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ATDEPARTMENT OF HEALTH AND HUMAN SERVICES
FOOD AND DRUG ADMINISTRATION
CENTER FOR BIOLOGICS EVALUATION AND RESEARCH

This transcript has not been edited or corrected, but appears as received from the commercial transcribing service. Accordingly the Food and Drug Administration makes no representation as to its accuracy

BLOOD PRODUCTS ADVISORY COMMITTEE


74th MEETING

Thursday, September 12, 2002


8:00 a.m.

Hilton Silver Spring Hotel

8727 Colesville Road

Silver Spring, Maryland

PARTICIPANTS
Kenrad E. Nelson, M.D., Chair

Linda A. Smallwood, Ph.D., Executive Secretary


Members

James R. Allen, M.D.

Charlotte Cunningham-Rundles, M.D., Ph.D.

Kenneth Davis, Jr., M.D.

Samuel H. Doppelt, M.D.

Michael G. Fitzpatrick, Ph.D.

Harvey G. Klein, M.D.

Raymond S. Koff, M.D.

Suman Laal, Ph.D.

Judy F. Lew, M.D.

Daniel L. McGee, Ph.D.

Terry V. Rice

Paul J. Schmidt, M.D.

Sherri O. Stuver, Sc.D.


Consumer Representative

Robert J. Fallat, M.D.


Non-Voting Industry Representative

Toby L. Simon, M.D.


Temporary Voting Member

Liana Harvath, Ph.D.



C O N T E N T S
PAGE
Welcome, Statement of Conflict of Interest 5
Announcements 8
Committee Updates
Meeting Summary: PHS Advisory Committee on Blood Safety and Availability Meeting Held on September 5, 2002

Virginia Wanamaker 10


Summary of Workshop on Pathogen Inactivation,

August 7-8, 2002

Jaroslav Vostal, M.D., Ph.D. 23
West Nile Virus and Blood Safety

Anthony Marfin, M.D. 33

Jesse Goodman, M.D. 69
Self-Administration of the Uniform Donor History

Questionnaire: First-Time Donors
Background and Introduction:

Alan Williams, Ph.D. 94

Presentation:

John Boyle, Ph.D. 105

Presentation:

Victoria Virvos, M.Ed 147


Open Public Hearing

Mary Townsend, M.D., AABB 174

Peter Page, M.D., American Red Cross 186

Celso Bianco, M.D., America's

Blood Centers 206

Paul D. Cumming, Ph.D., Talisman Limited 210


Committee Discussion and Recommendations 221
Update on Testing for Chagas Disease

(Informational)
Introduction:

Robert Duncan, Ph.D. 251

Latest Trends in Transfusion-Transmitted

Chagas Disease:

David Leiby, Ph.D. 254

Regulatory Pathway for Donor Screening:

Robert Duncan, Ph.D. 277
C O N T E N T S (CONTINUED)
Open Public Hearing

David Persing, M.D., Corixa 295

Kay Gregory, AABB 296
Window Period HIV Cases and Current Estimates

of Residual Risk (Informational)
Introduction and Background:

Indira Hewlett, Ph.D. 297

Case Report--Florida Blood Services:

German Leparc, M.D. 304

Viral Dynamics in Early Seroconversion:

Michael Busch, M.D. 311


Open Public Hearing

Wm. Andrew Heaton, M.D., Chiron 331

Dr. James Gallarda, Roche 342

Sherrol McDonough, Ph.D., Gen-Probe 350

Ronald O. Gilcher, M.D., 354

Oklahoma Blood Institute

Susan Stramer, Ph.D., American Red Cross 361

Paul Holland, Blood Source 369

Celso Bianco, M.D., America's

Blood Centers 375

Kay Gregory, AABB 380
Adjournement 383

P R O C E E D I N G S

Welcome, Statement of Conflict of Interest

DR. SMALLWOOD: Good morning. Welcome to the 74th meeting of the Blood Products Advisory Committee.

I am Linda Smallwood, the Executive Secretary of the committee. At this time, I will read the Conflict of Interest Statement that applies to this meeting.

