UNITED STATES OF AMERICA

 

DEPARTMENT OF HEALTH AND HUMAN SERVICES

 

FOOD AND DRUG ADMINISTRATION

 

CENTER FOR BIOLOGICS EVALUATION AND RESEARCH

 

BLOOD PRODUCTS ADVISORY COMMITTEE

 

MEETING

 

Thursday, August 16, 2007

 

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.

 

      This meeting came to order at 8:00 a.m. in the Doubletree Hotel and Executive Meeting Center, 8120 Wisconsin Avenue, Bethesda, Maryland.  Dr. Frederick Siegal, M.D., presiding.

 

PRESENT:

 

FREDERICK SIEGAL, MD, CHAIR

DONALD W. JEHN, MS, EXECUTIVE SECRETARY

MARK BALLOW, MD, MEMBER

HENRY M. CRYER, III, MD, MEMBER

ADRIAN DI BISCEGLIE, MD, MEMBER

WILLARDA V. EDWARDS, MD, MEMBER

MAUREEN A. FINNEGAN, MD, MEMBER

SIMONE A. GLYNN, MD, MEMBER

KEITH C. QUIROLO, MD, MEMBER

GEORGE B. SCHREIBER, SCD, MEMBER

IRMA SZYMANSKI, OV, MD, MEMBER

DONNA S. WHITTAKER, PHD, MEMBER

JUDITH R. BAKER, MHSA, CONSUMER REPRESENTATIVE

LOUIS M. KATZ, MD, NON-VOTING INDUSTRY REPRESENTATIVE

MELVIN BERGER, MD, PHD, TEMPORARY VOTING MEMBER

RICHARD A COLVIN, MD PHD TEMPORARY VOTING MEMBER

JAMES R. ALLEN, MD, MPH, NON-VOTING TEMPORARY MEMBER


           T-A-B-L-E O-F C-O-N-T-E-N-T-S

                                              Page

 

Statement of Conflict                            4

 

Opening Remarks                                 10

 

Committee Updates

 

      Summary of May 10-11 Meeting of DHHS      11

      Advisory committee on Blood Safety and

      Availability

 

      Summary of April 25-26 Workshop on Immune 20

      Globulins for Primary Immune Deficiency

      Diseases

 

      Summary of August 15 Workshop on          28

      Licensure of Apheresis Blood Products

 

Informational Presentations: WHO Biological Standards

 

      Summary of January 29-30 WHO meeting      34

 

      Potency and Safety Standards for Plasma   52

      Derivatives

 

      Joint FDA/WHO Minimum Potency Standards   72

      for Certain Blood Grouping Reagents

 

Topic I Response to the Office of Blood Research

  and Review Office Level Site Visit

 

      Introduction                              79

 

      Office Response                          100

 

Open Committee Discussion                      132

 

Topic II Measles Antibody Levels in U.S. Immune

  Globulin Products

 

      Introduction                             151

 

      Current Epidemiology of Measles in U.S.  172

 

      Measles Infections and Estimated         195

      Protective Titers

 

           T-A-B-L-E O-F C-O-N-T-E-N-T-S

                                              Page

Topic II cont'd.

 

Measles Antibody Titers in Plasma Donors       219

 

Measles Antibody Levels over Time in Licensed 236

  Immune Globulin Products and Patients with

  Primary Immune Deficiency Diseases

      (Baxter Healthcare and CSL Behring)

 

Open Public Hearing                            253

 

Open Committee Discussion                      261

     


               P-R-O-C-E-E-D-I-N-G-S

                                         8:05 a.m.

            EXECUTIVE SECRETARY JEHN:  Let's go ahead and get started.  Mr. Chairperson, Members of the Committee, invited guests, temporary voting members and public participants, I would like to welcome all of you to this 90th meeting of the Blood Products Advisory Committee.  I'm Donald Jehn, the Executive Secretary for this meeting.

            This meeting will be completely open to the public.  At this time, I would like introduce the individuals seated at the head table for today.  To my immediate left is our BPAC Chairperson Dr. Frederick Siegal, Medical Director of Comprehensive HIV Center, St. Vincent's Catholic Medical Centers, New York.

