16,000 liters, or between 54,000 and 60,000 

donations. 

Since mid-1996, the vast majority of Red Cross AHF-M and IVIg 

have been derived from pools containing fewer than 60,000 donations. Importantly, this process ensures that the albumin used to 

stabilize AHF-M and IVIg is also derived from the same pool; in 

other words, material from different pools is not mixed together. 

Efforts will continue over the next year to reduce pool size to similar levels for the production of albumin that’s intended for transfusion. 

These efforts to limit the number of donors in plasma pools will 

continue. Our commitment to safety is demonstrated by our record. 

Over 1 billion units of American Red Cross AHF-M have been infused since the latest generation of AHF-M was introduced in 1988, 

with no reported cases of viral transmission. 

Pool size is only one of the elements to consider in improving the 

safety of plasma derivatives. The Red Cross is actively exploring 

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new methods to inactivate or remove potentially transmissible 

agents from blood and plasma. These methods include gamma irradiation, iodine treatment, and the use of high-efficiency filters. 

These techniques can be effective against both known and newly 

emergent threats to plasma derivative safety. 

Within the next year, the Red Cross will also implement a highly 

sensitive testing technology called polymerase chain reaction, or 

PCR, to detect early evidence of infectious virus in plasma to be 

processed into derivatives. Preliminary studies suggests that PCR 

testing may prevent the transfusion of several hundred blood components each year that may be infectious for hepatitis C. 

I’ve also been asked to address the evidence regarding the potential for transmission of Creutzfeldt-Jakob disease, or CJD, through 

the blood supply and to review Red Cross research in this area. 

The Red Cross takes all potential threats to blood safety and 

plasma safety very seriously, and we’ve moved aggressively to expand the body of scientific information related to CJD. We have 

several research studies underway at our Jerome Holland Laboratory and, as you’ve heard this morning, in collaboration with Dr. 

Paul Brown at the NIH, and also with Dr. Robert Rohwer at the 

Veterans’ Administration. 

The Red Cross has committed over $1 million in research studying possible links between CJD and transfusion, probably more 

than any other private organization. We’ve also taken steps to reduce the likelihood that plasma from a donor subsequently diagnosed with CJD is included in pools for fractionation. 

CJD is a disease, as you’ve heard, of older people, with a mean 

age of incidence, to my understanding, of 67 years old. The Red 

Cross only uses plasma from donors 59 years old or younger for 

fractionation, thus eliminating the age group at greatest risk for 

CJD from plasma pools. Plasma from older donors continues to be 

used beneficially as single donor products. 

The Red Cross is also conducting a CJD lookback study with the 

CDC, as you have heard this morning from Dr. Satcher. That study 

is under the direction of Marion Sullivan at our Red Cross Holland 

Laboratory. She studied 179 recipients of blood transfusions from 

donors subsequently diagnosed with CJD. These recipients have 

been followed for up to 25 years following transfusion. None of the 

recipients has died of CJD, and none has shown any sign of the illness. These data are encouraging. Until there is further convincing 

evidence of nontransmissibility, however, the Red Cross will continue to quickly withdraw plasma derivatives following receipt of 

postdonation information from a donor or a donor’s family about a 

risk of CJD. 

In conclusion, Mr. Chairman, the American Red Cross is committed to providing an adequate supply of blood components and 

plasma derivatives to meet the highest standard of safety. Red 

Cross plasma derivatives are proven to be both safe and effective. 

We’ve taken steps to ensure this safety by reducing the number of 

volunteer recovered plasma donations in pools for fractionation and 

by eliminating plasma from donors in age brackets most likely to 

be affected by CJD. These steps are part of a larger program to improve safety by an aggressive quality assurance program, focused 

research programs, and improved donor screening and testing. The 

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Red Cross takes the issue of blood safety very seriously. We’re 

proud of our record and of our tradition of serving the American 

people. 

Thank you, Mr. Chairman. 

Mr. SHAYS. Thank you, Dr. Davey. 

[The prepared statement of Dr. Davey follows:]

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Mr. SHAYS. Mr. Reilly. 

Mr. REILLY. Thank you. My name is Robert Reilly. I’m the executive director of the International Plasma Products Industry Association [IPPIA]. Thank you for the opportunity to testify today. We 

applaud you and the subcommittee for your work and oversight in 

the complex area of maintaining the safety of our Nation’s blood 

supply. We view ourselves as partners in the effort to give the 

highest possible assurance to people who depend upon plasmabased therapies that safety is of paramount importance to us. 

Chairman Shays, we heard you at the November 1995 hearing, 

on the subject of protecting the Nation’s blood supply when you 

cited the need for leadership. As providers for plasma-based therapies, we are, and must continue to be, leaders in that commitment 

to safety. It is a responsibility that we take very seriously. 

I would like to begin by briefly describing the four main areas 

of focus in my testimony: First, the role of pool size as a component 

in the overall layers of safety. Second, the series of public policy 

issues that examine the fragile balance among safety, availability, 

and efficacy. Third, an industry initiative reducing pool size. Finally, we want to discuss our continuing commitment to make plasma-based therapies safer still. 

During testimony before a 1993 hearing of this subcommittee, 

FDA described five traditional layers of safety. Our industry can, 

and does, go beyond those five basic layers and employs additional 

layers. Each of these layers is a defense against both known and 

unknown agents. Together they form a protective safety barrier 

that is far stronger than each of the component parts. Yet all of 

the parts must be strong in order to provide the best assurance of 

safety. 

Let me summarize our industry programs and how they complement each of the layers of safety. Since its inception in 1991, the 

Quality Plasma Program [QPP] has required that all applicant donors undergo additional AIDS/high risk education and screening. 

The industry has introduced a series of four voluntary standards, 

the first of which requires that no unit of plasma be accepted for 

further processing unless the donor has successfully passed at least 

two health assessments. Plasma from one-time donors will not be 

accepted under this new standard. All companies and facilities 

maintain registries of donors who have been previously deferred for 

a variety of reasons. 

Beyond this, the American Blood Resources Association developed and received an FDA 510(k) authorization to operate the National Donor Deferral Registry. 

In addition to the specific FDA required tests, the industry is in 

the process of adopting Genome Amplification Technology, commonly known as PCR. A substantial improvement in this layer is 

the addition of a 60-day hold of plasma inventory, announced as 

one of the voluntary standards introduced by the IPPIA members. 

This voluntary standard will be fully implemented by year-end. 

Our quality assurance procedures provide a method to constantly 

monitor and further improve the margin of safety of plasma-based 

therapies. For example, QPP has set a standard that measures 

each collection center on an industry-wide basis. 

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Each of our member companies commits a significant investment 

of human and financial resources devoted to this area. In addition 

to the companies—in addition to the viral inactivation/removal procedures, the companies have created a consortium for plasma 

science which is providing additional funding for research focused 

on source plasma pathogen inactivation technologies. 

With respect to notification/recall, the industry is developing a 

well-publicized industry Web page with detailed information on 

plasma-based therapies. In addition, IPPIA is developing a formal 

network of user groups designed to directly contact consumers of 

plasma-based therapies. Together these layers form a web of protection against both the known and the unknown risks we face now 

and in the future. 

In addition, we must examine the balance between safety, efficacy, and availability. We must, however, balance those things 

carefully. 

In regard to product availability, we have to consider the effect 

limiting pool size may have on access to plasma-based therapies. 

The accompanying chart illustrates the effect on the supply of plasma-based therapies of an immediate application of FDA limits on 

donor exposures to 15,000. The chart shows the actual consumption 

for four major therapies for the calendar year 1996. Superimposed 

on each bar is the percent of each product industry would be able 

to produce under this limit. As you can see, the FDA’s suggestion 

would seriously compromise industry’s ability to provide an adequate supply of these life-saving therapies. The efficacy of the 

therapies, how well they perform, is important——

Mr. SHAYS. I’m going to interrupt you a second. If I forget to ask 

that question, I’ll need that explained——

Mr. REILLY. Yes, sir. 

Mr. SHAYS [continuing]. As to why that’s the case. 

Mr. REILLY. The efficacy of the therapies, how well they perform, 

is an important element in our consideration of the impact of pool 

size. That is why the effect of any changes in pool size on the efficacy and quality characteristics of these therapies must be aggressively monitored and studied to ensure that plasma-based therapies remain effective in treating the patients who rely upon them. 

Industry has taken an initiative to reduce the pool size. The industry recognizes the role of donor exposure and pool size in balancing the needs of product safety, availability, and efficacy. We 

have worked diligently to develop an industry effort to limit the 

number of donors to which patients are exposed. Our IPPIA proposal recognizes that, from data that we have collected, that donor 

exposures of some therapies can exceed the 100,000 level. We’re 

now confident that we can improve that situation. The IPPIA companies have committed to developing and implementing enhanced 

manufacturing practices for the major therapies. This will have the 

immediate impact of at least a 40 percent reduction in such levels 

of donor exposure. 

We believe that we can achieve this without creating product 

shortages, without major plant reconstruction or renovation, and 

without a lengthy FDA process that would otherwise delay implementation of these—of this initiative. Where, long-term, our members are committed to work with FDA product by product, company 

147

by company to further reduce the risks associated by donor exposure. That may require amendments to product licenses, plant reconstruction, or plant renovations. The industry will report on the 

continuing improvements being made in this area. 

What we are pursuing beyond our pool size initiative is a comprehensive plan that builds upon the seven layers of safety that I 

have just mentioned. That is our goal, our challenge and commitment. We will in the future verify the successes of our efforts and—

through accurate reporting measurements. 

People who depend upon plasma-based therapies for their health 

and their very lives can be reassured the industry is working diligently that those therapies are safe, available, and effective. 

We commend you, Mr. Chairman, for your leadership in provoking dialog on this important issue which has resulted in improvements in the Nation’s blood supply. Thank you. 

Mr. SHAYS. Thank you. 

[The prepared statement of Mr. Reilly follows:]

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Mr. SHAYS. Just since I had raised it, I’m not aware that anyone 

has suggested limiting the pool size to 15,000. I mean, this will be 

interesting dialog. But it’s not something I’m aware of that is 

being——

Mr. REILLY. The 15,000 number is a result of a recommendation 

from FDA discussed at an earlier blood products advisory committee meeting. 

Mr. SHAYS. OK. That they would limit it to 15,000? 

Mr. REILLY. Yes, sir. 

Mr. SHAYS. OK. Do I pronounce your name Fournel? 

Mr. FOURNEL. Fournel. 

Mr. SHAYS. Thank you. I think I didn’t pronounce properly the 

first time. Mr. Fournel, thank you. 

Mr. FOURNEL. Mr. Chairman, and members of the subcommittee, 

I would like to thank you on behalf of Bayer Corp., for inviting us 

to return to these hearings. We commend you for the leadership 

you have shown in your continuing efforts to safeguard our Nation’s blood supply. In 1995, Bayer pledged to work with you and 

the other members of this subcommittee. Today, we reaffirm this 

commitment. 

For the past 20 years, I have conducted research and development of plasma products that are used to manage serious illnesses 

that in many cases respond only to the proteins found in human 

plasma. 

Mr. Chairman, at Bayer, the development and application of new 

technologies to improve safety for patients is at the very core of our 

business. Since my last appearance before this committee, Bayer 

has continued to move forward. I would like to describe four examples of these efforts, which, together, have the potential to enhance 

the margin of safety for the patients who use our products. 

First, Bayer is developing genome amplification technology for 

use in detecting viral genomes in individual plasma donations. We 

are filing an IND to use a preliminary chain reaction, or PCR, test 

for the detection of hepatitis C virus in plasma. 

Our initial research shows that PCR will help to reduce the window period during which infection may be present, but detectable 

levels of viral antibodies or antigens have yet to appear. We expect 

that full use of PCR testing will reduce potential viral loads, which 

in combination with our validated clearance studies will provide an 

additional safety margin for our products. 