The following announcement is made part of the public record to preclude the appearance of a conflict of interest at this meeting. Pursuant to the authority granted under the Committee Charter, the Director of FDA's Center for Biologics Evaluation and Research has appointed Dr. Liana Harvath as a temporary voting member.

Based on the agenda, it has been determined that there are no products being approved at this meeting. The committee participants have been screened for their financial interests. To determine if any conflicts of interest existed, the agency reviewed the agenda and all relevant financial interests reported by the meeting participants.

The Food and Drug Administration has prepared general matters waivers for the special government employees participating in this meeting who require a waiver under Title 18, United States Code 208.

Because general topics impact on so many entities, it is not prudent to recite all potential conflicts of interest as they apply to each member. FDA acknowledges that there may be potential conflicts of interest, but because of the general nature of the discussion before the committee, these potential conflicts are mitigated.

We would like to note for the record that Dr. Toby Simon is participating in this meeting as an Industry Representative acting on behalf of regulated industry.

With regard to FDA's invited guests, the agency has determined that the services of these guests are essential. There are interests which are being made public to allow meeting participants to objectively evaluate any presentation and/or comments made by the participants.

For the discussions on the Window Period HIV Cases and Current Estimates of Residual Risk, Dr. Michael Busch is the Scientific Director, Blood Centers of the Pacific. He has grants, receives speaker fees and is an advisor for firms that would be affected by the discussion.

Dr. German Leparc is employed as the Chief Medical Officer for Florida Blood Services. In addition, listed on the agenda are speakers making industry presentations. These speakers are employed by industry and thus have interest in their employer and other regulated firms.

FDA participants are aware of the need to exclude themselves from the discussions involving specific products or firms for which they have not been screened for conflict of interest. Their exclusion will be noted for the public record.

With respect to all other meeting participants, we ask, in the interest of fairness, that you state your name, affiliation, and address any current or previous financial involvement with any firm whose products you wish to comment upon.

Waivers are available by written request under the Freedom of Information Act.

At this time, I would ask if there any additional declarations to be made from any meeting participants.

Hearing none, I would like at this time to introduce to you the members of the Blood Products Advisory Committee.

Members, when I call your name, if you would please raise your hand.

Dr. Kenrad Nelson, Chairman. Dr. Stuver. Dr. Allen. Dr. Harvath. Dr. Lew. Dr. Doppelt. Dr. Klein. Dr. Fitzpatrick. Dr. Fallat. Dr. Simon. Mr. Rice. Dr. Laal. Dr. McGee. Dr. Koff. Dr. Schmidt.



Announcements

DR. SMALLWOOD: Before we proceed with the formal meeting, we have two retiring members leaving the committee at this time, and I would like to ask Dr. Jay Epstein, the Director of the Office of Blood Research Review, to come forward and to make the presentations to Mr. Terry Rice and Dr. Toby Simon. If you would come forward, please.

DR. EPSTEIN: It is my sad pleasure and privilege to be awarding plaques in recognition of the years of good service that have been given to us both by Mr. Rice and Dr. Simon as members of the Blood Products Advisory Committee.

We know that it takes substantial effort on the part of the members to read the voluminous packets that we send you on very short notice and to deliberate long and hard on the many difficult questions that we bring before the committee.

I just want to express the thanks of the Food and Drug Administration to each of you for the work that you have done these last couple of years, and we do hope that you will agree to say on as special government employees, so that we can also tap your expertise ad hoc from time to time.

Thank you very much.

[Applause.]

DR. EPSTEIN: These are also letters of appreciation.

DR. SMALLWOOD: I would just like to remind everyone that this is a one-day meeting of the Blood Products Advisory Committee. We have a very full agenda today and we will try to adhere to our time range as best as we can. We would ask that when it is time for your presentation to be made, that you be prepared, and if you have a presentation for which you will need assistance with our audio-visual group, would you please let them know.

At this time, I would like to turn over the proceedings of the meeting to the Chairman, Dr. Kenrad Nelson.

