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Blood Safety Transcripts

ADVISORY COMMITTEE ON BLOOD SAFETY AND AVAILABILITY

Sixteenth Meeting

WHAT LESSONS CAN BE LEARNED FROM THE EVENTS
OF SEPTEMBER 11, 2001, THAT WOULD STRENGTHEN THE SAFETY
AND AVAILABILITY OF
THE UNITED STATES BLOOD SUPPLY?

Volume II

8:02 a.m.

Friday, February 1, 2002

Hyatt Regency Capitol Hill Hotel
400 New Jersey Avenue, N.W.
Washington, D.C. 20001

PARTICIPANTS

Voting Members

Mark Brecher, M.D., Chairman

Larry Allen

Celso Bianco, M.D.

Rajen Dalal, MBA

Richard Davey, M.D.

Ronald Gilcher, M.D.

Edward D. Gomperts, M.D.

Paul F. Haas, Ph.D.

W. Keith Hoots, M.D.

Dana Kuhn, Ph.D.

Jeanne Linden, M.D.

Karen Shoos Lipton, J.D.

Lola Lopes, Ph.D.

Gargi Pahuja

John Penner, M.D.

Mark Skinner, J.D.

Jerry Winkelstein, M.D.

Government Representatives [Non-voting]

Mary Chamberland, M.D.

Jay Epstein, M.D.

Colonel G. Michael Fitzpatrick

Harvey Klein, M.D.

David Snyder, D.D.S.

Consultants to the Committee [Non-voting]

Christopher Healey, J.D.

Allan S. Ross

CONTENTS

AGENDA and ITEM

FDA Perspective on Disaster Preparedness
in Relation to Blood Products
Dr. Richard Lewis
Food and Drug Administration

Potential Biological Threats to the Blood Supply
Dr. Edward Tabor
Food and Drug Administration

Development of Products to Counter Biologic
Threats to the Blood Supply
Dr. Mark Weinstein
Food and Drug Administration

Public Communication on Blood Issues
During a Disaster

Public Comment

Committee Discussion and Recommendations

Adjourn

PROCEEDINGS

DR. BRECHER: Welcome to the second day of this Blood Safety and Availability Advisory Committee meeting. Our first session is going to be presentations from the FDA and the FDA perspective. The first speaker will be Dr. Richard Lewis on the FDA perspective on disaster preparedness in relationship to blood products, and we will stay on time today.

DR. LEWIS: Good morning. Thank you, Mr. Chairman, Dr. Nightingale, I appreciate the invitation to address the committee, members of the committee. Thank you.

Last summer, late in the summer, in August, the Office of Blood began efforts to coordinate our efforts to address bioterrorism issues, in part, to best utilize resources because HHS has recognized that bioterrorism is an important activity or countering bioterrorism, and the events of September the 11th and subsequently the anthrax attacks in October heightened or focused our efforts a lot more on not only bioterrorism, but terrorism in general. So we've tried to coordinate throughout the Office of Blood what we can do to address this particular concern.

In looking at what we do and how we do it, as it applies to terrorism, we saw four different areas of effort. We hope to protect the blood supply, we hope to assure, in what way we can, that there is a continued supply of blood. Because we have therapeutic products, we want to take actions to assure that individuals are treated appropriately where our products can be of use.

And in recognizing that everything that we do depends on the industry, both the blood industry and the pharmaceutical industry, we need to interact with that industry.

These particular areas of focus very closely parallel the activities of the Divisions in the Office of Blood, and thus the division directors in our office and their divisions have taken the lead. On actions to protect the blood supply, our Division of Emerging Transfusion- Transmitted Diseases, with the leadership of Dr. Heron Makasi [ph], is taking the lead on this; to assure continued supply, the Division of Blood Applications, with Dr. Alan Williams; actions to treat affected individuals, our Division of Hematology, with the leadership of Dr. Mark Weinstein; and then outreach activities, we've assigned that to the immediate Office of the Director, and Dr. Ed Tabor, the associate director for Medical Affairs in the Office of Blood is taking the lead on that.

Dr. Tabor will address the committee later on this morning on another component of his activities; that is, emerging infectious diseases, but it's a component of his activities because of his interactions on emerging infectious diseases with the PHS working group.

This is what I was just describing. Each of the divisions is assigned a lead, and our counterterrorism efforts reflect those initiatives.

In actions to protect the blood supply, the Division of Emerging Transfusion-Transmitted Diseases has a number of functions. They are a research division, and thus their research is an important component of what they do. They also have responsibility for policy and regulation.

Dr. Makasi is not on the program this morning. Let me just comment briefly on those actions, and you will hear from some of the leaders later on this morning.

The research that FDA CBER does has a number of objectives. We hope to develop a new understanding in various methods of testing, to develop our own expertise in evaluating industry-submitted methods that we have to review for safety and efficacy. There have been a number of initiatives that have been completed in that division that have been transferred to industry for further development, and the Division of Emerging Transfusion-Transmitted Diseases has a large part in lot release testing for blood-screening test kits.

Some of the research that is ongoing there now that is rapidly under development includes microarray technology, as well as nucleic acid testing. In terms of pathogen removal and activation, there is a collaboration between the Division of Emerging Transfusion-Transmitted Diseases and the Division of Hematology, pathogen activation and removal with respect to both blood and blood products, as well as plasma derivatives, and the Division of Hematology has ongoing efforts in filtration methods, chemical and activation methods.

In terms of policy and regulation, we have a large part of our policy development in donor screening and suitability has to do with infectious agents. The expertise, again, lies in this division, as well as emergency release of blood components, and as I mentioned, product release and possible exemptions for product release.

I should say we heard a number of speakers yesterday comment on the lot release program at CBER. As you know, the biotechnology products are exempt from lot release, and there are mechanisms where industry products can be exempt from lot release, given that the particular manufacturer has a good record for their particular product in meeting their release specifications, as well as an overall good compliance record.

In the next category, actions to assure continued supply, we see the development of emergency response procedures as an important component. In part, again, speakers yesterday pointed out how our imagination is an important component of our response. And in identifying possible attack scenarios, we think that that is an important part of our imagination, trying to think like the enemy, to identify the way they may attack us. And the types of attacks that we're considering in developing our strategies include biological, chemical and nuclear attacks, and then to look at different ways that we might respond to attacks of various sizes.

We also heard yesterday from a number of speakers that evaluating the particular effect of an attack immediately, as well as the blood needs, is an important component. The people in the Division of Blood Applications are looking at various ways that one might be able to evaluate immediately short-term needs for blood as well as long-term needs.

We also heard how the blood that is on the shelves is an important part of our immediate response, and determining how much blood needs to be at a particular place at any one time is an important component of having a prepared response, and not only the blood, but test kits and other blood collection supplies.

You will hear more later from Dr. Weinstein about actions to treat affected individuals, but to help give you an overall framework of our plan, part of their work has to do with developing consistent advice and reviewer guidance for sponsors who may be developing investigational products.

We've recognized that immune globulin might be an important therapy in an anthrax attack, and the Division of Hematology has been coordinating with both CDC and the DOD in what it may take to develop such a product.

Also, in the event that there may be multiple types of products, licensed, as well as investigational, human derived versus animal derived immune globulins or plasma products, there needs to be strategies for prioritization, that is, which product would be used first and for which particular demographic.

And then another important component is the safety of these particular products in an emergency situation. We don't want to look at use of a particular product in retrospect and recognize that it was only used because of the immediacy of the situation, without giving it adequate safety evaluation.

I mentioned immune globulins for anthrax. There is a licensed product for botulism toxin. There was licensed products for the therapy of vaccinia, but we recognize, and I think Dr. Weinstein or some of his division will speak later about immune globulin for vaccinia in the event that there are efforts for smallpox vaccination nationally.

I mentioned previously, by way of introduction, to evaluate various inactivation methods for manufactured products. We heard yesterday from Chris Healey that it is important to the plasma industry and the plasma derivative industry to ensure that no particular bioterrorist agents contaminate their particular product. So inactivation for manufactured products are the first line of defense, one of the first lines of defense, rapid testing and release of licensed products in the event of an attack, as well as what we can do to assist in the evaluation of current supplies and possible useful products.

Finally, in our outreach activities, Dr. Tabor is leading our efforts in this, and we recognize the need to interact with blood organizations to develop emergency procedures. In fact, we have a number of representatives on the AABB Task Force that we heard from yesterday. We hope to interact with reagent and supply manufacturers in evaluating their particular reserves, as well as their strategic depots of product throughout the country.

We have seen, in a number of instances, that the interactions with other government agencies are important. We are interacting not only within CBER because the Office of Therapeutics and the Office of Vaccines have important strategies and plans are being developed so that there is a coordinated CBER effort, as well as a coordinated FDA effort, and we also recognize the need as both an HHS agency, as a federal agency, the need to interact with other groups there.

We also heard about transportation and how important transportation is, especially in the hours immediately following attack, and we recognize the need to be able to move both reagents and supplies, as well as samples. Our history tells us that sample movement was also a concern.

This is the overview of our plan. We hope that it is a coordinated plan. We would appreciate the comments of the committee, as well as the public this morning, and you will hear some more detail about the different aspects of this later on. You heard some of that yesterday from Dr. Williams as well.

Thank you.

[Applause.]

DR. BRECHER: Thank you, Dr. Lewis.

We have time for a few comments and questions.

[No response.]

DR. BRECHER: If not, we'll move on to the next speaker, Dr. Ed Tabor, on potential biologic threats to the blood supply.

DR. TABOR: Good morning. An important part of the Food and Drug Administration's response to the increased risk of a bioterrorist attack on the United States and the impact that such an attack might have on the blood supply has been the creation of a list of potential agents and their characteristics. This list can be used to guide research and policy decisions to enhance our preparedness should such an attack occur.

The FDA list is titled, "Infectious Agents Potentially Transmitted by a Transfusion of Blood Products with a Potential for use in Bioterrorism." A copy of this list was on the table outside the conference room yesterday. And, unfortunately, due to apparently a misunderstand, the list that was distributed to you is not, in fact, the most up-to-date version of the list and perhaps, if you're interested in the few changes that have occurred since that copy, just ask Dr. Nightingale, and he'll get it to you.

This list grew out of an earlier list of agents. For the past four and a half years, the U.S. Public Health Service Committee on Emerging Infectious Diseases, a working group that reports to the Interagency Working Group on Blood Safety and Availability, has met regularly to evaluate new developments in infectious diseases that might signal the emergence of any new threat to the blood supply.

The committee maintains a database of known emerging infectious agents with the potential to enter the blood supply. Most agents on that list were those whose pathogenicity was known and whose transmissibility by blood was considered to be possible. A copy of that list was also provided to the committee.

The Centers for Disease Control maintain another third list. This is a publicly available list of infectious and chemical agents that could be used by terrorists. This list can be seen at their website, www.bt.cdc.gov. Using the CDC list as a basis, we determined which of the agents on the CDC list could present a risk to the safety of the blood supply.

In general, this meant identifying agents on the CDC list that have an asymptomatic incubation period, during which someone might inadvertently donate blood. In practice, it meant comparing the CDC bioterrorism list with the PHS Emerging Infectious Diseases list for blood.

In the event of a bioterrorist attack, if infections caused by the attack remained asymptomatic for days or weeks, blood donations during that period could be infectious, and new infections could be transmitted by transfusion and be unrecognized for a period of time. Even after a bioterrorist attack had been recognized, it might be difficult to maintain an adequate blood supply if asymptomatic infected potential donors could not be easily separated from uninfected, healthy donors.

Clinical data are sparse for many of the agents on the list, so we've had to rely on expert advice rather than published studies in some situations. Much of that advice was obtained from various U.S. government agencies, including the CDC and the Department of Defense, and we are very grateful to all of those who took the time to answer our questions about the agents.

I will now present a brief summary of the characteristics of the agents on the FDA list. I want to emphasize that I am not an expert on any of these agents and that the purpose of this presentation is to provide an overview for you.

This information about the agents should provide a framework for discussion about measures that can be taken to anticipate potential bioterrorist threats to the blood supply. We need to consider potential strategies and how those strategies can be implemented efficiently. However, those strategies are beyond the scope of my present talk.

The CDC list is part of the CDC's strategic plan for biological and chemical terrorism, and the full website where the list can be seen is shown here on this slide. The agents on the CDC list are divided into Categories A, B, and C.

Category A organisms are those which are easily disseminated or are easily transmitted from person to person. They are organisms for which there is a high mortality, and they are organisms that cause diseases with the potential to cause panic in the general population.

Category B organisms are those that are less easily disseminated and have a somewhat lower mortality.

Category C organisms are in some ways nearly as important as Category A organisms. These are emerging agents that have the potential to cause the same kinds of problems that Category A agents have.

For the FDA list, we have designated each agent as being Priority 1, 2 or 3. Priority 1 are those agents that have an asymptomatic viremic or bacteremic phase, and this, of course, usually during the incubation period.

Priority 2 agents are those that may have an asymptomatic viremic or bacteremic phase, but there is either inadequate data or no data available, and Priority 3 agents are those for which there appears not to be viremia or bacteremia during an asymptomatic period, but they are agents that are transmissible by blood and appear on the two lists that I mentioned earlier.

The first and perhaps the most serious agent on this list is the agent of smallpox, variola major. As I'm sure most of you know, the last case of smallpox anywhere in the world was in 1977, and since that time the agent has been stored, perhaps somewhat naively, in only two locations--the former Soviet Union and the United States.

Our feeling, our false feeling of security with regard to smallpox, can be illustrated by two quotes from the leading virology text, the two-volume Fields Virology, and I've got those on this slide for you to see.

First of all, Fields Virology begins the smallpox section saying because smallpox is not extinct, we use the past tense in describing it. And later in the section, in the section dealing with the clinical manifestations of the disease--this is the latest edition of Fields Virology, it says, "There is little point in delineating the clinical features of this now extinct disease."

I think this illustrates some of the pitfalls in reviving lost information about an agent that was thought to be extinct.

Smallpox is Category A, Priority 1. It's an orthopox virus, a double-stranded DNA virus. Transmission is usually by oropharyngeal secretions. Now, even though the virus is present in smallpox scabs, and that formed the basis for the practice of variolation in the years before the development of a smallpox vaccination by Jenner, in actual fact, transmission by scabs is less common.

The incubation period is generally up to 12 days, and during those 12 days, there's a 2- to 4-day period viremia is present with no symptoms, and I will discuss that in a little more detail in a few minutes.

The main symptom is a rash. Death occurs in 20- to 50-percent of susceptible individuals, and death can precede the appearance of a rash. The agent is resistant to drying for very long periods of time, months at room temperature. It consists, in any one infected individual, of both enveloped and nonenveloped viruses. Both are infectious. Most of the virus particles are nonenveloped, and this could theoretically cause problems in our hopes to inactivate this in plasma derivatives if it were to enter the blood supply.

Now, as I mentioned, asymptomatic viremic smallpox can occur during the incubation period in individuals who have never been infected before. Asymptomatic smallpox can also occur in those individuals, some individuals who were previously vaccinated or were previously infected and have imperfect immunity.

There was a report in an article in 1971 that describes the detection of inapparent smallpox infections in 27 percent of contacts of new cases based on the detection of high-antibody titers. I'd like to say that I am indebted to Celso Bianco for directing me to some sources of early articles on smallpox, and if Celso will forgive me, I'd like to mention that during his medical training, he served on a ward that had 200 smallpox cases.

There is also a syndrome that occurs in small numbers of individuals infected with the smallpox virus called variola sine eruptione. These individuals have either pharyngitis and fever or conjunctivitis and no rash, and smallpox virus has been isolated from the pharynx and conjunctivia of these individuals, and I think it's safe to assume that their blood would probably also be infectious.

I'd like to just mention a corollary of concern about the smallpox virus, and that has to do with concern about the impact of vaccination against smallpox on the safety of the blood supply. There are a number of questions that come to mind, and I don't propose to answer them in this talk, but I'd like to call them to your attention.

One question is are potential donors who were vaccinated before we stopped vaccinating in 1971 in this country fully immune in some cases to smallpox or are they only partially immune and will they have the presence of vaccinia virus in their blood for some period of time or are they not immune at all to smallpox and what will be the impact of that on the blood supply?

And then, in addition, we need to ask the question will individuals who are vaccinated have a viremic period with vaccinia that will have an impact on the safety of blood that they might donate.

Another agent on the list is the agent of Rocky Mountain Spotted Fever, Rickettsia Rickettsii. This has no category. It does not appear on a CDC list, but we have designated it as Priority 1. It's a coccobacillus, with no specific gram-stain characteristics. Under natural conditions, it's transmitted by the dog tick in the Eastern and far-Western United States and by the wood tick in the Rocky Mountain regions. There is one reported case of transmission of this disease by blood transfusion.

It has an incubation period of 2 to 14 days and asymptomatic infections do occur. The symptoms are fever, rash, shock, seizures and coma, and death occurs in 3 percent of treated individuals.

Filo viruses, Marburg virus and Ebola virus are Category A, Priority 2. These are single-stranded, negative sense RNA viruses. They are transmitted by oropharyngeal secretions. This has been seen in experimental transmissions between monkeys and in transmissions to humans in the nosocomial setting. These have also been transmitted by needle stick.

The incubation period is 2 to 19 days, and there is no data available on whether viremia is present while the patient is asymptomatic. The symptoms are fever, nausea vomiting and diarrhea, wasting, and ultimately bleeding and coma, and death occurs in between 20 to 90 percent of individuals.

Yersinia pestis is the cause of plague. This is Category A, Priority 2. This agent is a gram-negative bacillus. It has an incubation period of 2 to 4 days. Yersinia pestis causes a zoonotic infection. Humans are only accidental hosts, the normal host being rats, and it's usually transmitted, under natural circumstances, from rodents to humans by fleas. Human-to-human contact spread does occur during epidemics.

The statement on the slide is incorrect. It's actually in epidemics transmitted from human-to-human by the pulmonary route. Death occurs in 8 percent of individuals, even with treatment. The death rate can be as high as 33 percent, individuals who have septicemia.

There are three major clinical forms of plague. Bubonic plague is characterized by fever and enlarged, painful lymph nodes called bubos, hence the name bubonic plague. The patients develop hypotension, shock and purpura, and the purpura gives it it's moniker, "Black Death."

The "Black Death" was the cause of about 40 million deaths in the 1,300 throughout Asia and Europe, and this included one-third of the population of Europe.

Another clinical form is a septicemic form. This is characterized by a fatal bacteremia and hypotension without bubos.

And, finally, the pneumonic form, the most contagious form of plague, occurs when the organism spreads to the lungs from the bubos. It's highly contagious and is spread by the pulmonary route to other exposed persons. It's always fatal if antibiotics are not given within 24 hours.

Tularemia, caused by Francisella tularensis, is Category A, Priority 2. This is a gram-negative coccobacillus. Under natural conditions, it's transmitted by ticks and by contact with infected mice, squirrels, beaver and rabbits. Occasionally, infections occur in hunters who handle infected animals. It can also be transmitted by food or water that is infected by such animals, and it can be transmitted by aerosol.

The incubation period ranges from 1 to 21 days, and it is not known whether bacteremia is present during an asymptomatic period. The primary symptoms are fever, lymph node enlargement and skin ulcers, and death occurs in 4 to 6 percent, even among treated individuals.

Typhus caused by Rickettsia prowazekii is not on the CDC list so it does not have a category, but we designated it Priority 2. This is caused by a coccobacillus, and it is normally transmitted by body louse or by contact with flying squirrels, in some cases. The incubation period is 6 to 15 days. It is not known whether bacteremia is present during an asymptomatic period. Symptoms include fever, rash, and central nervous system symptoms, including confusion, and death occurs in 3 to 4 percent of infected individuals and at a higher rate in individuals over age 60.

Q fever caused by coxiella burnetti is Category B, Priority 2. This is a gram-negative coccobacillus. It's transmitted by aerosols from infected farm animals. The incubation period is not known, and it is believed, although there is no data, it's believed that bacteremia during an asymptomatic period is possible. It causes pneumonia, endocarditis, hepatitis and central nervous system symptoms, and death occurs in 2 percent of treated individuals.

Crimean Congo hemorrhagic fever virus is Category C, Priority 2. This is a member of the Bunyaviridae family. It's transmitted under natural circumstances by ticks from carcasses of farm animals, contact with their blood or with the carcasses. Nosocomial transmission is occurred by blood and person-to-person spread can occur by aerosol. The incubation period is 1 to 9 days when transmitted by ticks, and from 5 to 13 days when transmitted by blood.

It is not known whether there is a viremic period in the absence of symptoms. The symptoms of this infection are shock, disseminated intravascular coagulation, bleeding thrombocytopenia, and death occurs in 10 to 50 percent of individuals.

The Hantaviruses cause two different syndromes. The Hantaan strain and Seoul strain of the Hantaviruses cause something called a hemorrhagic fever with renal syndrome. These agents are Category C, Priority 2.

The virus is normally transmitted by aerosols of rodent urine. In the case of these virus strains, it's urine of the striped field mouse and other species. The incubation period ranges from 4 to 42 days, and it appears that there are probably some individuals who are viremic in the absence of symptoms.

The symptoms of this syndrome are fever, thrombocytopenia, and nephritis. Death occurs in 1 to 15 percent of individuals and chronic renal insufficiency occurs in many of the survivors.

Other strains of Hantaviruses cause the Hantavirus pulmonary syndrome. These viruses are in Category C and Priority 2. They include the Sin Nombre and Andes strains. These are normally transmitted by aerosols of urine from the deer mouse. The incubation periods range from 9 to 33 days, and it is likely that there is a viremic period in the absence of symptoms. The symptoms of this syndrome include fever, shock, and pulmonary edema, and death occurs in 30 to 40 percent of individuals.

Finally, the tick-borne encephalitis viruses that appear as Category C on the CDC list are Priority 3. These probably include Colorado tick fever, which represents a disease caused by seven different Coltiviruses, members of the Reoviridae family. The incubation periods range from 5 to 15 days. The symptoms are meningitis and encephalitis, and death occurs in 2 to 22 percent of individuals.

This provides you with a summary of the agents on the list that we have prepared, and it should form the basis for future discussions today and in the future.

Thank you.

[Applause.]

DR. BRECHER: Thank you. We have time for some questions/comments.

Dr. Popovsky?

DR. POPOVSKY: Dr. Tabor, do your contingency planning include one of the two possible scenarios, other than the threat of actual infectivity of a unit of blood from an asymptomatic donor, that if terrorists struck a particular metropolitan area, thus, potentially exposing thousands, if not millions, of people, that then you would have to deal with one of two possibilities; one, deferrals, red blood donor referrals that would have an impact on the productivity, as it were, of blood donors for that area; or, B, that if, and I think we might hear some of that in the next presentation, we use immune globulins or other agents to defend against it, that that could cause reactivity in test results as we've seen with the influenza vaccine some years back with HTLV testing?

DR. TABOR: Well, I think this, like many things in the bioterrorism area, this is a moving target. First of all, I think the greatest immediate concern would be if donors donated and their blood entered the blood supply before we were aware of a terrorist attack, that would be our most immediate concern, and then, of course, if there were a terrorist attack, maintaining a blood supply thereafter.

If you had infections with agents for which we had no screening test, which probably would be the case, you would have to exclude large numbers of potential donors simply because of their geographic location.