Second, because first-time donors have a higher probability of 

viral infection than repeat donors, Bayer has recently placed special restrictions on plasma collected from them. We destroy all plasma from such donors if they do not return to make a second donation. This means that we will accept plasma only from qualified repeat donors. 

Third, Bayer has established an inventory hold program for all 

plasma units. We will store plasma for a minimum of 60 days before use. Should a donor on a repeat visit center to a plasma center 

fail our testing or screening procedures, we will retrieve and destroy all previously qualified units of plasma from that donor in 

our inventory. This program will reduce the possibility of a window 

case of hepatitis or HIV from contaminated plasma supplies. 

169

Fourth, the subcommittee has expressed concern about potential 

emerging infectious agents, particularly Creutzfeldt-Jakob disease. 

Bayer continues to invest its major scientific efforts to address 

these challenges. Our CJD work specifically centers on development of assays capable of detecting the potential, if any, for transmission of CJD in plasma products, process clearance studies to 

identify process methods with the greatest ability to remove pathogens that may be present in plasma, and potential transmission 

risk studies to define the clearance requirements, if any, for processing steps. 

The subcommittee has also asked Bayer to provide views on regulating the size of plasma pools, what I will call donor exposure in 

a final container product. Bayer agrees with the preceding testimony by the industry association. For most products, Bayer currently outperforms this commitment and will continue to strive to 

reduce donor exposure in all of our products. 

As you know, this is a complex issue which I will illustrate with 

an example of a product, Prolastin, for people with a genetic deficiency associated with emphysema. Successful therapy requires 

weekly injections of Prolastin. Thus the health of these patients depends not only on this product’s safety, but also on its availability. 

To assure that Prolastin is available to as many patients as possible, we now use about 60,000 donor exposures per final container 

product. There are several reasons for this. First, a unit of human 

plasma contains only a small fraction of the protein missing in 

those who use Prolastin. If everyone in this room donated plasma 

today, we could provide only a 1-month supply of this treatment for 

one patient. 

Second, scarce resources require efficient processing. Bayer relies 

on the economies of large-scale pool fractionation to obtain as much 

product as possible. The FDA has suggested a 15,000 donor exposure limit. Given the constraints of the technology and our current 

license for processing Prolastin, we estimate immediate implementation of this limit would cut our product availability in half. Further, making this reduction without breaking the product lifeline 

would require custom-built equipment, validation trials, and FDA 

approval of all changes in manufacturing processes. We estimate it 

would require several years to accomplish these changes. Meanwhile, we expect that our current efforts to improve yields from 

plasma, if successful, will achieve similar reductions in donor exposure without limiting supply. 

To fully demonstrate the science and vigilance behind our plasma 

products, I would like to invite the subcommittee members and 

staff to tour Bayer’s facilities and fractionation plant near Raleigh, 

NC. 

We believe, Mr. Chairman, that a rational approach toward improving product safety, which integrates both effective material 

management to reduce donor exposure and measures like those I’ve 

outlined today, affords the best opportunity to achieve our common 

goal of reducing safety risk to the patients who depend upon these 

life-saving therapies. 

Thank you. 

Mr. SHAYS. Thank you very much. 

[The prepared statement of Mr. Fournel follows:]

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FOUR AREAS OF PROGRESS SINCE 1995 HEARINGS


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Mr. SHAYS. Dr. Gomperts. Am I saying your name correctly? 

Mr. GOMPERTS. Yes, you have. 

Mr. SHAYS. Thank you, sir. 

Doctor. 

Dr. GOMPERTS. Mr. Chairman, members of the committee, I’m 

Dr. Edward Gomperts. I am the medical director of the Hyland Division of Baxter Healthcare Corp. In addition, I’m on staff in the 

Division of Hematology Oncology at the Children’s Hospital of Los 

Angeles. 

Baxter firmly believes that the task of ensuring that our patients 

have access to the highest quality therapies requires that the entire system of producing these therapies be subject to continuous 

improvement and critical examination. No one aspect of the process 

alone can ensure safety. That is why Baxter supports research and 

development focused on new processes for viral inactivation, and 

replacing donated proteins with synthesized proteins, and on developing cures for inherited conditions. 

In particular, through our Aegis project, Baxter has recruited a 

panel of world-class scientists to work with our staff to scout out 

emerging pathogens and devise strategies to prevent introduction 

of such pathogens into our products. 

In today’s discussion, I would like to focus my comments on three 

areas: safety, pool size, and Creutzfeldt-Jakob disease. Let me 

begin by saying that plasma derived therapeutics are safe. However, speaking as a physician, the reality is no useful medicine is 

without risk. 

We at Baxter focus on patient welfare and strive to achieve maximum safety and efficacy for our products. We have a comprehensive safety and quality assurance program, which is detailed in my 

written testimony. We try, we learn, but, at times, we make mistakes. When we err, our staff, FDA, our competitors and this committee and outside critics keep our attention on the target of patient welfare. 

Before changing our well-established processes, however, we 

must guard against making choices for the wrong reasons. Science, 

reason, and patient welfare should dictate what we do, not political 

pressure, not media scrutiny, not a desire for profit. 

Baxter has been asked to re-examine its production processes 

and determine whether the number of donors per pool has a relationship to safety. This is a very complex issue. Baxter agrees to 

take steps as outlined in my written testimony to decrease the total 

number of donors who contribute to the finished product. We believe, however, that pool size reduction is not a panacea. Moreover, 

there is a compelling need for these therapies. 

Currently, our facilities are operating 7 days a week, 24 hours 

per day, and there is still unmet demand for certain products. Even 

under the most favorable conditions, additional manufacturing facilities take upwards of 3 to 5 years before they are permitted to 

make a meaningful contribution to overall supply. 

An international crisis resulting in conflict or a major disaster 

could result in demand exceeding the current supply. Therefore, we 

want to caution against ill-advised decisions on manufacturing 

techniques which could skew product supply and alter safety and 

180

efficacy needed by one group of patients to the detriment of another 

set. 

In reducing pool size, we anticipate working closely with the 

FDA to develop and implement a strategy that would allow us to 

appropriately implement practical pool size limitations which will 

not undermine the important objective of ensuring access to an 

adequate supply of plasma-based therapies. 

Now, let me turn to the issue of CJD. Extensive worldwide analysis of the transmission of sporadic CJD and its variant continues 

to point toward food contamination, and the ingestion of contaminated material is the key medium of transmission for a yet-to-beidentified infectious agent. In contrast, epidemiologic studies, ongoing and completed, have not today identified a blood mediated 

transmission mechanism. Unfortunately, I fear that the theoretical 

risk of blood transmission is receiving more attention in this country than the documented potential for food contamination. 

An understanding of the potential risk of blood transmission will 

require completed, analyzed, peer-reviewed data for multiple carefully conducted and appropriately controlled animal studies. 

Through our Aegis project, my own company is advanced in the design of a research study to be carried out on primates as well as 

mice. Yet, in these studies, time is a serious problem. From development of a scientifically valid research plan to final results takes 

years. 

In summary, I would like to affirm that Baxter utilizes the best 

scientific research and newest technologies to develop and improve 

our therapies and products for saving and enhancing patients’ lives 

worldwide. We follow a policy of critical examination of our processes and continuous improvement. We remain committed to an 

open dialog with patients, treaters, the FDA, and Congress on our 

responses to scientific and medical changes. Thank you. 

Mr. SHAYS. Thank you, Dr. Gomperts. I appreciate both your testimony and the previous testimony being within the 5-minute limit. 

Thank you very much. It’s very helpful testimony. 

[The prepared statement of Dr. Gomperts follows:]

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Mr. SHAYS. Dr. Feldman. 

Mr. FELDMAN. Is this OK? 

Mr. SHAYS. I think it will do. Let’s see how it sounds. 

Mr. FELDMAN. Mr. Chairman, and members of the subcommittee, 

my name is Fred Feldman, and I’m vice president of Preclinical Research and Development for Centeon. I’ve dedicated my efforts for 

more than 20 years to the development of new and improved therapeutics from plasma, and I’m happy to contribute to the deliberations of this committee on the topic of pool sizes. 

This is without doubt a highly specialized area. I have endeavored at every opportunity to assist several blood product advisory 

committees as well as the staff of this committee in understanding 

this area and hope that I can be of assistance today as well. 

This is not a trivial manufacturing issue, and a decision to constrain manufacturing to a substantially reduced total pool volume 

can have the effect of reducing the total therapeutic product supply. 

Mr. Chairman, in the interest of time, I ask that the full written 

testimony which I have provided be included in the record. 

Mr. SHAYS. Yours will be, as we will as all the other witnesses. 

Mr. FELDMAN. Thank you. 

Appendix 1 to my full testimony provides a report describing the 

impact of plasma batch sizes, described in liters, on the manufacture of our Factor VIII Concentrate. It was motivated by reported 

concerns that to significantly enhance viral safety for chronic users, 

a very drastic reduction of process volumes and batch sizes would 

be needed, and it explored the impact of large reduction of process 

batch volumes. 

The report shows that for such a reduction in batch size, that 

such a reduction greatly increases the complexity of production and 

places a greater burden on GMP and quality assurance, while reducing usable product from existing plants by huge amounts. 

It can be seen in the poster of table 9 from this report that 

changing from production batches at 15,000 liter equivalents to 500 

liter equivalents could decrease product supply over 96 percent. 

From the throughput capability of our plant, we could serve the 

needs of over 4,500 people per year with hemophilia A. We would 

be reduced to being able to serve the needs of only 160. 

As an industry, however, our products serve a wide range of the 

public. We assessed the impact of batch size on the other products 

we manufacture using the Cohn fractionation method. Deliberations on risks and disadvantages of changing manufacturing of 

human albumin and human intravenous gammaglobulin are detailed in the second appendix to this report as well as opportunities 

for improvement in these processes. 

As we have participated in and learned from this dialog, we must 

consider not only benefit for the chronic user, but also benefits 

which could result to the patient who only occasionally receives our 

therapy. 

We believe that it is incumbent upon manufacturers of critical 

drugs not only to continue to supply product reliably, but to look 

for improvement opportunities. Although we believe that substantial changes to process volumes are difficult to achieve, potentially 

disruptive of supply, and even in instances frought with risk of reVerDate Jan 31 2003 09:52 Apr 14, 2003 Jkt 086131 PO 00000 Frm 00198 Fmt 6633 Sfmt 6602 W:\DISC\45902 45902
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duced safety, we have asked where there are opportunities within 

the existing fractionation system, where improvements in control 

and donor exposure can be made without creating significant, regulatory, or supply disruptions, and where risk reduction benefit 

could result at least to that patient infrequently exposed to pooled 

plasma derivatives. 

We have identified opportunities for Centeon to reduce the total 

donor exposure from a given batch and have initiated the nine 

point program of improvement shown on the poster. These specific 

initiatives can decrease the maximum number of donors in our 

processing and reduce the overall variation in the number of donors associated with any given batch of therapeutic. The specific 

process-by-process changes as well as the equipment-related opportunities which may offer other means for improvement will be reviewed with FDA to ensure compliance with cGMP and control of 

quality assurance before changes are initiated. 

We would hope that the committee recognizes that such change, 

such validation, takes not only resources, but takes time, and that 

even seemingly trivial changes in production equipment require us 

to develop assurance that our processes remain in total control, 

that our changes do not impact the stability of our therapies, nor 

adversely impact their safety, efficacy, or availability to the patient 

community. 

Let me conclude by saying that we continue to dedicate our R&D 

resources to understand where other threats to safety might originate and to design and implement yet further barriers to these 

threats, through increased surveillance using an outside panel of 

top worldwide experts, through working to develop and improve 

tests for donors and products, and through efforts to provide even 

more choices for powerful separation and inactivation method. 