DR. NELSON: Thank you, Dr. Smallwood.

The first part of the agenda is a series of summaries of workshops and of other evolving issues. First, on the agenda, is Virginia Wanamaker summarizing the Advisory Committee on Blood Safety and Availability meeting that was held about a week ago.



Summary of PHS Advisory Committee on Blood Safety

and Availability Meeting, 9-5-02

Virginia Wanamaker

MS. WANAMAKER: Good morning. I am pleased to be here this morning to tell you a little bit about the Advisory Committee on Blood Safety and Availability that met last Thursday, September 5th, and the topic of our meeting was how can government and industry work together to assure the availability of blood and blood products.

There were actually two issues at the meeting, the first being the CMS proposed rule on new payments for outpatient services, and the other was the blood supply.

So, right away, fairly shortly after the meeting started early in the morning, the committee proceeded with two recommendations. One of the recommendations was for HHS to direct CMS to establish 2003 Medicare hospital outpatient prospective payment system payment rates for blood and blood components, transfusion services, and the transfusion laboratory procedures based on the current year acquisition and actual total cost rather than hospital outpatient claims from previous years.

Then, there was another recommendation relatively similar, but this one addressed payment for plasma-derived therapies and their recombinant analogs and that they be based on current year acquisition and total actual cost of providing such products and services both within hospitals and non-patient settings to include physicians' offices to assure patient access to care.

From that, we moved on to looking at the blood supply. There were actually two components of this. One was monitoring of the blood supply, and the other was to look at the question how much is enough. We also, at the end of the day, had a brief updating on the West Nile virus, but I believe that is on your program and I will just merely mention that and move on.

In the Monitoring Section, we heard from about five monitoring systems that are currently in process.

The first was the Department of Health and Human Services monitoring system, which is a sentinel site blood monitoring project. This project has 26 hospitals and 3 community sites. It collects quantitative data.

From this project report, it appears that the overall supply, especially from these sentinel sites, is adequate, however, there are a few of these sentinel sites that have chronic issues or chronic shortage problems.

The next was FDA's TransNet. It is not yet fully functional, but it is a web-based plan with daily entry. It has various markers of shortage. There will be a daily--once the web site is up--there will be a daily map displaying areas, and it will highlight the areas with shortages. This is a qualitative system with no quantitative data.

Next, we heard from ABC, America's Blood Centers. My understanding of their system is that it is a two-phase system. The first phase monitors the day's supply. The second phase will show members areas of access, however, to date, they have mostly had shortage issues, and that is mostly what they are displaying.

Then, we had a presentation from the National Blood Data Resource Center. There were about four points from their presentation, that total collections information 2001 were over 50 million units; more surgeries were affected by shortages in 2001 than in 1999.

The collections and inventory total so far this year are unchanged in comparison with last year prior to September 11. By the year 2020, there will be 12 million people added to the age group that are at risk for transfusion. NBDRC believes that long-term quantitative monitoring is an essential part of the blood monitoring system.

We also heard from the American Red Cross. They manage inventory across 36 regions. They consider a two-day supply to be critical inventory, and they did fall to this level at the end of last month. They do consider a seven-day supply to be optimal.

We had a small session on forecasting, which actually was an overview of the monitoring programs. The speaker or the presenter favored quantitative programs or the need for quantitative programs. He actually liked the sentinel site, and he did state that a shotgun effect, if you have a lot of different monitoring systems, and they approach monitoring in various ways, that they give you a comparable end result, then, they are doing a good job.

We also heard from the Department of Defense on strategic reserves, that there are problems with frozen reserves, and a liquid reserve on a national basis would be advantageous to all.

There was a suggestion that there would be four to six sites throughout the U.S. located near large international airports or large military bases.

Then, we moved to session of how much is enough. We heard from Puget Sound Blood Center, which says that about two-thirds of the blood they collect is used in the Seattle metropolitan region, the other one-third goes to surrounding counties, and they can export small amounts.