DR. POPOVSKY: Right.

DR. TABOR: And you'd have a challenge in maintaining the blood supply in a metropolitan area where perhaps everybody was excluded as a donor.

And then if the attack were with an agent for which we have let's say a globulin that will be described in one of the talks later this morning, we would have to make determinations as to whether people who had received those globulins should be deferred and for how long.

But it's also a moving target because research is underway to develop screening methods to detect some of these agents in the blood setting, and I think once you have a screening--if you have the ability to screen, and I don't think that's something you're going to see in the very short term, but we might see it in the foreseeable future, that would change the regulatory picture also.

DR. POPOVSKY: Thank you.

DR. BRECHER: Celso?

DR. BIANCO: You gave a very nice summary, Ed, and I was looking at our package, and even if I don't have the right table, it's a very nice table of agents.

One observation is that there is only one Category 1, that is, smallpox, that would be the most concerning and devastating. There are other things that I think would be very interesting if they were added to the table.

The first one I think is this table actually should be widely distributed among our community so that people know a lot about it more than they do. But one thing is would those agents be inactivated by any of the plasma methods that are currently used to treat plasma derivatives, and the second one, if they partition, if they are predominantly cell associated or plasma associated, because certain products could be available still with a lower risk and others wouldn't.

I, also, think that this would encourage the people that are working with methods to inactivate infectious agents even in cellular products, to try to test their systems and see how those agents would be treated.

DR. TABOR: Those are very good suggestions, and we'll follow up on that.

Thank you.

DR. BRECHER: Rick?

DR. DAVEY: Ed, a very nice presentation.

A couple of questions about smallpox. Is the Agency aware of studies underway or are you considering studies to look at the extent and the robustness of the population's immune status with smallpox because that would--

DR. TABOR: You are referring to populations who are previously vaccinated.

DR. DAVEY: Yes.

DR. TABOR: Let me give a short answer, and then I think I'll ask one of the other people from the Office of Blood to add onto it. I know that, from discussions I've heard at NIH, that there are groups in NIID that are looking at that, and I don't know what stage those studies have reached, but I would say I first heard of them two or three months ago. So, as you are probably aware, there are ongoing vaccination programs.

I think it should be possible to look at levels of antibody in people who had been vaccinated, say, between 1940 and 1970, and also to look at the antibody response in people who are revaccinated. I wonder if, Dr. Scott, could you or Dr. Golding answer that further? Can you say something about studies that are ongoing to look at the duration of immunity in people who are vaccinated against smallpox in the past?

DR. SCOTT: I just arrived, so I missed the original question.

DR. TABOR: I'm sorry. I didn't mean to catch you off guard.

The question was are there studies ongoing to look at the duration of immunity to smallpox, which effectively means looking at vaccinia titers, antivaccinia titers, in individuals who were vaccinated in the distant past?

DR. SCOTT: Right. Our understanding is that, historically, antibody immunity can last for up to 30 to 40 years, but it isn't predictable in any one individual whether this may be the case.

I am not aware of current papers which have published data about the level of immunity, but I do know that this is being looked at by various groups. We also think that licensed immune globulins, which are not specific immune globulins, have some antivaccinia titers, which indicate that some members of the population do have antibodies.

DR. HOOTS: Can I follow that up?

DR. BRECHER: Keith?

DR. HOOTS: What about cellular immunity? Have people looked at, I mean, we know that in hepatitis B, for instance, you can over the years lose your humeral, at least detectable humeral, immunity and still have very good cellular immunity and be relatively resistant, if not completely resistant to reinfection?

Has anybody looked at specific smallpox antigen response to ex vivo T-cell responses like is done with HIV and hep B and that sort of thing?

DR. SCOTT: I attended a CDC meeting last March, and this was part of the topic, and there are some members of industry and academia who are looking at this, although the assays for cellular immunity in vitro haven't been well developed. But another thing suggests that some cellular immunity exists, and that is that some people with low antibody titers still don't have a very good response to the vaccine when they're revaccinated, suggesting that they have active cellular immunity.

DR. BRECHER: Ron?

DR. GILCHER: Mike, my question relates to a different virus, one that's very common, hepatitis A.

My question is this: Bioterrorism doesn't necessarily have to kill. All it has to do is create tremendous fear, anxiety, disrupt everything we do. Hepatitis A is easily spread. On the other hand, it's very easy to vaccinate, as far as numbers of people, which we're doing in the U.S. Have you considered hepatitis A as a potential bioterrorism virus and, if not, why?

DR. TABOR: We haven't. Let me start out by saying I feel that the whole topic and the list are dynamic, and we welcome suggestions. Sometimes it takes a new view to be able to see something that one wishes one saw beforehand.

I think in the case of hepatitis A, the risk to the supply of blood for transfusion would probably be quite low because the period of infectivity for hepatitis A is really, well, it's short, but I guess it does occur before symptoms appear, so there could be a period when people would donate. It's worth considering.

DR. GILCHER: I have done two studies in my life, one at the University of Pittsburgh, about 25/28 years ago, and one when I came to Oklahoma, where I looked at 2,000 blood donors who said I have never had hepatitis. So they had passed the screening.

Of interest, one-third of those individuals in Pittsburgh, now this is almost 30 years ago, had anti-HAV, and in Oklahoma about 28 percent, one out of four, had anti-HAV. So these are old studies, but it showed how common the infection was.

The point is that I think we've been protected in the past by the fact that so many people have had subclinical infections, and that may even true today, but I don't know. But it does get into the blood supply, in rare instances, and would pose a threat, and it would potentially remove large numbers of potential donors. That's my concern, and we would take out huge numbers of donors. They would be deferred for six months to a year, depending on what criteria we would put in at that point.

DR. TABOR: Well, in fact, if there were--the suggestion about hepatitis A is a good one, and we'll consider that. I don't think it would cause a problem for up to a year, however.

In the American population, I think the prevalence of antibody to hepatitis A is probably, in young adults, somewhere around 20 percent and substantially higher in middle age and older adults. But the infectivity period for hepatitis A virus ranges from 2 weeks before the onset of symptoms until very slightly after the onset of symptoms.

So, once we were aware of a bioterrorist attack with hepatitis A, it would be something that we could deal with, I think, quite easily, and really the risk would be before we were aware that we had, for instance, that the water supply of a major metropolitan area had been contaminated or something like that, but hepatitis A is a good suggestion, and we'll consider that.

DR. BRECHER: Ed, following up on what Ron said; you know, the goal often is to create terror. Has the FDA taken any specific actions to try to prevent sabotage of pharmaceuticals or blood bank manufacturers or even thought along those lines? I mean, I would think someone could come in and spray bacteria at some stage of processing after the QC that would have major ramifications.

DR. TABOR: If it's all right with you, I'd like to refer that question to someone else, if I could.

Dr. Epstein, could you try to answer that?

DR. EPSTEIN: We have certainly thought about sabotage, and it would include chemical, as well as biological threats. I would just have to say that thinking about response plans is just at a very primitive stage. Likewise, the whole issue of dealing with mass disruption of the donor base, thinking is at an early stage.

So, you know, we're aware that these concerns are part of the spectrum. It's just that we're trying to focus here and now on identifying the biological agents of concern, and we are going to have to deal with these other concerns.

DR. BRECHER: Question from the audience? Please identify yourself.

MS. KHABBAZ: I'm Rima Khabbaz from the CDC.

I just wanted to mention, if people are interested, there is a recent, the February issue of the Emerging Infectious Diseases Journal has an article that outlines the criteria and rationale for the Category A, B, C lists for Bt agents that Ed mentioned, and these categories, these lists, are not meant to be extensive or all agents that could be used for Bt, but, really, the division by category is to guide public health preparedness, and I would refer you to that article to clarify how the process took place.

DR. TABOR: Yes, that article is actually very good and provides an historical perspective on the development of that list.

DR. BRECHER: Celso?

DR. BIANCO: I think that we can think a lot, but what I think very valuable from the CDC criteria and in the way this has been done, is that gives a set of priorities; thinking that a terrorist or whoever wants to have impact, which ones would have the biggest impact and which ones we would be forced to address. We can't do focus groups with the terrorists to see--

[Laughter.]

DR. BIANCO: So, in a certain way, I think that the most important thing is to prioritize and to see where we put our initial effort.

DR. TABOR: I think, similarly, you may want to think about putting a priority, in terms of ease of manufacturing. Some of these organisms are much easier to grow than others.

DR. HEALEY: As I mentioned yesterday, at least at the fractionation facilities, they do have emergence response plans in place for what might be considered anticipated events, such as a fire or a HAZMAT spill, things like that.

I can also tell you that, post-September 11th, security at the facilities has been on heightened stage of alert for most of these facilities. Most of them are secure facilities, to begin with; you know, pass card entry and so forth and so on. But through our working groups, we are looking at sabotage and things like that, so it's something that is on the table.

DR. BRECHER: Okay. If there are no more questions or comments, we'll move on to our third speaker, Dr. Mark Weinstein, talking about development of products to counter biologic threats to the blood supply.

DR. WEINSTEIN: It will take a few minutes to boot up the computer.

[Pause.]

DR. PENNER: I'd like to add a comment while we're waiting, and it's already been brought up, but from the committee's viewpoint, we'd really like to know which of these agents are going to be susceptible to withstanding what is normally used as protective measures for blood and blood products. How many of them can withstand the cold for two weeks or a month? How many of them can withstand heat, detergent, et cetera? So if that information was suggested, I think it would be very important if we could get it.

DR. WEINSTEIN: We'll be addressing some of those issues as we go along in this discussion.

Dr. Lewis has already given you an overview of the Office of Blood's strategic plan to counter terrorism. Part of that plan is to help in the development of biological products to treat individuals who have been infected by certain pathogenic agents that might be used as terrorist weapons.

The focus of today's discussion will be about our efforts to address the threat posed by Category A infectious agents that have been identified by the Centers for Disease Control and Prevention.

I will talk in general terms about our overall strategy, after which my colleagues at the FDA will speak more specifically about our progress in developing hyperimmune globulin products directed against anthrax, botulinum, and vaccinia.

One of the first things that we did to develop our strategic plans was to form small working groups within the Office of Blood to evaluate each of these agents identified as potential threats.

These working groups interacted with other groups within CBER, with our sister agencies in the Department of Health and Human Services, and with the Department of Defense to form interagency working groups. I'd like to emphasize how good these interactions have been and how necessary they are to really develop a comprehensive plan to address these agents, potential pathogenic agents and threats.

One of our objectives was to identify those pathogens in Category A that might be amenable to treatment with biological products, particularly immune globulins. At present, we are focusing on anthrax, botulism and vaccinia. However, potentially, immune globulin products could also be developed against plague and hemorrhagic fever viruses such as lassa, Argentine and Marburg viruses. It is unlikely that an immune globulin product will be effective against tularemia. We are also interested in developing immune globulin products directed against other infectious agents, not on the A list, but these efforts are of lower priority at present.

We assessed the potential of hyperimmune globulin therapy to be effective against the three pathogens. In the case of botulism, high titer immune globulins from human and animal sources are considered effective. Vaccinia immune globulin is thought to be effective against certain complications of smallpox vaccination. In both cases, however, our conclusions are based on small, uncontrolled studies. Less is known about the effectiveness of immune globulin therapy against anthrax. The less that is known, the more work that has to be done by way of preclinical and clinical trials to establish the safety and efficacy of the product.

To help us focus and prioritize our efforts, we estimated how much product is currently available and the potential need in the future. The latter calculation was based on estimating the number of individuals likely to be affected, the effective dose, the amount of material presently available, and the presence of supportive care.

From this assessment, we can estimate how much high titer immune globulin needs to be made. In all cases, it is clear it would be beneficial to have larger amounts of hyperimmune globulin products than we have currently available. To produce these products in large quantities, we will need a scale of manufacture several orders of magnitude larger than any done in the past.

Polyclonal immune globulins can be derived from human or animal sources. Before these products can be prepared in large quantities, high titer human plasma might be useful as potential therapy in some situations; for example, a treatment for anthrax, where no manufactured product is now available.

Another source of therapy that bears consideration is that from immune globulin products that contain high titers of vaccinia immune globulin. They might prove useful as an interim measure before large amounts of the hyperimmune product can be developed. We are actively considering this, but this is not the focus of today's discussion.

To obtain potential sources of hyperimmune globulin, the Office of Vaccines at CBER, the NIH, and the DOD have helped to identify vacinees as potential plasma donors. Once identified, efforts will be needed to recruit these vacinees for plasma donation. For the manufacture of plasma derivatives, plasma must be collected under specified screening and testing requirements for source or recovered plasma.

In some cases, particularly for botulinum immune globulin, it is unlikely that large numbers of human donors will be available. It may be necessary to rely on animal sources to prepare large amounts of this product. FDA has helped to clarify what are the requirements to collect plasma from each of these sources.

Finally, the large-scale manufacture of these products is dependent on obtaining a sponsor who may or may not be the manufacturer and a suitable manufacturing facility. FDA has assisted CDC in identifying potential manufacturers of immune globulin products so that CDC could make decisions about whom they might want to approach. The pool of vacinees is limited, so it is important that there be a coordinated effort to use this resource most efficiently. Another issue that must be resolved is who is to pay for the development and manufacture of these products.

The Office of Blood is heavily engaged in helping to design criteria for the licensure of these products and in evaluating preclinical and clinical protocols.

In some cases, there are no recognized surrogate markers for clinical efficacy.

Given the current state of knowledge, some products may be licensed on the basis of PK, and safety results by surrogate markers for efficacy will be obtained in post-marketing studies. Today you will hear about our current thinking regarding the clinical development of the VIG.

The Office of Blood is involved in the development of new potency assays. Research work is required to establish which of these assays will be predictive of clinical utility. We are also developing new potency working and reference standards for some of these products. These standards are essential as references to establish potency of new manufactured products.

Now, there are a number of unresolved issues. One is the funding for development and manufacture of new products. The manufacture of large amounts of products that we hope will never have to be used does not seem to be commercially viable. Decisions have to be made about who is to fund and what is to be funded. This issue of funding is part of the problem of coordination and prioritization. Potential products have been identified, and as you will hear, a great amount of preparatory work has been done already on the feasibility of large-scale manufacture. But we have to decide which, if any, of these products are to be manufactured.

If these products are developed, decisions will have to be made about how they will be distributed, who will distribute them, and who will receive them.

I would now like to introduce my colleagues, who will tell you in more detail about our plans to develop these products. Dr. Golding from the FDA will talk about the development of botulinum and anthrax immunoglobulin products from the perspective of the FDA.

Nina Marano from the CDC was expected to talk about their plans to develop anthrax immunoglobulin, but she is stuck in Atlanta. However, Dr. Golding has reviewed her slides, and we will see whether he can carry it off and tell you about what she had intended.

Finally, Dr. Scott from the FDA will speak about our plans for a vaccinia immunoglobulin.

Thank you.

DR. GOLDING: Good morning. I'll be talking about the FDA role in botulism and anthrax immunoglobulin preparation.

As you probably know, Clostridium botulinum is a gram-positive bacillus, and it makes an exotoxin, in other words, secreted toxin, and that there are eight different strains. And, unfortunately, these eight different strains are non-cross-reactive, so an antibody against one strain does not neutralize the other strains. So you have to make antibodies against all strains.

The toxins can be aerosolized and used as biological weapons. The toxins act by binding to nerve endings and interfering with nerve impulse transmission to muscles resulting in paralysis. This is a very distressing condition because the victim cannot talk, cannot breathe, and is in very dire straits unless the victim is helped. And the treatment consists of respiratory support and antitoxins.

We did this back in '96 and we did in again September 11th and we did it again recently for the Winter Olympics. We assessed what are the current supplies, and we do this on a routine basis in the Office of Blood. And there is one licensed product made from horses in limited amounts, and there are some IND products made by various sponsors, mainly the Department of Defense, and these products are now available through agreements between the CDC and the DOD under INDs so that they will be accessible should there be any biological threat with botulinum. And the DOD, in other words, has agreed to ship a large amount of its material to depots that will be accessible to the CDC in case of an attack.

So this has involved obviously all kinds of logistics and discussions between us, the CDC, Department of Defense, and including the NIH.

As I mentioned, an IND was drafted for the Olympic Games in '96, and this IND not only mentioned all the products that were available under licensed products and IND products, but also gave an algorithm, providing the algorithm for treatment. In other words, what do you start with first? What do we think is the most appropriate of the antitoxins to use first? And when that's used up, how do you go to the next product and so on?

It's clear that these products have a finite life, and we have to be interested in facilitating development of new products. And through our BOONS (?)--that's our computer system--we've been able to identify INDs that are actually regulated by the Office of Vaccines and communicated with them and identified groups of individuals that are being vaccinated with botulinum toxin and could be a potential source of new product. And we've entered into discussions regarding this with CDC, DOD, and NIH, and we are trying to encourage sponsorship--well, the FDA cannot sponsor the actual IND. It has to be a sister agency that sponsors the IND.

An important aspect that Dr. Weinstein already mentioned is to develop and validate the in-house standards and assays. Part of the problem is, because there isn't a lot of commercial interest in any of these products, that the government has to step in and provide the background for potency assays and to make sure that standards and assays are available. And a lot of work is being done in this respect by different agencies, including the FDA, and this is done mainly in the Office of Vaccines and Bacterial Products.

So this can be done by us or it can be done by other government agencies or by contractors to ensure that standards and validated assays are available.

So the current status of botulinum immunoglobulin, as I mentioned, there are licensed and IND products. The human licensed product is a relatively old product made in horses, and it is only active against three of the toxins: A, B, and E. The equine product that is available from the Department of Defense is a heptavalent product and is available against--and is potent against seven of the different toxins, and there are various human INDs that are pentavalent and are active against five of the toxins.

So we do have product available for any bioterrorist threat at this moment in time, but I think it's important to emphasize that for the future there needs to be some kind of plan to develop new products, one, because these products have a finite lifetime and, two, because we have--if we are in a situation where we're using up some these products, we need to have some kind of back-up in case of additional threats.

Moving to anthrax, bacillus anthracis is gram-positive. It can be aerosolized, as we found out recently, and used as a bioterrorist agent. Contact can cause cutaneous or skin anthrax, but the severe form of the disease is due to inhalation and various forms of pulmonary involvement, particularly hemorrhagic mediastinitis.

But, again, like botulinum, important in the pathogenesis are the release or secretion of exotoxins, and there are three actual proteins that are secreted by the bacillus that are critical. The protective antigen actually provides a docking space on the cells that binds to cells, forms a pore, and the other two toxins can then bind and gain entry to the cell and do their damage. So the other two toxins are named edema factor and lethal factor.

So treatment or prevention, I'd just remind you that in this last set of events where anthrax inhalation was occurring, five of the eleven patients with inhalational anthrax died, and that was despite intensive antibiotic therapy. So, clearly, antibiotics are important, but if we had other agents that were effective, we should try them, and immunoglobulin's obviously something that is worthwhile trying.

The other option, of course, is vaccines. This is the human vaccine called AVA. As you may have read from your newspaper this morning or heard yesterday, it has been released now and is again available. This is mainly against the protective antigen. The data that we've seen, multiple injections are required to get some kind of titer, and those titers follow very quickly after the last immunization. So the titers don't last for much longer than three to six months.

This is a treatment modality that's important, but, again, it's not optimal treatment for this condition. And that's why the equation of antibodies and immunoglobulin products was raised as a potential for treating anthrax.

The evidence for the antibody role is scanty. Experiments have been carried out in vitro showing toxin neutralization. Experiments have been done mainly in rodents showing protection, and this has been done to a large extent mainly with the horse serum or horse product and a very limited extent of any human serum or product.

So the possible clinical indications for antibody use would be inhalational anthrax not responding to antibiotics, but this could be expanded if we had enough product to consider post-exposure prophylaxis. If anthrax organism was used that was designed to be antibiotic resistant, as far as I know the only the Internet we have is to use antibodies, and then you would also maybe consider high-risk patients such as the elderly, immunosuppressed, diabetics, and so on.

So what have we done? We've identified vaccinees. This is obviously together with other agencies. Our first identification involved contacting the Office of Vaccines, speaking to the reviewers and then speaking to people in CDC, Department of Defense, and NIH. Independently of us, the CDC obviously had been thinking about this, and together with the CDC and other agencies, an IND was drafted by the CDC and submitted to us for advice, and this IND is expected to be submitted as a basis for use of human anthrax immunoglobulin for treatment of inhalation anthrax.

We also have research plans at the FDA to provide a basis for development of a sheep anthrax immunoglobulin.

And that plan, just a few points about that plan. We want to study different vaccines or immunogens in animals, and the advantage of using animals is that you can use the whole bacillus. There is an attenuated strain that is approved by the USDA for vaccination of animals, and this contains all three toxins and some other cellular components of the bacteria, and there is at least a theoretical possibility that using this antigen will give rise to more extensive antibody response that may be beneficial in treatment. So we'll chose the immunogen that elicits the highest titer and identify manufacturers or sponsors to make products in animals. We also need to facilitate preclinical testing in mice, rabbits, and possibly monkeys, and, very critical, we need to develop standards and assays. Some of these assays are already up and running in the Office of Vaccines, and we need to work with them in order to validate them and make them available for these products.

Again, with animal anthrax immunoglobulin, we need to facilitate IND submission and product approval.

I think I've covered this slide. So the assays that are available, there's an ELISA assay in laboratories at the NIH and FDA. There's the toxin neutralization assay that's available at CDC, USAMRIID, and at the Food and Drug Administration, and rodent testing available at CDC and USAMRIID. And there's potentially monkey testing in Rhesus macaques, and this would be the critical test for any product. But the problem is that there's a shortage of monkeys, and this is a bottleneck. So you're only going to do this testing when you have developed a product to a point where it's very close to human use, and this would be the final critical test of efficacy using monkeys and using inhalational anthrax as a challenge.

So the current status of the anthrax program, high-titer fresh frozen plasma units are available for inhalational anthrax and for production of a pilot lot of anthrax immunoglobulin, and there's a plan to test animals with human high-titer anthrax immunoglobulin. And there's a consensus of the anthrax immunoglobulin working group to plasmapherese vaccinees for manufacture of an anthrax immunoglobulin product.

I just wanted to give this slide--this pertains, I think, to all the products that we're talking about, and this is a hypothetical calculation. But it's just to give you some feel for how our thinking is--how we calculate the dosages and the needs in terms of actual human doses. So the variables, when you think about it, are the antibody titer in the product, the expected toxin level of viral or bacterial loads in the victim, and the relative affinities.

What I mean by that is the antibody will have a certain affinity for the toxin or the virus, but the toxin will have a certain affinity for a cell receptor. And you want to have an advantage with your antibody so its affinities are at least in the range of binding that would enable it to compete with the toxins binding to the receptor.

So rough estimates--and I've used as an example here anthrax immunoglobulin. If you consider a dose--and this is a ball park figure--of 100 milligrams per kilogram, and you're considering a 70-kilogram person, this is 7 grams of product. To obtain 7 grams of product, you would need two units of plasma; in other words, plasmapheresis of about 750, 800 ml. And the reason why you need two units is because during the manufacture you lose 50 percent of the immunoglobulin.

So if you had 100,000 victims of a particular attack, you would need to have started with 200,000 units of plasma to manufacture the product, and one way to do this is to have a donor pool in the range of, say, 20,000 and have plasmapheresed these donors ten times.