Mr. Chairman, thank you for allowing me to appear here today, 

and I’m happy to answer whatever questions I can from the committee. 

Mr. SHAYS. Thank you very much, Dr. Feldman. 

[The prepared statement of Mr. Feldman follows:]

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Mr. SHAYS. Ms. Preston, and then we’ll get to questions. 

I would like to note for the record that we’re joined by the truly 

distinguished chairman of our committee, Mr. Burton, and we appreciate his being here. I was thinking as he walked in he thought, 

what am I getting myself into here, bringing out one chart after 

another. This is what one of your committees does, Mr. Chairman. 

Ms. PRESTON. Mr. Chairman, and members of the committee, ladies and gentlemen, I am Sue Preston, vice president of Quality 

and Regulatory Affairs, Alpha Therapeutic Corp., located in Los 

Angeles, CA. We process human plasma into life-saving treatments 

for patients with immunodeficiency, hemophilia, and trauma victims. Immunoglobulins, Factor VIII, Factor IX, and albumin are 

some of the products that are licensed by the Food and Drug Administration. We have additional biologic products and drugs in 

clinical trials. Alpha Therapeutic Corp. markets products in the 

United States and in over 50 countries worldwide. 

I would like to talk to you today about the multiple measures 

that our industry and Alpha Therapeutic Corp. have incorporated 

to ensure safe and effective products. Reduction in the risk of donor 

exposure, sometimes referred to as pool size reduction, is only one 

measure of many measures, some of which are more than effective 

and have a broader impact. The chart depicts many of the voluntary and mandatory safety measures incorporated in our processes. 

Beginning with the population of donors, we voluntarily have implemented industry quality plasma program standards for viral 

marker testing. Each and every donor from whom we collect plasma, we have an extensive medical screening and testing program. 

The FDA has regulations which require asking the donor about 

high-risk behavior, medical history, and CJD. We have voluntarily 

added several additional requirements, such as an age limit less 

than 60 years, and deferring donors with a history of corneal transplants to further preclude the risk of CJD. Every donor is screened 

against the National Donor Deferral Registry for a history of positive viral marker testing. Furthermore, we conduct drug screening 

as part of our donor acceptance program. 

Every donor is examined at each donation for health status, and 

samples of blood are tested for normal levels of protein and hemoglobin as required by regulations. Alpha Therapeutic Corp. performs physician-supervised extended medical screening and adheres to the industry voluntary standards for accepting donations 

from only qualified donors; that is, those with two or more donations with all negative viral marker tests. 

Over 95 percent of our donations come from repeat donors. These 

donors are well known to our plasmapheresis medical staff, as we 

see these donors several times each month. Our donors in plasmapheresis centers are part of the communities in which they’re located. 

The next step in the process is testing samples from each and 

every donation for the presence of viral markers, such as hepatitis 

B antigen, hepatitis C antibodies, human immunodeficiency virus 

antigen, and antibodies. 

At our Memphis laboratory, we test for the level of liver enzymes 

so that donors with liver disease are deferred appropriately. We 

253

have a double identification system on our plasma collection bottles 

and our sample tubes so that sample mixups with test results are 

virtually eliminated. We adhere to the industry standards with respect to holding plasma units to assist in retrieving units from donors who subsequently test positive for viral markers. We maintain 

backup samples of our donations if additional testing is necessary. 

Alpha Therapeutic Corp. has implemented many voluntary measures such as testing for viral markers in minipools over and above 

the individual units testing. For instance, we utilize a different test 

kit for detection of HIV antibodies to exclude test errors. We have 

begun clinical trials on the ability of the most sensitive test method 

available, polymerase chain reaction, in minipools to detect viral 

nucleic acid material from HIV and HCV. 

Our manufacturing process begins with the voluntary testing of 

samples from our plasma pool after all of the donations are pooled 

for hepatitis B antigen and hepatitis C antibodies and with two different test kits for the absence of HIV antibodies. 

We have already incorporated steps to reduce the donor exposure 

in the final products as outlined in our IPPIA presentation. 

For our products, safety is a combination of many factors, but the 

most important for currently known pathogenic acts and possibly 

for those that are unknown remains our manufacturing process 

itself. 

The FDA mandates the viral inactivation step of heat treatment 

or pasteurization for albumin products. In each of our processes, we 

incorporate steps to remove or inactivate viruses such as solvent 

detergent treatment that inactivates HIV, HBV, and HCV very efficiently. 

Other steps have been added to reduce the potential for other 

types of viruses such as hepatitis A or parvovirus. We are exploring 

a step with some preliminary information on CJD infectivity removal. However, much additional research will be necessary to confirm these very preliminary results. 

During the course of the manufacturing process, samples are 

taken for testing. Samples of the final container batch are subjected to a large battery of tests. Sterility, potency, purity, safety, 

and stability are mandated by the regulations or in our product licenses. We have implemented voluntary testing for hepatitis B 

antigen and antibodies for hepatitis C and HIV. 

Since March 1996, Alpha Therapeutic Corp. has also tested samples from each final container batch for the absence of viral nucleic 

acids by polymerase chain reaction, for hepatitis A, hepatitis B, 

hepatitis C, and HIV. Only negative lots are released for distribution. 

Alpha Therapeutic continues to monitor the product safety once 

it leaves our doors through marketing surveillance. We report adverse events promptly to the FDA. We conduct ongoing clinical 

trials with our products to continuously monitor the safety and efficacy as we improve processes. We seek and receive constant feedback from recipients of our products. In the event that we have discovered subsequent to product distribution a potential risk, we 

work with our customers, consumer groups, and regulatory agencies to take the appropriate actions to eliminate the risk through 

254

quarantine or recall notifications. We support the initiatives as described in the IPPIA testimony with respect to notification. 

We will never rest in our vigilance for safety. Our scientists work 

tirelessly to develop improved methods for ensuring safety through 

better manufacturing processes or improved tests. We cooperate 

with other corporations to develop more sensitive methods for detecting disease. We participate in the research consortium for plasma science for developing better viral inactivation processes. We 

encourage our industry organization to increase standards of excellence. We continue to work with regulatory agencies around the 

world——

Mr. SHAYS. OK. 

Ms. PRESTON [continuing]. To ensure we can supply the most 

safest and efficacious products. Thank you. 

Mr. SHAYS. Thank you. 

[The prepared statement of Ms. Preston follows:]

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Mr. SHAYS. Let me just say for the record so we don’t have to 

dispute these issues, this committee believes and the Department—

HHS believes that we have the safest blood supply in the world. 

This is not an issue. It’s also not an issue of whether you all have 

made significant strides—the industry has made significant strides 

in the last few years to improve the quality of the blood supply. I 

think we all acknowledge that in the 1980’s, we just weren’t as 

vigilant as we should be. HHS acknowledges it wasn’t as vigilant 

as it should be in monitoring the safety of the blood supply. 

The issue that I am—I know, Mr. Chairman, you have some 

questions. And you’ve given the option of whether I can just go first 

and so on, because I need to leave. I have an appointment at 1, and 

Mr. Snowbarger will come in to Chair the rest of the hearing. So 

I just want to focus in on a few issues, and I don’t need a response 

from everyone if you all agree with the response. I want to just 

focus in on the size of the pools, the lot size, and I just want to 

understand certain elements of it a little better. 

First off, I will say to you that both this committee and the FDA 

were surprised by focusing on the pool size and then not focusing 

in on what I guess becomes the lot size, when you take different 

pools and then you combine these pools, and you end up with a lot 

size that can get into the hundreds of thousands. And so I’m just 

going to say to you that that was a surprise to this committee. And 

we need to understand its implications. 

First, explain to me, and I’ll go with you, Mr. Reilly, the difficulty of having a smaller pool size, whether it’s 30,000 or 15,000. 

Why are smaller pool sizes costly and reduce supply? 

Mr. REILLY. Let me break that into two or three parts perhaps, 

and then my colleagues might want to chime in with some additional detail. 

First of all, with respect to costs, let me say that the Association 

has not dealt with the cost question at all. We’ve tried to deal with 

the size of the pools as purely a safety question. There can be little 

question that there is a cost. At this point, we simply have not 

made an assessment of that issue. 

What we’ve tried to do and what we’ve said to you today is that 

we have determined, after a great deal of discussion, that there are 

opportunities for us to immediately reduce the size of the pool off 

the highs that have been reported. That means at least a 40 percent reduction off the hundred thousand. 

So what we’re saying is, clearly, we are going to set a ceiling 

then at 60,000 for the major products that we have described for 

you. So I think that is an important point that I want to reiterate. 

I want to make a second point, and that is throughout the discussion of pool size, there has been confusion about the unit of 

measure. That confusion has led to, I think, a sense that perhaps 

people are not being forthright in the discussion or perhaps are 

being deceptive. I would like to try to dispel that because I genuinely do not believe that that’s true. 

Mr. SHAYS. You have your own agenda right now, but that’s not 

my question. And with all due respect, my question is just trying 

to understand why, when you reduce the pool size, we create inefficiencies and we reduce supply of product. That’s what I’m trying 

to understand. 

395

Mr. REILLY. Let me try to answer that in two ways. 

Mr. SHAYS. And someone else can. Maybe I should go to a manufacturer. 

Mr. REILLY. If you are looking for a highly technical answer, then 

I would defer to a manufacturer. Maybe I can answer it on the 

basis of the comment that you made earlier, which was to say you 

wanted to come back and look at the chart we provided. So perhaps 

if we look at the chart again, I can make one point, and then I can 

allow one of my colleagues to come back with more of a technical 

response. 

Can we put that chart back up on the easel? 

When we made this chart, the goal was to make an assessment 

of the consequence if we went to full implementation of the FDA’s 

proposal of 15,000 liters which had been suggested in the previous 

BPPA. Each of the companies internally looked at their systems, 

and they acknowledged to each other in the conversations that we 

had of trying to assess what was—what opportunities were here, 

that within their systems, their systems were very different. And 

those differences made simple explanations very hard. 

What we attempted to do was have each manufacturer look at 

their own systems and assess what would happen if they fully applied the proposal that FDA had put forth at a previous BPPA 

meeting. We then turned that data over to an outside third party 

along with the consumption data for 1996 and said, if, in 1996, the 

full implications of this standard were to be applied with all of the 

elements that the individual companies have to take into consideration, what would be the consequence on supply? And the consequence, as this chart shows, is that there are substantial, then, 

reductions over what——

Mr. SHAYS. Mr. Reilly, I don’t mean to be rude, but I’m with you 

there. I just want to know why. Just tell me why. That’s all I want 

to know. 

Dr. Feldman. 

Mr. FELDMAN. Maybe I could have a try at it. I think there are 

a number of questions, Mr. Chairman, and I’ll try to focus on trying to answer what’s the problem in making it smaller, maybe 

making it more often, what are the difficulties there. I think there 

are potentially several different answers. 

Now, one answer is it depends upon what range you talk about. 

If you’re talking about from very large, like you quoted 400,000 

down to 15,000, that’s one set of answers. If you talk about making 

it small to try to improve the risk of potential exposure below that, 

there’s another set of answers. But I’ve tried to detail——

Mr. SHAYS. You know what I’m going to do, I’m going to cancel 

my next meeting. I’m going to go to you, Mr. Burton. I’m sorry. I’m 

going to stay as long as I have to stay. Why don’t you start, Mr. 

Burton. 

Mr. BURTON. I won’t take much time, Mr. Chairman. I was interested in the CJD issue. Before I get to that, though, is there any 

attempt being made to come up with synthetic supplies for these 

various problems for hemophiliacs or other diseases? 

Mr. FOURNEL. Sure. There is a recombinant form of Factor VIII 

that is available. 

Mr. BURTON. I can’t hear you. I’m sorry. 