We heard from Georgetown University Hospital on the hospital perspective. The point here was stressed that appropriate usage is a very important issue, and that their oversight is driven by educational programs and that blood utilization reviews play into this. The speaker did point out that platelets can sometimes be an issue.

Then, we heard from the New York Blood Center, who says they continue to struggle with the aftermath of 9/11. They have lost some of their blood drives due to loss of offices or companies that participated in these blood drives. They continue to struggle with the CJD deferral, the summer slump, and self-deferral of some donors.

We heard from the Oklahoma Blood Center, which said that really blood serves two purposes. One of the purposes that we don't really speak to are addressed quite often, but is very significant and very important, is the availability of the blood.

Even though blood is not used, it is still an insurance policy that allows for a procedure to occur. Quite often a unit of blood may never be used, but it may have been cross-matched three or four times, so it has indeed served a purpose because it was available for those medical procedures to go forward.

The presenter did tell us that their blood center supplies 89 hospitals with 11,000 units. They have in excess a 17-day supply with their liquid, and they are moving to having a frozen supply that will allow them to have a 23-day supply.

We heard from the Mississippi Valley Regional Blood Center, which says they are able to supply their hospitals with a 5-day supply, keep a 10- to 12-day supply in their center, and export up to 50 percent of the red blood cells they produce.

After that, we move to Recommendations. These, of course, are paraphrased. One of the recommendations was that the Department should support initiatives to improve management of blood inventories--I am sorry, I skipped the first one--that DHS should promote increased public awareness of the ongoing need for routine blood donations by healthy persons, and this could be done through periodic public service announcements, visible blood donations by top officials, and paid advertising campaigns, also by funding of demonstration projects, supporting specific initiatives to encourage routine donations by young persons and minorities, and play a leading role in increasing participation of federal employees in donating blood.

Another recommendation was that DHS should maintain and/or increase funded support for blood supply monitoring. Some of the ways to do this would be long-term trends in blood collection and use or some of things that should be done, should be addressed.

Data on daily national distributed blood inventories, indicators of blood shortages and excesses, predictive models to identify trigger points for coordinated national donation campaigns, and coordination of government and non-government initiatives.

There was another recommendation that has not yet been voted on, but I will go ahead and mention it to you, that DHS should support initiatives to improve management of blood inventories. This would include defining the roles of liquid into frozen reserves and by integration of supply forecasting into intervention strategies, and also strategies to facilitate movement of blood from areas of surplus to areas of shortage.

I failed to mention earlier, under the "how much is enough," that we also had a presentation from American Red Cross, and they did mention that they monitor some 36 sites and that on occasion, it has fallen to a two-day supply.

Actually, that is my presentation for today. I notice that many of the speakers are in the audience, so I would like to take this opportunity to apologize if I misquoted or missed the point of your presentation, but I thank you very much for his opportunity, and I hope I did highlight the main points of the meeting.

DR. NELSON: Thank you.

Any question or comments? Toby.

DR. SIMON: When these discussions are held, for the most part people tend to forget that in the late 1980s, there was a program called the National Blood Resource Education Program that was funded by the National Heart, Lung, and Blood Institute. It was designed to use the same techniques that the institute had used for awareness on cholesterol and high blood pressure, for awareness on blood donation. They created a huge advertising campaign. There were ads in airport billboards, and other such things, and it was largely regarded as a failure.

So, I think if we are going to move forward or if there are recommendations to move forward, I would suggest that people look back at that program and try to diagnose the problems it had before investing in a similar program in the future.

DR. KLEIN: I just wanted to comment that there was one other presentation that you didn't review. After the major blood organizations reported surprising shortages, especially over the past two months and especially in terms of O-positive blood, and the New York Blood Center told us that they were transfusing increasing amounts of O-positive to O-negative patients because they didn't have sufficient supplies of O-negative blood.

The American Hospital Association gave us what I thought was a very startling page of data, which included the fact that of their 5,000 transfusing members, some 57 percent had delayed surgery during the past year because of unavailability of blood, and that in urban areas, 77 percent of their membership had delayed surgery because of lack of blood for transfusion. I found that startling.