Now, this is eminently feasible because there are many more than 20,000 people out there in the military that have been vaccinated against anthrax. For this scenario, this would be a feasible project to pursue.

Acknowledgments. I couldn't fit everybody on one slide, so I'm going to start out by saying that the most important people are not here. The upper management of CBER--Jesse Goodman, who's in the audience, Jay Epstein, Mark Weinstein, Richard Lewis--have supported and directed this effort and made sure that we have kept our nose to the grindstone. But we have had considerable help from other people within the agency and in other agencies. So regarding the botulinum, in the FDA Marian Gruber and Cynthia Kleppinger are experts in this area and are reviewers of the INDs. Nisha Jain and Toby Silverman are in our division and are clinical reviewers and have helped prepare the data. In the CDC, we've had frequent contacts with John Beecher, Debbie Dodson, and I'm probably missing some names.

Regarding anthrax, again, in the FDA, Cynthia Kleppinger and Bruce Meade as the research basis and has been developing the assays, and Ross Pierce is a clinical reviewer that's worked extensively with the CDC in talking about the need--what is needed to be done in order to prepare an IND. And in the CDC, some of the people involved are Jai Liapapo and Nina Marano, who is going to give the next--was giving the next talk. And I guess I'm going to need help to find her talk.

Should I ask for questions?

[No response.]

DR. GOLDING: Actually, this is a test because I didn't actually plan it that way, but the ability of me to present Nina's talk would reflect on how good our communications have been and whether I really understand what they're doing.

This is going to be somewhat repetitive, but this is from the CDC perspective, the anthrax immunoglobulin for prophylaxis and treatment, an interagency product, the development plan, and she has CDC, NIH, DOD, and FDA is hidden somewhere down there.

Immunoglobulin as adjunctive therapy for inhalational anthrax. So the toxin plays a important role in the pathophysiology of acute inhalational anthrax disease. Recent anthrax bioterrorism events have shown that treatment with antibiotics alone is not fully effective, 45 percent case fatality rate, and immunoglobulin as an antitoxin is used for other toxin-mediated diseases such as botulism, tetanus. And I would add here that I think the same principles are involved in neutralizing a toxin as you would for neutralizing a drug. And as some of you may know, there are polyclonal immunoglobulin products licensed for treatment of the digoxin overdosage.

Anti-anthrax immunoglobulin equine is currently generated using live strain anthrax vaccine in Russia and China. We have tried to get data from those sources, but I haven't seen anything apart from verbal reports of efficacy.

Potential use for infection with antibiotic-resistant strains, and there's limited animal data, equine antisera in particular, on efficacy with no information on dose, timing, and potency. And what this points out is some of the work that we have to do, either in the FDA or other agencies. There's a lot of preclinical testing that needs to be done that would help in decisionmaking regarding treatment of patients.

Okay. What the CDC has been doing and the way I like to think about it is this is what they were doing pre-September 11th, starting out in March of 2001. They had an interagency agreement with USAMRIID and NIH to recruit and screen the AVA vaccinees. So these are military vaccinees receiving the human-licensed anthrax vaccine, and they were going to obtain anthrax immune plasma by plasmapheresis, and then they were going to use this to make reagents for quality control of serology assays, in other words, set up standards, and they would also use the IG preparation for animal studies of passive protection. So, in other words, they were going to make a product from some plasmapheresed military personnel and use that to make standards and use that to do preclinical testing.

So they collected 115 600 ml plasma units. They were collected at the NIH and stored at USAMRIID, and they were screened by an ELISA assay, which measures protective antigen, and you can see at the bottom of the slide the range was quite variable. The median was 277 micrograms per ml, which I would say, considering other hybrid immunoglobulins and other infections and toxins, is a very respectable titer. Obviously this is just a binding titer, and we don't know anything about functionality. But as binding titers go, this would compare favorably with other infectious states or other situations where you--or the type of antibody levels you would like in order to neutralize a toxin.

So in mid-October 2001--this is obviously post-September 11th--discussions were held with the CDC for possible uses of the anthrax immune plasma and anthrax immunoglobulin for treatment of future anthrax cases. So what happened, we said, okay, you know, now this is a real situation. We have anthrax cases. What do we have and how can we use it? And what they had was these plasmapheresed units, and the idea was to set aside some of those units for compassionate use and then to go on and to make a product with the remaining units.

October 26th, the FDA convened a multi-agency conference call chaired by Jesse Goodman, and December 7th, an IND protocol was submitted to CDC IRB. December 12th, the Department of Transfusion Medicine at the NIH submitted a protocol to their IRB for plasma collection from AVA vaccinees. And this was in order to allow collection of plasma and to prepare fresh frozen plasma for compassionate use, and, in addition, to use these units to prepare an anthrax immunoglobulin product.

So for these considerations for making the anthrax immunoglobulin intravenous product, the plan should ensure an adequate number of doses for civilian and military use. So this is several--on the order of several thousand treatment doses. And enough was prepared--you know, I would say this slightly differently. I mean, the immediate need, I think everybody would agree, is that you have material for patients who are dying because they're not responding to antibiotics. But in addition to that, you could consider adequate quantities for repeat dosing. You could consider adequate supply for post-exposure prophylaxis and treatment for antibiotic-resistant strains if this were to be found. And you would need full cooperation and enthusiasm of industrial partners for product expansion.

And as you go from bullet to bullet, I think you're increasing the total amount that you need by an order of magnitude, at least.

Okay. So the product development, and this Mark Weinstein said several times and is very critical to the success of this whole policy. We need to identify industry partners to process existing units to AIG, and the GMP material has to be used for preclinical animal testing and manufacturer must be capable of appropriate product characterization, and CDC bioassays and reagents should be available for technology transfer.

The idea is that CDC or other government agencies would have standards and assays in place so if a manufacturer was identified and funding was available, they could go ahead and make the product, and they wouldn't have to spend a down period developing assays, that these assays would be made available by government agencies. And we need to establish a continuity of supply of at least 500 to 1,000 liters.

So what is in progress is collaboration with USAMRIID, NIH, and a commercial plasmapheresis partner, and the idea is to perform GMP fractionation to AIG IV for animal and human clinical studies, and maintenance of some of this material as a reference standard.

So the product that is made, according to GMP, ideally would be used for the preclinical animal testing. If you make something offline and it's not under GMP and you do preclinical testing, it's somewhat problematic to the FDA. So it is important, if possible, to do the preclinical animal testing with a product that is made by a manufacturing scheme that can then be used to make subsequent products. This preclinical animal testing would be in small animals, rabbits, and rodents, and we've mentioned the monkey model, which is really inhalational anthrax. And human testing would be used to determine safety, tolerability, dose ranging, and PK, pharmacokinetic studies. And based on these results, you could make recommendations hopefully about dosing, and this would probably be the basis for licensure.

So the goal is to obtain a larger lot of plasma for manufacture, a donor pool. These could be donors from U.S. military bases. There are many, many thousands of soldiers out there that have been vaccinated and have a high titer. The military vaccinees, they know already on the basis of studies that have been completed that they need at least four doses of the current vaccine and a booster within 12 months to have reasonably high titers. And in order to do this in an efficient way, you need to use a commercial plasmapheresis facility, and you need an industrial partner who is in from Ground Zero, I would say, to develop this product and that has the infrastructure to do this in an efficient manner.

So what is required? Extensive interagency interaction and collaboration, expert preclinical and animal studies, expert laboratory support for testing of pilot efficacy, an experienced industry partner, coordinated, ethical IRB review process, intensive partnership with the FDA, dedication of adequate personnel and funding, and the funding should be underlined three times.

Acknowledgments. These are Nina's acknowledgments: Jai Lingapapo, who's at the CDC and prepared the IND; Bradley Perkins, who's at the CDC; Dave Stephens at the CDC; Conrad Quinn at CDC. So all these people are involved with anthrax. Phillip Pittman, who's actually in charge of the IND trials for the anthrax vaccinees; Susan Leitman, who's at the NIH, the Director of the Transfusion Service; Chris Ockenhouse, who's an M.D. at Walter Reed, who has come up with a development plan in parallel, and a lot of his points are now being taken into consideration; Robert Gasser, also at Walter Reed. The rest of the players I think you know: Mark Weinstein, Jay Epstein, myself and Jesse, all from the FDA.

Thank you for your attention. If there are any questions?

[Applause.]

DR. BRECHER: We have time for some questions. Keith?

DR. HOOTS: It seems like what we've heard a lot of are the types of bioterrorism that one would traditionally think of as state-sponsored or device-delivered, the sort of thing that militaries would have developed over time for that use, insidiously, perhaps. How much thought--I'm sure a lot of thought has--but we just haven't heard anything about it today, and I just thought I would ask. In terms of the blood supply, there's another way to think of things--getting back to what Ron's point was--in terms of terror, you know, there's the type of terror we've all felt after September 11th, which is acute. But if you think about how it came to be, it actually was very insidious because all the processes that allowed that to come to be took two or three years underground to develop. So obviously time is not an issue, really, when you're thinking about it. It's more how do you get the most impact and how could you possibly deliver things insidiously so that you actually build terrorism over time.

If you were going to do that, one of the ways, it seems to me, is if you had an agent, probably some sort of infectious agent, that was easily delivered internally, that would then become, you know, incorporated, you know, and then perhaps be transmitted by blood down the road in its resting phase, what kind of--you know, I mean, obviously that's almost impossible to answer. I understand that. But I raise it because those--you know, we're talking about PPTA and all the stringencies that have gone into trying to protect their plasma. But if you were going to do something very insidiously and you chose a product that was widely available, table salt, table sugar, something like that that you could get into, you know, how those kinds of things--are they on the table for discussion as far as how to prevent that kind of thing from happening?

DR. GOLDING: Well, you know, I think you're opening up the discussion to a very wide area, and, you know, table salt, for example, I don't know what the Center for Foods is doing to protect foods. There obviously have been attacks where people have sprayed salmonella on salads and stuff and things like that. So I don't think I'm in a position to answer that question.

I think that for the most part what we're talking about here are agents that could be treated by antibodies, and that's what we've focused on. It may be, again, regarding a previous question, that, you know, what we've done is focused on the Category A agents, and even there we're narrowing it down to anthrax, smallpox, and botulism. So we are narrowing our focus, and maybe that is a mistake. But I think that if there were evidence in the literature, first of all, that these threats are potential and real and that antibodies would be protective, I think that would--any area like that we should look into. So we should keep our eyes open and try and be aware of other threats, and if you can make antibodies against it, we should think about that seriously.

DR. BRECHER: Chris?

MR. HEALEY: This isn't focused on the bioterrorism point, but it does go to the issue of blood and plasma availability and terrorism along those lines. Has the agency looked at all the suppliers of materials that go into, you know, blood and plasma production, particularly where there may be sole suppliers or relatively few suppliers, and trying to assure that stockpiles are--those supplies are available in the event that there was some action against one of those?

DR. GOLDING: I'm trying to understand your question. You're saying that this is not necessarily to treat bioterrorist agents. You're saying, just to give an example, there's a hyper-immunoglobulin against hepatitis B and somebody targets that manufacturer because it's--and there's a limited supply and that's what caused the problem. Is that your question?

MR. HEALEY: Actually, no. My question is more along the lines of if--and this is completely hypothetical. If, for example, there were a sole supplier of a certain type of glass used for vials for products, has the agency looked at those types of components to assure that if one of those suppliers were suddenly unavailable, that there may be alternative sources available?

DR. GOLDING: I think I'll defer that to Jay.

DR. EPSTEIN: Why do I always get the hard questions?

Well, I think the way I look at it is that we're at war, that what we're talking about is part of homeland defense, and that the effort has to be an all-court press; and that we are here, at least in part, to get the best possible perspective on what concerns we should be focusing on.

Now, having said that, we can only be where we are, and we have finite resources. And there's a need, at least at this stage of the effort, to have very clearly focused priorities. And where we have gone first is to focus on what appear to be the leading threats.

That's not to say that we will disregard or can afford to disregard other potential threats. But if the committee or other organizing groups, you know, within government or the private sector, have a different perspective on where the priorities ought to be at this stage or as we go along, we certainly have an open mind because, you know, the goal is to address all threats. It's just that we cannot do everything at once.

MS. LIPTON: Jay, I agree with you. I think that Chris' point, though, is something that we were looking at yesterday, and that is, that in the long term you need to build redundancy into the system. And, you know, we are in a very peculiar environment, I think, in blood banking and transfusion medicine, where, instead of seeing people coming into the field and developing multiple suppliers, we're seeing a consolidation, I think primarily related to economic issues. So you're right, it's nothing we can focus on right now, but the same way we worry about building in redundant capabilities, you know, to respond to disaster, we ought to be thinking about that.

DR. BRECHER: Let me just say one thing, Jay, then you can go ahead. I think the sense of what we've heard this morning is that the blood supply is a secondary target, where the perception is that it would not be a primary target of a terrorist act.

However, I could see that if somehow they contaminated 50 units around the country, the tenuous confidence that the blood community has built with the public would be shattered, and no one would want a blood transfusion all of a sudden. And so it is, I think a potential primary target, and we need to at least think along those lines as well.

Jay?

DR. EPSTEIN: I couldn't agree more, Mark, and you just have to remember cyanide in Chilean grapes to realize what kind of panic can come from a minuscule outbreak.

But to Chris' point and Karen's comment, I quite agree that managing supply in the face of disruptions is one of the key objectives in counterterrorism planning. It's one of the things that Dr. Lewis highlighted. And I think that the entire set of presentations yesterday was meant to be eye-opening about what the issues are.

I would only say that we should not assume that every answer comes from government, and one of the issues that this committee is here to deliberate is the proper role of government versus private sector initiative. So I agree with you, Karen, and I'm glad as representative of AABB that it's you that said it, because I do think that the industry needs to examine how it is currently structured and how it currently functions in terms of becoming robust to threats, threats to the system. And that would include the spectrum of threats. You know, it would include outbreaks. It would include vaccinations. It would include, you know, physical disasters. And it would include tampering and sabotage. It's all of the above.

DR. DAVEY: Along those lines of preparedness, we focused on blood and donors and the public. I'd like to put on the table the impact on the staff of our facilities itself. In New York City, you know we had not only the Twin Towers disasters, but then the anthrax consideration both here in Washington and New York. We had blood drives at NBC when those letters were discovered. We had a blood drive at Governor Pataki's government building when that issue was discovered. We had a death of a person who worked two blocks from our blood center. And our staff was understandably very, very concerned about the potential impact of this threat on them, on their personal health.

So I think in my experience, I found very quickly that I had to become an expert on anthrax and cutaneous anthrax--and I must say I haven't seen a lot of cases in my life. But I do want to thank the CDC for getting the material together very quickly that helped. A number of employees came to me with skin lesions. You had to know a little bit on what to tell them, and it was a little rough.

Our mailroom people were especially concerned about handling bulk mail. We took a couple steps. We moved all activities that weren't related to mail out of that area, like copying machines, et cetera. We put in HEPA filters so that big mailbags could be opened in a negative pressure atmosphere. Again, that was along with some CDC recommendations. Whether this was too much or too little, we don't know. But it certainly was something we could do for our staff to reassure them that we cared and there was somebody, some leadership at the blood center that had their interests in mind.

We also let the staff know very carefully that we had very clear links with CDC and our local public health authorities so that if additional threats, whether anthrax or something else, occurred, that they had someone on board who was looking out for their interests.

I think the point I'm trying to make is our staff can be very concerned, disrupted, distracted, and may not even come to work at times of biological threats like this. And that in itself can be a very significant threat to the blood supply.

DR. BRECHER: Okay. Last comment, Dr. Popovsky?

DR. POPOVSKY: Thank you, Mark.

Something you said a moment ago, Mark, dealing with the potential ramifications of an infection, or two or three, of contaminated units on recipients, conversely the same could be said about the fear that could be spread through misinformation to blood donors. We dealt with the HIV fear, tangible, unquantified, but very real, in the blood banking community for 15 years. And I can envision that through scientific illiteracy and misunderstanding, a case that would be widely reported in the press could somehow be translated that it would be a personal risk for a blood donor to come in. And I think we should consider that in our contingency planning, how we will deal with the donor education side of bioterrorism. It just occurred to me, as you were speaking.

DR. BRECHER: All right. Dr. Scott, you're on.

DR. SCOTT: Now we're going to switch from bacterial threats to a viral threat, and so I'm going to talk about the FDA role in counterterrorism with regard to the use of vaccinia immunoglobulins to treat adverse events after smallpox vaccination.

First, I'd like to give you just a small amount of background. I think many members are already familiar with the facts. The smallpox vaccine is a live-virus vaccine. The organism is vaccinia, and, in particular, this vaccinia strain is called Dryvax. It's an attenuated New York City Board of Health strain.

Routine vaccinations in the U.S. stopped in 1971, and this was after a risk/benefit assessment where it was believed that the risk of deaths from continuing smallpox vaccination was greater than the risk of deaths from smallpox itself in the U.S.

The last case of smallpox occurred in Somalia in 1977. Other routine vaccinations were stopped in the U.S. subsequent to that of health care workers in 1976, actually, of travelers routinely in 1982, and of the U.S. military, we understand, in 1990. So the only people who are routinely vaccinated anymore are laboratory workers who are working with certain strains of pox viruses. You can find this information on the CDC website.

I'm listing here the complications of smallpox vaccination, and the ones in bolded yellow are the ones that are considered to be treatable with vaccinia immunoglobulin, which I'm going to refer to as VIG, V-I-G, but VIG technically is for the IM preparation. There's also an IV preparation, VIGIV.

The first of these is eczema vaccinatum, and that is a disseminated viral infection on the skin of people who have eczema, whether or not the eczema itself was active at the time of vaccination, or in some cases in people with other exfoliative skin disorders, and the case fatality rate in the literature has been reported to be 10 to 80 percent prior to the use of vaccinia immunoglobulin. Now the case fatality rate after VIG is thought to be about 1 to 6 percent.

Progressive vaccinia, also known as vaccinia necrosum or gangrenosum, is necrosis in the area of vaccination, and this just continued to necrose, to take over whole limbs. Usually there are metastatic lesions. And this was always fatal prior to the advent of VIG treatment. Now the case fatality rate after VIG--and this is based, of course, just on anecdotal reports--is thought to be somewhere in the range of 20 to 50 percent.

Ocular vaccinia, usually the accidental inoculation of the eye, is also VIG treatable, but I would point out that corneal infection is not.

Generalized vaccinia is a rash, usually in people without underlying illnesses. And I should go back to progressive vaccinia. That occurs in people with some kind of immunosuppression. But generalized vaccinia is typically mild. Perhaps in up to 10 percent of cases it's more severe, and the patient will look toxic. And treatment is usually not needed for these people to recover, and it's not a fatal reaction.

The other reactions that are not VIG treatable, these include skin hypersensitivity reactions and encephalitis.

There are two preparations of vaccinia immunoglobulins which currently exist. The first of these is VIG, the IM preparation, and this is available from the CDC under IND. It was made from source plasma from vaccinated military donors, and it was manufactured in 1994.

VIGIV is an IND product. It, of course, is an IV preparation. These studies are in progress, and it also made from source plasma from vaccinated military donors. The VIGIV was not made in 1994. It was made in 1999 and 2000, I believe, and it is still being made. But the source plasma from which it is made is the same source plasma as the VIG was made from. It was just frozen over all these years.

How much VIG might we need in the case of a smallpox attack? Well, this would depend upon the scenario, whether or not there was mass vaccination of the whole U.S. population, regardless of contraindications to vaccination such as eczema, or whether there was selective vaccination, meaning vaccination not of people who have immunosuppression or eczema or other conditions. And it may also mean selective vaccination only of smallpox, primary and secondary contacts. Obviously you need less VIG if you vaccinated fewer people under these conditions. And the question also arises the extent to which VIG might be used for prophylaxis. In the past it was used for people who were exposed to smallpox who had eczema as a prophylaxis against development of eczema vaccinatum, and it was believed to have worked at that time. It also may be used as prophylaxis if pregnant women need to be vaccinated.

Future production of more VIGIV depends on a number of things, and we are in the process of exploring all of these, as are some of our sister agencies. This would be identification, recruitment, and plasmapheresis of high-titer donors and/or immunization of new donors to make vaccinia immunoglobulin.

It also necessitates the identification of fractionators who are willing to produce this product. It also needs from our end an IND process for safety studies and assessments of potency.

Now, trials of vaccinia immunoglobulins are obviously complicated because we can't perform a clinical trial on affected individuals who are already suffering the side effects, the severe side effects of smallpox vaccination, because these are still relatively rare.

We also don't know from the past literature, which pretty much stops in the 1970s, what the effective serum titer would be for treatment of these vaccine complications. So this complicates the development of an efficacy study. So we need to determine what would be the optimal clinical study now for licensure since real treatment studies aren't possible.

We also need to figure out how to monitor the effects of treatment when people are treated, how to ascertain efficacy, and how to determine effective serum levels of antibodies for treatment. Right now we only have historical information, and we don't really have serum levels, we just know how much of a product was given and whether or not people got better, or the rate at which they got better.

We also need to assure adequate supplies of VIG or VIGIV for all the possible scenarios, and we need to assure delivery of this product where it's needed if we ever should need it.

I'm now going to present our current thinking about clinical trials for licensure of VIGIV. Licensure may be based on PK equivalence and safety data, and the PK would not be inferior to that of VIG given IM. Human surrogate markers, for example, the influence of VIGIV on vaccine take experimentally or lesion size, would not be required prior to approval because these are yet to be validated. However, I think these would be greatly encouraged.

An accelerated approval designation would be desirable, and this is described in 21 CFR 601.40, and I'm going to review that in more detail for you in a minute. This would expedite availability of licensed product, and this carries with it a commitment to Phase IV studies, which I'll go into right now.

The scope of accelerated approvals is for biological products that have been studied for their safety and effective in treating serious or life-threatening illnesses and that provide meaningful therapeutic benefits over existing treatments. Incidentally, there's no licensed other existing treatment for complications of smallpox vaccine.

Approval may be granted on the basis of adequate and well-controlled clinical trials establishing that the product has an effect on a surrogate endpoint, and that's what we need to underline. And this effect needs to be reasonably likely, based on other information and evidence, to predict clinical benefit. And I think that's where we are with VIG and VIGIV. This is the kind of situation we find ourselves in where we only have surrogate markers to depend upon.

One of the most critical elements of an accelerated approval is that the applicant continues to study the product after licensure, and the purpose of this is to verify and describe the clinical benefit when there's uncertainty as to the relation of the surrogate endpoint to the clinical benefit. Post-marketing studies will be expected to be promptly underway, if not before approval. Such studies must be, and I quote from the CFR, "adequate and well-controlled and carried out with due diligence," and, of course, the product would still be subject to the same standard post-marketing recordkeeping and safety reporting as other biologics.

These commitments would no longer apply once FDA determined that post-marketing studies had indeed verified and described the product's clinical benefits.

So that was your CFR review. Now I'm going to continue on with the rest of our current thinking about clinical trials for licensure of VIGIV.

New product indications would be limited to treatment of VIG-treatable vaccinia vaccine complications, and the labeling would also be specific to the data provided by the manufacturer of each product. We would encourage the development of animal model studies. We would also encourage human surrogate efficacy studies.