396

Mr. FOURNEL. There is a recombinant form, recombinant DNAderived form of Factor VIII, for example, and recently for Factor IX 

deficiency, that’s available from several companies. So there are efforts where possible. But there are reasons why that can’t be done 

for all products. 

Mr. BURTON. With that shortfall that the chairman was just talking about, because of the pool size, is that something that can be 

overcome with the development of synthetic products? 

Mr. FOURNEL. Potentially in some, by not all cases. 

Mr. BURTON. How long would that take? 

Mr. FOURNEL. Well, it’s quite a long process, of course, to develop 

products. But, for example, a recombinant Factor VIII is available 

now in the United States from two or three companies. And it is, 

in fact, impacting the market significantly in terms of providing 

this therapy as an alternative to the plasma-derived form that you 

saw. 

Mr. BURTON. So the problem that the chairman was talking 

about at some point in the future might very well be overcome——

Mr. FOURNEL. Potentially. 

Mr. BURTON [continuing]. For that safety factor because of the 

synthetic products. 

Mr. FOURNEL. For that case, yes. 

Mr. BURTON. OK. Now, getting back to the CJD quickly. Is there 

any scientific evidence to support that conclusion that it’s spread 

through blood transfusions? 

Dr. GOMPERTS. May I answer that one? From the epidemiologic 

point of view, studies were already mentioned by—carried out 

through the American Red Cross and the Center for Disease Control. Studies in Australia, Germany, United Kingdom that have 

been completed as well as those that are ongoing showed that this 

agent, whatever it is, because we don’t know what is causing this 

disease, is not being transmitted or cannot be detected to be transmitted through the blood supply or the products that we make. 

However, there are experiments that have started. They take many 

months, and some cases years, to do. And these experiments, the 

very first indication is that it is possible under some circumstances 

in mice or hamsters for transmission to occur. 

Mr. BURTON. So it’s not conclusive yet. 

Dr. GOMPERTS. It will take some years to finalize. 

Mr. BURTON. OK. Do scientists know how it’s spread in humans? 

And is there any reliable way to diagnose it? 

Dr. GOMPERTS. The methods of spreading have been documented 

to be, in my opinion, two forms. The one is through the food supply. 

And this has been documented through the unfortunate episodes in 

the United Kingdom and also in other countries in Europe, the 

‘‘mad cow disease’’ situation. 

Mr. BURTON. And the diagnosis? 

Dr. GOMPERTS. I beg your pardon? And the diagnosis is made by 

a clinical evaluation. There is no laboratory test. And also at autopsy or biopsy of brain tissue. 

Mr. BURTON. So it’s mainly after the person has been——

Dr. GOMPERTS. Impacted by the disease, exactly. 

Dr. DAVEY. If I may add, there’s also some evidence that the disease—there is evidence that the disease has been transmitted by 

397

transplantation of dura matter, which is a covering of brain, and 

as well as by human-derived pituitary growth hormone, which was 

used in the 1980’s and is not used anymore. So those are risk factors for transmission of the disease. 

Mr. BURTON. OK. Is there anything that the blood products industry can do to guard against the possibility that CJD is transmitted through blood products? 

Dr. DAVEY. I think Dr. Gomperts has already touched on that—

some of those issues, Mr. Burton. 

In the Red Cross, we are very concerned about this issue; and 

we do, as I believe I outlined in my testimony, have several research projects under way. We are working with Dr. Brown at the 

NIH, looking at transmission studies to see how the agent is transmitted in an animal model. 

We are also anxious to look at inactivation of the virus and 

whether or not it can be filtered out of blood and blood components, 

and we have active research with Dr. Robert Rohwer at the VA. 

We also have epidemiological studies looking at recipients who 

have received products from donors subsequently diagnosed as CJD 

and have an extensive look-back study. Those data, as I mentioned, 

are encouraging and support the conclusion, I think, of the moment 

that we don’t have good evidence that this disease is transmitted 

by transfusion. 

Mr. BURTON. I don’t mean to be redundant, because I know some 

of you probably covered some of this in testimony before I got here, 

so I apologize for that. 

How many cases of CJD were reported in 1996 in the United 

States? And I am sure that doesn’t compare at all hardly with England, for instance. But can you give me a number? I don’t recall. 

Dr. DAVEY. I can’t give you the exact number for 1996, but the 

incidence has been very stable at one case per million per year. So 

we are experiencing about 250, 260 cases per year in the United 

States. That incidence has held steady since the disease was first 

described in the 1920’s. 

Mr. BURTON. And, I presume, that, in all of your views, that the 

industry is doing everything they can possibly to make sure that 

that is minimized and the public is protected? 

Mr. REILLY. Well, what has been described is a variety of research initiatives that are under way to assess some of the unknown, but clearly that is what we are dealing with here, is a great 

deal of unknown. What we have learned over the years is that, in 

areas of the unknown, there is a pretty good consensus that says 

you incrementally deal with what you do know and find your opportunities. 

What we are doing at the collection end is to impose donor criteria that allow us to identify potential donors who might have 

some risk and remove them from the donor population. 

At the other end, in the product area, what we do is when, postdonation, we learn information that suggests that a donor was 

somehow at risk and not captured at the donation period, then we 

have been taking what I think most people would consider a very 

conservative strategy of retrieving product from the marketplace 

when those kinds of occurrences happen. 

398

Mr. BURTON. Mr. Chairman, thank you very much for your hospitality. I appreciate it. 

Mr. SHAYS. Any time. We appreciate your being here. 

Mr. Towns. 

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

Could you help me very quickly? What is the distinction between 

pool size and lot size, as brief as possible? I need some help. 

Mr. FELDMAN. Let me try, and I will try to be brief in my answer. 

The pool size in its strict test definition is how many donors start 

the process going. But because of combinations of fractions in order 

to make sufficient quantity of drug, at the end of the process the 

pool size is represented in a final vial from the batch in terms of 

all of the donors that have been encountered by processing from 

the beginning. 

The lot size, the batch, is the final product that is released for 

distribution, that has gone through a combination of steps along 

the way. 

Mr. SHAYS. Could I just try to answer, and you tell me if I am 

right? You have pool A, pool B, and pool C. A lot can be a combination drawing from pool A, pool B and pool C. 

Then you have this lot that you disseminate—you draw from all 

three different pools; and then, in effect, if you had a pool size of 

50,000, you would have a pool size of 50,000 here and here. It 

comes down to one lot distribution combining these products, and 

you end up with 150,000 of donors to participant donors. Is that 

an accurate description? 

Mr. FELDMAN. That is a good example of how a batch can be put 

together, yes. But the donors that contribute to that are a function 

of the fractions that are combined, as you have stated, and a function of the stabilizer that is added as well. 

Mr. SHAYS. Still, if you have three pools combined into one lot, 

you add up all the donors to each pool. 

Mr. FELDMAN. That is right. 

Mr. FOURNEL. Don’t forget, you can also have repeat donors. It 

doesn’t mean you have 150,000 donors. 

Mr. SHAYS. You would have some reduction factor, that is true. 

Mr. TOWNS. That leads me to my next question. Would members 

of the industry be able to conduct a consumer-level recall program? 

Dr. DAVEY. That is an important question, and I think we heard 

some very powerful reasons that we need to do better at notifying 

the patients when a recall is in effect. 

In the Red Cross, we have been concerned about this because we 

feel the system is inadequate. I can review briefly what we do 

when a recall occurs. 

We notify as quickly as possible the NHF, hemophilia treating 

centers, hospitals, other intermediate providers as quickly as possible with information about a recall. We also are very attentive to 

education programs for hemophilia treaters and their patients 

about recalls and what they mean. 

We support the right of a patient to know as soon as possible 

when a recall takes place; and, therefore, we have supported regulations that would require intermediate distributors of our products 

399

to record lot numbers. We feel that is an important step for us to 

trace the material to the end user. 

So we feel that this is an important issue, and we need to do better. 

Dr. GOMPERTS. Congressman Towns, the products that we are licensed to manufacture and market are prescription products, so 

that we are not permitted to know the end user. The physician 

writes the prescription for his or her patient. So the communication 

between my company and the specific end user, the patient, is not 

appropriate. It is not permitted. 

The issue of recall through to the end user is an important one. 

This has to be addressed satisfactorily to the end user, ultimately 

the end user patient welfare, because that is what we are all about. 

So that activities are ongoing, communication is ongoing, in trying 

to resolve this issue; and these communications are between industry and between the FDA and also the representatives of the Hemophilia Foundation. 

Mr. TOWNS. Mr. Chairman, if I am understanding this correctly—I really have a concern, because you are not telling me that 

you have any way to tell whose refrigerator this is in or whose 

house this is in. I think that is the bottom line; and I think that—

as Dr. Davey indicated, I think that is where we have to go. I appreciate your comments, but that is a real concern. I think, Mr. 

Chairman, we need to look at this very carefully. 

Yes, Mr. Reilly? 

Mr. REILLY. I think we share that concern. You know—and I 

don’t want to use this a lot—but we are in a very complicated area. 

We make a variety of products that are used by a diverse variety 

of patient populations. 

In some circumstances, it is very practical for us to think we are 

going to be able to identify the groups who effectively represent 

those patient populations and know them quite well. In other 

cases, we distribute products in which that is not as easy to do. 

For example, with our albumin product, which is used in burn 

treatment, it is frequently not very practical to get right to a user 

group who would represent that audience. 

What the industry has attempted to do is we, in conversations 

with the Food and Drug Administration and the Blood Products 

Advisory Committee, recently acknowledged that we thought there 

were some things that could be done immediately or quickly without a lot of barriers toward improving the communication; and 

there were other things that perhaps needed more discussion and 

ultimately might need laws or regulations to deal with the barriers 

that are there. 

So what we have suggested is that we would undertake the responsibility to create, within our group, a Web page that would be 

hyper-linked to a variety of different groups so we could improve 

or make a contribution toward improving information that flowed 

out to at least the well-defined populations of patients who use 

plasma products. 

Beyond that, we would work and network with, if you will, those 

user groups so that we could identify specific parties, that we could 

ensure that the information got to them so that they, in turn, could 

ensure the information got to the constituents that they represent. 

400

Beyond that, we have suggested to the FDA that, because there 

are very real legal privacy barriers that make notification directly 

to all patients difficult, that we encouraged FDA to consider convening some open public meeting where all those issues could be 

aired; and then we could determine which kinds of notification systems might be available and what regulatory or legislative barriers 

might exist to accomplish these. 

So I think what we have tried to do is do this in two-steps: try 

to do those things we can do quickly, and then let’s try to find out 

where the barriers are to a more substantial and comprehensive 

program. 

Thank you. 

Mr. TOWNS. Mr. Chairman, I am going to yield back. I feel I 

know what we need to do, so I am going to yield back. 

Mr. SHAYS. Mr. Snowbarger. 

Let me just say, we are going to go on for a bit. We are really 

nailed down on where we see our agreement and disagreement, so 

we have time. 

Mr. SNOWBARGER. Thank you, Mr. Chairman. 

As I hear more and more about this, I guess I am getting more 

and more confused, particularly about CJD. My understanding—

and, again, I forget which witness mentioned it in the answer to 

Mr. Burton—was that we have not yet been able to isolate the factors that cause CJD, and yet we are performing experiments all 

over the world to see how we can pass it on. Somebody lost me 

somewhere. 

You know, what kind of experiments are we doing—with what? 

To whom—when we don’t know what factor it is that causes this 

particular disease? Anybody? 

Dr. DAVEY. I will do my best. I am not in active research on this, 

Mr. Snowbarger, but I think you have hit a very important point, 

that the research that is being conducted now is hampered by the 

fact that we haven’t identified the agent that actually causes CJD, 

and we have no tests for it. 

