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Blood Safety Summary - August 2001

DATE: September 5, 2001

TO: Interested Parties

FROM: Stephen D. Nightingale, MD

Executive Secretary, Advisory Committee on Blood Safety and Availability

SUBJECT: Summary of August 24, 2001 Meeting

The Advisory Committee on Blood Safety and Availability met for the fifteenth time on August 24, 2001 at the Hyatt Regency Capitol Hill Hotel, 400 New Jersey Ave. NW, Washington, DC 20001. Present were Dr. Caplan, the Chairman; Mr. Allen; Drs. Busch and Chamberland; Mr. Dalal; Drs. Davey and Epstein; COL Fitzpatrick; Drs. Gilcher, Gomperts, Haas, Hoots, Klein, and Kuhn; Ms. Lipton; Drs. Lopes, Penner, and Piliavin; Mr. Walsh; and Dr. Winkelstein. Also present were Dr. Nightingale, CAPT McMurtry, and approximately 100 members of the public.

The agenda for the meeting was a review of the current status of monitoring supply of and demand for blood products and plasma derivatives.

Dr. Darrell Triulzi of the Institute for Transfusion Medicine in Pittsburgh opened the meeting with a review of a conference held the previous day for contractors participating in the DHHS sentinel program to monitor the availability of blood. The participants discussed how to define the parameters this program would monitor (such as total inventory), and what additional parameters it should monitor. A summary of the contractor's conference is appended to this document.

Dr. Triulzi was asked about specific characteristics of the participating sites and how well they represented transfusion services as a whole; he indicated that such data would be forthcoming from DHHS. Dr. Gilcher commented on the issue of determining whether inventory reported by a hospital was sufficient for its needs. Dr. Busch commented on the need for continuity in the study, and he expressed concern that participants in the study might receive more favorable treatment from suppliers than other hospitals. COL Fitzpatrick asked what response would be made to the identification of a sentinel event, and Dr. Triulzi responded that this remained to be determined. Dr. Caplan expressed hope that this project would promote standardized reporting of data from transfusion services.

Dr. Nightingale reviewed previous discussions by the Advisory Committee on the availability of blood products and plasma derivatives, and the programs to monitor the supply of these products and derivatives that were established after these meetings. He noted that, in response to concerns about the adequacy of the blood supply that had been raised at the April 1999 meeting, DHHS had incorporated monitoring of the blood supply into its Blood Action Plan, and that, in January 2001, responsibility for this monitoring had been assigned to the Office of the Assistant Secretary for Health, who serves as the Blood Safety Director for the Department. Dr. Nightingale praised previous monitoring efforts, but he noted that Departmental review of these efforts had identified three issues that needed to be addressed: the timeliness of the reports; whether the monitored supplies were reflective of demand; and the transparency of the reporting process.

Dr. Nightingale noted that it was easier to measure supply than to measure demand. Supply can be counted. Demand in an ideal market is measured by price, but the market for blood lacks many characteristics that the concept of an ideal market assumes. Dr. Nightingale then discussed inventory, and the ratio of inventory to product released, as an alternative measure of demand. He then discussed plans to analyze inventory data for trends, cycles, transient events (such as the effect of a holiday), aftershocks (such as the return to normal use patterns after a holiday), and non-linear events (such as a change in donor deferral policy). He then discussed how inventory at a particular time would be correlated with reports of shortages, and how trends in inventory prior to reports of shortages might be used in the future to anticipate shortages.

Dr. Nightingale then identified the contractors in the Blood Demand Monitoring Program, and presented very preliminary data from that program. During the week of August 13-19, 2001, in which 25 of the 29 contractors had reported data, the median daily ratio of inventory to release of all blood products was 7.4, the median daily ratio of inventory to release of random donor platelets was 1.4, and the median daily ratio of inventory to release of apheresis platelets was 1.1.

In response to questions, Dr. Nightingale noted that the data obtained was verifiable because each contractor was required to submit a standard operating procedure for the collection of this data, and that adherence to standard operating procedures by transfusion services is subject to FDA inspection. COL Fitzpatrick noted that the Department of Defense had the capacity to collect and report similar data, and that he would be receptive to a formal request to do so.

After a break, Ms. Jacquelyn Fredrick of the American Red Cross (ARC) described her organization's plans for monitoring its own supply of blood products and the demand of its clients for these products. She described a recent survey that indicated ARC would lose about 3 +/- 0.6 percent of its current donors when its new deferral policy is implemented, and that another 1 percent would erroneously self-defer, for a total of approximately 225,000 donations. However, ARC has taken actions to compensate for these anticipated losses, and these actions have been productive. Ms. Fredrick reported that ARC July 2001 collections were 551,949 units, an almost 8 percent increase over July 2000, and that August 2001 group A and O inventories were 33 and 83 percent, respectively, higher than in August 2000.