I would like to point out that licensure in this case, the requirements may change as a result of animal and human studies and improved surrogate marker studies. Therefore, manufacturers even of approved products might have to update their data in accordance with new CBER standards, and lot release could be affected by failure to adhere to new standards. And by new standards, I am really speaking of standards for potency.

VIG potency assays face some challenges. I've listed here some of the potency assays that may be used, and currently the plaque reduction/neutralization assay is the one most commonly used, and it's sort of a modern version of what used to be used in the 1970s, which was a chick embryo pox model, where they looked at the ability of vaccinia immunoglobulin to prevent pox formation on these chick embryos.

Well, now this is much more conveniently done using plaque neutralization on susceptible cells with vaccinia.

The plaque reduction/neutralization assay has been developed by industry and is validated or nearly validated. There are also some academic institutions which have developed this, and we are also working on this within CBER, both in OBRR and OVRR.

In OVRR, there's a new neutralization assay which is being developed in Hannah Golding's lab. The advantage to this, the virus itself expresses a beta-galatocidase (ph) protein. The value of this assay is that it may be high throughput and actually a simpler assay to perform than the plaque reduction/neutralization.

The comet assay, which we are working on in CBER, beginning to work on, and is also somewhat developed elsewhere, detects ability to neutralize a form of virus that's important in in vivo spread. This form of the virus is not assayed for in these more conventional assays.

We're working on a mouse lethality model to look at potency in vivo at CBER, and there are other in vivo models that we're aware of that are being developed by industry, CDC, and others.

Well, if we're going to develop new potency assays and try to select the best or more relevant one for in vivo or actually for products, what we do need also is a standard. We have an anti-vaccinia antibody preparation which has been set aside for use as an interim standard, and this is being aliquotted and lyophilized at FDA. Distribution will be through CBER by request after potency is internally validated by the plaque reduction/neutralization assay, and we expect this will be available to anyone who asks in the near future.

This is some more of the ongoing research at CBER. We're developing and comparing in vitro and in vivo potency tests, and we are trying to assess these as relevant surrogate markers for treatment of vaccine complications. We're establishing the interim standard, as I mentioned. We're testing licensed immunoglobulin IV lots for the presence of anti-vaccinia antibodies. I alluded to this earlier, and we believe now that there are titers present in certain lots of licensed immunoglobulins, although, of course, they're not as high as what you see for the specific VIG and VIGIV.

We're also, of course, looking after the long-term evaluation of VIG and VIGIV stability and potency because these are preparations which may need to be used tomorrow or may need to be used in five years, and so we think it's important to make sure that we have a stable and consistently--persistently potent product.

Addressing VIG needs has involved a lot of cooperation and collaboration, and here I list some of the participants in these endeavors. The CDC has assisted us with the assessment of VIGIV needs under various scenarios for vaccination. The CDC, Department of Defense, and others have generated INDs and are planning to generate INDs for assessment of new products. And with NIH, we are coordinating to identify people who might be able to donate for plasmapheresis for a new specific immunoglobulin.

We're also collaborating with our sister office, OVRR, both on the vaccine INDs that they regulate and in the laboratory.

In addition, we are aware that both on the industry side and in academia there has been an effort and continues to be a good effort to develop and validate relevant potency assays.

So the current status, of course, as I've mentioned, is that VIG is available under IND for current vaccine complications; that there is good potential for new VIGIV products. We are studying the high anti-vaccinia titer lots of licensed IGIV to estimate their potential efficacy using various potency assays, and we are thinking about mechanisms for provision of high-titer lots of licensed IGIV in case of emergent need.

And, finally, I think we and everybody need to focus efforts on identifying the optimal surrogate markers for potency assays of these products.

Thank you for your attention.

[Applause.]

DR. BRECHER: Thank you, Dr. Scott.

We have time for maybe one comment or question.

[No response.]

DR. BRECHER: If not, we're going to take a break. We'll reconvene in half an hour at 10:40.

[Recess.]

DR. BRECHER: We're going to open this session on public communication on blood issues during a disaster with a statement from the government. Steve Nightingale has a brief statement to make.

DR. NIGHTINGALE: I can have stereo, but the people to which I want to address this statement aren't here yet. Could I move back from my role as speaker to my role as Executive Secretary and ask you all to come back to the table?

DR. BRECHER: Sit down.

[Laughter.]

DR. NIGHTINGALE: Your reservations are subject to cancellation.

All right. The last scheduled session before we go into public comment and committee discussion is a brief session, I hope, on public communication on blood issues during disaster. As you heard earlier this morning, the FDA has a four-pronged plan. The first three prongs I think are fairly straightforward, and they demonstrated that they were: protect the blood supply, assure continued supply and treat affected individuals, and then there was the broader segment of outreach activities, and there was understandably, I think, less of that because outreach activities is really an open-ended commitment. It is a commitment that we have made, but, nevertheless, it's a commitment that we need to get some input on, if not resolution for.

The private sector has also emphasized public communication as an essential component of their plans to manage an emergency. We realize that communications is essential. We probably think we know how to do it, but I haven't heard a whole lot of discussion about it. I've heard a lot more about anthrax immunoglobulin rather than communications specifically.

I, therefore, wanted to take about 20 minutes of this committee's meeting at the tail end to ask the members of the committee and to ask the public who is attending the committee with us to comment for the benefit of the government on how you think we could do better in the area of communications. This is neither an offensive nor a defensive question on our part. It's part of the statement of this whole committee process. We want to know if there are things that we can do better than we are doing right now to prepare for an emergency in the future.

The one comment that I want to put in as I ask you to prepare any comments that you would want to make to us is this: In January of 1998, at the third Advisory Committee meeting, the first one that I scheduled myself, I had invited Dr. Lola Lopes to come and talk to us on the subject of management of risk. Dr. Lopes talked a bit about distribution theory, and those of you who have not majored in that discipline probably don't remember everything she said, but I hope you remember something that she said at the tail end of the meeting, because I certainly do. She said that the public as a general rule is much more likely to trust an institution--to believe in an institution, public or private, in which it has trust. So I think that there are two related issues that I'd like to hear your comments on: What can we do, we as the government, to communicate with you better? And what can we do better than we are doing right now to earn your trust?

And with that, I know that Mr. Allen was here briefly and had to leave the meeting early. If I could ask the members of the committee as we go around the table if you have any thoughts on these to give us those, if any of the public has, and hopefully give us those by 11:05 so we can get on with the rest of the meeting.

Dr. Bianco, do you have any comments?

DR. BIANCO: Yes, I do, and this has been a superb meeting. I heard a lot of--even if all of us knew most of the things that were presented, we got a different sense, a more global sense, a more organized, integrated sense, and communications obviously was the one.

It made me also think a lot about what issues in communications we had, and there is one that was initially raised somewhat by Dr. Schmidt and Danny became part of it: the response of donors, for instance, that was one issue, to major disasters and their desires to contribute. I think--and trust, as you said, too.

I think that in part we in the blood community are responsible for some of that in the way we operate, in the fact that we always have shortages, the fact that we are always dealing with issues, and our marketing people that showed that people respond to disasters, people respond to appeals. If they are not too frequent, they come and donate blood.

And every ad that I have seen recruiting blood donors somewhere has an ambulance, a car accident, or something. So we have in a certain way placed in the minds of the public the fact that you donate blood when there is a disaster.

I don't see in the usual promotions that we make a cancer patient that is under chemotherapy receiving units of platelets several times a week that is dependent totally on those platelets, but as the subject of those things is more dramatic, because people respond to drama and that's what TV did to us, and to our children more than to us.

The other part that I think is important in the communication and trust, as you mentioned, is that we give donors continuously very conflicting messages. Since we are trying to serve a population of recipients, they are very sensitive to the messages of safety. And we have to take sometimes very draconian measures in terms of preserving that safety. If we look like we have now these CJD deferrals, that is, we don't--we are unable today to explain effectively to the donors and the public why we do it, why we are taking the measures, why so rigorous, why even the donor history is so complex and trying. That is, it is worse than the medical history that they have to give to their own physicians.

And so that in a certain way creates a sense of discomfort, and we have not learned yet on how to communicate that to the donors and explain these conflicting messages. You have these test that's positive that has no significance to your health, but you cannot donate blood. And the donor will tell you, If I can't donate blood, I'm not okay, what is wrong?

And deferrals are contagious, as contagious as smallpox, because a donor that is deferred, even for hemoglobin, a low hemoglobin, will go home and say, They told me that I'm not okay, and tells the friends, the husband, the wife, the children, and everybody then starts getting being afraid of going to donate blood.

And other things that we have not learned yet in terms of communication is how to maintain, sustain the blood supply with a cadre of people that feel that this is a civic duty to donate blood. It's not an emergency event. It is a civic duty.

So what the government can help us, and I think that this would fall in the purview of NIH and behavioral science and all that, I think that we did and we saw studies in the past like the Piliavin studies about altruism and why people donate. I think we have a different world in terms of media, in terms of communications, in terms of all the issues. I'd like to see these become a focus of an RFP, something that is really studied, because it's fundamental, blood donation is an issue of public health. And it's fundamental for us to maintain a population of donors that allows our health care to proceed.

DR. HAAS: I second all of that. I think the other problem is that we're a society of 30-second sound bites. That probably contributes to the very image that Celso was talking about.

I think the problem is that the benefit of blood to society in general is an abstraction that's hard to put some concrete picture to, but I think that's the direction we ought to be looking to try and sell the story of what blood really does.

DR. GILCHER: I'm going to reiterate the same things, but in a slightly different way. If I were making the recommendations, the first would be the importance of blood on the shelf, and I say that in terms of pre-donation--or, I'm sorry, pre-disaster donations, that is, the regular blood supply and the importance of getting that message out to the public all the time.

The second point is the unified message that needs to come from some high level of government after there is a very rapid assessment of the disaster that has occurred so that we don't end up with an overwhelming response and also two different messages. I think that's very important.

And that leads to my third point, which is that the massive donations that do occur lead to two things: the increased risks of error and, in addition, the decreased ability to make all the components from the blood because we're handling so much on the front end.

But those would be my recommendations.

DR. BRECHER: Do we have any comments from the public--oh, I'm sorry.

MR. DALAL: I'm sorry. I thought we were going in line here, but probably not, but I'll make a comment since I have the mike now.

I do want to reiterate this issue of trust. There is a unique bond, I believe, between the American blood donor and the blood banking communities. And I think this is a fundamental trust that needs to be maintained, and I suspect from the discussions that I've been privy to that this trust is being frayed as a result of, for example, mixed messages, mixed signals from different parts of the community.

That being the case, I think the situation is always going to be a dynamic situation where at times we're going to be going to the community and asking to down--or reduce the number of donations at a time of national emergency; at other times as related to CJD, we're looking to increase the number. And so there will be different messages, and the question then becomes: How do you manage this dynamic environment? And what type of an organization do you want to put in place?

And, Steve, to your comment earlier about the private nature of the way we're organized, I would encourage us thinking about putting in place an interim structure that has the right representation of organizations such as the ARC, the ABC, AABB, FDA, HHS, and even manufacturers, to deal with a situation if, for example, the news media's talking about further emergencies. What would happen if tomorrow there was another emergency? What would we on an interim basis do? How would we respond to that crisis while we're trying to solve the longer-term strategic issues related to communication.

DR. DAVEY: Yes, I certainly agree with what's been said.

First, I personally think trust is pretty good. I think most people are fairly confident that the people involved in this are clearly moving in the right direction and are caring and dedicated to doing the job. But I think there are some things we can do, and maybe just--I hope I'm not repeating too much, but I would also encourage--I don't know what we want to call it, but some kind of a definitely clearly designated and rapid response group that would include not just the government, because I know the government does have their conference calls on blood and that's very well and good, but one that would include--again, I think the obvious players are Red Cross, ABC, AABB, CDC, FDA, DOD, and those key players that can quickly and very specifically be brought together immediately when any kind of a disaster occurs. I think it's a very good idea.

Also, in addition, with regard to this specific committee, I would like to see that recommendations that we make with regard to anything, funding, whatever, that we are assured that they are brought to the highest levels and there are decisions and actions on those recommendations. I'm not sure that's always conveyed back to us very clearly.

And I guess, thirdly, I would think that perhaps this committee or the government could take a more active role in encouraging public officials to step forward--this has been mentioned earlier--to donate blood, to make PSAs, to see if we can get the President, the Vice President, somebody very prominent, to come on board in a very public way and saying this is important.

DR. HOOTS: I walked away from the discussions with a number of pieces of important information, I think, and I'll finish up with how I think we might should go with it, but I may, depending upon what the chairman's prerogative is, now or maybe when we discuss it later.

But the first was actually information that was imparted to this group yesterday morning, which I had received earlier from Harvey at the American Society of Hematology, where he reviewed the response to September 11th. And he showed to me, at least, for the first time what the age demography was of the donors and how many first-time donors and how many young first-time donors there were. And then we have subsequently heard, and he had already--he showed at that time that, you know, obviously what happened in terms of the huge outpouring and what that did in terms of oversupply.

So that communication which we heard yesterday as, "Pray, donate blood," or "donate money and donate blood," was heard. It was heard loud and clear, and it was heard by people who otherwise probably wouldn't have listened to other messages. I was particularly proud because I have two adult children who heard that message, independent of me, went out and donated in two disparate parts of the country for the first time in their life. So it was heard.

And I was therefore somewhat dismayed to know later that, first of all, that these are not returning donors. Secondly, that the blood was in excess at that moment in time. And, Bill, as a member of this committee and also as a citizen of the United States, we have got to correct that. We have to take this precious resource that was spontaneous and find a way to exploit it beneficially as a national resource for whenever we need it, but not use it when we don't need it.

So the second piece of information that came out was from what Ron was talking about in terms of his experience in Oklahoma and the really strong message about the value of redundancy and decentralization of capacity in response to disasters. And I think that's something that we all know intuitively, but has been proven now pragmatically on a number of occasions. And I think any new recommendations have to keep that in mind.

I think another one was from Mike when he was talking about the military, and I was thinking about the young reserve of individuals who donated for the first time. In the military they have a built-in system. People come in with the expectation that they might be asked or probably will be asked to donate. They may not be asked to donate four times a year every year, but they are asked if they are needed.

We have that prerogative, at least not so much to coerce but to cajole in the general population as well, but in order I think for us to effectively use that capacity, we have to develop a system so we don't exploit it like happened with excessive donations at one time and then inadvertent loss of donations later.

And so that's where the communication didn't work from the government. The government got the message out loud and clear to these people: You need to donate blood. Probably the wrong message. Part of the reason was probably because the message was wrong. "Donate money" was right. "Pray" was right. "Donate blood" was probably not right. "Offer blood" probably was the right advice to have been given. And if we had a system where the system could say, "If you're willing to offer your blood, we're going to make sure it's used at the time and the place where it's most efficiently utilized," then I think we will have done a very great service not only as a committee but as citizens.

And so finally, then, I will come back this afternoon with some ideas that I came up with after trying to put some things together.

DR. HEALEY: Thanks. I think in a lot of respects the government communicated too well in the wake of September 11th. I think that's clear from the outpouring of donors and the inundation or deluge of donations that came. That was a very effective message that was sent and was heard and people responded to, as Dr. Hoots has mentioned.

I think, though, it was clear from the testimony of Red Cross and others that it wasn't just Red Cross; that the government played a strong hand in having that message communicated to the country. But I think it really raises questions about the role of government, working with NGOs, non-governmental entities, and others in developing communication messages that are going to be sent by a private or quasi-private sector.

And those are questions raised that I don't particularly have answers to. I think that that relationship has to be carefully assessed anytime that the government is helping develop or setting messages to be delivered by the private sector.

And I'm sympathetic to the role of government here because I really think they have sort of a Hobson's choice. I think on the one hand they are charged with the responsibility of helping assure the safety and availability of products, and we see that through CJD deferral questions and other things which may raise questions and concerns on the part of donors. And on the other hand they're charged with the responsibility of helping maintain adequate supplies and reassuring the public about the availability and adequacy of blood and plasma therapeutics.

So I think they are really charged with, you know, walking a tightrope, and I think by and large do a really good job at it. There are obviously examples where it's more or less problematic. September 11th was one of them. Some of the confusion about the anthrax vaccine for postal workers might be another. But overall I think those questions have to be examined, those issues have to be examined kind of case-by-case, and by and large I think it works fairly well.

DR. LINDEN: My thoughts were very nicely articulated by Ron, although I really agree with everything that has been said, so I won't repeat everything. Basically, I think there is a need for a strong, effective, consistent message up front, so that we can maintain a good supply on the shelves, and then when there is a disaster of some sort, a strong, effective, uniform message at that point I think would be really helpful.

MS. LIPTON: I think most of what I wanted to say has been said. I absolutely agree with Celso. This issue of transparency, transparency builds trust, and we need to be transparent in terms of why we collect blood and what we use it for. And it really starts from the bottom, and not worrying so much about, well, what method do we think is going to sell, as much as getting out there what we really need blood for.

The next thing I'm going to say, I'm confident will not be universally embraced by every member of this committee, but I remain distressed that in all of the communications, that we still cannot seem to come to grips with the fact that donors are a public resource. They do not belong to any organization. They belong to all of us, and they belong to the public. And I really believe that there is a role for public education to which all organizations subscribe. That's different from donor recruitment, which is a one-to-one.

But when we talk about public messaging, we should all be at the table, we should all have one message, and we should be out there. It shouldn't be somebody's campaign, it should be all of our campaign. And, you know, I think it's just a shame that we have been unable in the past year now to come to grips with that. I think everyone expects us to do this, and I think we ought to get on with the business of doing it.

CHAIRMAN BRECKER: Okay. Well, I think there clearly were some miscommunications that occurred, mixed messages that went out to the public that we can learn from. In this most recent crisis, our blood collections doubled and our outdates quintupled, so that we collected over 500,000 additional units and in excess of 100,000 units were discarded, and I don't think we want to do that again.

In the context of blood donation, the Constitution does not guarantee the right to bear arms for donation. Sorry. I wish to reiterate that those units that were most important in the crisis were already on the shelf.

And I think it was Mike that said that there is no currently identified scenario in which the medical need for blood in a domestic disaster would exceed the ability of industry to respond. We can do it. We may need a better job of coordinating those efforts and knowing where the inventory is, to move it to the proper places, but the inventory is there for virtually any disaster that we can imagine.

We also learned from this that the use of emergency personnel, which the agency did allow in this instance, at least on a temporary basis, although well-intentioned, led to high rates of unusable units. So that's something I think we need to reconsider.

And another side effect of this overcollection is that there was decreased fractionation of whole blood, which led to decreased production of platelets. The laboratories were overwhelmed, again leading to decreased availability of platelets. And so we have to consider prioritizing platelets if this sort of disaster happens again, and we need to communicate that clearly.

Finally, I have to agree with Karen and everybody else that we really need a coordinated response. We need to know who to call to run this, and we need redundancy in the system, because wherever we put our coordination center, our crisis center, that may be the site of the next terrorist attack. I think New York learned that when the crisis center for New York City was located in the basement of the World Trade Center. So whatever we do, we have to have complete redundancy.

And then I think we need to look at the model from the U.K. for the monitoring of the blood supply. That does, I think, a wonderful job and picks up, I think they had close to 70 percent of their inventory was being monitored. If they can do it, we can do that as well.

DR. LOPES: I agree with everything that has been said about the short-run, immediate need situations. I'd like to raise an issue here about longer-run communication with the public.

I think that there is a serious problem, that we underestimate the intelligence of the public and their desire for deeper information. We blame sound bites on people's lack of knowledge about these things, but there are relatively few alternatives. People who have access to the internet know now that if you really want to find some information about something, say anthrax, you go to the internet because you are not going to find it on any of the media sources.

I think that we have a role to play here in providing better information to people about some of the very issues that have been brought before this committee. Obviously, the language needs to be changed to talk to a general public, but I think of things like the taxonomy yesterday about the relationship between blood type and what is done with particular blood types.

Things like substitutes for blood; educating the public about thinking about doing with less blood. I have a friend who is an OB/GYN. She has to fight with her patients who don't want to take iron pills. They want, if they have lost blood, they feel tired, they think they should have had a transfusion. But her own experience has led her to say no, this is not something that we should have as our only model here.

The profiles of the past events, we had an article in the package that was mailed to us about the actual needs for blood in major catastrophes are much, much smaller, I think, than the public could possibly understand. To have some public profiling of the kinds of events such as Dr. Gilcher has experienced firsthand.

I think that this can be done through the media, but not through public service announcements and certainly not through marketing. We see people turning sometimes to cable sources like Discovery, and they are really fascinated by programs that have some content for them.

I think that this group might be thinking ahead to how we actually create educational programs that people would find interesting, particularly in times of need. They maybe wouldn't turn to these in preference to other kinds of entertaining shows at other times, but when there are times of need, I think that we can speak more deeply to the public and satisfy their need for good information.

MS. PAHUJA: I think that in a manner of speaking we've gone about using the word "disaster" in a little bit of a wrong way. The disaster issue here is really that the situation in terms of blood supply was the same before September 11th as it is after September 11th.

That's really what needs to be communicated, this idea that disaster in the blood community is an issue of consistency of supply, not a natural disaster or a terrorist event. While those are very important and very fear-provoking, the real issue is, as many people have said before, this idea of having blood on the shelf that will help the people in need immediately. And without a consistency, it doesn't really matter how much blood you collect afterwards, which was really the education I kind of received today.

Also, this idea of mixed messages, personally I think it was very powerful to see media campaigns showing people standing in lines outside the New York Blood Center, seeing this kind of overwhelming response of the need to give. On the other hand, I also received a different message, a message from my local hospital telling me that I wouldn't be able to get blood because the blood bank wasn't releasing units that week.

Whether that is the correct answer or not, that's what I was told, and that's what other members of my community were told. And it brings about this fear and this disconnect in terms of understanding, well, wait a minute, there's a thousand people standing in line across the street a the New York Blood Center, but I'm not going to be able to be transfused?

And granted, there is this prioritization in terms of we were, you know, under attack so to speak and had other pressing issues, but still it was a conflicting message and conflicting idea that brought about a lot of frustration, and that frustration gets passed on to other people. In addition, I had several friends and colleagues that tried to donate blood, that were then turned away, and I hope not disenchanted but probably were.

I also think it's important to keep in mind some of the issues we talked about yesterday in terms of safety compromises in terms of supply issues. That's something the public is definitely not going to respond well to, and I think would do to thwart any kind of positive effort we bring out. Safety should not be an issue regardless of overwhelming supply or lack of supply.

DR. PENNER: From our discussions yesterday, I think the lessons have been learned and I think the solutions are at hand. The armed services program, and I think the U.K. experiences, provide us with the blueprint, and the AABB already has done some of the heavy lifting, so I think our actions are going to be pretty simple.

MR. ROSS: I'd like to suggest that we have an opportunity, an opportunity with the AABB Interorganizational Task Force. I would suggest to the committee that we endorse the efforts of the AABB Interorganizational Task Force and utilize that body during not just times of disaster but times in preparing for disasters and ensuring that we address all the issues that have been surfaced this week.

MR. SKINNER: To avoid repetition, the point that I would like to make is, in addition to the general messages that we have for the broader public, I think it's important that we also keep in mind the messages that we need to deliver to the special communities that are dependent upon the blood supply day-to-day.