DR. ALLEN: A question for any member of the blood banking community that might have an answer. My guess is that most people, when they donate, do so with a certain sense of civic responsibility and under the assumption that their blood probably is going to be used in the geographic area. The Puget Sound Blood Center was mentioned, the majority is within the Seattle area of surrounding counties, and I suspect that that is what most donors would expect.

Is there a reaction on the part of donors if they understand, if they are in an area where there is excess red cells being collected, that it may be sent anywhere around the country? Does that tend to defer people from coming in to donate, and is that an issue that needs to be addressed as we look at the supply and distribution of blood?

DR. SIMON: The general rule over the years is if you educate donors about that, they are agreeable to having their blood used for anyone who is in need. So, as long as people have been educated appropriately, this does not seem to be a serious issue.

DR. FITZPATRICK: We heard an excellent report from Iowa at the meeting on a community blood center that produces an excess and exports, and the community is very supportive of that. I think there is proven community blood centers that are able to do that.

DR. EPSTEIN: I think that we have not really looked strategically at what I would call large system issues, and I think one of the points that came across I mean clearly in a disaster, it is obvious that there is enough blood out there, in other words, there are enough qualified donors if you can bring them in.

It has been said by many people that the crux of the matter is investing in recruitment efforts, but then that has a collateral effect on raising the cost of blood, and then we have, on the other side, problems with reimbursing any additive costs of blood, and I think that we haven't really looked at the economic issues that affect the whole issue of trying to bring in donors and that it is sort of an unspoken part of the problem.

DR. NELSON: The cost of blood has really increased quite a bit recently. It was interesting that there was a mention of the reimbursement for that. I don't know if that is a continuing problem, but the cost has certainly increased, yes.

DR. SCHMIDT: One often forgotten point in relation to what Jim Allen and the other statement is that local blood centers are not really operated by their CEOs who see this big picture, and if they are operated by their boards of directors, who are local citizens who are charged with having enough blood locally, but also cutting down the expenses or looking for other sources of income over expenses, and shipping blood out to a place like New York and supplying hospitals can bring income to those blood centers, so policies are made by those people and we generally just talk to the CEOs who, when they go home, they may hear a different story from their board of directors.

DR. FITZPATRICK: Just to follow up on Jay's comment, while we know that there are plenty of donors available and that we can collect the blood after a tragedy or a disaster, the key element is that we have to have it available, on the shelf, at the right place, at the right time to meet the needs of the disaster, and 24 to 48 to 72 hours later is not the solution to the problem. The solution is having it available at the time we need it.

DR. NELSON: The second item, if there are no more comments, is the summary of a workshop, an important workshop on pathogen inactivation. This was held in August at NIH.

Dr. Vostal.

DR. SMALLWOOD: While Dr. Vostal is coming, I would just like to apologize to the speakers. We are having some obvious technical difficulties. I am told that this LCD is not accepting the signal from the laptop, so we are trying to secure another one, hopefully, very shortly.



Summary of Workshop on Pathogen Inactivation

August 7-8, 2002

Jaroslav Vostal, M.D., Ph.D.

DR. VOSTAL: Thank you. Thank you for this opportunity to share with you the summary of a workshop we had in August. The title of the workshop was Safety and Efficacy of Methods for Reducing Pathogens in Cellular Blood Products.

The objectives of the workshop were to review the different approaches to evaluating efficacy of pathogen reduction methods in cellular blood products, to establish the appropriate methodology for testing efficacy, to obtain consensus on what is the minimum level of efficacy required, to discuss appropriate evaluation of toxicity of the methods, and that is toxicity to the cellular product, as well as to toxicity to the recipient of the treated cellular products, and finally, to summarize the risks and benefits of using the pathogen-reduced cellular products in clinical situations.

The outline of the workshop. The workshop was presented over two days. On the first day, we had an overview of the pathogens found in cellular transfusion products and the risk of transfusion-transmitted diseases from these pathogens and the ones we focused on were bacteria, viruses, and parasites.