            To my right and going down the table is Dr. James Allen, Medical Advisor, American Social Health Association; Dr. Mark Ballow, Chief Division of Allergy and Immunology, SUNY New York and Women's and Children's Hospital of Buffalo; Dr. Richard Colvin, Clinical Assistant in Medicine, Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital East; Dr. Henry Cryer, Chief of Trauma and Clinical Care at UCLA; Dr. Adrian Di Bisceglie, Chief of Hepatology, St. Louis University School of Medicine; Dr. Willarda Edwards, President and Chief Operating Officer of Sickle Cell Disease Association of America; Dr. Maureen Finnegan, Associate Professor, Department of Orthopedic Surgery, University of Texas Southwestern Medical Center; Dr. Simone Glynn, Branch Chief Transfusion and Medicine and Therapeutics Branch, NHLBI.

            And then on my left side going down, Dr. Keith Quirolo, Clinical Director, Apheresis Program, Department of Hematology, Children's Hospital at Oakland; Dr. George Schreiber, Vice President of Health Studies, Westat; Dr. Irma Szymanski, Professor of Pathology, Emerita, University of Massachusetts Medical Center; Dr. Donna Whittaker, Chief Department of Clinical Support Services, U.S. Army Medical Department Center and School, Fort Sam, Houston; and Ms. Judith Baker, our Consumer Rep located at UCLA; and, finally, our Industry Rep, Dr. Louis Katz, Executive Vice President, Medical Affairs, Mississippi Valley Regional Blood Center.

            Committee members not in attendance are Drs. Cooner, Kulkarni, Manno and Quinn.  Dr. Allen is at the table for the discussion of the response of the Office of Blood, Research and Review Office Level Site Visit for Research.  I would like to thank all of you for attending this meeting.

            Now if I could have Dr. Goodman.  We have four retiring members after this meeting and we would like to recognize them.  Dr. Szymanski. 

            (Applause.)

            EXECUTIVE SECRETARY JEHN:  Dr. Donna Whittaker.

            (Applause.)

            EXECUTIVE SECRETARY JEHN:  Dr. Keith Quirolo.

            (Applause.)

            DR. WHITTAKER:  And Dr. George Schreiber.

            (Applause.)

            EXECUTIVE SECRETARY JEHN:  We thank them all.  Thanks very much.

            Okay.  Before we start the meeting, I do have a conflict of interest statement to read.  It's rather lengthy, so please bear with me.

            The Food and Drug Administration, FDA, is convening today's meeting of the Blood Products Advisory Committee under the authority of the Federal Advisory Committee Act, FACA, of 1972.  With the exception of the Industry Representative, all participants of the Committee are special government employees, SGEs, or regular federal employees from other agencies and are subject to the Federal Conflict of Interest laws and regulations.

            The following information on the status of this advisory committee's compliance with Federal Ethics and Conflict of Interest laws including, but not limited to, 18 USC Section 208 and 21 USC Section 355(n)(4) is being provided to participants in today's meeting and to the public.  FDA has determined that participants of this advisory committee are in compliance with Federal Ethics and Conflict of Interest Laws including, but not limited to, 18 USC Section 208 and 21 USC 355 (n)(4).  Under 18 USC 208 applicable to all government agencies and 21 USC 355(n)(4) applicable to certain FDA committees, Congress has authorized FDA to grant waivers to special government employees who have financial conflicts when it is determined that the Agency's need for a particular individual's services outweighs his or her potential financial conflict of interest, Section 208, and where participation is necessary to afford essential expertise, Section 355.

            Members of the Committee who are special government employees at today's meeting including special government employees appointed as temporary voting members have been screened for potential financial conflicts of interest of their own as well as those imputed to them, including those of their employers, spouse or minor child related to the discussion of (1) FDA's response to the Officer of Blood Research and Review Office Site Visit held on July 22, 2005 and (2) measles antibody levels in U.S. immune globulin products.  These interests may include investments, consulting, expert witness testimony, contracts, grants, CRADAs, teaching, speaking, writing, patents and royalties and primary employment.