And I think there are a lot of things that need to be done in advance of the general messaging to assure and address the continuity of supply, and to reassure those special populations that their needs are taken care of in terms of any kind of post-disaster availability. Be it if there was a disruption at one of the manufacturing facilities and what that would do, be it a disruption of the transportation system, I think that we can use the opportunity before another event to do targeted messaging, and I think that's an important part of it.

On thing that I heard only one presentation touch on yesterday was the importation issue, and I know that there are regulations pending that would prohibit the importation for personal use for a number of medications, which would include medications that are used in the bleeding disorders community. And I would hope that somewhere along the line we would take a look at both what the opportunities are for importation of medications to take care of the needs post-disaster, and then finally in terms of bioterrorism, again messaging to those special populations.

Certainly a number of the communities represented here also are immune deficient, and when we talk about treatment for smallpox or others that would require a live vaccine, that we also take the opportunity in advance to talk about what kind of messaging should be used for those communities so that they aren't caught post-emergency being forced into a situation where they would be asked to take a live vaccine that would further compromise their health. So I think there's some special messaging that needs to occur beyond the general messaging.

DR. WINKELSTEIN: I think there has been some very good recommendations from my colleagues on the committee. I would just like to reemphasize, there has been a lot of negative publicity about the waste from the excessive donations.

I think that we ought to emphasize what we heard yesterday and we are deliberating on today, that that product on the shelf was there; that there is credibility and trust in the blood supply; that there are adequate supplies and we need to maintain those adequate supplies, and that should be the message. I think that at all levels, government, private industry, and general public, we need to take that responsibility.

I think the mobilization and inclusion of plasma derivatives, the users of plasma derivatives and other blood products need to go to the blood centers and thank donors personally. That's a very effective way to do it. And I think we need to roll our sleeves up and create a consistent program that we maintain, and not just do it sporadically like in the past.

With respect to national disasters, Mark just indicated some of the specific risk factors to communities that might be predisposed genetically, but I think the airborne pollutants and the hearing and Senator Lieberman is going to have is of considerable concern to the people in New York City, especially those with genetic risk factors. I think we ought to, as we plan our scientific conferences and workshops and meetings, we ought to expand that to make certain we cover bioterrorism. We are doing a workshop with the NIEHS, cosponsored by the Office of Rare Disorders at NIH, on environmental risk factors, and I think we're definitely going to include a component on that.

So I think it's our responsibility as a community to make certain that we encompass our deliberations as broadly as possible, and I would encourage the government to help with that.

DR. CHAMBERLAND: To be brief here, certainly I want to re-echo and support the previous comments regarding the consistency and coordination in the delivery of any messages about supply and donation needs during a disaster.

Secondly, I want to emphasize what I think is critical in terms of the importance of planning and preparedness, and in advance of a disaster, the development of a communication plan within the government, specifically within the Department of Health and Human Services, with input and participation from the relevant blood and plasma organizations and other stakeholders in advance, so we have an idea of what we need to do and how to go about implementing it in advance.

I think whenever possible the development of such a plan needs to be data-driven. I for one hadn't appreciated the wealth of information that had been obtained from previous disaster experiences in terms of donation, numbers of units collected versus number of those actually used.

I think other data that has been alluded to in this meeting that would be critical to inform the development of a communication plan would be, for example, the data that's being collected by Jeanne Linden in New York State about what actually happened in what appears to be largely hospital-based collection venues. Also the data from Ron Gilcher's experience in Oklahoma City, in terms of coming up with alternative strategies about handling the inevitable donor outpouring. How does the collection of a tube of blood and it's subsequent testing, and then follow-up with donors in terms of scheduling an appointment, work?

And then finally, I think, in terms of developing a communication plan, we need to think about special audiences, and some of those have already been articulated. Again, thinking back to some of the presentations yesterday, a couple came to mind that haven't been mentioned, for example, educating hospitals, be it via umbrella organizations such as the American Hospital Association or the Joint Commission, and again using data whenever possible. Educating the legislative and executive branches of our own government about some of these important issues would perhaps be another approach.

I think while everybody had the very best of intentions in terms of be it the private sector, industry, government wanting to get up and rolling with blood drives, etcetera, and videotaping well-known personalities and officials, I couldn't help but think what would the impact be--and maybe I'm just a little naive here--but kind of developing a media spot where instead of showing a recognized figure donating blood, some sort of interchange where such an individual got an appointment card, made an appointment for a future donation, and then was videoed at that subsequent donation weeks to months later, that this person had actually followed through.

So there are obviously a lot of other creative ideas out there, and I think a need, as someone else also said, for real focused research on what it is, what strategies might work, how do you deal with this? As someone put it, the donor heal/help phenomenon, because it's clear that that has to be addressed.

DR. EPSTEIN: Just a few thoughts. I think that we have three key things to try to address.

Preparing for disruptions, we have seen that there is significant potential for disruption, and I think that the message s that we have heard are a need for a nationally coordinated system, whether on the model of the Department of Defense or the U.K., but that there has to be a global perspective on the system. Second, that Ron Gilcher and others have taught us that you need to gear the level of the inventory to anticipate the potential for disruptions; and that there is an essential element to rethink the system in terms of system redundances as a safeguard.

The second issue I think is the problem of massive donations. I don't think I need to reiterate what has been said about the problems that massive donations cause to the system, and indeed how counterproductive they are in relation to the projected needs in the face of foreseeable disasters. But my perspective is that that phenomenon will not be turned off overnight; that although we may commit ourselves to changing how our system operates and changing the public messages, that for the foreseeable future, at least in the near term, when disasters strike people are likely to queue up, as was said, around a Manhattan block.

So what should we really do, then? I think that we need to heed what we've been told about the lessons: to have preparation in advance for adequate staffing; to seriously consider the model of registering and taking blood samples from donors, rather than having collections. And I agree with Dr. Chamberland's comment that that requires education of political leaders and specifically of hospitals.

And I think that we need to consider better strategies for the creation of reserves when there are gluts. What can be done to create frozen reserves, walking reserves, and what I see as something in between, which is a rollover liquid reserve? And those are, if you will, reservoirs that can deal with fluctuation on the glut side and then offset spot shortage on the other side, but we need to build that concept into also response to mass donation.

Then on the issue of communication, which is I think the third key point, Steve Nightingale started with the question of what can government and industry do to earn and maintain the public trust. This is a question that has bedeviled us, particularly in the AIDS era, and which we have given a lot of thought.

I think that Karen Lipton got it right. The central issue is transparency. I would link that, however, to the ethical point of view. And to dissect that a little bit, what I mean is that first of all the providers and the overseers need to tell the truth. Telling the truth is difficult because it means sharing uncertainties and showing clay feet, but it still remains essential that we tell the truth, tell the public both what we know and what we do not know.

Second, I think that it's critical that we have the will to do the right thing. Now, that's a little bit tough, partly because it's sometimes very hard to do the right thing, and perhaps most importantly because in circumstances of uncertainty it is often impossible to know the right thing.

And I think that those of us who have lived for any time in political life know that when you are judged with the retrospectoscope, it's very harsh, and the most well-meaning actions taken with the benefit of the available information can prove to be wrong in retrospect. And unfortunately, you are judged by whether you got it right, not by whether you intended the right thing. Nonetheless, the challenge is to rise to the occasion, to do the right thing as best as it can be perceived.

And finally, I think the ethical dimension has to do with being perceived and being in reality the champion of the good. And what I mean by that is that the industry as well as the government must rise above any reality and perception of conflicted interests; that you have to have the pure motive of the public health and the public good ever present, both in action and in message.

Now, more to the specific point of our cooperative process in getting out public messages related to the blood system in the face of both normal times and disaster, I am fully in agreement with everything that has been said about establishing cooperative mechanisms. I would add the suggestion that I think that this committee could take the opportunity at the meeting to strongly endorse the role of the Assistant Secretary for Health as the ultimate focal point for the national message.

You know, certainly there can be additional voices operating in lock step, but we need to have the stakeholders, who after all are represented around the table, endorse the concept of central leadership. Now, you know, I suppose there could be a debate on where that ought to reside, but it's my view that the best home, and consistent with the FEMA response plan, really is the Assistant Secretary for Health, and so I would submit that that should be a key recommendation.

As to the content of the message itself, it's very clear to me that we have a long-range task of trying to shift the way our system operates from ad hoc drives and, you know, crisis campaigns to needs-driven collection which operates equally in times of calm and crisis. And the question is, what's the message that has to go to donors to make that happen?

And I think that the kinds of concepts that we're trying to impart are these? That people perceive it as their civic duty, both in times of calm or crisis, to donate when asked. That we need to inculcate the concept of pride in being a committed, perhaps a registered donor who stands ready to donate on demand, and who is part and proud to be part of maintaining the stability and security of our national system by keeping blood on the shelf.

We have heard these words, and I'm trying to link them together into an image of a mind set which is what we're trying to impart. And I think that, as has been said before, to accomplish needs-driven collection we really need a rather coordinated and aggressive education campaign targeted to political leaders.

I would like to add one more point, which is that it has struck me that in the United States we do not have as organized a political voice of the donor community as exists in some parts of the world, particularly in Europe. And I think that one of the things that we can do to try to harness the public spirit and the public altruism in the right way is to see if e can't reinforce the advocacy functions of donor organizations who could be come advocates for the public voice because they will be indeed and perceived as closer to the people.

So that's just a suggestion, so for example there's no one sitting at this table that represents the donor community, except to the extent that many of us already are donors. But notion of a voice of the donor I think could in fact be reinforced. So these are my various scattered thoughts.

COLONEL FITZPATRICK: Even with the rearrangement, I get to follow Jay, and that's always a pleasure because that leaves me not a lot to say.

[Laughter.]

And I want to endorse what everyone has said and just bring up a couple things. When we were, prior to 9/11, we were in crisis supposedly because of variant CJD, and during those discussions and the deferral discussions the Department of Defense brought to the table that we considered blood a critical resource, and that we considered the impact of variant CJD, depending on how the deferral guidelines turned out, could have an impact on that critical resource.

9/11 and the aftermath is going to change how we look at everything, and what distresses me the most is that, to a man and woman, everyone who spoke yesterday said, "This is not news. We knew this would happen. We knew what would happen. We knew it was going to happen."

I want to compliment Jay because behind the scenes, after 9/11, he worked extremely hard to try to get a national message out. And we all know that that didn't happen, but that was not his fault. We need and have a mechanism within the federal response plan, through Human Health Services, a way to nominate an individual to speak for the nation when times of disaster require it. I think it is our duty to recommend to the Secretary that that method be put in place and be used in those times of national disaster.

We keep bringing together people from the blood community to figure out how to appeal to donors. Variant CJD forced me within DOD to reach outside of the blood community and go to a marketing group and figure out how to reach out to donors.

If blood is a national resource, and if there were going to be a national stockpile and we're going to develop a national reserve, then it becomes a national responsibility. And the cries of community-oriented blood banking need to be maintained, but the part of the community within the national responsibility needs to be profoundly communicated to the donor.

Funding is essential for that national responsibility. We can't ask each and every community to fund itself to hold a reserve.

And we need to ask HHS and NIH, I believe, to find an alternative for us. If we need further clinical trials of oxygen-carrying solutions, then if this is a national responsibility and we need a national reserve and it's a better alternative and a more economically efficient alternative, then let's make the decision to fund it and find out if it can be safely done.

Let's change the stigma of a donor who is rejected, because that's why people sometimes don't donate, for the fear of being rejected, and let's figure out a way to have a national campaign of, "If you can't donate, here's something else you can do," and "Oh, by the way, if you came in to donate and we found out you have hepatitis C, we may have saved your life." Let's focus on the positive and not the negative.

Let's accept some realities. Not every community may be able to collect enough blood to support itself. Other parts of the nation may need to collect more blood than they need in order to support those areas that can't for whatever reason. Will they get it for free? No, they should pay for the blood that they receive, but let's accept the realities.

Let's find a way internally, within our own industry, to resolve the consent decrees that are in the press on a daily, weekly, or monthly basis. We as an industry know how to resolve those issues. We know how to fix those issues. We need to fix them.

The only way to restore the confidence of the American public is to have headlines that say the blood supply is safe, not that 80 percent is collected under a consent decree, so let's fix it. Let's put politics aside, personalities aside, look at the reality of the situation, because we are now a country under attack.

My job for the past 27 years has been to figure out how to supply blood to people under attack in other areas of the world. Now our focus is internal. We have Senator Ridge--not Senator Ridge, Mr. Ridge--for homeland defense, and in the Washington Post today it said the Joint Chiefs of Staff are considering creating a national command to look domestically at the United States.

We have to change our mind set. We have a window of opportunity that rarely arises within an organization's time. We missed the window of opportunity on September 12th, 13th and 14th because I do believe, as you said, that the public is smart. They are educatable. If we explain to them the situation and provide an alternative, most of them will go along with that.

And we missed a window there, and now we have a new window. We have a President in his State of the Union message, we have patriotism at its highest degree that it has ever been. We can't take a lot of time to capitalize on that and send out the right message.

So what I would implore you is to quickly figure out a message to capitalize on this window of opportunity, to educate the public, put together a system, put aside our individual differences and understand that we have to pull together to put a system in place for the next time. Because, as Secretary Rumsfeld and the President said, at this point in time we all believe there will be a next time.

And we don't know when that next time will be, and if we don't do the right thing, as Jay said, which is pull together a coordinated message quickly, we may be in the same situation again as we were on September 12th, and then we have done the wrong thing. So that's what I would ask that we do during this day. Thank you.

DR. KLEIN: One of the disadvantages of being the last one around the table with such a stellar committee is that there are very few new ideas, and you can't say them much better than several of the people have already, but I have a couple of thoughts that I would like to emphasize, at least.

First of all, I don't think under ordinary circumstances that different messages are necessarily bad. When you don't have all the facts, discussion and even healthy debate is good. But we're not talking about usual times. I think this committee today and yesterday has been addressing a disaster, and during disaster times I think a single message is critical, not necessarily a single voice but a single or, as Jay said, a coordinated message.

And I certainly would endorse the lead voice to be that of the Assistant Secretary of Health. However, neither the Assistant Secretary nor any of the individuals in government are usually at the front line of the disaster. It's usually the people at the front line. And so in order to provide the substrate for that coordinated lead voice, I would endorse Alan Ross's suggestion that this committee endorse the work of the interorganizational task force.

In my understanding, this is the first time since the advent of the AIDS epidemic that the blood collectors, all representatives from hospitals, representatives from government, has gotten together and crafted a single plan, and I would like to see that continue. I think it was a marvelous effort and one that shouldn't be lost at this point.

I think that in order to avoid some of the problems that we saw with blood donors and collections and errors and all during the disaster, we need to have what some have called an unbranded, but I prefer to call a multi-branded program for donor recruitment. And perhaps there's a role for government there, at least perhaps in funding if not in suggesting ways to do this.

Perhaps everyone should give on their birthday, their mother's birthday, and anytime in between, but in any case there should be a multi-branded campaign to make this a national service. As the President has suggested, we all ought to think about, this is a national issue.

On two practical issues, we saw a lot of donors come out 9/11, 12, 13, and 14, and many of their names are still available. We shouldn't lose that opportunity. I disagree that we lost the opportunity. I think the opportunity is still there. We need to get them back. We need to convince them that regular donation is important. And for the most part, as they say, "We know who you are."

And, finally, data on errors. I think we have known for a long time that mass appeals are not either efficient or safe. We now have a little bit of data, and in all due respect I would disagree that most of the errors were occurring at the hospital level. They were occurring everywhere, and those of us who were at the front lines know that.

I think we have a responsibility now, not only to gather those data and analyze those data but to make those data public, because one of the best ways to discourage an outpouring and appeal in the way that we saw during 9/11 is to provide data to show that that's not a good way to do it. Otherwise, we're just providing opinions.

And finally, in a research mode, and I see George Nemo taking notes there, we do need to know what to do about donor healing. It's not very sexy. I mean, it's not basic science and it's not cellular biology and molecular biology, but it's extremely important to know how to address this issue. People do want to do something, and the social sciences could help us find out exactly how we can address this issue so that the nation can heal itself adequately during this period of time when we have the next disaster, which will surely come, and yet not cause harm to systems that are so critical to supporting the country.

Thank you.

DR. GOMPERTS: Mr. Chairman?

CHAIRMAN BRECKER: I'm sorry. You weren't here before.

DR. GOMPERTS: I apologize for coming in late to the committee. If I have a chance, the committee members have made a number of important and useful observations and recommendations. If I could just add, point out a couple of gaps that I have seen over these last two days.

I would have benefitted to hear an analysis of potential problems that could occur beyond the worse level than has happened, such as a nuclear episode, and how the blood banking community, the donor community, would be able to respond to that.

There were two separate terrorist episodes that occurred almost simultaneously. It would be useful to have heard how the two programs, the two areas, communicated or did not communicate. Were there issues arising out of that? Because the potential for multiple terrorist attacks to occur one after another or concurrently may well happen again.

And, finally, I am concerned that as the smallpox immunization moves ahead, which is a most likely situation, and we are concerned about adverse events, and I do see some forward-looking thinking around that, but this is of some concern particular for the immune deficiency population and many individuals who are not aware of immune deficiencies and the negative consequences.

It is clear that there are major positives that have come out of this, and one of them that was particularly reassuring is the way I have heard that government agencies have interacted: FDA, CDC, NIH, DOD, etcetera. Thank you.

CHAIRMAN BRECKER: Thank you, Ed.

I think we can open this for public comment.

DR. NIGHTINGALE: Dennis Goldfinger. He is going to talk about earthquakes.

CHAIRMAN BRECKER: Oh, okay. We'll let Dennis Goldfinger go first, because he wants to say a few words about earthquake disasters.

DR. NIGHTINGALE: Dr. Gomperts, we can't address all of your concerns, but we at least did have one of them planned for in the public comments.

DR. GOMPERTS: Thank you.

DR. GOLDFINGER: Thank you, Mark. Actually, Dr. Nightingale asked me to address this issue. We all know of California as being the seat of the odd, the unusual, the macabre, and he did recall this long fault running down the State of California. Actually, there are many such faults.

And so earthquakes certainly could pose the kind of major national disaster that could result in the need for large quantities of blood, and also could easily disrupt the transportation system that is required to deliver that blood. In Los Angeles, the last big earthquake that we had

--and let me tell you, it was really a frightening experience--I think it was like 1995. Fortunately, it occurred at 4:30 in the morning, so that most people were in their homes asleep and people were not, for example, in shopping centers. There were some large shopping centers that collapsed but nobody was injured.

Los Angeles has a large population, as does San Francisco, but in the case of Los Angeles it's more spread out than New York. We don't have many high rise buildings. What that translates to, though, is that in the event of collapse of buildings, it's more likely that there would be living survivors, living and injured, and so therefore the need for a blood transfusion.

Interestingly, when we had a big blood shortage last time, last year at this time, which is typically the time for the worst shortages, and really these are the disasters that we face throughout the year, we noted that the State of California has a system of trauma centers, as do many states in this country have the system for trauma centers. We happen to be one of those. And we noted that with such short supplies, that we didn't think that we would be able to, we might not be able to deal with paramedics and such who might come to the emergency room.

So we went to the Red Cross and asked them what the plan was for our blood supply, and could we have a special plan to supply these trauma centers. And interestingly, they said that the person responsible in Los Angeles for heading up the trauma center network had never even considered the need for blood. They had never even discussed with the American Red Cross, which is our blood supplier in Los Angeles, the potential need for blood.

So out of this comes first of all the fact that on the one hand there are organizations already available that could help in this transportation/distribution system, and those are the state-wide centers. And I would recommend that we consider state government as a way of helping with this kind of distribution of blood during emergencies.

And then, finally, we hear a lot about September 11th and the problems that resulted following that with the over-supply of blood, the over-collection of blood. But one good thing that has come out of this certainly is that there has least been a recognition at the highest levels of government that blood is an important national resource, and certainly then this committee can play a very valuable role in assuring that that supply is constant.

Thank you.

CHAIRMAN BRECKER: Thank you, Dennis.

MR. CAVENAUGH: Thank you. Dave Cavenaugh again, the government relations for the Committee of Ten Thousand. It has been very gratifying to hear the amount of good comments here this morning, covering some of the things that we spoke of yesterday and acknowledging the very much greater importance of trust in the blood supply safety that the public has, than any other single factor.

We have a recruitment problem as a result of the way some incidents went down last fall. Now we have that problem. They are not done with. The over-collection, the fund usage. But I also would like you to bear in mind as you discuss this that the problem of a lack of a single message or spokesperson was exacerbated by the similar and very close on the heels of situation regarding anthrax, especially for those of us in Washington.

The number of national leaders on health in those two weeks included Tom Thompson; Dennis Hastert; Ivan Walks, the city health commissioner; Tom Daschle; David Satcher; Anthony Williams, mayor; various Senators who were reporting what they heard in private briefings, to the displeasure of those who gave the briefings; the Postmaster General, whose name I forget at the moment, and Anthony Fauci.

And people came out of that without any plan to believe in the government again. My postman for my office, four blocks from here, had his picture in the New York Times, rather large, holding up his little baggie of Cipro. And I congratulated him on it when I saw him, it was weeks later, actually, and he said, "It's not over yet." So, really, the incidents are tied, and in the public's mind that is very important.

I would also suggest that the task force include the patient community, as well. Thank you.

MR. COLLINS: Good afternoon. My name is Patrick Collins, and I'm with Aventis Behring. I would like to laud the committee for yesterday and today's discussions with regard to the lessons that we have learned in the aftermath of September 11th, and I do this not as an employee of a particular company. But really as an American and as a native of New York City, I would just say thank you very much for the discussions that have been held today.

I would also just like to thank this committee for the actions that they have taken in the past. I've had the opportunity to work with many of you on this committee, and I commend you for what you have done.

I would also like to comment Dr. Nightingale and Captain McMurtry, who I have had the pleasure to work with over the years, and I must say that they really do have a get-go, can-do attitude, and I think that's exemplary.

What caused me to come up here now was a comment that Dr. Davies said, that actually inspired me to come up here. I know Dr. Davies suggested soliciting feedback from HHS. One concern that I do have is that to my knowledge, the Department has yet to act on I believe the last two recommendations, or the last two sessions, the recommendations that came from those committee hearings.

As we are all aware, this committee handles very important issues in both blood and plasma safety, as well as access-to-care issues. The recommendations that come from this committee are not only important but they are also very time-sensitive, and I think they deserve, if not an endorsement from HHS, at least a reaction from HHS for further guidance.

It would be my hope that with Dr. Slater now in place as Assistant Secretary of Health, that there will be some further guidance from HHS. But I would just like to ask this committee to reassert itself to HHS, and to ask that HHS give feedback on not only the recommendations from this important meeting but on the recommendations from the last two meetings, as well. So I thank you.

CHAIRMAN BRECKER: Thank you. Any other comments? Come to the microphone.

MR. BABLAK: Good afternoon. My name is Jason Bablak, and I'm the Vice President of the Immune Deficiency Foundation. IDF is the national organization dedicated to improving the lives of primary immune deficient patients through research and education. You have a copy of this statement there, if you want to follow along.

The threat of bioterrorism in the United States has been labeled a clear and present danger by government officials. Smallpox, a category A agent, is of particular concern to our community. The threat is posed not only by the smallpox agent itself but also by the public health large-scale vaccination response to the agent.