We then had an overview of the molecular mechanisms of pathogen reduction systems. Then, we had a discussion on the evaluation of efficacy for the methods against each class of the pathogens, and this was followed by a panel discussion.

The first day ended with a presentation from the manufacturers, and they presented their own data on their individual systems.

On the second day, we focused on toxicity. We started off with evaluation of toxicity to the cellular products, and we focused on platelets and red cells, and each session was followed by a panel discussion.

We then moved on to an overview of toxicity and carcinogenicity evaluations for biologic products as is usually done by FDA, ad this was also followed by a panel discussion. Then, we had two talks on risk-benefit analysis, and this was followed by a public comment period.

So, to get into the actual summary, for the transfusion-transmitted pathogens, it was pointed out that bacteria posed the highest risk, and the risk of a serious adverse reaction is probably somewhere between 1 per 10,000 to 1 per 100,000 platelet transfusions.

For viruses, the transfusion-transmitted risk is a lot lower. It ranges somewhere between 1 per 1 million transfusions to 1 per 5 million transfusions when these products are screened by NAT testing.

Of interest was that the window period viral load can be very high, up to 108, 1010, and 1012 particles/ml for HAV and B19 viruses, and also interesting was that low levels of virus maybe at 102 genomes/ml can transmit disease.

For parasites, it was noted that these are emerging diseases that we should be concerned about. An example is Chagas disease, which there is 1 in 25,000 donor seropositive for Chagas disease, and 63 percent of these are parasitemic.

We then moved on to a discussion of the mechanisms or overview of the mechanisms of pathogen reductions, and it was pointed out that all methods involve addition of a chemical to a cell product that interacts with nucleic acids to kill the pathogens. All are therefore potentially mutagenic and carcinogenic. They also bind proteins and lipids, which may lead to unexpected toxicity to the product itself or to the recipient of those products.

They do reduce the titer of extracellular or intracellular envelope viruses, however, their activity against non-envelope viruses is less defined. They can increase the titers of bacteria and parasites in blood, however, they are not effective against spores or endotoxin.

The next session was a presentation or several presentations followed by discussions on the efficacy against viral agents. It is difficult to capture the discussion in a summary like this, but I will just try to point out some of the statements that were made.

It was agreed that treatment will not eliminate current testing. The treatments may have potential to inactivate new and emerging pathogens not detected by testing, and they should have capability of 6 to 10 log reduction in the viral load based on the window period loads.

Again, it was pointed out that low levels of viral load can transmit infectivity, therefore, it would be good that the methodology would have excess pathogen kill.

There was a discussion about a need for standard methodology for testing efficacy, for example, to define log reduction per ml of product, for the total bag of product.

Then, we moved on to a session with bacterial pathogens, and some of the points made in that discussion was that contaminants are most often skin organisms, but donors with occult bacteremia contribute significantly.

Both gram positive and gram negatives are associated with fatalities. Gram negatives produce endotoxin and do not require extended storage to reach toxic levels. Therefore, to eliminate these, the treatment needs to be pre-storage.

In terms of what bacteria should be used to establish efficacy, it was suggested that a limited list of bacteria is sufficient. The list should include the most commonly found organisms.

Finally, the clinical isolates of the bacteria should be used to model real life conditions.

We then moved on to discussions of toxicity to the cellular product, and I am going to summarize the discussion that went on for both platelets and red cells.

This evaluation is usually done in three parts. The first phase is in vitro studies, and it was pointed out that in vitro studies have limited predictive value for in vivo performance, and they should serve as a screening method for identifying gross damage to different aspects of cellular function.

In Phase II, these are small clinical studies. These are usually done with radiolabeling and reinfusion of controlled and treated cells. Recovery and survival and circulation post-infusion are the readouts of these experiments.

There was a discussion on the necessity for establishment of uniform control and for platelets, this was considered to be fresh platelets, and a discussion on the minimal acceptable values for recovery and survival of these products.