            Today's agenda also includes several updates.  In accordance with 18 USC Section 208(b)(3), waivers were granted to Dr. Mark Ballow and Dr. Melvin Berger for the discussion of topic two on Measles Antibody Levels in U.S. Globulin Products.  A copy of the written waiver may be obtained by submitting a written request to the Agency's Freedom of Information Office, Room 12A-30 of the Parklawn Building.

            With regard to the FDA's guest speakers for Topic two, the Agency has determined that the information provided by these speakers is essential.  The following information is being made public to allow the audience to objectively evaluate any presentation and/or comments made.  Dr. Donald Baker is employed by Baxter Healthcare Corporation.  Dr. Baker has financial interests in his employer.  Dr. William Moss is employed by Johns Hopkins Bloomberg's School of Public Health as an Associate Professor in the Departments of Epidemiology, International Health  and Molecular Microbiology and Immunology.  Dr. Jane Seward is employed by CDC as a Deputy Director, Division of Viral Disease, National Center of Immunization, Respiratory Diseases.  Dr. Toby Simon is representing Plasma Protein Therapeutics Association.  He is employed by ZLB Plasma as the Corporate Medical Director.  Dr. Simon has a financial interest in his employer.  Dr. Othmar Zenker is employed by CSL Behring.  As guests, they will not participate in the Committee deliberations.  Nor will they vote.

            In addition, there may be regulated industry and other outside organizations' speakers making presentations.  These speakers may have financial interests associated with their employer and with other regulated firms.  The FDA asks in the interest of fairness that they address any current or previous financial involvement with any firm whose product they may wish to comment upon.  These individuals were not screened by the FDA for conflicts of interest.

            Dr. Louis Katz is serving as the Industry Representative acting on behalf of all related industry and is employed by the Mississippi Valley Regional Blood Center.  Industry Representatives are not special government employees and do not vote.

            This conflict of interest statement will be available for review at the registration table.  We would like to remind members that if the discussions involve any other products or firms not already on the agenda for which an FDA participant has a personal or imputed financial interest, the participants need to exclude themselves from such involvement and their exclusion will be noted for the record.  The FDA encourages all other participants to advise the Committee of any financial relationships that you may have with any sponsor, products, direct competitors and firms that could be affected by the discussions.

            Before I turn the microphone over to the Chair, I would like to request that everybody take a moment and check to make sure they have their cell phones and pagers set to silent or turned off.  Thank you.  Dr. Siegal, I'll turn it over to you.

            CHAIRMAN SIEGAL:  Thank you, Don.  I would like to welcome you all to this glorious summer meeting of the Blood Products Advisory Committee. Fortunately, we don't have a lot of controversial topics, but we have a fair amount to cover.  I particularly want to welcome back Jim Allen, an old friend from the AIDS wars.  Can you not hear me?  Well, it's not really important anyway.

            (Laughter)

            CHAIRMAN SIEGAL:  But Jim was, of course, my predecessor on this committee and we've known one another since about 1981 maybe.

            Our first set of topics are the Committee updates and we're going to start with Jerry Holmberg who is going to review and summarize the meeting of the DHHS Advisory Committee on Blood Safety and Availability.  Jerry.

            DR. HOLMBERG:  While we are waiting to get that up on the screen, I'll just give you a little disclosure.  I do have financial interests in my company, the Federal Government, and that financial interest is not only receiving a salary, but paying taxes.

            (Laughter.)

            DR. HOLMBERG:  And if anybody would like to know, I have had my annual financial review with the Ethics Office.

            What I would like to do today is to give you an update on the Advisory Committee on Blood Safety and Availability and the Office of Blood Safety and Availability and also primarily give you a summary of the May 10 and 11, 2007 meeting.

            First of all, I would like to note that we have some staff changes.  The biggest staff change that I would like to mention that is not on the slide here is that Dr. Aquinobi, the Assistant Secretary for Health, has resigned from the Administration and that  resignation is as effective as of September 3rd.  In my office, we do have Lt. Commander Rich Henry who has moved up to the Deputy Director position and we have a new Public Health Officer, LTjg Jennifer Lunney who is our Senior Health Preparedness Advisor.