Because the vaccine contains a live virus, it is highly probable that many immune compromised individuals exposed to the vaccination virus will suffer significant complications. Additionally, the persistence of the virus in the general population and its ability to spread could pose further risks to these fragile individuals.

Prior to the elimination of the smallpox vaccine from routine childhood immunization programs, a vaccinia immune globulin preparation was used to treat complications from the vaccine. This product is no longer in production, as was told to us earlier today. The CDC has stated that due to the limited remaining supplies of VIG, concomitant administration with the vaccine is not possible, and VIG should only be used for the treatment of the most serious or life-threatening complications.

The IDF encourages the government to quickly develop a new product specifically designed to contain high titers of vaccinia antibody, and we were pleased to hear earlier today that the FDA is making progress in this area. In the interim, we would like to propose the following strategy to protect immune-compromised individuals, should a smallpox vaccination program of any dimension be implemented.

The FDA, as well as some of the manufacturers of intravenous immune globulin, have determined that several of the licensed products contain detectable levels of vaccinia antibodies. While not licensed for this application, we believe that the IGIV products with vaccinia antibodies may be useful in preventing adverse consequences in immune compromised individuals that might result from a smallpox vaccination program. It is also likely that these products would be useful in treating complications from the smallpox vaccine in "normal" individuals, as well.

We estimate that as many as 10,000 primary immune deficient patients have a T call defect that would result in adverse health consequences to them should they be exposed to the vaccinia virus. There probably are as many as 45,000 individuals with HIV and AIDS who would be adversely affected, as well, and also VIG is indicated for several of the known adverse events, adverse reactions, to the current vaccine as well.

We believe that as many as approximately 200,000 people could benefit from the treatment of IGIV either prior to or immediately subsequent to the initiation of a smallpox vaccination program. However, due to the current government plan to employ a ring vaccination in the event of a smallpox outbreak we believe a smaller number of individuals might require treatment with this IGIV at any one time.

We strongly recommend that the U.S. Government work with us to identify and store sufficient quantities of this IGIV containing vaccinia antibodies to meet the needs of these individuals, should a smallpox vaccination program be initiated. The IGIV required for this purpose could be maintained in a rolling inventory, managed by a distributor familiar with the biologics market.

An initial volume of this product could be purchased and held at the distributor. Because IGIV is labeled for two years, the inventory would need to be rotated on a three- or six-month schedule so that the stockpile always contained in-dated material. This would also prevent the expiration of large volumes of an important therapeutic.

The IDF believes that the current level of threat to individuals with defective immune systems mandates that the U.S. Government take the necessary steps to implement this type of a program. Immediate action to put a system like this in place to protect this fragile population will both provide a level of reassurance to our community, while at the same time provide public health officials with better options in the event of a terrorist attack with smallpox.

We have developed the first draft of a plan that identifies a starting volume of the stockpile and strategies necessary to implement such a system. And we have shared it with individuals at the FDA, CDC, and NIH, and I have attached a copy of this to your written statement there. We would appreciate any feedback that you might have to offer, either individually or as a community.

We stand ready to continue to lead on this issue and assist the government in any way necessary to achieve these goals. Thank you.

CHAIRMAN BRECKER: Thank you. Do we have any other comments?

MS. O'DAY: Good afternoon. I'm Miriam O'Day, and I'm senior director of public policy with the Alpha One Foundation, and we are here today because we have an urgent and time-sensitive concern regarding availability. We'd like to thank this committee for their deliberations over the past two days on emergency preparedness and the lessons learned after 9/11.

We believe that our community is about to return to a crisis situation. We'd like to respectfully request that this committee review the proposed CMS changes that will be implemented or are scheduled to be implemented April 1st, 2002, and threaten access to the only life-extending therapy available to individuals diagnosed with Alpha One antitrypsin deficiency.

Alpha One is a devastating disorder. It's both a pediatric liver disease that requires transplantation and an adult onset degenerative lung disease that leads to repeated infections and progressive loss of lung function. Diagnosis usually occurs when the individual is in his or her most productive life stage personally and professionally, and inevitably the whole family suffers.

Alpha One is frequently misdiagnosed, and on average a patient sees five doctors over seven years from the onset of symptoms before receiving an accurate diagnosis, even though Alpha One is more common than cystic fibrosis and can be diagnosed with a simple blood test. The median age of survival is 54 years.

And aside from transplantation there is only one treatment for Alpha One, a plasma-derived replacement therapy that is infused weekly. The sole manufacturer of this therapy does not have the capacity to produce supply adequate to treat all eligible patients, and the Alpha One community faces ongoing shortages resulting in health exacerbations.

We are not requesting an increase in benefits. We are only asking that our benefits be maintained. And while we commend this committee for the positive action you have taken to ensure that the scarce supply of product is adequately reimbursed, we are here today to ask that you take action again to ensure that we do not lose precious benefits.

I would like to ask that the advisory committee resolutions from April of 2000 and August of 2001 be submitted as a part of my statement, and these were resolutions that you passed regarding reimbursement in the outpatient prospective payment system.

The facts are as follows: An Alpha receives 5,000 milligrams per infusion on a weekly basis. The cost of drug alone, not including storage, supplies, administration, nursing, or physician fees, is 22 cents per milligram. This is the present AWP. Hospitals purchase the product at 19 cents per milligram, and Medicare allows 95 percent of AWP or 20.9 cents.

The hospital can see a benefit, after reimbursement from Medicare and patients' co-insurance, of at most 1.9 cents per milligram or $95 for one administration of the plasma-derived product, and this 1.9 cents covers paperwork, storage, mixing of the product, and supplies necessary to administer it. Medicare pays 80 percent of 20.9 cents a milligram or 16.7 cents. You can see how it's difficult to administer a drug if the patient doesn't have adequate co-insurance. The hospital can't do it.

Annualized, the cost of therapy is roughly $57,000, and our calculations of the final CMS ruling for the outpatient setting is a loss of benefits close to $10,000 over a one-year period. The CMS proposal is a threat to patient access. Implementation is being done without adequate understanding of treatment.

It's crucial that reimbursement reflect the cost of care and that benefits be maintained at a level that sustains patient access. It's unacceptable that an individual who may become eligible to share in a precious resource of product through an allocation program may be unable to receive that product due to a lack of reimbursement.

We are requesting respectfully that the committee take all action within their capability to recommend that the Secretary reconsider the final ruling regarding the outpatient setting for the treatment of Alpha One. Further, we do not want to see current benefits diminish as strategies are derived to move treatment for Alpha One from the pass-through pool into a permanent ambulatory product code in 2003.

We recommend that CMS work with the Alpha One community to gain an understanding of the true cost of this illness so that they are able to understand the impact of changes in the reimbursement structure. We want to ensure that all eligible patients continue to have access to this life-sustaining therapy. Thank you.

CHAIRMAN BRECKER: Thank you. Last comment?

MR. VOGEL: Hi. I'm Rich Vogel from the Hemophilia Federation of America, and I too am pleased with all the comments we heard this morning, but there are several events that are happening concurrently in the health care arena that could cause major impediments to patient access to care for persons with coagulation disorders and other health concerns requiring the administration of plasma therapeutic products.

The Hemophilia Federation of America would like to ask the Chair of the Advisory Committee on Blood Safety and Availability and your fellow members to come to the aid of these persons at this time, since you will not meet again until the beginning of May. On April 1st, 2002, the carve-out for the plasma products that benefit these populations will be reduced in the hospital outpatient prospective payment system, and will sunset in April 2003.

Hemophilia Federation of America would like to ask your assistance in requesting that this carve-out be made permanent and eliminate the need to make repeated pleas on behalf of these patient populations. This comes at a time when there are other financial and reimbursement issues that are assaulting these communities.

For almost two years the hemophilia community has been advocating for a more reasonable AWP for Medicaid and Medicare. The Medicaid issues are ongoing. The Medicare issue is about to be addressed by legislation, and we can only hope that it will be in our favor, after innumerable pleas throughout Congress and governmental agencies. In addition, we have just had to deal with a revised set of listings by the Social Security Administration that set eligibility criteria for determination of Social Security disability for persons with hematological disorders that does not correctly acknowledge current treatment protocols.

It is our request that this committee revisit your prior recommendations on August 24th, 2001, which have not yet been acted on by the Secretary, and request the permanent carve-out for the Alpha One, immune deficiency, and hemophilia communities in the hospital outpatient prospective payment system. Thank you for this opportunity to make this request.

In addition, as a severe hemophiliac who travels this great country of our by plane and train, I am also concerned about traveling not only with my factor but syringes and needles on my person. I would request that this committee reach out to the FAA and encourage them to enforce the newly stated ruling that allows this practice with proper credentials from patients' physicians. Under this stated FAA regulation, patients should always be able to carry their medications and accompanying ancillaries without fear. Because of this regulation, there is no need to check supplies or track them down at some sort of home depot upon your arrival at your destination.

We have followed the activities and recommendations of this committee very closely since its inception, and would like to go on record to thank you all for your efforts in support of a safer blood supply for all. It is our sincere hope that Secretary Thompson will be adamant in recommending to the Bush Administration that its charter be renewed.

At this point in time, where we have seen the onset of HIV, HCV, CJD, and other threats, we cannot lower our vigilance in protecting American citizens from future threats to the blood supply. We are riding a wave of patriotism and support rarely seen, and there is a heightened interest in blood donation. We strongly urge that we take full advantage of this enthusiasm and institute some of the suggestions that arose from the last meeting, where we discussed involving the President, Cabinet member, and others in highly visible positions to encourage citizens not to forget their responsibility to continue to keep the blood bank shelves filled.

Thank you.

CHAIRMAN BRECKER: Thank you.

Do you want a short--

MR. CARONNA: You want this short? Is that what I heard? Okay.

CHAIRMAN BRECKER: Brief. Brief, please.

MR. CARONNA: Good morning. Actually, good afternoon. My name is Joe Caronna. I'm a volunteer at the Hemophilia Association of New Jersey, serving as vice president. My role there is to be an advocate for people with bleeding disorders. I am also a professional computer technologist, serving as global director of database operations. There my role is to design and build the most secure, robust, large-scale database systems as possible. I am also a father of a seven-year-old boy with severe hemophilia. Here my role is to get him through life until he can be independent in an environment that is safe and secure as possible.

In each of these three roles I consider myself an expert, and I take each one very, very seriously. Some time ago I began reading documentation regarding the creation of a centralized database to track pertinent hemophilia-related information. I was extremely excited because this is what I do, and I saw a need for it, so I was extremely happy. I fully appreciate the amount of the power a database system can provide, and how a tracking system can greatly improve so many aspects of hemophilia care. I also read hat our hemophilia community was going to address the issue of enhancing our current product distribution system. Again, I was extremely excited.

Over time I learned that a home care company was interested in creating these systems, and I began to get a little concerned. I'm concerned as a leader in the hemophilia community because we as a community lived through a period of rampant conflict of interest which dictated our fate. The detrimental effect of these conflicts is well known to the people in this room. I am also concerned as a computer professional because the integrity of these systems would be in question. But, most importantly, I'm concerned as a father because I refuse to have my son repeat the past.

I hope this committee will carefully weigh the comments of ambitious entities to determine if there in fact is a conflict of interest. I really refuse, as I said before, to repeat the past. And I offer my expertise to this community in any way I can be of service to make sure that doesn't happen.

Thank you.

CHAIRMAN BRECKER: Okay. Thank you. We will take a lunch break and reconvene at 1 o'clock.

[Luncheon recess.]

AFTERNOON SESSION

1:22 p.m.

CHAIRMAN BRECKER: All right. We now move to the committee discussion and recommendations. Before we begin, I just wanted to remind the committee members what the function of this committee is, what the charter says.

Briefly, the Advisory Committee on Blood Safety and Availability shall provide advice to the Secretary and to the Assistant Secretary for Health. The committee shall advise on a range of issues, to include, number one, the implications for blood safety and availability of various economic factors affecting blood cost and supply; the definition of public health parameters around safety and availability of the blood supply; and, three, broad public health, ethical and legal issues related to blood safety.

And I think the thrust of this particular meeting is mainly in that category three, broad public health issues, and our major focus for this meeting is dealing with crisis management. So I would like to prioritize how we address some of these issues that have been discussed, and I think the first priority we need to talk about is a coordinated response. A secondary priority is I think national real time monitoring of the blood supply. And I'm open to other suggestions, but I would like to get through the first two initially.

Before we adjourn, I would like to open up the floor to suggestions for other issues that the committee needs to or should address in the future, and then we can present these to the Assistant Secretary and ask her what it is she would like us to address at our next meeting in May.

So I thought for purposes of discussion I would put up the seven focus points from the Interorganizational Task Force that the AABB organized. And so, Mac, could we get that up on the screen? These are six of the seven. There's a seventh one further down. These were the major focus points from the AABB Interorganizational Task Force.

And I gathered from the sentiment of the group that we were all impressed with the organization that went into this, and feel that this sort of body is what we were looking for for a coordinated effort. And so I'll open this to further comments.

Clearly there has to be redundancy built into any system we take. There has to be a line of command, and the sense this morning was that it probably has to go to the Assistant Secretary of Health, although she can designate--he or she, she right now--can designate a spokesperson in times of crisis, acknowledging that the Assistant Secretary of Health may not be expert in every area that there is a medical crisis.

So I am opening this to comments. Celso?

DR. BIANCO: First, I think that the task force came at the right time, in the right shape. There were comments that we heard even from the audience, that maybe we should attempt to include other people, but I think the basics in terms of the working of things are there, and I want to support it entirely.

I think that there is one piece that is missing from this, even if it is addressed in another point of the task force report, is that that task force and the Assistant Secretary for Health are two pieces of it, but there has to be an integration of the activities of the task force with the activities of FEMA in a more direct way. That is, in the way it is currently, it didn't work on September 11th, even if people tried, that is, everybody does it with very good intentions.

I think we have a wonderful opportunity now, since we are all together. I heard from Alan Ross that the Red Cross is a full participant. I can guarantee the full participation of ABC and ABC members. And we all join under the AABB umbrella to work together to get this done.

And the coordination with FEMA, the naming of other blood organizations in the plans according to each state--and in some states it will be difficult, obviously, but we will find a way--is an important piece, because the Assistant Secretary, while controlling the whole system, will not be in the day-to-day activity, and we have to establish some of those shortcuts.

CHAIRMAN BRECKER: I agree. I think timeliness is very important, too. We could have another disaster this Sunday or during the Olympics, the Winter Olympics.

DR. BIANCO: Let's hope not.

CHAIRMAN BRECKER: So I think whatever we do, we need to recommend that it move forward on a fast track.

DR. HOOTS: I heartily endorse the task force, and I don't think necessarily that we should try in any way to micromanage the plans, but I think it wouldn't hurt necessarily to throw out some things that are kind of in between the lines here but not necessarily addressed.

And, as I said this morning, the one thing that I think--the two things that really stick out is integration, being able to react regardless of what geography is impaired in a disaster, but also making sure that the national resource that we call our blood supply has a reserve. And the reserve I think could actually be developed but also implemented in such a way that the reserve is there, but also that it serves as an engendering of the actual blood supply itself.

And what I was thinking was--and I started, as I said earlier, thinking about this when Ron was talking yesterday--that all those young people and other first-time donors who donated and don't tend to come back, perhaps part of it, as other people have said, is we probably didn't reinforce their behavior strongly enough, and I think we need to get much better at that.

Perhaps one way to do that would be to implement a plan not too dissimilar from an organ donor plan, where people are prescreened as Ron did in Oklahoma, so they are identified voluntarily. They are assigned numbers, which could actually be geographically distributed so that you could draw from them, depending on the insult to the community, in a time of crisis.

But the important thing would be that based on those numbers, call-ups for donors could be handled so that if you only needed a few units, you can know, just as they do when they call juries, how many people need to be called up for any given thing, and the integral of numbers, FDA statistics, could pretty well predict that. And then that group would go to the bottom of the list and the next numbers would go to the top.

And as they come in, not only are they congratulated and reassured that they are doing great things for their community, for the country at large, because this would be a national resource, but in fact for young people I think it could serve as an opportunity to reinforce their behavior. And then one-time donors would be hopefully more likely to become repeat donors, who would then more likely hopefully become long-term donors.

And by having this be national and perhaps adjusted regionally, I think one could create a resource similar to what they have in the U.S. military. Karen, did you want to comment about that? I mean--

MS. LIPTON: I was just going to say, you know, one of the things that we don't have up here and I think we could perhaps add, is we said we were going to address short-term, medium-term, long-term, and perhaps something as simple as saying "addressing long-term issues, including exploration of this possibility." I would hate to have us design it a the table.

But I think looking at that and maybe also looking at the potential for the role of frozen blood reserves. I mean, maybe there is a role, maybe there isn't, but I think we could task this group with looking at that from a national perspective.

DR. BIANCO: I'd like to suggest, I think that before when Harvey was speaking and now repeats comments, something came to my mind as a suggestion. It may be a suggestion where the government could help us.

I think that I'd like to see created a national blood donor corps in which people would enroll, would make the commitment to donate once or twice a year and to be ready to be called for duty at the time of emergency, if it arises, where it arises, in an organized fashion. This we could have, and I think that there were comments here, I think from Jay, of the French system that retained actually a bit of a military organization in which they give medals for the numbers of donations and it's a state-sponsored thing.

I don't think that that would be an expensive proposition, but it could, if the Assistant Secretary and high levels of government support that, we could convey the messages of communication, would facilitate future interactions, and probably would allow us in more elegant and efficient way to maybe look forward to a stable donor base.

DR. PENNER: But that will disenfranchise our regular donors around the country, who won't feel that they are special, so if you don't include them--

DR. BIANCO: We have to make everybody special.

DR. PENNER: Then every donor in the country, and that would be fine, but I think if you get a corps of very specific people who come in, the other donors who are coming in regularly, donating their 20 gallons like they do over the years, are going to feel like they're second-class citizens.

CHAIRMAN BRECKER: We're straying from task, Rick, and then I think we need to move toward our resolution.

DR. DAVEY: Yes. I think these ideas are very good, but they maybe can be brought up after we deal with this.

I would just like to also endorse the AABB task force. I think what they have done is good work and provides a good framework to move forward, and I'm delighted that Red Cross, ABC, and the others are all fully on board with this.

The one thing we haven't I think addressed fully is who is going to speak for the conclusions or recommendations of this task force if we so endorse it. There has been a suggestion that the Assistant Secretary for Health would do that. I would suggest that there not be maybe one person but there be one voice that speaks, and that could include the members of the task force that hopefully can come to a unanimous recommendation on whatever issue is placed before them, or at least a consensus recommendation.

And then perhaps the Secretary, we might want to recommend--I'd like to hear what others think--that the Assistant Secretary delegate to the FDA and/or the CDC or some other party to be the primary spokesperson for the Assistant Secretary, and that government lead agency would reflect as much as possible the recommendations of the task force. So I think the point is, we speak with one voice, not necessarily one person.

DR. EPSTEIN: I certainly agree with the committee endorsing the principles that were enunciated by the AABB Interorganizational Task Force. However, I see that as a preamble to any set of recommendations directed to the Secretary, because the issue here is how does this advisory group think the Secretary's role should be defined? And I don't think anyone would contend that the Secretary's role is defined by these seven principles, because the indirect and unclear implication is that the Secretary is supposed to do each of these things, and I think that's wrong.

So I think endorsement of these principles as guiding principles should be part of the background statement. In other words, in recognition of, you know, the challenge faced by the American people in addressing the implications of terrorism or natural disasters, that the advisory committee endorses the principles that have been articulated by the AABB Interorganizational Task Force.

Consistent with these principles, we recommend, and then the task that lies before us is to say, well, what exactly do we think we want to tell the Secretary? And I think it would be things like that the Assistant Secretary should be established as the leadership voice for the blood message in times of crisis; for, for example, a proposal we heard yesterday, that the functions of major blood organizations, including the AABB, should be better defined in the FEMA response plan; or the concept that we heard, I think from Ed, that targeted funding should be focused on development of a national approach to donation such as what we just heard coined, the national blood donor corps or national blood donor reserve.

So I just think that we have to be very clear here to distinguish this set of principles from the recommendations we want to make to the Secretary.

MS. LIPTON: But I think what at least I have been hearing around the table and I think what Harvey articulated is, I think that the clear message to whoever is the government spokesperson has to be, "You need to consult with this task group." Because one thing we discussed in the deliberations was that you need to get the information from the people who are on the front line, and people should not be drawing conclusions who don't have the facts. And this group is set to get the facts, so I would like to see some integration of the task group with whatever the Assistant Secretary of Health or, you know, whatever the message is. That's where we ran into problems I think before at the government level, was that they, the people who were speaking were speaking to different parties and not getting a clear picture.

COLONEL FITZPATRICK: I want to take Jay's suggestion I think one step further. I think as a committee we could specifically recommend that the federal response plan, ESF-8, which under health and medical services currently tasks the Red Cross to be the manager of blood during a national crisis, that it's apparent from the recommendations of the task force and the deliberations of the committee that that section of the federal response plan needs to be rewritten to incorporate the recommendations of the task force in such a way as to meet the national need. And then a subgroup would do that within the federal response plan, and incorporate the membership of the task force in that section of the federal response plan. There's a number of ways to do that, but I think we could be very specific to the Secretary in our recommendation.

CHAIRMAN BRECKER: Okay. Why don't we try to draft a recommendation briefly, just to get the points down. These are going to be recommendations to the Assistant Secretary and to the Secretary, and it sounds like the first recommendation is that we would recommend support for the Interorganizational Task Force on Domestic Disasters and Acts of Terrorism in regard to the management of the blood supply. Get all that? Recommend support of the Interorganizational Task Force on Domestic Disasters and Acts of Terrorism in regard to management of the blood supply in times of crisis.

Now, under this I think we'll need several sub-recommendations that we've heard around the table, so this will be (a). Oh, "in regard to the management of the blood supply in times of crisis," "management of the blood supply in times of crisis." Okay, (a). I think probably the highest priority we've been talking about is, you know, whose desk does that really land on, or is this--"the spokesperson for the blood supply will be the Assistant Secretary of Health or their designee."

For the--no, no, not the secretary, "The spokesperson for the blood community will be the Assistant Secretary of Health or their designee." We can wordsmith this a little bit later. Let's just try to get the content down.

We can change that to lead spokesperson, Secretary or their designee, "Secretary of Health or their designee." And we'll make that "the lead spokesperson."

Okay. Let's take this to (b). "FEMA needs to be integrally involved in the"--Mike, want to phrase that one? Give you a crack at it.

COL. FITZPATRICK: I'll take a stab at it.

"Emergency Support Function 8 of the Federal Response Plan"--"ESF 8 of the Federal Response Plan, Health and Medical Services, be reviewed or be rewritten to incorporate the recommendations of the task force, and the elements of the task force," or something along those lines.

DR. BRECHER: Mike, you want to get up there and type that out and fix it? You know what you want to say. See, on this Committee you get put to work.

Okay, while he fixes that, let's talk about what a possible third or letter (c) might be for this.

DR. PENNER: Going to identify Central Command, establish a Central Command?

DR. BRECHER: We could have--there would be a Central Command with--I think there needs to be redundancy as to the backup command as well. And I think we need to say something about timeliness, that this needs to be fast-tracked, so that would be (c) and (d).