Ms. Fredrick then stated that the present goal of ARC was to sustain these increases by expanding its facilities, improving communication with donors, and expediting the donor experience. She said that ARC has developed models to anticipate increased needs, and allocates its inventories around the country based on these models. She commended the announcement of the DHHS sentinel system for monitoring the blood supply, and she concluded by stating that it was a shared responsibility of blood collection organizations and hospitals to collect data on supply and demand in order to institute programs to assure blood availability.

In response to questions, Ms. Fredrick said ARC had not yet been asked to participate in the DHHS initiative, but that ARC would be glad to provide data if asked to do so, and that ARC would like to participate in determining how that data would be used. Dr. Nightingale thanked Ms. Fredrick for her offer and assured her it would be accepted. Ms. Fredrick said she did not yet know whether the recent increases she reported were due to an increased number of new donors or an increased frequency of donation by prior donors. She said that the impact of the pending ARC donor deferral policies was projected to be somewhat higher on platelet than on blood donors. Dr. Klein commended ARC for its efforts, and asked if ARC could provide data on partially filled or unfilled orders as a way of estimating whether supply was sufficient to meet demand. Ms. Fredrick said she had such data but felt there were limitations to its use; Dr. Nightingale concurred with Ms. Fredrick on this point. Finally, Ms. Fredrick said that ARC moved approximately one million units from one of its regions to another in the past year.

Dr. Celso Bianco of America's Blood Centers (ABC) complemented DHHS for its efforts to establish a sentinel system to monitor demand for blood at the hospital level. He noted that CDC sentinel systems to monitor hepatitis and to monitor West Nile Virus were not located in institutions representative of the United States as a whole, but they nevertheless provided much useful information. He announced that ABC would provide supply data from its members that would complement the DHHS demand data. Each member will report to ABC, on a daily basis, whether it has one, two, or three or greater days supply of blood in its inventory. ABC will report this data in aggregate by regions that correspond to the aggregate regions in the DHHS reporting system. Dr. Bianco indicated ABC's willingness to provide additional data as appropriate to DHHS and to investigators studying the blood system.

Dr. Bianco then expressed concern about the impact of pending FDA policies on donor deferrals. He expressed the hope that these policies would permit gradual implementation, and that these policies would not be implemented prematurely, in order to minimize their impact on the blood system.

Dr. Bianco concluded by announcing that ABC had pledged to provide an additional 75,000 units of blood to the New York Blood Center, and that ARC had made a similar pledge, in order to minimize the impact of the pending donor deferral policies on New York City, which currently obtains about 140,000 units per year, or about one fourth of its blood supply, from European sources.

In response to questions, Dr. Bianco indicated that ABC would be willing to discuss standardization of its supply data reporting system with than of ARC. He also indicated that efforts were under way to standardized supply data reporting within ABC, and that he would consider reporting platelet as well as red cell inventories. Dr. McCarthy asked if the cooperation between ABC and ARC would extend throughout the countries to institutions that might at some moment find that their primary supplier was unable to meet their needs. Dr. Bianco indicated that some relief in such circumstances was already available, for example the American Association of Blood Banks (AABB) Blood Exchange; he added that he hoped that, because of increased awareness of potential shortages, he would be able to give a better answer to Dr. McCarthy's question in a year or so.

Next, Dr. James Louie of the New York Blood Center (NYBC) addressed the Advisory Committee. He commended DHHS for its monitoring initiative, and indicated that NYBC would like to participate in it. He also thanked ABC and ARC for their pledges of support to NYBC. Dr. Louie then conveyed his concern about the impact of pending donor deferral policies. He urged that there be an orderly transition to these new policies so that the public would not become confused by them, and that the special needs of the New York area be considered. Dr. Epstein indicated that FDA was aware of the concerns Dr. Louie had raised and would attempt to be responsive to them.

Ms. Theresa Weigmann of AABB then summarized the written statement AABB had provided to the Advisory Committee. She expressed concern that DHHS monitoring efforts be representative on a national scope, and concern on how this data would be analyzed. She asked how the DHHS data would be compared to previously collected data, and she emphasized the need for uniform definitions of the data that would be collected. She urged DHHS to establish an expert panel to answer these questions before data collections begin. She asked it be recognized that neither the Advisory Committee nor the government representatives have the necessary expertise to answer all the questions about blood supply and utilization that AABB has. She stated that AABB believes the National Blood Data Resource Center should continue to play a valuable role in collecting and analyzing blood supply data. She concluded by urging that adequate federal funding be provided now and in the future for this effort.