In Phase III clinical studies, these will be large clinical studies that look at the function and some of the functional endpoints of these products should be bleeding for platelets and oxygen delivery for red cells.

These kind of studies should also follow kinetic endpoints, such as transfusion response and frequency of transfusions.

We then moved on to a discussion on evaluation of toxicity to the recipient of these products, and this was a presentation to demonstrate how FDA reviews toxicity in general and to get advice on whether this is appropriate for pathogen-reduced products.

So, we covered general toxicity studies for biologic products, and these are usual animal models in small clinical trials. We talked about genotoxicity studies, which are aimed at identifying gene mutations and chromosomal aberrations, and usually, this required two in vitro studies and one in vivo study.

Carcinogenicity studies usually require a long-term carcinogenicity study in rodents, usually up to two years. We are moving towards using transgenic animals, which shorten that period down to six months. CDER guidances are available for design interpretation of these studies.

These products will likely be transfused to pregnant women, so reproductive toxicity is also an issue, and reproductive toxicity is studied in three phases. The initial phase evaluates toxicity to fertility, in general, reproductive performance.

This is followed by the second phase is a teratological study in rodents and non-rodents, and this will be followed by perinatal and postnatal toxicity in rodents, a unique toxicity that may be associated with these products with the generation of immunogenicity, so we had a presentation that dealt with how to evaluate this.

This is actually a difficult problem for not only these cells, but for other products. We found out that immunologic response to novel entity is not dose dependent and response could be to the original compound, metabolites, treated cells, or treated plasma proteins.

Animal models for immunogenicity may not be relevant to humans, and it was pointed out that this may be a low frequency event, it might not be detected in preclinical or clinical studies, and that postmarket surveillance would most likely be the way to attract these problems.

Another unique toxicity that may be associated with these products is toxicity to the health care workers. These individuals will be handling high concentration of the chemical compounds and may be actually the highest risk population when these methods go into clinical use, and safeguards need to be in place for their protection.

So, then, we moved on to the final portion of the workshop, which was a risk-benefit analysis, and we had two talks. I think the main point was that the blood supply is very safe, as it is today, that bacterial contamination is the highest infectious risk, but there are other risks, such as medical errors, that are even 10- to 100-fold higher risk category.

The chemical treatment of blood decreases effectiveness of the transfused product and adds toxicity to the recipient that is not clearly defined. Pathogen reduction may be appropriate for certain patients, and the use pathogen-reduced products should be a medical decision, not a regulatory decision.

Finally, the cost of implementing universal pathogen reduction should be weighed against other approaches, such as bacterial detection.

So, that concluded our workshop. I would be happy to answer any questions.

DR. NELSON: Questions? Toby.

DR. SIMON: This may be a question you can't answer, but can you give any further guidance timewise as to when we might expect to see such technologies be approved and come into use?

DR. VOSTAL: It is difficult to say because there are problems on the company side, as well as on the regulatory side, in terms of review, so I would say we are still maybe five years away from routine use.

DR. FITZPATRICK: Based on the meeting, do you see the need to revise or change any of the guidance documents that are currently used by industry to develop the path for submission of applications for these products?

DR. VOSTAL: I am sorry, I didn't catch the first part.

DR. FITZPATRICK: Based on the meeting, do you see the need for FDA to revise or put out different information regarding any guidance documents that industry uses to submit applications for approval of these products?

DR. VOSTAL: I think that is a good suggestion. We have certainly covered a lot of area in terms of how to evaluate platelets and red cells, so we have a platelet testing guidance we would like to update with that information. We would also like to put together a red cell guidance to have a similar type of thing.

Of course, we do not yet have a guidance for pathogen reduction, and that will be very helpful to have for other companies to follow, so based on what was presented at the workshop, we will try to put something like that together.

DR. NELSON: Thank you.

Next, our two speakers are going to review an emerging issue, mainly West Nile virus and blood safety.

First, is Dr. Marfin from the Division of Vector- Borne Infectious Diseases from CDC.

Dr. Marfin.


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