            At the May 10th and 11th meeting, Dr. Aquinobi asked the committee to review several commonalities between transfusion and transplantation safety.  The reason for that is in October the charter for the Advisory Committee on Blood Safety and Availability was modified to include interests or concerns of transfusion and transplantation safety.  This sort of opens up the scope of issues that we can deal with at the committee and Dr. Aquinobi was looking to see are there areas of commonality.

            So the first question was is there a process, an opportunity, to lay out a process for transfusion and transplantation safety for the future and the committee overwhelmingly said that, yes, there is a need to develop a process to enhance the quality and improvement in transfusion medicine and transplantation medicine.

            Is there scientific evidence to support a need for a master strategy?  In this particular area, the committee really struggled as far as finding scientific evidence, but based on surveillance evidence there is a limited reports of infectious disease transmission and therefore, substantiate the need for a master strategy and you can read on there as far as the differences in the risk/benefit profiles between transfusion tissue and transplantation recipients but that all these patients have the potential for acquiring life-threatening infections if an infectious disease screening is flawed or emerging or unknown diseases evolve unchecked over time.

            So another question that was asked was what should be the scope of a master strategy and the number one issue that came out was a recipient outcome surveillance or a biovigilance system to identify all donors using common identification numbers linked to biological products that are uniquely identified; mandatory adverse event reporting process for tissues, organs and blood therapy through appropriate mechanisms to designated public health authorities and to recipients and donors and timely and efficiently trace all biological products to the clinical user, recipient, and donor and to recognize transmissible events resulting in adverse outcomes including infectious agents, malignancies and toxins; also to build communication and education networks to disseminate data to users; to develop informatics to support surveillance, process, involvement, improvement and evidence-based research; and to include other strategic plan elements as needed such as donor recruitment, donor screening, research coordination and emergency preparedness.

            What are the areas of commonality of blood products, cohort progenitor cells and bone marrow tissues and organs?  Key elements in common with transfusion required for ensuring high quality include donor recruitment; donor screening; and, of course, eligibility; collection; infectious disease testing; transportation; storage; processing; labeling; traceability; good manufacturing practices; good tissue practices.  I would also say probably good transplantation practices; outcome analysis; adverse event reporting.  And in addition, there needs to be a way to evaluate the differences between the different transfusion and transplantation products, modalities.

            How best should this be done with the stakeholders and how do we begin?  The recommendation was that HHS should convene a forum of stakeholders to include public health agencies, accrediting agencies, manufacturers, clinicians, consumers and endusers and HHS should be responsible for implementing a master strategy with appropriate resources based on input from stakeholders.

            And what are the resources needed and what are the estimated costs?  The committee really do not get to that area and had a difficult time trying to put a price tag on what this would mean.

            Let me just go back to that slide there.  As an outcome of the recommendations, Dr. Aquinobi has sent a letter to Dr. Bracey who is the Chairman of the Advisory Committee on Blood Safety and Availability.  In that letter, he does recognize the recommendations and the answers to the questions and also reassures Dr. Bracey that the Department has already moved forward in various aspects on bioviligence and we have already put resources towards those bioviligence endeavors through not only the recipient side but also through the donor side of surveillance and also CDC is supporting a collaborative effort with the TTSN for tissues and transplantation.

            Our next meeting is next week.  The two issues that we're primarily looking at ethical considerations and risk benefits for ensuring transfusion and transplantation safety during focal periods of shortages.  Those focal periods of shortages could be seasonal shortages, preparation for pandemic, disasters both manmade or natural and then also to review and discuss the elasticity of the blood supply to support transfusion and transplantation safety as well as strategies and barriers to those strategies.

            And that's all I have.  If there are any questions, I'll be happy to entertain those.

            CHAIRMAN SIEGAL:  Questions from the Committee?

            DR. FINNEGAN:  One of my questions and I realize I'm a little bit naive about what the infrastructure for IT is within this environment, but would you consider having IT infrastructure as one of the stakeholders?  Because it would seem to me if you had a good IT infrastructure, that the cost long term would be much less.