Mr. David Cavenaugh of the Committee of Ten Thousand requested that greater federal effort be devoted to promoting blood donations as part of a broad national policy that is inclusive of all aspects of how blood and plasma are collected, processed, distributed, and used.

Ms. Jan Hamilton of the Hemophilia Federation of America discussed monitoring supply and demand in the plasma products sector. She stressed the need to adapt any monitoring system to the specific characteristics of different patient communities that use particular products. She specifically commented on the importance of the issue of scheduled and unscheduled closure of manufacturing lines, and the issue of portability of health insurance, to her community.

Mr. Mark Skinner of the National Hemophilia Foundation commented on the need for additional supply and demand data in the context of the current shortage of clotting factors. He stressed the need for real-time information on the availability of both plasma derivatives and their recombinant analogs. He asked that the Hemophilia Treatment Centers as well as manufacturers, home health care companies, distributors, and hospitals be represented in any monitoring effort. He concluded by emphasizing that monitoring alone would not address the central concern of his community, which was expansion of production facilities to meet already known demand.

After lunch, Mr. Patrick Gage of Wyeth-Ayerst presented an update on his company's new recombinant Factor VIII product. He described the role that Genetics Institute, now part of Wyeth-Ayerst, had played in the development of recombinant Factor VIII and Factor IX. He described his company's current manufacturing capabilities, and the plans for their expansion. These include increasing production of recombinant Factor IX by 2003, expanding distribution of its recently approved recombinant Factor VIII as soon as its St. Louis manufacturing facility is completed and approved for production, and development of an albumin-free recombinant Factor VIII in the foreseeable future.

Following this presentation, Dr. Nightingale indicated that one reason Mr. Gage had been invited to address the Advisory Committee was to discuss why, almost six months after United States approval of the Wyeth-Ayerst recombinant Factor VIII (ReFacto), it was still not widely available in the United States. Mr. Gage responded that although filings were made essentially simultaneously in the United States and in the European Community, the product was approved by the European Community several months before it was approved in the United States. Wyeth-Ayerst decided to use its resources to supply patients in Europe as soon as approval was received, rather than retain inventory until United States approval. Mr. Gage noted that his company's American facility, if approved, would have three times the capacity of the European facility where ReFacto is currently produced. He estimated current worldwide demand for recombinant Factor VIII to be about 3 billion units per year, with 1.2 billion of that demand from the United States, and that his company ultimately hoped to produce 1.5 billion units of its albumin-free recombinant Factor VIII per year. Following Mr. Gage's presentation, Dr. Hoots suggested that by the time Wyeth-Ayerst reached its own goals, global demand may have increased further

Mr. Jason Bablak of the Immune Deficiency Foundation (IDF) then described a proposal by his organization for monitoring the availability of plasma derivatives. In this proposal, manufacturers would continue their present reporting of inventory and release data. They would also report the anticipated date of release of lots and the quantity to be released, and any anticipated closures of their production lines for maintenance, or for other reasons. In order to obtain information on distribution and use as well as production, the IDF proposal also calls for voluntary reporting by four additional levels of the product chain: distributors, group purchasing organizations, and national home health care companies; hospital pharmacies, hemophilia treatment centers, and regional and local home health care agencies; physician practices; and consumers themselves.

Mr. Bablak estimated that at there were at present about six manufacturers of immunoglobulin preparations licensed in the United States. At the first level of distribution, he estimated that there were about ten major distributors, and about the same number of group purchasing organizations and national home health care companies. He indicated that further investigation would be required to determine where the supply of each plasma derivative should be monitored at this level of the distribution chain, but he felt that the number of sites would be manageable. At the second level of distribution, Mr. Bablak suggested a monthly telephone survey of inventory in about one hundred hospital pharmacies, selected by size and type. At the third level of distribution, he suggested a monthly telephone survey of about one hundred providers to determine current prescribing practices, and whether these practices were influenced by availability of product. At the fourth and final level of distribution, the end user, Mr. Bablak suggested monthly telephone surveys of about one hundred patients, augmented by less frequent but larger samples of the patient community.

Mr. Bablak indicated that the next step for this proposal wold be to get producers, intermediaries, and consumers to work together to develop a detailed proposal, and then identify a contractor to perform the proposed work, a data management plan, and a funding source. He described short-term plans to recruit distributors into this effort. To create a model of demand for plasma products, he would analyze information on the indications for which a product is prescribed, the number of users per indication, the average amount prescribed, and the frequency of the prescription.