We do know that there is a transmissible agent involved. This 

has been documented, because pituitary human-derived a growth 

hormone, dura mater and other means have transmitted the disease in very isolated circumstances. 

So what we have tried to do——

Mr. SNOWBARGER. Excuse me. We have incidents of those transfers that are specific enough to know that that is the only factor 

that could be the explanation? 

Dr. DAVEY. Yes, sir, that is correct. With the growth hormone 

and dura mater, that has been documented that that is the mode 

of transmission. So the experiments have to be done in an animal 

model using evidence of transmission without actually being able 

to identify or test for the agent itself. This complicates the research. 

But I think Dr. Brown and Dr. Rohwer and Dr. Dronan at our 

lab are expert at working on some of these issues, and they are 

conducting experiments that I think can follow transmissibility in 

animals and can follow an activation process in animals without 

actually having a test for the agent itself. 

Mr. SNOWBARGER. Yes? 

401

Mr. FELDMAN. Could I answer that, Mr. Snowbarger? I think you 

have identified exactly the right questions that we are all trying to 

grapple with, in terms of how do you do experiments in this area 

to tell you some things so you can decide what to do with that. 

Mr. SNOWBARGER. Very frankly, that is the reason for my question. We stand here prepared to tell you how you are supposed to 

operate your business, when if you don’t understand what you are 

doing, I am not sure how we understand what you are doing. 

Therefore, I don’t understand how we feel like we——

Mr. SHAYS. Would the gentleman yield? 

The reason is that we had hearings in the previous Congress and 

we got into this whole issue of what happened in the 1980’s. When 

you have hemophiliac patients who can tell you of the loss of their 

brothers and sisters and sons and parents and that half of the hemophiliac patients contracted AIDS, you begin to say, I am going 

to wake up, and I am not going to go on the assumption that, because I can’t prove it, it doesn’t equal no threat. 

We went through that in AIDS. This committee is going through 

it right now with chemical exposure. We had the DOD tell us if our 

troops didn’t fall on the spot, they weren’t exposed to chemicals; 

therefore, there is no chemical threat. We are now learning that 

90,000 of our troops and more were exposed to low-level exposure. 

DOD says low-level exposure doesn’t equal chronic illness and 

death. That is not proven. We can’t prove the opposite, but we can’t 

prove that statement. 

Therefore, we have to go under some assumptions that it may or 

may not be a problem. And the issue that this committee is interested in is partly because the consumers would like smaller lot 

sizes. They would like smaller pool sizes. They don’t want to wait 

a long, long, long time to find out if we have a problem with a particular pool size. It is a fair request for them to make. And I am 

really happy you are here, because we need to have this kind of 

dialog. 

But we haven’t even scratched the surface of what you presented 

today, and we are going to try to find out where Mr. Snowbarger 

and I happen to agree. 

If the pool size doesn’t need to be larger, then why not make it 

smaller? And I want to have someone prove to me—and you can, 

because you are in the business—why the pool size has to be larger. 

So, you know, we will come to some conclusion, and then we will 

realize where we have disagreements. 

Mr. SNOWBARGER. I understand that, Mr. Chairman; and I agree 

with you that we ought to be attempting to find a good solution for 

consumers. But in the initial panel that we heard from, we heard—

at my questioning, we heard that the ideal pool size is either one 

or infinite, because we think we can dilute the CJD. Nobody knows 

that either. 

Mr. SHAYS. Would the gentleman yield? I think what we heard 

is we don’t know. 

Mr. SNOWBARGER. That is what I am trying to say. I don’t know 

what infinite means, so we must not know. We know that if we can 

get the unit size down or the lot size down to one, then you can 

402

know what with relative certainty. Obviously, that is not a practical solution either. 

Mr. Reilly, just so that you have an opportunity, you had indicated in questioning from the chairman that there is some confusion about discussion on units. Would you like to pursue that and 

finish your answer? 

Mr. REILLY. As the chairman has pointed out, this committee focused on pool size some time back. I think the debate has gone on 

for quite a while. Certainly it dates back to 1995. 

Over the period of time, as the discussion has proceeded, the unit 

of measure has changed. We initially started talking about donations in the starting pool of an active ingredient and then progressively scaled that up. The discussion evolved to donors being the 

more appropriate unit of measure to decide what risk might exist 

or how to ameliorate the risk. 

As we got into the question of donors, and as our people started 

looking at whether there were opportunities to do something, what 

became clear is that there was a wide range of practices; and when 

you look at FDA’s testimony and discussions of how they would like 

to see the problem resolved, you find different numbers being used 

for different sets of circumstances. 

For example, the 15,000 liter number is a number which doesn’t 

take into account excipients. When you add excipients, which is a 

dilution we add to the product to stabilize it, it changes the numbers. 

Our members looked at and determined they have a variety of 

practices that cause the numbers to move around. 

As the discussion continues, it depends on where you walk into 

the conversation as to what you hear. I can’t do anything, and I 

don’t think our industry can do anything, about what happened in 

the past with this. But what we have attempted to do today in preparing our testimony and preparing our statement about where we 

can change the number is to try and not have that confusion persist past this point and talk in absolute donor exposure numbers. 

By taking into account all of the different issues that go into this 

and hope that if all of the other parties engaged in this debate look 

at it that way, we will have a less confusing conversation. 

Mr. SNOWBARGER. Thank you. 

Again, this kind of goes to my basic education in this whole area. 

When you are producing your products, you take this pool of donations, donated blood. Do you use that one pool for several different 

products, I presume? 

Dr. GOMPERTS. Yes. 

Mr. SNOWBARGER. Then are there different optimal pools, depending on the product that you are trying to produce? I saw heads 

shaking on the last one—I have to say that for the record—one 

shaking on this one. 

Mr. REILLY. Let me start the answer, because I think the answer 

is multiple. It is complex. 

The fact of the matter is that the variables are from company to 

company, product to product. So the answer that the Bayer representative would give for his constraints and his way of building 

his products would probably be different than the answer that the 

403

Centeon representative would give you. That is where some of the 

confusion arises. 

Dr. DAVEY. Just a point I would like to raise. I think in terms 

of the voluntarily donated recovered plasma, the issue may be a bit 

clearer, in that when we talk about the number of donations in a 

pool, it is a fairly clear number, because we don’t have repeat donations essentially in the recovered plasma pool. Our donors donate 

every 8 weeks and no more frequently. 

So when I outlined our efforts to reduce our pools to fewer than 

60,000 donations, I think we can focus on that number. We have 

been successful with the Red Cross material in limiting our pools 

that we use to manufacture IVIg and AHF to fewer than 60,000 donations. We are not quite at 100 percent but we are well in the 

range. More than 90 percent of our pools now meet that criteria, 

and we intend to press on, especially with our albumin derivatives. 

Mr. SNOWBARGER. And you feel fairly confident about that number. What tells you 60,000 is appropriate, as opposed to 30,000? 

Mr. REILLY. The 60,000 number was arrived at through consultation with the experts in the companies with the first objective of 

trying to do something immediately—or rapidly, if not immediately. 

The criteria were related to where the opportunities today are that 

will allow us to make a change and come down to a number less 

than the highs that you heard, recognizing that there are barriers 

below some number. These barriers are: the need to reconstruct 

parts of the plant; the need to revalidate equipment; and, the need 

to engage in a variety of activities that are the result of changing 

the volumes, all of which require FDA approval. Any one of those 

things causes delays. 

So what the companies concluded is, let’s see where the opportunity is to set a precise number below which we assure you we 

will be. Then each of the companies individually will continue to 

examine that question, company by company, product by product, 

and engage in direct conversations with FDA about what other opportunities may exist beyond the 60,000 cap that we have agreed 

to. 

Many of the companies, and I think it is reflected in their testimony, believe that today, in many of the cases, they are already 

there. So what we are really dealing with is the odd situation that 

is over the 60,000. We are committing to bring those down. Maybe 

some of the companies might want to comment on—with some of 

the detail. 

Dr. GOMPERTS. I think part of the problem, in trying to answer 

your question and also Congressman Shays’ question, is I don’t believe there is any member of this panel who has sufficient experience and is qualified to talk about the reasons for these particular 

constraints, and that is the manufacturing constraints. I certainly 

am not. 

But there are constraints as the volume and the particular components and the fractions are moved through the fractionation supply. There is equipment constraints. There is constraints right at 

the end, for example, in putting the product into the bottle and ensuring it dries properly. There are constraints in the equipment 

that purifies the specific products. 

404

But I certainly don’t have the expertise to provide the answers 

in depth. 

Mr. SNOWBARGER. Mr. Chairman, I know you have been involved 

in conversation here, but I think that Dr. Gomperts made a very 

good point. That is, if we are trying to get a full understanding of 

pool size and its impact, particularly on supply ultimately, we don’t 

have the engineers and the manufacturers before us to tell us what 

those constraints are. 

As was indicated—I don’t know if you want to restate the point 

you are trying to make, but there are constraints in the manufacturing process that make smaller amounts maybe less efficient. 

Maybe efficiency is what we are talking about. 

Mr. SHAYS. You mean you all aren’t prepared to talk about that? 

Mr. SNOWBARGER. There are some. 

Mr. FOURNEL. In my written testimony—I had to read through 

this so quickly, unfortunately—we tried to offer a very specific example for our product, and I talk about specific——

Mr. SHAYS. Hit the mic just a little. 

Mr. FOURNEL. I talk about specific equipment constraints, so I 

can certainly refer you to that. 

While I agree with Dr. Gomperts that I am, at least, not prepared to talk about every detail of processes, I think we can certainly provide testimony. 

Mr. SHAYS. We are going to walk through that. I am going to be 

around for a while. 

I want to understand the whole issue of the equipment, the dryer 

size, a little bit. I want to know if that is the nature of what you 

have established today or whether that is just inherent in the process to—generic need to have a certain size, or whether that is what 

the industry has now. I mean, we don’t have many in the industry. 

How many players do we have? 

Excuse me, are you done? 

Mr. SNOWBARGER. Well, Dr. Feldman had a comment on the last 

question, and then I would be happy to yield back. 

Mr. SHAYS. You don’t have to yield back. Yes, sir? 

Mr. FELDMAN. I would like to try to address the question again, 

and maybe an example would help clarify it. 

I have a table that shows what happens with different vat sizes. 

It is table 9–B, if you could put it up. I don’t want to overwhelm 

you with details, but sometimes it helps if you can see an example. 

Mr. SHAYS. That did kind of overwhelm me. If you could simplify 

that, it would help. 

Mr. FELDMAN. Most of the numbers we don’t need to talk about, 

but we can talk about two things—the batch size in terms of volume, the top line, and it shows a range from 15,000 to 500. That 

is in liters. 

Mr. SHAYS. These are different size vats. 

Mr. FELDMAN. Different size final batches, this is everything contained in that. This is asking what can you do across the range. 

The second line shows the number of donors contained in this 

process and each calculation from that volume. So for 15,000 for 

our process, going into the details of production and counting how 

many there were, it is in a range between 53,000 and 81, or it 

could be all the way down to 500 liters in this process. And looking 

405

at the number of donors, there could be, even at 500 liters, a major 

reduction. There could still be 42,000 to 64,000 donors. 

The reason is because as—even as we decrease the bath size, the 

product that is there, that factor has stabilizer added. That is albumin. It brings its own donors in. And unless we address that separately, even though we decrease the effect of principal, the fact is 

the donors are still there. 

While we do that, because we are decreasing the volume, the 

quantity units we can make decreases. So what we can do to serve 

our patients drops. So that is not a very effective way of addressing 

that. 

The question that we have asked is, without attempting to so 

radically redesign our plants, can we still address improvement? 

So if you look in one column at a time—let me take the 15,000 

liter column—the question is the donors per batch range, even at 

that fixed volume, can we address those independently of how big 

the vats are? And the answer is, yes, we can. 