DR. BIANCO: Mark, in terms of the Central Command, I think the redundancy, it's not necessary in the Central Command. We are not going to be all in the same place when we convene the task force. We'll attempt--what we need is alternative ways of communication, if the phones go down, all that. But then each one of the members of that are linked to huge infrastructures like the CDC or DOD and all those, and that's where you need replication and things like that. What they need is to designate alternates to the task force.

DR. BRECHER: Well, I think maybe we're micro-managing the task force, and so maybe--

DR. BIANCO: Right. So I think if we leave it with the task force and kind of encourage the task force to develop redundance and alternative means of communication and all that, I think that we stop there.

DR. BRECHER: Okay. We could draft that we would encourage the Committee to develop redundancy and--how did you phrase that, Celso? Say it again.

DR. BIANCO: Now you've got me.

MS. LIPTON: It's really redundancy in its coordinating function, you know, because that's the--how do we all get together if one things's down; how do we know what to do?

DR. BRECHER: Okay. So let's go to--well, that's okay, got the idea. We'll wordsmith it later. Let's go to (c), that the Inter-organizational Task Force will develop redundancy?

DR. BIANCO: Well, it has to do more than redundancy. The Organizational Task Force will develop--

DR. BRECHER: You can abbreviate it OTF.

DR. BIANCO: --interactions, redundancy, and develop a more detailed plan of communications and management.

DR. PENNER: So you want to develop structure.

DR. BIANCO: That's--John, you always come with last words and more meaning. That's good.

DR. BRECHER: I tell you what, why don't we abbreviate Organizational Task Force as OTF? I think that will speed us up.

[Laughter.]

DR. BRECHER: Okay. "The OTF will coordinate"--how do you want to phrase this, "with redundancy?" Okay.

MS. LIPTON: I mean what you have said before, "Will be encouraged to"--I don't know if it's build in, but "redundancy in its coordinating function." It's already actually in the task force recommendation, so I mean--

DR. BRECHER: So why don't we just back off on (c). Does anyone have any other points?

DR. BIANCO: We have to say--I thought that the (c) has to the existence of the task force. You're recommending support but now specifically. You changed the writing according to Mike off the No. 8 provision. But now what is the part that the task force has in terms of adding direction. That is, what is the task force in general terms supposed to do?

DR. BRECHER: I think what we wanted to do is coordinate the national response of the blood community.

MS. LIPTON: To be communicated to the Assistant Secretary of Health, right.

DR. BRECHER: Right. Okay, Mary?

DR. CHAMBERLAND: Yeah. I guess I'm still having some difficulties with maybe the flow or the linkage of the statements, because I tend to envision it more as Jay articulated a few minutes ago, which is that a recommendation of the Committee to the Assistant Secretary should be more--should start maybe with our recommendation that the Office of the Assistant Secretary of Health be the lead spokesperson or whatever for the blood community in terms of a disaster. The Secretary, the Assistant Secretary in turn should draw on the Inter-organizational Task Force as an important resource in terms of information coordination, et cetera. I see (b) as being important, but something different and separate, you know, kind of more stand alone if you will.

But I think that's my first--the first thing that I'm having difficulty with is figuring out the sequence and the fit of the Inter-organizational Task Force, because I don't think we want to rewrite, redo what they're doing, but we certainly have to acknowledge their critical role, but it can't overtake or do what the government and the Department is supposed to do.

DR. BRECHER: So it's not--so number one is not really, you're saying it's not support, but will draw on--

DR. KLEIN: How about "endorse the principles?"

DR. BRECHER: I like that.

I'm sorry, Jay?

DR. EPSTEIN: Yeah. I tried to put this thought in writing, and let me read something, and if the group likes it, I can pass it off to a transcriber.

I think what we're looking for is an opening paragraph that goes something like this. "The PHS Advisory Committee on Blood Safety and Availability recognizes the need to improve preparedness of the domestic bloody system to address natural and man-made disasters including acts of terrorism. The Committee endorses the principles that have been articulated by the AABB Inter-organizational Task Force on domestic disaster and terrorism, which are", and then enumerate 1 through 7. "Consistent with these principles, the Committee recommends the following."

And then I think that the first should be that the lead spokesman for the blood community, I think it should say "should be the Assistant Secretary for Health or his or her designee." I think, in my opinion, the point on "support function 8" is redundant with what's been stated as bullet 1. They're the same thing. So I would make the recommendation that "Emergency Support Function 8, Health and Medical Services, of the Federal Response Plan, be reviewed to incorporate the recommendations and organizational membership or participation of the task force." And then you could elaborate that to say, "in regard to the management of the blood supply in times of crisis." Because I think those are the same thing.

What you want is the function of the task force integrated into the response plan.

DR. KLEIN: Jay, I'd like, if I could, to modify your thought, that instead of just the lead person, that there be a single voice or a single message, and that the lead person be the Assistant Secretary, because I think that the single message or the coordinated message is really the key regardless of who delivers it. We want someone with the maximum visibility and influence to deliver it, but the message is the medium or the medium is the message.

DR. BRECHER: I think in concept what you've proposed, Jay, is very good, and I'd like to see it typed out so we can look at it.

MS. LIPTON: My one concern--and I think this is the right to go--I just want to be very clear. When there is a disaster and the media calls, they will not be reaching the Assistant Secretary of Health first, trust me. And I think we have to, you know, understand the role of the other organizations, because for me to say, "Well, no comment. We're waiting to hear from the"--I mean it could take a while to get a real statement out of there. So I don't know how to handle that, but I think we ought to think about it a little.

DR. BRECHER: Well, other than this Committee would be the designee in times of crisis. I mean I think the Assistant Secretary could designate that ahead of time.

MR. DALAL: It would help me, and maybe others, if somebody could just list the organizations and the participants in this Inter-organizational Task Force.

MS. LIPTON: Look--on the back of the statement of the Inter-organizational Task Force are the participating organizations. It's page--I don't know what page it is. Page 6 has the--

DR. BRECHER: Why don't you just read them out so they go into the minutes here.

MS. LIPTON: Yeah, do you want to put them in the--

DR. BRECHER: Well, why don't you just read them so they go into the transcript.

MS. LIPTON: Okay. It's the government departments and agencies as represented by the Department of Defense Armed Services Blood Program, Department of Health and Human Services. Right now it's the Office of Public Health Preparedness. We might want to make an amendment to that. I don't know. Federal Emergency Management Agency, the Centers for Disease Control and Prevention, the Food and Drug Administration.

Of the blood organizations, there's the American Association of Blood Banks, America's Blood Centers, American Red Cross, Blood Centers of America, Plasma Protein Therapeutics Association.

And then the commercial organizations as represented by Advomed.

DR. BRECHER: The only organization that seem to be missing is the hospitals.

DR. DAVEY: While Jay's putting up his comments, which I think are very well taken as usual. Jay does a great job. I don't think that even--and I think your point is well taken, Karen, that often I would think in a major disaster, the Assistant Secretary of Health is going to be overwhelmed with issues to deal with, and blood may not rise to his or her top priority, although I still think that the government spokesperson, I do agree should ultimately reside--the spokesperson's responsibility should reside in that office.

However, I don't think it precludes the task force from coming to a consensus and issuing a consensus view even before the government may be able to mobilize. The task force can still speak. They have First Amendment rights to speak. And if they can arrive at consensus, I would say they have every right to be forthcoming on that.

DR. NIGHTINGALE: I would like to make a comment from personal experience in the days immediately after 9-11. Blood did reach the Assistant Secretary for Health and it was not a major preoccupation we sought or particularly cared to have, but we did spend a fair amount of fairly precious time addressing it, and I see no reason why that would not occur in the future.

DR. BRECHER: At a minimum, there wouldn't be disjointed messages from the blood community.

MR. SKINNER: Can I back up just a moment and ask a question about the membership? It strikes me that the end user somewhere ought to be represented in what the final message is, and that there ought to be a role in the task force, either an advisory capacity or membership capacity for the end users of the products that we're talking about, be it blood or the derivatives. And I would suggest that we articulate that as one of our goals, that there be some kind of representation from that community.

DR. BRECHER: Mark, do you want to be more specific? What organization would you recommend specifically?

MR. SKINNER: I don't know that we have to name an organization by name. I mean I think there's a variety of organizations represented here, and whether its one or several, I don't know that it has to be a large contingency, and probably it's a limited number of--I think the important thing is to communicate that the voice needs to be there, and then we could work out the logistics in the final details.

DR. BRECHER: So how are we doing up there? Do we want to inject a sense of urgency into our recommendations? I think so.

Jay?

DR. EPSTEIN: I just wanted to take a stab at Bullet (a), which is in essence the first recommendation, trying to synthesize what's being said here. What I'm hearing is something along the following lines. "Mindful of the needs of all stakeholders, the Department should act to promote a single consistent public message on blood issues and the ultimate spokesperson for the blood community should be the Assistant Secretary for Health or designee."

DR. BRECHER: Jay, you've written things like this before, haven't you?

[Laughter.]

DR. EPSTEIN: Pays the rent. It's called "Federal Speak."

DR. BRECHER: I would endorse that. I think that that sounded exactly to the point.

All right. Now, how about under item (d), I think we need to, as I said, inject a sense of urgency that this should proceed with--in a--well, how do you say fast track--how do you say it in governmentese?

DR. BIANCO: Mark, while Jay crafts with his powerful mighty pen our next words, I think that probably it would be appropriate to ask the rest of the people in this room if we are missing any other representation as was just mentioned in the task force.

MS. LIPTON: One that was suggested to me was NHLBI, and you know, it's hard right in a disaster to think of a research role, but, you know. I think our intent in putting together a small group of people that were going to focus on the issues was our immediate--there may be a role for a very small group at first to assess medical need and determine supplies. Then the group probably needs to branch out beyond that to other stakeholders, but in the initial stages, what we're trying to find out is how many casualties and where's the blood?

DR. BIANCO: Yes, but Karen, it would be appropriate at the time that a message is being developed to involve the other groups, and I think that they will help us carry the message. They will help us.

MS. LIPTON: I agree. You know, I'm struggling as we've always struggled in the transfusion medicine community, who represents the end user, and on our committees we've just used what we call a public representative because there really aren't organized groups, but just putting someone who is a public member.

DR. BRECHER: Possibly a bio-ethicist.

DR. KLEIN: While you're thinking about that, there's another thought that I'd like to have in this message if the Committee agrees, and that is that we need to really endorse the national campaign to assure that there is adequate blood on the shelves prior to the next disaster. Now, whether you want that to be a volunteer corps or some other concept but I think that we'll be missing a chance if we don't have that in these recommendations.

DR. HAAS: Mark, I actually think that should be a totally separate item. I mean here we're looking at crisis, and I think to separate out the day-to-day stuff and make a big issue right along the lines that you're saying is important. It should be separate from this.

DR. BRECHER: I agree with that. I will make that a separate item, a separate recommendation.

DR. PENNER: Karen, how about an elected member of the community? Which means that it's someone who is representing the community, so it could be a legislator. And at least then it would have someone selected--

MS. LIPTON: What do you mean? You mean elected to a public office?

DR. PENNER: Yeah, would be fine, because representing a community, and at least by election it isn't just by an appointment. And that might give an opportunity for one of the legislators to be on board which could be helpful all the way around, someone from the House, for example.

DR. HAAS: John, are you saying that in reaction to Mark's comment, because if you--

DR. PENNER: Yeah.

DR. HAAS: That legislator may not understand the needs of the recipients of the blood products. It may make sense to have the political end on there, but I don't think for what Mark wanted.

DR. PENNER: But he's got to represent the recipients, who are the public, not specialized organizations, who are recipients.

DR. HAAS: Well, you're making some assumptions that the politician would know--

DR. NIGHTINGALE: A point of order, or at least a point of constitutional order. We are the Executive Branch. Congress is the Legislative Branch. There is a document written in 1776 that splits the two.

DR. HAAS: I stand corrected.

[Laughter.]

COL. FITZPATRICK: But, Mark, I think some of the key players from the 12th through the 24th or whenever that meeting was, was New York Hospital Association and the AHA, so I think those are you--I'm not saying to make them part of the Committee, but they could be gone to for that purposes.

MS. LIPTON: We did think about bringing them on again as a bigger group, but we actually have a very good, through AABB, sort of a primary contact with the transfusion services. At the AHA it's a different level. We could get a representative in there, and, you know, and I think actually, you know, we should get them to the table on that.

DR. BRECHER: All right. Lets get back to task a little bit. We wanted to inject some urgency into these recommendations. And so does anyone have a recommendation for (d) in terms of correcting the words? Where did Jay go to?

DR. PENNER: Something about recognizing the urgency of the present situation, that we would urge haste in implementing the recommendations.

DR. BRECHER: Yes, I like that. "We urge haste in implementing these recommendations."

DR. PENNER: Present situation. "We advise haste"--I think I said something different before. "Haste in implementing these recommendations." Yeah, "expediency" might be another term, from my colleague here, instead of "implementing"--instead of "haste." Don't know how to spell that. Go ahead.

DR. DAVEY: John, do you think we could just say something more crisp like, "We urge the Secretary to attend to these recommendations with urgency," or "to review these recommendations with urgency."

COL. FITZPATRICK: How about, "We request the Secretary expeditiously act on these recommendations."

DR. BRECHER: Jay?

DR. EPSTEIN: Could I suggest that maybe we could just add the word "urgent" to the preamble statement? "The PHS Advisory Committee recognizes the urgent need to improve preparedness?"

DR. BRECHER: That would work too. Is that the sense of the Committee? Okay. So we're going to drop the--we're going to move the word "urgent" up to the introduction. So we say, let's see--"recognizes the urgent need." All right.

Everyone pretty much happy with this? Should we have a vote? All those in favor of this recommendation, voting member?

[Show of hands.]

DR. BRECHER: All those opposed?

[Show of hands.]

DR. BRECHER: You're opposed? The vote was unanimous.

The second item, I think, in terms of priority is the national monitoring of the blood supply, and built into that I think is the sense of do we need to increase the inventory, possible as a subheading. You know we saw what can be done in the United Kingdom. Can we do the same in the U.S., and should we recommend that HHS support a real-time inventory of the blood supply in this country? What does the Committee think?

DR. BIANCO: I think I said that at a prior meeting, every Monday we hear on TV how many millions of dollars the best movie made over the weekend, but we don't know how much blood we have on our shelves. And I think that that's a very important project. I think the British got there first, but I think that we have started, and I like what I see with the initial stages of the HHS program. I am not sure that this is the final location or the final structure that that should have, but I think that we should support the concept entirely, because it is very important.

DR. GILCHER: The comment that I'd like to make, Celso, is that we need some definitions here of what inventory is, and let me give you an example. I can tell you at any single point in time exactly the number of units that are contained within all of the centers for the Oklahoma Blood Institute, but I cannot tell you at any single point in time, the number of units that are available in the hospitals. I get that inventory once a day from every hospital in my system and put it together. So we really need to define that, because the blood centers I believe probably most could tell you at almost any point in time the number of units that are actually immediately available on the shelf, but in addition you have the units that are out in the hospital. That's a little harder to pull that data in at any single point in time.

DR. BIANCO: I think that you are correct, Ron, but I don't think that this Committee should micro manage. I think that we have to find words that encompass both sides of the equation. I think that that was the intent of Nightingale's program, was to look at the hospital side, because we could look at the blood center side in a certain way.

DR. GILCHER: But that's exactly my point. For the disaster that has occurred, the single point in time, as an example, the bombing in Oklahoma City. The other side of that was the tornadoes. It was a disaster in progress because it occurred over a long period of time, and the media in both instances wanted to know--they called in, talked to myself, "What is available in the way of the blood supply?" We hadn't even assessed the need for the blood at that point in time. One was the disaster--it was over in one sense. In the other case the disaster was ongoing. That really was true with the World Trade Center or what happened on September 11th. It was a disaster in progress, and what is, I think, critical with respect to blood supply is also what's immediately available at the blood centers. And we can assess that pretty quickly, Celso, but not the hospitals.

DR. GOMPERTS: How about this, just to get something down in the system. "The Advisory Committee recommend that HHS support procedures and processes to build inventory of blood and component across the nation. To this end, the Committee recommends a number of points, one being a public health education program to enhance awareness, risks and benefits of being a blood donor, establishing processes for national and regional registries of, in parentheses, donors in emergency, and so on. Would that help?

DR. BRECHER: I think that's a good start. I think we need to push that--somehow we've got to get the message in that the majority of the blood supply should be tracked, that it has to be a big program. If we're going to do it, do it right.

DR. NIGHTINGALE: May I speak?

DR. BRECHER: Yes.

DR. NIGHTINGALE: I think the key to the issue on the table is the availability of data from the two major suppliers, the request for aggregate data, total inventory by AB, O, and Rh, and platelets by random, and distribution, outdate--we don't need transfers here--has been delivered for some time now to both organizations, and while discussions continue, I have not gotten the response that I asked for.

As I've said repeatedly here before, that's not necessarily a bad thing because that data is not for the government to arbitrarily grab. That data is the property of individual citizens or institutions in the state. They can provide that voluntarily. There can be a recommendation here that they provide that data, but at the same time, this is a quasi-governmental committee and, as you consider this, you must consider the rights of the individual to their private property.

DR. EPSTEIN: I think that it would be helpful to separate the concept of studying and potentially developing reserves from the concept of moving toward demand-driven donation, because I don't want to dilute this concept that we call the Blood Corps. I think the notion of blood donation as national service deserves highlighting. So I'm all for Ed's point, but I'd like it to be a stand-alone.

Conversely, I've taken a stab at the statement we're trying to make about reserves and monitoring along these lines: The Department should fund the evaluation and potential development of blood reserves in parallel with supporting the development of an ongoing program for monitoring of blood supplies and shortages, including related reagents and supplies.

So what I'm trying to link here is the monitoring function with the reserve, and then I would like the mechanism of recruiting donors to be a stand-alone objective.

DR. BRECHER: I would motion that we take Jay's wording and insert that on the screen.

DR. BIANCO: Jay, do you want to define what shape or at least temperature of the reserve?

DR. EPSTEIN: I have deliberately not done that because, you know, there's this concept of a walking reserve--

DR. BIANCO: It could be at 37 degrees or minus--

DR. EPSTEIN: Right. Okay.

DR. WINKELSTEIN: Mr. Chairman, we might either in the preamble or in each section make certain that we make some arrangement for funding to support the federal agencies that are having to put extra effort into these activities and/or any public awareness. I mean, without money there's no teeth at all in this.

DR. BRECHER: Well, what good would our committee be if we didn't recommend the spending of money.

DR. WINKELSTEIN: Hear, hear.

DR. HAAS: Just so it doesn't get lost, Jay in his great craftsmanship in terms of getting ideas, I think this section needs the preamble, just as John was saying. So it sets the context just like it did for the crisis list that we have.

DR. PENNER: Do you want to put support with adequate funding? We're assuming support means funding, but not necessarily.

DR. HAAS: I think it should be very explicit, so support with appropriate funding.

DR. BRECHER: The way it's going up on the screen is: should fund the evaluation and development.

I would actually say take out the word "potential." I would say just "development."

Karen?

MS. LIPTON: I think we should leave it at potential until we find out what--I mean, I've listened to this, and this sounds great, but this sounds--

DR. BRECHER: Okay.

MS. LIPTON: It's a huge undertaking. So, I mean, I'd like to say evaluation and--you know, and we are not the United Kingdom.

DR. BRECHER: Well, maybe we could add 40 pence per unit.

[Laughter.]

DR. HAAS: That must be the lawyer speaking in Karen.

DR. BRECHER: But, seriously, funding does not necessarily have to come from the government to make monitoring occur. We could add 40 cents to a unit to pay for a monitoring system.

MS. LIPTON: We don't know whether it's 40 cents in the United States or not. They're in a very different system than we are. That's my concern.

DR. HAAS: I think there is an underlying principle. I have heard several times over these two days about this national resource, and in the concept of public-private, a national resource is more like a public good, and public goods get funded or supported through centralized funding. So I would think we need to make that point explicit, not that we can't draw in the private sector, but when the private sector is doing it alone, you tend to lose some of the coordination. So I'd like to see it explicit.

DR. BRECHER: I think you're right. In fact, in Judy's presentation, the hospitals they were having the trouble with were the private hospitals.

DR. NIGHTINGALE: That is what we have here in America.

DR. BRECHER: Is everybody happy with that wording?

[Pause.]

DR. BRECHER: "The HHS should fund the evaluation and potential development of broad reserves in parallel with supporting the development of ongoing programs"--it should be plural--"for monitoring blood availability and shortages, including related reagents and supplies."

Jay?

DR. EPSTEIN: Could I just suggest that text, if retained, is merely point (D)? It's just another of a series of recommendations. I don't see it as a thing apart.

DR. BRECHER: How does the committee feel about moving that up to (D)? Okay. Why don't we just make that (D).

Okay. Now, I guess the third priority--

DR. HOOTS: Is that what you were going to bring up the one, the core--I just have something to take a shot at.

DR. BRECHER: Go right ahead.

DR. HOOTS: "Inasmuch as there has been a demonstrated willingness of previously untapped donor populations to respond affirmatively to perceived needs for blood in terms of crisis, a voluntary corps of blood reserve prescreened donors be recruited. This group would be an identified national resource readily mobilizable in times of need to replace or augment our nation's blood supply. Participation should be widely recognized and lauded by the community at large."

DR. BRECHER: Would the Blood Corps have uniforms?

DR. HOOTS: I don't know. I just used it because it had been used before. It captures it.

DR. BRECHER: Keith, why don't you give that wording--take that up to the front and they'll put it up on the screen and take a look at it.

DR. PENNER: I really disagree with this situation of identifying a corps when you have, as I've said before, the regular donors coming in, putting in their blood, and suddenly having no recognition, while this super-special little group is going to be out there. I think we have to recognize all of them, that there is--all the donors who provide blood in the United States, who have done so regularly, be recognized as the corps of blood donors and participants and be given the same kind of discretionary recognition.

DR. KLEIN: I agree with John. I think what we need to do is to define blood donation as a national service, and then develop our blood donor base sufficiently that we have reserves for such a time when we might need more. But, you know, inherent in that is to have enough blood on the shelf at all times prior to the next disaster.

DR. PENNER: And we constantly, whenever we're suddenly out of O, you just run through your O list and you call Joe whatever, and he comes in.

DR. GOMPERTS: I think all of these are compatible and fit in with an overall program. But underpinning all of this, I do feel having looked at and reviewed what happened immediately after the September 11th, a public health donor education program is probably needed because in the event of another episode, terrorist attack, catastrophe, whatever, there will be leaders of the community, in order to deal with the response in some way or another, make independent pleas for blood donors. In that event, if there is a basic understanding of blood transfusion, blood donation out in the community, obviously not everybody, this will certainly help in managing that.

DR. BRECHER: Mike, do you want to--or, Harvey, why don't you go ahead?

DR. KLEIN: I agree with the concept. I'm not quite sure how we word it, but it seems to me there were two parts to that, and part one is we need possibly either research or a better understanding of how to recruit some of the people who came out during this period of time and some of the populations, because, clearly, this is a different group. A different dynamic brought them out, and they have different demographics.

The second part of that is figuring out--again, research might be needed--how to deal with the imperative to donate blood during time of crisis, because we don't want to turn off the energy and the willingness, but we want to channel it into a socially usable mode.