Dr. Hoots and Mr. Walsh complimented Mr. Bablak on his presentation. Both also mentioned the issue of portability of a patient's supply of plasma derivatives from one provider to another. Mr. Walsh also commended the previous statement of Ms. Hamilton, and he briefly reviewed the specific concerns of the alpha-1 antitrypsin (A1AT) deficient community about availability of product. He noted that A1AT remains in extremely short supply, and he discussed actions of the A1AT-deficient community to assure optimal allocation of scarce product. Mr. Allen noted that an issue in the sickle-cell community was a uniform national standard of care, and that this was clearly an interest shared by other patient communities.

Mr. Christopher Healy of the Plasma Protein Therapeutics Association (PPTA) reviewed past efforts of his organization to provide inventory and release data requested by consumers, including the recent move to release this data every two weeks. Mr. Healy expressed thanks for consumer support of PPTA data collection and reporting efforts. He said he was pleased to lend support to the concept outlined by Mr. Bablak, and to further discussion of it. Mr. Healy also expressed the view that the data set currently collected by PPTA might be the more useful for consumers, regulators, and the industry.

Following this presentation, the Chairman opened the floor to general discussion and motions. Dr. Caplan proposed that, since the recommendations he anticipated the Advisory Committee would make would be so friendly, and that the record of the meeting would reflect the intent of these recommendations, that Dr. Nightingale use the record of the meeting to draft specific recommendations that would express the sense of the Advisory Committee. At the suggestion of Dr. Caplan, Mr. Walsh proposed and Dr. Klein seconded a motion that, stated in words subsequently approved by Dr. Caplan, reads

The Advisory Committee supports the proposals before it to monitor supply and demand of blood products, plasma derivatives, and their recombinant analogs, and recommends that there be adequate infrastructure, expert advice, and long term funding for these initiatives.

The motion was approved unanimously.

Dr. Gilcher had previously reminded the Advisory Committee of a workshop convened by the National Institutes of Health in February 1999 to discuss donor recruitment. The three conclusions reached at that meeting were that, first, reimbursement was insufficient to support recruitment efforts; second, support for blood donation was needed at the highest levels of government; and third, that education about the need for blood donation had to begin at the grade school level. After further discussion of this issue, Dr. Gilcher proposed a motion that, stated in words subsequently approved by Dr. Caplan, reads

The President of the United States should join with other leaders of government and industry to make blood donation a national priority, including the creation of national events coordinated with the private sector to encourage donation, and to support efforts by commercial as well as non-profit organizations that have successfully promoted blood donation.

The motion was passed unanimously.

There was then discussion of management, and of the establishment of an executive committee, of the DHHS blood demand sentinel monitoring program initiative. Dr. Caplan proposed a motion that, in words subsequently approved by Dr. Caplan, reads

The Secretary be encouraged to move the blood demand sentinel monitoring program forward as quickly as possible, and that funding and the number of sites monitored be appropriate for its needs.

The motion was passed unanimously.

Mr. Walsh then proposed a motion that, stated in words subsequently approved by Dr. Caplan, reads

All plasma derivatives and their recombinant analogs be placed in permanent and separate payment categories, similar to blood products, in the Medicare Outpatient Prospective Payment System. Maintaining unique reimbursement will ensure that the current and future costs of these products to providers and patients are recognized, and therefore safeguard patient access to these critical therapies.

The motion was passed unanimously.

Dr. Davey asked why the Advisory Committee had not been asked to address the issue of donor deferrals to reduce the risk of transmitting variant Creutzfeldt-Jakob disease by transfusion, since it was clearly within the Committee's mandate. Dr. Nightingale responded that the interest of the government was in a full and open discussion of the issue, rather than a particular venue for it, and that the FDA Transmissible Spongiform Encephalopathy Advisory Committee had provided such a venue. Dr. Nightingale said there were circumstances that could bring this issue to this Advisory Committee in the future, but he hoped the need would not arise.

Dr. Penner requested that, at the next meeting of the Advisory Committee, there be a report on the status of the hepatitis C lookback.

Dr. Nightingale then thanked Dr. Guerra, Dr. Piliavin, Dr. Haas, Dr. Kuhn, Dr. Busch, and Dr. Caplan for their many contributions to the Advisory Committee during their four year terms, which conclude on September 30, 2001. Dr. Nightingale then said that nominations to replace the retiring members would be received until close of business on August 31, 2001. Dr. Nightingale noted that there were strict administrative procedures that would be observed in the forwarding of nominations to the Secretary, and he emphasized that the final decision on this matter would be the Secretary's.

Dr. Kuhn expressed hope that in the future the Advisory Committee would address the issues of a national blood policy, of no-fault compensation for blood industry, and the outcome of the hepatitis C lookback effort.

Dr. Caplan thanked and complemented his colleagues on the Advisory Committee for their service.

The meeting was then adjourned.

This summary was approved by the Chairman, Dr. Caplan, on September 4, 2001