We can—in our case, because I don’t know of the details of my 

colleagues’ processes, we have asked what is in there that we can 

address to make the numbers smaller? And we have found ways to 

do that without having to go and ask for a whole new plant to be 

built. That is part of the initiatives I spoke to. 

But I believe we can address those questions so that, even if 

there isn’t agreement on does it matter in a safety perspective if 

we have a small batch or not, that we can still talk about improvement for improvement’s sake; and I think we have all agreed that 

we can do that. 

Mr. SHAYS. When I use the words ‘‘manufacturing economies of 

scale,’’ I can view it two ways: I can view it just in your ability to 

produce enough product or I can view it in terms of cost. 

Let’s just make the assumption I mean it in terms of your ability 

to produce enough product. I want to go over the pluses and 

minuses of a large pool, and I want to see if we have some agreement on that. 

One would be manufacturing economies of scale. I am just thinking of your ability to produce more in the same amount of time. 

There is the theoretic risk of dilution. There is the concept of what 

I gather was—dilution would be, in my judgment, you just spread 

it out. Ultimately, this one bad donor spread throughout the entire 

system, that donor no longer becomes a threat. 

I look at naturalization as being kind of good cells battling to 

overcome bad cells. You probably use another word than ‘‘cells’’, 

and it probably offends you, but you get my point. 

Then the concept that we had enhanced genetic diversity. You 

needed—what—enough different antibodies. That is what I have 

down as plus. 

Mr. FOURNEL. If I can make one comment, sir. 

While I appreciate what you want to do, I wanted to add one 

thing to the list Dr. Zoon provided on the plus side, and that is 

product availability. I realize you just put that together with efficiency. But I would suggest they are actually different. I think 

most of my colleagues——

Mr. SHAYS. Instead of my saying manufacturing economies of 

scales, you want me to think in terms of that, in terms of cost. I 

406

will do that. And then you want me to think of product availability 

as a separate one. That is a fair way to do it. That is a good way. 

Now on the other side you have one—and maybe there are ways 

to get around this. One is the recalls are much more difficult, as 

there is so much product to recall and different kinds of products. 

So that would be one. 

Then, there is the concept of what I call spread. One bad donor 

can harm not just 1 person, but can harm 10 or 20. In other words, 

it can spread out. Using this contaminated supply, one bad donor 

results in many people being infected. 

There is the concept of exposure. The opposite of naturalization 

is enhancement. In other words, naturalization, where the good 

cells overcome the bad, you could have the opposite, the bad cells 

overcome the good. Would that be the concept of enhancement? 

Mr. SNOWBARGER. I think the word Dr. Zoon used was neutralization. 

Mr. SHAYS. Excuse me, that is what it was—neutralization. 

Thank you. 

Mr. FOURNEL. If I can suggest—the issue of neutralization is because we know that individuals may have a preexisting antibody 

to the very infectious agent that another donor might——

Mr. SHAYS. She basically acknowledged it is more proven that 

you have neutralization than enhancement. I accept that. 

And then the big kind of scary thing is you would have an epidemic. In other words, you just simply don’t know of something 

now and then you discover it, and you discover it in a large pool 

rather than a small pool. 

Now, what would I add on the negative side? Anything else? 

Mr. FOURNEL. I just had one comment to her negatives. 

Mr. SHAYS. All right, I am encouraging that. 

Mr. FOURNEL. The issue of bigger recalls or withdrawals assumes 

something—it is a little technical, but the repeat rate of the donors 

contributing to the product pools is an important factor. That is, 

the more times that an individual donor contributes to a pool, then 

the reduction in pool size really starts to be mitigated by the fact 

that that donor is represented in——

Mr. SHAYS. Are you tying to tell me one bad donor in five pools 

is no different than the five pools being in one lot? 

Mr. FOURNEL. Than having that same donor—all units from that 

donor going into one large pool. 

Mr. SHAYS. OK, that is fair. 

Tell me, when you have said that you could easily reduce from 

100 to 65, explain to me, that you could reduce the lot size a bit—

I want to do it this way. You could reduce the donor exposure to 

a user from 100 to, say, 65. Why is that the case? What makes 

that—am I correct? Has that been said? 

Mr. REILLY. That is correct. 

Mr. SHAYS. And does the industry agree? You are the representative of the industry. 

Mr. REILLY. What the industry has said is when they examined 

their current practices they saw an opportunity to move rapidly to 

move to a limit of 60. In the course of the discussion, what they 

also acknowledged is that, for each company, the method that they 

407

would use to accomplish that would vary, depending upon their 

unique situation. 

Dr. Feldman, in his presentation, catalogued for you a number 

of things that his company believed that they would engage in to 

accomplish that goal. 

In Dr. Davey’s testimony, he talked about being able to be at 

that same goal as well. In the Red Cross’s case, they would use a 

different menu of options in order to get there. 

Mr. SHAYS. Anybody else want to respond? Is it your testimony 

that, basically, you can reduce the donor exposure to a user—let 

me back up a second, just because I made assumptions that I 

shouldn’t assume. Let’s take each of you. 

What is your basic donor to user size? Let’s just start with you, 

Ms. Preston. 

Ms. PRESTON. I need a little help with ‘‘donor to user size.’’ I 

think we have provided it to the FDA, and I think even in our written testimony——

Mr. SHAYS. Is this proprietary information? 

Ms. PRESTON. To some extent, yes, I think all of us have——

Mr. SHAYS. Then I am going to take an average. 

Ms. PRESTON. An average? Excuse me? 

Mr. SHAYS. Would average help us out here? 

Ms. PRESTON. Maybe by product would be better. I think for 

some of our products we are at 30,000, 40,000. Some of our products are higher than that, at somewhere in 80—or 60 or 70 or 80, 

and we have to look at our practices. 

There is a menu. I agree with what has been said. There are 

ways we can look at reducing the donor exposure in a given lot. 

Mr. SHAYS. Dr. Feldman. 

Mr. FELDMAN. I am not clear exactly what you are asking me in 

terms of donor to user. 

Mr. SHAYS. I guess what I am trying to do is get around the difference between pool and lot size. When we had this hearing 2 

years ago—and my understanding of the FDA, in private conversations as well as their public statement, was that they, too, were 

surprised by the number of the lot size when we go in the 400,000 

range. That blew their mind, and it blows our mind. 

It just tells me that wasn’t something the industry was eager to 

share with us 2 years ago, or I guess you could say, well, we just 

didn’t know what question to ask. But, we are trying to get a handle on it. 

Ms. PRESTON. If I could, please, I used to work at the FDA from 

1980 to 1988. 

Mr. SHAYS. So it is your fault. 

Ms. PRESTON. It is all my fault. No. So I wasn’t surprised at 

100,000. I wasn’t surprised at less. 

Mr. SHAYS. They weren’t surprised at 100,000. They were surprised when it got over 100,000. 

Ms. PRESTON. I think part of it is people being familiar with how 

we do our batches, and people who have been out to our facilities 

do see our batch records and see how many donors it does take for 

a given set of products. So I think, depending on who at the FDA 

was looking at things, some may have seen where we were and others may not have. 

408

Mr. SHAYS. They didn’t know the answer to our question when 

they asked the question. They had to go out and find out. That tells 

us they were surprised. 

Yes, sir? 

Mr. FOURNEL. Can I just address this specific question? 

Mr. SHAYS. I am going to come back to you. 

Mr. FOURNEL. I don’t know the statistics that you have from the 

other companies, but I do know what we provided to the FDA, and 

I believe we were responsible for at least one of the 400,000 number you are speaking of, if there is more than one. 

At the risk of confusing the issue more, I want you to recall that 

there are two sources of plasma they were talking about. One is 

source plasma and one is recovered. And recovered plasma is generally much smaller volume, as has been explained earlier. 

In our case, the product in question that had the 400,000 donor 

exposure was all derived from recovered plasma, so it represented 

a factor, as we have been talking about, the fact that we had so 

much less plasma per donation, that, in fact, it represented 400,000 

donors. 

To explain again, in other words——

Mr. SHAYS. I am fine with that, and you just triggered another 

question. 

Dr. Feldman. 

Mr. FELDMAN. I guess what I want to say is I don’t want to add 

additional confusion, but even within one manufacturer and within 

one product there is variation in how many donors there are. 

Mr. SHAYS. Give me your high and give me your low. 

Mr. FELDMAN. So what I want to say is the initiative that the 

IPPIA spoke of is to adopt a ceiling to limit what the high is and 

to reduce the variation. 

Mr. SHAYS. Dr. Feldman, I agree with Vince in that, if we don’t 

have to limit the top end, why should we? You all are saying you 

can go from 100 to 65. You seem to be comfortable to describe that 

and that you can do it. 

In each case, I want to know your highest level; and I want to 

know your lowest level. That is what we are going to do. That is 

not a hard question. Is it a hard question? 

Mr. FELDMAN. Yes. 

Mr. SHAYS. Why? 

Mr. FELDMAN. Because we have to know what terms you want 

us to include in there. Is it with or without the albumin stabilizer? 

Is it the high end of our range for that? 

We have been asked different questions. Sometimes it includes 

that, sometimes it hasn’t. 

Mr. SHAYS. OK. Give me two choices. What else? 

Mr. FELDMAN. Let’s include it, and let’s include the most number 

of donors that there could be in a batch. 

Mr. SHAYS. What I am trying to avoid is I am trying to avoid you 

all having to come back again. Maybe that is impossible. But, as 

it stands now, you are raising a lot more questions; and we will 

just be back and just try to iron it out. If you can try to help me 

out here, this won’t have to be where you have to keep coming 

back. 

Mr. FELDMAN. I really want to answer your question. 

409

Mr. SHAYS. OK. 

Mr. FELDMAN. For our different products, for our Factor VIII, for 

our Factor IX, for our albumin, for our IVIg, we have a different 

total number of donors. 

For our Factor VIII, we have numbers in excess of 60,000, but 

believe we can come down significantly below that. 

Mr. SHAYS. Dr. Feldman, ‘‘in excess’’ is 68 or is it 200,000? 

Mr. FELDMAN. Up to 94,000, 94–95, including the albumin stabilizer and not taking credit for repeat donors. 

Mr. SHAYS. I understand about the repeat donors. Believe me, I 

understand that. 

Mr. FELDMAN. If I take credit for repeat donors and can demonstrate that, then that 95,000 number comes down to 63. 

Mr. SHAYS. What does albumin take it down to? 

Mr. FELDMAN. Without taking into account the albumin, it is 

21,000 donors. It is very different. So that is why I need to clarify 

the term. 

For our Factor IX, and I think most of our Factor IX’s, it is much 

lower. The worst case, taking into account stabilizers for us and a 

non-repeat donor rate, is around 28,000. 

Ignoring the non-donor repeat rate, if we can verify that there 

are repeat donors in there, the 28,000 in our case becomes 18,000. 

We are not talking about 400,000 at all. For our albumin, we are 

talking about a range of 20 to 30,000 for us. 

For our IVIg, our numbers are higher. Without a repeat rate and 

with albumin accounting for the donors for the albumin, it can be 

150,000. If I can verify the repeat rate, that number drops to 

100,000, roughly; and if I don’t take into account the albumin, it 

is 63. So that is the range of donors. 

Mr. SHAYS. OK. The highest number you gave was 150; and you 

said if you could take in repeat, it would be 100? 

Mr. FELDMAN. Right. 

Mr. SHAYS. Ms. Preston. 

Thank you, Dr. Feldman. 

Ms. PRESTON. For Factor VIII—and again this is using sort of 

the same analogy—right now it is around 22,000 to 28,000 donors 

in the lot. When we add albumin, that puts it up significantly with 

another 46,000 to 52,000 donors there. And we can do a similar 

type of calculation with repeat donors also, but I think that needs 

to be verified and validated. 