COLONEL FITZPATRICK: We have a proposal: "The Secretary should promote blood donation as a national service to maintain enough `blood on the shelf' to permit rational management of routine needs and disaster response."

DR. BRECHER: It's clearly not as strong as a corps, but I guess the sense to me seems to be moving away from a separate corps. So, okay, why don't we substitute that motion?

COLONEL FITZPATRICK: Within "promote," you could identify a number of different elements.

DR. BIANCO: Can you find something that you can put in bold, Mike, that makes these--well, readable, not necessarily, but a little bit--gives it more weight, more teeth?

DR. EPSTEIN: I think that the idea that we're trying to work toward is not so much a specific set of people who are the corps and everybody else isn't, as the notion of moving people from an identity of having donated perhaps once, to an identity as a donor. And this is actually a concept that's been discussed in various international fora, and I think that that's really the notion that we're trying to capture, which is not quite yet captured. But we want people to cultivate the identity of a donor.

DR. WINKELSTEIN: Mr. Chairman, I really think that the corps is the active duty--that's the regular donors that John's concerned about, plus that reserve element that's called on when they're needed. But to be part of a unit that's identifiable that can be applauded and recognized I think is valuable. I think that the term "corps" or whatever term we select, you know, can incorporate those active on a regular basis that are 20-gallon and 30-gallon donors, as well as the reserve which are called up because they've been identified in crises that they're ready, willing, and able to donate on call.

DR. HOOTS: I think Jay captured what--I mean, that was the first stab, but that's exactly--it's not either/or. I think the idea is to take untapped resources and turn them into perpetually tappable resources, however we want to say that. People who haven't been involved get involved. By getting involved, they get reinforced in their behavior, and the behavior continues in a greater degree over a lifetime. That's really what I was trying to push.

DR. EPSTEIN: I think the term that we're looking for is a self-committed donor willing to donate on demand. I don't know where we put it, but that's the concept we're after.

DR. PENNER: We already have these donors on demand out there that come in for platelets whenever we call on them, and, I mean, this is a whole team and they're recognized. So, again, it seems to be a general recognition, I think.

DR. EPSTEIN: But I think the idea is that we now need them potentially by the tens or hundreds of thousands, so that when we hit these nadirs we have people who we know will come.

DR. BIANCO: And, John, I think that there is another aspect that will probably help everybody, that is, we move the recognition from our local blood centers where we give them the pins and the parties and all that, now to a national recognition that is to--like everybody that participates in an emergency, will be the emergency service, the firemen, and the blood donors. That's the parity that I'd like to see.

DR. PENNER: I agree with you, and I think it ought to be all of them recognized because they are all volunteering for a need when they bring blood in, but we recognize them all.

DR. BIANCO: Put the blood on the shelf--

DR. PENNER: Nationally, yes. I agree with that.

COLONEL FITZPATRICK: I think everybody's in agreement with that, and when I talked to Dr. Chapman from the U.K., I asked her, What do you do when you're at 0.8 days of supply? And she said, We turn it over to the marketing firm that we hired to recruit donors, and they have managed to meet the need. So, I mean, I know we all have good ideas, but I think it might be best if we tried not to micromanage what we call them or what we do to them, but that we identify the need to recognize all donors and the fact that they are a resource and we need to develop somehow a marketing group that recruits them for us.

MS. LIPTON: I'd like to echo that, too. I like the idea of a corps, but my concern is that I frankly don't know what the next generation is going to want to be called, and I think we ought to, you know, not sit here at this time and maybe just say what we want to do is promote this, and then we can explore a lot of different ideas. I like the way Celso captured it, was that they're a part of a national cadre of, you know--I don't know--donors or something. But that's the important part, and that it is a national service.

Now, however we attract people into that, I don't feel competent to figure out sitting ere.

DR. BRECHER: I propose that we simplify this. We keep the bottom paragraph, delete the paragraph above it, and vote on that. The bottom paragraph, we keep the bottom paragraph.

It says that we promote--it's a national resource, and we promote donation, DHHS would promote donation.

DR. BIANCO: So this would become Item (E)?

DR. BRECHER: No, I think it would be a separate recommendation.

DR. BIANCO: Okay. But then it needs an introductory paragraph.

DR. PENNER: Why don't we identify the donors as a national resource.

DR. BRECHER: Yes, blood donors.

DR. BIANCO: That's correct.

DR. PENNER: That's what we're really dealing with.

DR. BRECHER: We change it to "should identify blood donors as a critical national resource," insert the word "donors." Bottom paragraph, all the way to the bottom of the page, where it's in bold, "identify blood donors."

I don't think it needs an introductory paragraph. I think it can stand alone. Or we could say that, "This committee recommends that DHHS..."

DR. BIANCO: To follow the previous section, "In addition"--

DR. BRECHER: Right, we could do that.

DR. BIANCO: --"the committee recommends that..."

DR. BRECHER: Okay. So go to the beginning of the sentence. "In addition, the Advisory Committee on Blood Safety and Availability"--whatever abbreviation we're using today, thank you--"recommends that..." Good. And let's delete the paragraph above it. Oh, yes, we'll get there. Delete that paragraph. Then in that paragraph that we have at the bottom there, the word right before the bold letters, "should," let's get rid of "should."

Okay. Let's have a vote. All in favor? All opposed? Okay. Unanimous.

DR. NIGHTINGALE: Unanimous?

DR. BRECHER: Unanimous.

DR. BIANCO: Mac, can you do us a favor? Oh, she just it. It just was to save it.

DR. BRECHER: Shall we put that to a vote?

[Laughter.]

DR. BRECHER: In my mind, these were the two most critical--two or three most critical items that we needed to address in terms of crises.

The next order of business that I would like the committee to address is what other topics does this committee need to address in the future so that we can have a list to present to the Assistant Secretary of these are what we consider important issues, and let her pick what it is she would like the committee to address.

Jay?

DR. EPSTEIN: Yes, thanks, Mark. I wanted to add a subsidiary bullet to this paragraph to capture the notion of committed donors, and the words I've been playing with are these: "It should be a national goal to promote self-identification of lifetime committed donors willing to donate annually and on demand."

DR. BRECHER: Does the committee agree with that?

DR. EPSTEIN: I mean, one could go even further. We do know that if we were to get the percent of the population donating annually up from, say, 5 percent to 7 percent, most of our problems would go away. We could, in fact, provide a target benchmark. I don't know that that's exactly the right number, but somebody in the room probably knows the right number.

DR. BIANCO: Yes, but, Jay, what I would suggest is instead of saying annually, saying regularly and letting it be managed. Because for some centers it may be easier to drive them to donate instead of 1.5 times a year, twice a year or otherwise, so we leave it open.

DR. BRECHER: I don't know that the wording "on-demand donors" is quite right. It makes the donors sound kind of odd, o-d-d, on-demand donors.

DR. EPSTEIN: Well, we could say "or as needed."

DR. BRECHER: Yes, I prefer that.

All right. Ron?

DR. GILCHER: Jay, I totally endorse what you said. I interestingly sat here and was writing something down before you made your talk, but I want to read this, but I want to comment on what Celso said. I wrote down "national blood donor force." This is an idea that I'm going to take back to my recruitment. "A group who will respond to a crisis whenever it occurs as well as be a regular blood donor," because I think that's the critical issue, is that we really want our regular donors. But they must donate at least one time per year, and there's a reason why I say that, and that is because the likelihood that we will have data in terms of repeat donors and negative test results is more likely if that person's coming in every year, because we're going to sort them out. We want them to be there at least once a year.

And then I added something else that I think is important. I said, "The name goes into a national pool so that this person receives recognition not just from the local level but from the national level," such as the AABB or HHS, so that they get some sort of recognition from the national level.

DR. BRECHER: Let's get something up on the screen. Jay, did you revise your wording?

Okay. While that's going up on the screen, why don't we talk about additional issues for future meetings.

DR. BIANCO: Already for future meetings? No more additional issues here?

DR. BRECHER: Well, we can come back in a second. I want to give them some time to type up there. But while they're typing--then we'll take a look at that--let me just go around and see what issues we think are important that we can cover in the future.

DR. WINKELSTEIN: I think to expand the current pilot project for monitoring blood supply to monitoring plasma supply, including those in the plasma derivative consumer communities.

DR. BRECHER: Okay. I had one thought in that this committee has in the past addressed the errors which are known to be the leading cause of death from blood transfusion. At least this committee has talked about it.

We have not talked about the second leading cause of death, which is bacterial contamination. So I would toss that out as a possible safety issue that this committee ought to address.

DR. HAAS: I don't know if this is going to be picked up in what we've just been working on, but yesterday we were hearing a lot about having a three-day shelf blood up to 21 to 24 days, and at least from my perspective, it would seem to me we ought to address that. What's going on with such a huge gap? Is there a preferred gap--not gap, shelf life.

DR. BRECHER: Okay. That gets to the reserve, the liquid reserve.

DR. PENNER: Mark?

DR. BRECHER: Yes, John?

DR. PENNER: I wanted to address a situation that a lot of us have been discussing here separately, and that is manpower, medical manpower. And I've put together just a topic as a possibility: development of transfusion medicine scientists, and I'll read it as you have it up on the board there. An interest of this committee is the need for physicians and scientists devoted to the transfusion sciences as they include the blood and blood products, and that also includes management of blood disorders. There's a recognized deficiency of such individuals who specialize in this area and an absence of training programs to develop the expertise. I believe the situation is very critical now, and I think will get worse over the next decade. I'm suggesting that the committee consider this topic for future--for recognition that funds be made available--I should say funds we believe are available for training programs if the directions are offered and support is elicited for governmental agencies.

Essentially what we've come up with is, after this--in this next ten years and as this generation of gray hairs disappears, we don't have anybody in the wings coming up who know anything about transfusion medicine or know anything about hemostasis and thrombosis, and we're essentially devoid of these people because they've all been encouraged to go in other directions because this has not been a good career path. They've gone into oncology, which pays a great deal better, and the pathologists also have been subverted into other areas of minding their store and getting the business end of it going.

So we have then a situation where we're out scrambling to try to get people to take up our positions in handling the hemophilia population and handling the transfusion requirements and handling all of these things that we're dealing with--sickle cell, and we can go on from there.

So hematology has been a very, very diminished field as such that we all recognize, and I think most of us here--and we've talked about, Al, you'll add your comments, and we've got Harvey also, who I think is in agreement, Bruce was here and was very supportive, Andy Heaton. We can go on and on. But the situation is that this is known, and we're not doing anything about it, and we understand that there are funds available to support these kinds of training programs and maybe career development if we're able to at least bring it to the surface and get it to a significant level that something is going to be done.

If we could present this or have some sort of activity in the future at one of our meetings, that at least would get it to surface, and from that point on, we might be able to carry it on and encourage some of our young scientists to go in that direction.

DR. PENNER: We had so little science added to transfusion medicine in the past 15 to 20 years, it's just a sad state. No one is working very much with the platelet preservation, with the means of improving some of the products we presently have, and I think this is where we need some attention.

DR. WINKELSTEIN: Mr. Chairman, I think it's appropriate for this committee to make some comment on the OBRR strategic plan, as presented by Dr. Lewis. And even if it's just to pass a resolution to endorse that, but I think it would be valuable if the committee looked at that when we had time and more detail and made some comment on it.

Secondly, I'd like an additional item in the future to maintain some position to monitor access to therapeutics, and specifically plasma derivatives, not only on the reimbursement side, but other access issues that affect the communities.

MR. HEALEY: I'd like to suggest that maybe the committee take up the issue of international harmonization for blood and plasma requirements. I know this is an issue that committees kind of flirted with before. We've heard from or you all have heard from Emanuelle, from WHO, and others, and I think a more directed topic would be appropriate.

DR. BRECHER: Rick?

DR. DAVEY: Mark, it might be useful from time to time for the committee to get updates on current developmental issues that are going to affect blood safety and availability. Two that come to mind right now are perhaps updates on pathogen inactivation and how it is moving toward incorporation into our system and artificial oxygen carriers.

While I don't think we perhaps will make recommendations there, I think it will be useful for the committee to get periodic updates.

DR. BRECHER: The word that I see creeping into the literature is pathogen reduction.

DR. HAAS: Again, I'm not sure if this is something for our committee or for the task force, but when we're talking about the crises, we talked about real crises, and then we talk about day-to-day, but then there's this huge gray area, and what happens when the inventory levels fall, how far do they have to fall before we call it a crisis? That's part of that uniform message or straight message.

So, again, I don't care what it goes, but I think that has to be discussed.

DR. BRECHER: Keith?

DR. HOOTS: I hesitate to bring this one up because it's such a can of worms, but I think every time there's public comment there's some change in federal regs related to reimbursement that impacts people, and I think we really ought to look or at least think about the process, I mean, obviously Congress makes the laws, but the implementation and how that affects individual constituents, particularly of the type of populations represented by blood replacement products.

DR. BRECHER: Blood reimbursement has been covered by this committee in the past, but I agree, I think it's something that we need to revisit, and we've heard comments to that regard.

Celso?

DR. BIANCO: Certainly, that's part of it, but I think that we have looked or this committee, I haven't, but the committee has looked at various aspects of supply, of reimbursement, of errors. I think we haven't looked at the practice of transfusion medicine. That would include the need for physicians. It would include some of the new products and how they come. It would include guidelines, that I remember that the last meeting of the NIH on that was in 1995, January of 1995, things that we have left to the past as if all of those issues had been resolved.

As Dr. Penner reminds, many of us are not going to be here, as many of you will, but some of us will not be here for too long, and it's time for renewal, and it could include, obviously, as part of the practice, the effects of reimbursement in each one of the aspects of the way transfusion medicine and replacement therapy is practiced.

DR. BRECHER: Okay. Well, I think that that is quite a few ideas that we can present to the assistant secretary.

The wording has been added to the screen. Let's go back to task. Does that seem acceptable to everyone? "It should be a national goal to promote self-identification of lifetime committed donors willing to donate regularly, at least once per year, and as needed." Is that acceptable?

Jay?

DR. EPSTEIN: I would just suggest that that either be a second sentence of the previous paragraph or a subparagraph bullet. I believe it's a subsidiary explaining the previous paragraph.

DR. BRECHER: Yes, I think we can just tack it onto that paragraph. Okay.

DR. DAVEY: Mark, I think the suggestion of recognition and perhaps national recognition was a good one and might be able to be incorporated as part of the thought that these people who do identify themselves, donate regularly, should be appropriately recognized. And it would be nice, I don't know about a national pool, but a national way of signifying their participation.

DR. BRECHER: Separate license plates?

DR. DAVEY: License plates.

[Laughter.]

DR. BRECHER: Jay?

DR. EPSTEIN: Perhaps that can be done by just adding the words "recognize and promote."

"It should be a national goal to recognize and promote" or "promote and recognize" or "promote and give recognition to," something like that. Do you like "recognize and promote"?

DR. WINKELSTEIN: Mr. Chairman, I hate to be the nudge, but in reaffirmation of the committee's resolution of August 24, 2001, I'd like to propose the following:

"Due to the life-sustaining qualities associated with plasma-derived therapies used for the treatment of chronic disorders such as Alpha 1-Antitrypsin Deficiency, hemophilia and immune deficiencies, the Department of Health and Human Services Advisory Committee on Blood Safety and Availability recommends that for the Medicare outpatient prospective payment system, proposed changes that will result in a loss of benefits, be suspended until these therapies are placed in a permanent separate payment category.

Further, the committee requests that CMS carefully review the costs associated with these therapies when structuring a permanent payment category to ensure that the patient access is not compromised."

DR. BRECHER: Thoughts and comments from the committee? This is basically a reaffirmation of a previous recommendation. In effect, we would be somewhat of a--I like your choice of word "nudge," it's a good one, to the assistant secretary. I agree with it, but I wonder if it will distract from our current message about crisis?

DR. WINKELSTEIN: With all due respect, Mr. Chairman, we have a crises that's starting 1 April for about 20 percent of our infused populations that will not have access to product due to financial or disability hardship under Medicare.

DR. BRECHER: Committee members, what do you think?

DR. PENNER: If we make this, with respect to a previous resolution that was forwarded to the previous administration really, we would like to bring to your attention the following, so that it doesn't seem to be something coming out of the blue, but something that is already on the table. Maybe that would diffuse it a bit.

DR. BIANCO: I think that, actually, it could be done, Mark, as a letter from you recommending a vote in sentiment of this committee to the new assistant secretary, and using as justification to the new assistant, we are confronting this issue now, and the committee asked me to convey to you the following message, and that was a resolution that was adopted by the entire committee in the last year.

DR. BRECHER: I would prefer doing it that way. Is that agreeable with the committee? Maybe if you could get me the wording of what you read, I can incorporate it.

DR. BIANCO: I would be glad to.

DR. PENNER: Do you want to vote on that just so you can conclude?

DR. BRECHER: Those in favor of a letter from the chairman to the assistant secretary?

DR. PENNER: Unanimous support.

DR. BRECHER: All right. Any other issues? Mike or Harvey--that end of the table?

DR. KLEIN: Before the meeting closes, I just want to state for the record, endorse recent recognition for Mr. Howard Drew, who began his lifetime donations while in the military, subsequently for the Red Cross and for many years at the National Institutes of Health.

He has recently been recognized by the Guiness Book of World Records as the human being who has donated more whole blood and blood components than any other. I just wanted to put that into the record.

COL FITZPATRICK: Mark, I know you discussed reviewing the OBR strategic plan in the future, at a future meeting, but it would probably be important in order to get support for the plan, for the committee to recognize the need for the Secretary to support the plan and incorporate it into future plans. So maybe as one last recommendation, recommend that the Secretary recognize and incorporate the OBRR strategic plan into the DHHS response plan for counterterrorism and disaster preparedness in support of the Agency.

DR. BRECHER: Do we want to do that as a resolution or as another letter to the assistant secretary?

Jay, how do you feel about that?

DR. EPSTEIN: I think that it is often hard for blood issues to become visible at the highest levels of government. I recognize that we get air time and that, you know, we were graced by Dr. Slater spending a morning with us yesterday, but I think that a statement from this group highlighting the importance of the concepts that were heard and the initiatives that were heard into the larger framework exists because it will give us the vehicle to try to promote these objectives as part of a much, much bigger context.

I mean, you can't imagine how many times we're told that the powers that be have bigger fish to fry, but, you know, transfusion medicine supports a very large part of modern medical care, and the needs in this domain cannot be made secondary. So it's simply my personal view, and I'm not stating a position of my agency, I'm just giving you my personal view, having hung around the halls of bureaucracy for some years, that this would be a helpful statement, and I don't know if anybody else agrees, but that's open to discussion.

DR. NIGHTINGALE: I would like to agree, and I think the particular problem that you might want to address is the problem in the highest halls; is that the phrase that you used? I work there from time to time.

[Laughter.]

DR. NIGHTINGALE: The question is how to fit this in. The blood issues don't fall into a convenient package. Perhaps because they're episodic, when things go well, there's no particular place to put them.

So I think that Jay's recommendation is particularly timely with a new administration, which, in my view, has not yet figured out where blood fits and could use a nudge in that direction.

DR. BIANCO: I'm not sure that I agree entirely with Steve. Bioterrorism is part of the title. So, in a certain way, we have to find a way to insert the concept, and we are recognizing that there is one group that is doing the work at this point there. I don't know. Now I am confused about what is there, and we will have to see, again, but, yes, Steve?

DR. NIGHTINGALE: If I might clarify, there are some issues that rise to the top, and I think that there is a common thread to this within health. The ones that I have seen have been AIDS, vaccines, blood, mad cow for a while, and the fifth one will come to me in a minute, and I'm blanking on it. Vaccines, biologics, blood, mad cow, and as I said, the fifth will come.

DR. EPSTEIN: Gene therapy and xeno transplantation.

DR. NIGHTINGALE: Recombinant, we've talked about this. You'll figure out the fifth.

But the reason that they rise is because they're not resolvable at an individual agency level, and I think that's the thread that has brought blood up. Blood is not just manageable by FDA. It's not just manageable by CDC. It's not just manageable by the government for that matter, and that's the common thread that's brought it up, and that's the realization that never really caught on in the last administration. Perhaps it will this time.

MS. LIPTON: Can I just get a clarification. John, you want us to look at the strategic plan as it relates to blood and bioterrorism; is that what you were saying?

DR. WINKELSTEIN: No, I'd like us to look at the strategic plan, period, and comment on it, and react to it as another agenda item for the strategic plan for OBRR.

DR. EPSTEIN: Perhaps I can be a little bit more concrete. We spent the morning showing you what we're up to. Do you think we've got it right? I mean, does it get endorsement or not? In other words, are we on the right track? Should we continue pursuing the things that you heard?

DR. BIANCO: Yes, you should.

[Laughter.]

DR. BRECHER: Yes, I think the sentiment is, of course, you should. For us to say no, I think would be foolhardy because we don't know what's coming, and we need to be prepared for all--

MS. LIPTON: My concern is that above all other things, and that's what I was sort of reacting to. I mean, are we putting this in the context of just bioterrorism? I mean, I see a lot of other very urgent blood issues that I would see, frankly, might be above some of the issues.

DR. BRECHER: Jay, I think the sentiment I'm hearing is we think you're on track. You're doing the right thing. I'm not sure that we want to put it in here as another bullet point to the assistant secretary or do we? How does the committee feel?

DR. WINKELSTEIN: I put it forward as a recommendation that the committee discuss it and either resolve that we would concur, endorse it, or make some recommendations, not necessarily to go to the assistant secretary. We haven't even reviewed it in detail.

DR. BRECHER: Let's just take a vote. All of those who feel that we think the FDA is on the right track and should continue, all in favor?

I didn't get a second, but--

DR. WINKELSTEIN: Second.

[Show of hands.]

DR. BRECHER: Okay. All opposed?

[No response.]

DR. BRECHER: Okay. It's not a recommendation to the assistant secretary.

DR. NIGHTINGALE: No, no, but it was a vote, it's in the record, and I need for the record the precise recommendation.

DR. BRECHER: Okay. The ACBSA endorses the OBRR initiatives that were summarized in the meeting today.

Mike, do you want to read your statement again?

COL FITZPATRICK: I'll take out the Secretary's part. I said it'll be, "ACBSA recognizes the OBRR strategic plan for counterterrorism and disaster preparedness and endorses its continued--"

DR. BRECHER: We--

COL FITZPATRICK: What I had before was, "Recommend the Secretary recognize and incorporate the OBRR's strategic plan into the DHHS response plan for counterterrorism and disaster preparedness."

DR. BRECHER: I think we could live with that one. We endorse that one. We'll go with that one. Is everyone in favor of that?

Vote? All in favor?

[Show of hands.]

DR. BRECHER: All opposed?

[No response.]

DR. BRECHER: Unanimous.

DR. KLEIN: This way he doesn't get a free hand to do anything in the future.

DR. BRECHER: That's the recommendation. We'll go with that wording.

DR. PENNER: Mark, one other quick one. We need a report on the hepatitis C look-back program sometime in the future.

DR. BRECHER: That's another topic, yes.

All right. It is 3:01. We're a little over.

[Laughter.]

DR. BRECHER: This meeting is adjourned.

[Whereupon, at 3:01 p.m., the proceedings were adjourned.]