With some of our other products, such as albumin, we are somewhere higher than that. Albumin ranges from around 6,000 to 

102,000, depending on whether it is 5 percent or 25 percent. IVIg, 

75,000 to 125,000. But, again, we can get to the 60,000 ceiling for 

those. 

Mr. SHAYS. OK. Dr. Gomperts. 

Dr. GOMPERTS. Mr. Chairman, I don’t have the specific data for 

my organization with me. The numbers are approximately the 

same as to my colleagues on the left. 

Mr. SHAYS. OK. When you get back, if they are higher, we would 

request that you would contact the committee. 

Dr. GOMPERTS. I will do that. 

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Mr. SHAYS. We are making a sense that under oath you are telling us they are the same; and if you find they are higher, then we 

would like you to notify us. 

Dr. GOMPERTS. Sure. 

Mr. SHAYS. Mr. Fournel. 

Mr. FOURNEL. You want it by each product? 

Mr. SHAYS. You can just do similar. 

Mr. FOURNEL. I think, in most cases, it is similar. We, in fact, 

do believe we can document our repeat rate, so we would cite a 

lower number. But, without that repeat rate, the numbers are not 

too different from what you have heard. 

Mr. SHAYS. Is the number higher than 150 in any product? 

Mr. FOURNEL. No. 

Mr. SHAYS. OK. If you are pretty convinced that these numbers 

don’t represent a threat to anyone, why would you want to bring 

down the donor size? I am just going to ask you the reverse of what 

I have been asking you. Why would we do that? Why should you 

do that? I don’t want you to do anything you shouldn’t do. 

Ms. PRESTON. Can I answer? 

Mr. SHAYS. Yes. 

Ms. PRESTON. I think when we look at our practices it is a good 

way of being more consistent. So, in that sense, for us it is a way 

of adding consistency, which is part of good manufacturing practices. So that is one way of looking at it. 

It doesn’t mean that there won’t be some minimal effect on supply as some of the partial lots that we might have used would not 

be utilized under the proposed scenario of 60,000. 

Mr. SHAYS. OK. Dr. Feldman? I mean, why bother? Why not just 

continue the way you are doing it? 

Mr. FELDMAN. First of all, most of the batches we make aren’t 

in this large size range. Most of our batches are lower than this. 

And we provided numbers——

Mr. SHAYS. Dr. Feldman, is your testimony that, like the others, 

you are going to reduce your donor size, your pool size? 

Mr. FELDMAN. Unless instructed not to, we are planning to. 

Mr. SHAYS. You are planning to. Why? 

Mr. FELDMAN. We are planning to decrease the variation in the 

batch size range. We don’t need to operate at this range and still 

put product out. There is no benefit to us in operating at a high 

end range like that. If we can operate in a narrower range without 

providing these numbers of donors, there is no reason for us to continue that. 

Mr. SHAYS. So your testimony is you can reduce your donor size, 

your pool size, without changing significantly your supply side; and 

so your testimony is there is no reason to have a higher donor size 

if you don’t need to? Is that what you are saying to us? 

Mr. FELDMAN. I gave you three sets of ranges of numbers. On the 

high end, we believe that we can address those and bring them 

down to the lower range of variation. If we have agreement with 

FDA that we are not impacting any of our validation data or quality assurance, we are prepared to go ahead and do it. 

Mr. SHAYS. I know you are prepared to do it. I want to know why 

you would do it. 

411

Mr. FELDMAN. To decrease the variation. As my colleague said, 

because part of GMP says that process is under control. We would 

also like to have less variation batch to batch, just to have more 

control on it. 

Mr. SHAYS. Dr. Gomperts. 

Dr. GOMPERTS. As I see it today, the issue of batch size, pool size, 

does not impact the safety of our products. There is growing pressure from this committee and also the FDA. We have heard certain 

numbers, there is debate going on. It is important that we look at 

our processes to determine what the impact of reducing batch size 

will be, and the proposal that is put forward has indicated to us 

that the impact on supply will not be substantial. 

Mr. SHAYS. Dr. Fournel. 

Mr. FOURNEL. I would more or less concur with my colleagues. 

The only point I would want to make is that I think it is intuitively apparent that having 400,000 donors to a single lot of product is probably not a good idea. In fact, in a very unfortunate sequence of timing, that very lot is implicated or that very material 

is implicated in a withdrawal that we are having today associated 

with CJD in potential six lots of our Prolastin product. 

So it is clear, with the CJD case in particular, having lots of that 

size or donor exposure of that size is probably contributing to the 

withdrawals that we have certainly experienced. In fact, all of our 

withdrawals——

Mr. SHAYS. So when you get up to 400,000, you are basically relating it to the whole issue of recall. 

Mr. FOURNEL. I was trying to relate it to the issue of safety insofar as the donor exposure at that level would seem to—clearly, it 

is associated with the higher incidence of recall, because that has 

been our experience. So I think there is some rationale for reducing 

from those kinds of numbers. 

I think the problem is, when we get below the 100,000 range or 

the 60,000 range, it becomes a much more difficult argument to 

have; and there are many, many factors that impact that argument. I think, as everyone said here today, the real reason we can 

all sign on to the 60,000 limit is we think it will improve our manufacturing processes more than necessarily impact the safety of the 

products. 

Mr. SHAYS. One of the whole issues was availability of product, 

and the other issue is economy of scales. In the short range, there 

are economies of scale. Excuse me, are there economies of scale the 

larger the batch or the larger the donor pool? I am sorry. 

Mr. FOURNEL. To some extent. Maybe if I can use the Prolastin 

example that I have in my testimony——

Mr. SHAYS. Can you talk louder? 

Mr. FOURNEL. If I can use the Prolastin example I have in my 

written testimony, perhaps that would help. What ultimately constrains or sets the size of our batches is the size of our freeze dryer. 

We want to fill our freeze dryers completely. They are operated 7 

days a week, 24 hours a day, in order to provide this product. So 

the size of that freeze dryer is what sets the basic size of our 

batches or our lots. 

That being said, it turns out, for the reasons again that I have 

discussed in my written testimony and will not go through, that a 

412

donor exposure of 60,000 using source plasma is what we need in 

order to get batches that would fill that freeze dryer and enable us 

to make the most product available with the equipment that we 

have. 

Mr. SHAYS. OK. Explain to me why you take different pools and 

combine them? There has got to be a reason why you do that. 

Mr. FOURNEL. Because the freeze dryer holds a certain number 

of vials. Let’s say 5,000. I don’t know the exact number. 

Mr. SHAYS. So it is basically determined by the freeze dryer? 

Mr. FOURNEL. That is right. At this level, at this particular example, that is the case. 

Mr. SHAYS. In your judgment, are there medical reasons to have 

larger pool size, in excess of 60,000? Are there health reasons that 

you would want a pool size larger than 60, a donor-to-user size of 

larger than 60? 

Mr. FOURNEL. Apart from the arguments that Dr. CunninghamRundles mentioned earlier, no, I can’t see a medical reason. 

Mr. SHAYS. Refresh me what her reason was again? 

Mr. FOURNEL. Diversity in the spectrum of antibodies that are 

provided——

Mr. SHAYS. Antibodies. Is that the key issue of why you would 

want a larger lot size? I am talking about what we can agree on 

and what is proven. We were given these lists of what is being 

studied and looked at, but haven’t been determined to be scientifically true, correct? I just want to know, are there scientific reasons 

and health reasons why you would want a smaller pool size, other 

than recall issues? 

Mr. FOURNEL. Why you would want a smaller or larger? 

Mr. SHAYS. Smaller. I am going to ask each of you. 

Mr. FOURNEL. I thought you were asking me larger. 

Mr. SHAYS. I asked larger first, and then I am going to go to 

smaller. You already have answered. You said none other than the 

issue of the antibodies. OK, yes, sir? 

Dr. GOMPERTS. You mentioned the level of 60,000. Is that what 

you are focusing on? 

Mr. SHAYS. Are there health reasons to have a larger donor to 

user pool size? 

Mr. FELDMAN. I don’t believe so. 

Mr. SHAYS. Dr. Feldman? That is proven. I am not saying we 

may suspect or believe. 

Mr. FELDMAN. Mr. Chairman, I know there are differences of 

opinion on this——

Mr. SHAYS. Fair enough. 

Mr. FELDMAN [continuing]. And I have seen and I have heard 

cited, in fact, at the December 1996 Blood Product Advisory Committee from a Mr. Tankersly, also an expert in this area, that he 

believes there is an importance to pool size as a safety issue. I don’t 

know that I can fully represent his opinion. 

I think—in regard to our pools and 60,000, I think that we can 

operate within that range and that there aren’t safety issues in operating below that. There are not. 

Mr. SHAYS. The one thing I don’t want to have happen is 10 

years from now I look back on a hearing I had 10 years ago and 

413

find out that we limited the pool size and then determine that that 

was a mistake, that you want a large pool size for whatever reason. 

So I am putting you on record, and I am putting you on record 

to understand this, and then this is an issue we are going to proceed with. It is my sense that we simply don’t know. We don’t 

know if a larger pool size is better or not. We don’t know if a smaller pool size is better or not, only based on intuition. We do know 

that availability of product would be affected, and that is fair. But 

I just want to know if you disagree. 

Dr. DAVEY. Mr. Shays, if I could speak on that——

Mr. SHAYS. I am sorry, I didn’t focus that way. 

Dr. DAVEY. I think you summarized the issue very well, and I 

think the exercise we went through earlier in the day about listing 

pros and cons of a larger pool size was very instructive, and I think 

the answer is indeed that we don’t know what an optimal pool size 

may be in a given situation. 

But I think, at least in terms of the Red Cross position, we have 

taken the position that, given what we know, it is prudent to limit 

pool size where we can, to have a practical upper limit for different 

products that are manufactured from Red Cross-recovered plasma. 

Therefore, we have instructed our contract fractionator to have a 

60,000 limit for IVIg and for our AHF and to use albumin stabilizer 

from that lot for that material. We feel that is prudent. 

And where we can limit our pool sizes for albumin, we are going 

to move on that also. 

But you are right. Pool size variation in the context of other 

issues and other measures that we can take to improve the safety 

of plasma derivatives and whole blood is just one of many issues 

and perhaps not the most important. 

Mr. SHAYS. I think the only other issue, and then we can move 

forward—I am going to summarize, and it is basically repeating 

some of what you are saying. 

What I am hearing the industry tell us, this committee, is that 

you are going to, in some cases, reduce the pool size. And in some 

cases where you have been using a figure of 100,000 down to 

65,000, it is the testimony before this committee that there is no 

scientific knowledge that says a larger pool size is better or a 

smaller pool size is better in terms of the quality of the product, 

but that in some cases your pool size had been larger and you are 

going to bring them down a bit. 

It is the testimony of this chairman that we are not putting—we 

do not both publicly or privately seek to have an artificial number, 

because we don’t know what that number is. 

It is the testimony of this chairman as well, though, that we 

were led to believe the pool size was much smaller. Given how we 

found out and the surprise notwithstanding, Ms. Preston, your 

comment of the FDA as not being able to get a handle on that figure, on that number soon enough, we felt that there was just simply not a candid dialog between the industry and Congress in 

terms of what that number was. We were surprised by it, and it 

raises a real concern. 

There is always going to be a concern on the part of Congress 

that economies of scale, not availability of product, can sometimes 

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portant rolls that Congress plays, is to say, is there an economy of 

scale coming in here to the detriment of public health? And we are 

going to ask questions to determine that, and this is one area that 

we will pursue a bit because we don’t pretend to have this knowledge now. 

The area, though, that I feel very important to end up with is 

what do we do for the consumers in terms of recall, particularly a 

recall of 400,000. I understand your testimony is that is unusual, 

correct? 

Mr. FOURNEL. No, sir. The situation for us with Prolastin and 

the reason I used it as an example in my testimony is that we are 

the only supplier currently in the United States of this product; 

and this patient population has a very desperate need for this product, not just on a one-time basis but on a regular repeat basis. We 

have been doing everything we can to provide as much product as 

we can to this patient population, and that includes the purchase 

of intermediate fractions from other manufacturers that we can use 

in our process. 

Mr. SHAYS. So that increases the donor size? 

Mr. FOURNEL. That is what happened. Because we, as a commercial operation, only use source plasma for our pooling efforts. But 

in order to again augment the supply of Prolastin we purchased socalled 41 intermediate that was made from recovered plasma to use 

in the manufacture of the Prolastin product. When we combined 

those intermediates, all these recovered plasma intermediates, that 

is how we get up to the very high numbers because the numbers 

we have for Prolastin using source plasma are in the 60,000 to 

100,000 range in general. 

So the point I was getting at is that, because of the use of recovered plasma, we do have cases where we have these very high 

donor numbers. However, because all of our experience with CJD 

withdrawals with respect to Prolastin have been because of the use 

of recovered plasma intermediates, effective June of this year we 

discontinued procurement of these intermediates. So we no longer 

use them. 

Mr. SHAYS. Just as a segue into this point before I talk about recall, there has got to be a tremendous economic incentive not to 

make your pool size too large, because when you do have recalls, 

I would think it would be quite expensive. 

Mr. FOURNEL. Well, again, sir, understanding that a 400,000 

donor recovered plasma number, you can equate to 100,000 donor 

source plasma. 

Mr. SHAYS. OK. 

Mr. FOURNEL. In other words, they—because the donor, the volume of the donation is so much smaller, recovered plasma—so it 

doesn’t mean the lot is four times bigger. 

Mr. SHAYS. Fair enough. 

Mr. FOURNEL. So the same size lot—is the same size final product content. 

Mr. SHAYS. Is it true that, as alluded to by one of the consumers 

who spoke to us, that you have had a significant number of recalls? 

Have your recalls become greater than in the past? I would like to 

know with each of your companies. Do you have more recalls today 

415

than you had a few years ago? That may be just that we are just 

being more vigilant. 

Mr. FOURNEL. Again, I’m sorry. As I put in my written testimony, seven of nine. Now, I have to say 8 of 10 recalls that we 

have had in the last 2 years have been because of CJD. So, yes, 

we have had more. 

Mr. SHAYS. OK. CJD has been the reason why you have had 

the——

Mr. FOURNEL. That’s the vast majority. 

Mr. SHAYS. Not any of any of the other factors that in the past 

might have been the problem. 

Mr. FOURNEL. I’m saying that we might have had two recalls 

that are associated with GMP issues, but that’s more or less the 

nature of the business for us. 

Mr. SHAYS. Dr. Gomperts. 

Dr. GOMPERTS. The majority of our recalls have been CJD related. 

Mr. SHAYS. How many have you had in the last year? 

Dr. GOMPERTS. In the last 6 months, there have been five. 

Mr. SHAYS. In the last year? 

Dr. GOMPERTS. I can’t tell you. Probably double. 

Mr. SHAYS. OK. Dr. Feldman. 

Mr. FELDMAN. Centeon has not had a recall for CJD. But we 

have had recalls for GMP-associated issues. We’ve recalled albumin 

last year. And we also had precautionary recalls for a Factor VIII 

and Factor IX. They were small recalls. 

Mr. SHAYS. So during a 12-month period, the last one you could 

state to us, what would be the number of recalls? 

Mr. FELDMAN. I’m not sure, maybe four or five. 

Mr. SHAYS. OK. If it is larger than that, you will notify the committee. 

Mr. FELDMAN. Yes. 

Mr. SHAYS. Thank you. 

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Mr. SHAYS. Ms. Preston. 

Ms. PRESTON. Alpha has not had any recalls for CJD as of yet. 

That doesn’t mean that in the future we won’t. We’ve had one recall of our intravenous immunoglobulin because this particular lot 

was associated with a higher rate of adverse events than we had 

experienced, so we took a precautionary action and recalled that. 

That—those are—I think that is the only recalls we had in 1997. 

And in 1996, we had, I don’t know the exact number of recalls related to Hepatitis A. 

Mr. SHAYS. So the total amount in the 12-month period? 

Ms. PRESTON. I would say less than five. 

Mr. SHAYS. OK. 

Ms. PRESTON. But I will check on that and make sure. 

Mr. SHAYS. If it is different than that or higher. 

Ms. PRESTON. Yes, sir. 

Dr. DAVEY. We, Mr. Chairman, and the Red Cross have definitely 

noted an increase in the number of CJD recalls since August 1995. 

And we think some of that reason is because, at that point, the 

FDA recommended that we begin asking our donors questions 

about family exposure to CJD. We’re receiving a lot more information from our donors. As a matter of fact, 85 percent of our recalls 

are because of postdonation information we get from our donors. 

And so this is impacted on the number of our recalls. 

Mr. SHAYS. OK. 

Is it fair to say that most of the recalls 5 years ago would have 

not been because of CJD, it would have been for other reasons? 

And my assumption is that some of the reasons you have had in 

the past have been dealt with. Some of the—there have been improvements in your process that have resulted in your not having 

a need to have as many recalls for some of these other reasons. 

Dr. DAVEY. I would think that’s fair. I think recalls are always 

instructive because they indicate an issue that needs to be addressed, whether it’s an issue in postdonation information that perhaps we’re not eliciting properly or questions could be answered 

better or perhaps it’s an issue in the way we handle producing or 

manufacturing our components. So recalls are instructive. And I 

think we’ve learned from them. 

Mr. SHAYS. Let me just take the last question. If I were a user 

of blood products on a continual basis, I would become pretty well 

informed. And I would think, and maybe this is happening, that 

every manufacturer would be able to have a number I could call. 

I could literally call that number, hit whatever the batch number 

is. I don’t—I’ve never seen how you would identify it, but is it a 

batch—what is it? It is a lot number. And I would be able to hit 

that lot number. And so, for instance, Mr. Feldman, when I called 

your company up, I could hit that lot number and it would tell me 

the status, that there is no problem with this lot number or that 

there is because of so and so. Does that happen? 

Mr. FELDMAN. I’m not aware that we have something like that. 

But a system like that could be considered, yes. 

Mr. SHAYS. Well, it is my understanding that you do not have to 

tell the end user of the product directly. It would be rather impractical to track down the end user, correct? You could contact where 

you sell it, but not the end user. And so then the question I would 

418

have is, what are you all doing to make it easier for the buyer do 

that? I mean, on either the Internet or on the telephone? Do any 

of you do it? Yes, Mr. Reilly. 

Mr. REILLY. Well, the association is in the process of initiating 

a project that is aimed in that direction. It’s not quite as comprehensive or user-friendly as the proposal that you just made, 

clearly, but it has two elements to it. First, it is to create an association Web page to provide easier access to the withdrawal information that is available. And, second, to engage in a dialog and 

create a network with the major patient groups that have organized programs so that we can have a way to more rapidly disseminate information. It’s not quite as elaborate as what you just proposed, but it’s a step in that direction. 

Mr. SHAYS. Well, why would that be elaborate? That to me 

wouldn’t seem like a difficult thing at all. You just have a number—maybe I have a false impression. There aren’t that many 

manufacturers; are there? Are we talking about hundreds or are we 

talking about a handful? This is it; isn’t it? So it would seem to 

me—and so wouldn’t every blood product that I have identify one 

of your companies? 

Dr. GOMPERTS. True. 

Mr. SHAYS. Would it identify the Red Cross? Would it identify it? 

It would. So I could—yes, sir. 

Dr. GOMPERTS. I’m not quite sure what you’re saying, but I think 

what, and correct me if I’m wrong, what you’re asking is if a consumer of one of our products had used a particular lot——

Mr. SHAYS. Not had used or is planning to use. I look at it, and 

I want to check before I——

Dr. GOMPERTS. There is a question around that particular product and that particular lot. And if that individual has such a question, certainly there is customer service——

Mr. SHAYS. OK. Dr. Gomperts, I would like you to think about 

this. If I were a hemophiliac patient, and I had this blood product 

that I was using, and it had a particular identification number on 

it, I would want to just be able to call up your company. I would 

want to see the phone number on the bottle maybe. And I would 

call that company up, I hit these numbers, and I would get a readout. It said this product is good to use; there has been no recall of 

this product. And it just strikes me that, since you are not required 

to go and ultimately contact the end user, at least make it easier 

for the end user to contact you. 

Dr. GOMPERTS. I believe we have such a system in place. 

Mr. SHAYS. Well, if you end up calling someone who refers to you 

someone else, that wouldn’t be very friendly, but if you do, that is 

good. 

Dr. GOMPERTS. They come to my desk. 

Mr. SHAYS. Let me say I believe you do or know you do is a difference. Describe to me how the system works, then. 

Dr. GOMPERTS. I can give you—this occurs on a daily basis. 

Mr. SHAYS. OK. Let me just say to you I don’t want to be—I don’t 

want to take a cheap shot. 

Dr. GOMPERTS. Yes. 

Mr. SHAYS. But if I were a hemophiliac patient, I would like to 

think that your company or any of the other companies would have 

419

a system that you were so well aware of that you could just tell 

me chapter and verse how it worked. And maybe—yes, Mr. Reilly. 

Mr. REILLY. Let me just make two observations and then a 

pledge. 

First of all, what you have proposed has to do with providing an 

opportunity for recipients of our products across the full spectrum 

of all products available. What we’ve been discussing is an effort 

by the industry to try and enhance the communication where there 

is a product with a question specifically. I think those are really 

two different things. But what I do pledge to you on behalf of the 

industry, is that we will examine the question you raised and determine whether we can do something positive that is more responsive. 

Mr. SHAYS. I think that that would be helpful. Because, what we 

may have ended up in this hearing is no real answer about donor 

size. So I am saying to you I am not sure how this committee is 

going to go in that area. But if, at the very least, we can’t say a 

large donor size or smaller donor size is preferable, I would say we 

would say smaller is preferable where practical as long as we don’t 

negatively impact the availability of the product. 

It seems to me that one of the outcomes of this hearing may be 

that, at the very least, to the consumers who use your product, 

they should feel very comfortable in using your product. And while 

they are using this product, there isn’t a letter on the way telling 

them not to use the product. 

And given the number of recalls that you have said, they are 

not—it is not one every 3 years, it is something that happens. It 

would seem to me a very logical way to proceed. 

So maybe one of the outcomes of this hearing will be that you 

will focus a little more attention on that. And I will say to you that 

this committee, and before we draft our report, will want to know 

what you are doing. And if you are doing something that we think 

is meeting the consumer, we are going to make sure that we publicize it and congratulate you for it. 

Is there any final comment? 

Mr. Davey, I kind of left you out and yet you are probably—Dr. 

Davey. I want to make you a mister, and I want to make Mr. Reilly 

a doctor. 

Dr. DAVEY. I would just like to comment, Mr. Shays, I think your 

idea is excellent. And it actually was proposed by one of my colleagues, Dr. Peter Page, at the Blood Product Advisory Committee 

hearing a year, year and a half ago. And I think it’s time we look 

at this again. I think it’s an excellent idea. I want to compliment 

you. We thought about that before. 

Mr. SHAYS. Let me end by apologizing to you, Mr. Reilly, and 

you, Dr. Feldman, because I think it was very unrealistic of me to 

think that I could have a few questions and then leave. So I apologize for my impatience and your trying to respond to my questions. 

I appreciate your being here and thank you. 

I call this meeting to a close. 

[Whereupon, at 2:27 p.m., the subcommittee was adjourned.] 

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