            DR. HOLMBERG:  Absolutely.  We have already initiated some of those discussions primarily using some of the infrastructure that is already in place within the Federal Government and outside the Federal Government.  Also within the Department of Health and Human Services is a health information technology office that is personally -- that reports directly to Secretary Leavitt.  They've done case studies analysis for electronic health records and also for laboratory surveillance.

            So we're moving in that direction, but, yes, definitely in our stakeholder meetings, we will consider IT so that there are stakeholders, there are placeholders, I should say, for future systems that are developed that we can mine the data down into.

            The other thing that I want to emphasize there is that we are really looking at this as a quality system in such a way that this will be a system to develop or to get data that we can analysis in hopes of being able to share it throughout the entire community and not to be punitive against a stakeholder.  So it's trying to be very open in the way we collect the data and for that reason, we have already involved many of the stakeholders such as the AABB and the UNIS and the various -- the American Association of Tissue Banks.  Yes.  Dr. Ballow.

            DR. BALLOW:  So is this to include all fractionated blood banks as well?

            DR. HOLMBERG:  Well, we do have them --

            DR. BALLOW:  Coagulation products, IV, IG, etc.?

            DR. HOLMBERG:  We do have them as one of the stakeholders and we have not had the meeting yet, but they are on the list to participate.

            The other thing I want to draw the attention to is that we do have a federal registry notice out that came out on July 30th seeking nominations to the Advisory Committee on Blood Safety and Availability.  I would like to take this opportunity to draw your attention to that and to remind people that nominations are due by August 31st.

Thank you.

            DR. SZYMANSKI:  I had one more question.  I notice an interesting word "malignancy" and how are you going to screen for that?  In donors or in the recipients?  Is that something new that is not being done now when you screen donors?

            DR. HOLMBERG:  I didn't understand the word that you were referring to.

            DR. SZYMANSKI:  You said you are going to not only worry about infectious diseases, but transmission or something with malignancy and I was wondering.  Do you have any other approaches than what are used right now when you screen donors for blood donation?

            DR. HOLMBERG:  As far as blood donations, we do not have a mechanism to be able to track that.  However, in the organ community they do have the adverse event reporting and that does get passed back to UNIS.  But it's open.  We're the point right now of just developing this and, of course, as we move forward in bioviligence, I'm sure there will be other avenues that we want to investigate.  I think that what he want to do is to not only look at what we know today but also to look towards the future and to be able to look beyond the horizon for anything that may potentially affect the blood organ or tissue products.

            CHAIRMAN SIEGAL:  Are there any other questions for Dr. Holmberg?  Okay.  If not, Jerry, thank you.  The next speaker will be Jennifer Scharpf who is going to review the FDA workshop from last April on immune globulins for primary immune deficiency disease referencing antibody specificity, potency and testing.  Dr. Scharpf.

            DR. SCHARPF:  Thank you, Dr. Siegal, and good morning.  This morning I will provide the Committee on the FDA's workshop on immune globulins for primary immune deficiency diseases and the workshop was officially titled "Immune Globulins for Primary Immune Deficiency Diseases; Antibody Specificity, Potency and Testing."  And the workshop was held on April 25 through 26 of this year at the National Institutes of Health.  FDA is grateful to The Immune Deficiency Foundation, The Plasma Protein Therapeutic Association and Dr. Holmberg and the Office of the Secretary, Office of Public Health and Science at HHS for their sponsorship of the workshop.  And we thank the sponsors not only for their financial support but also their scientific contributions to the program.  Additionally, I would like to recognize Dr. Dorothy Scott for her role as organizer and chair of the program.

            The goals of the workshop were fourfold:  (1) to assess the current potency testing of immune globulins.  The potency tests currently required are for antibodies to measles, polio and diphtheria and at the workshop, we wished to examine the potential for potency tests for antibodies against pathogens most commonly associated with infection in PIDD patients; (2) to list antibodies needed to protect primary immune deficient patients from infections; (3) to identify candidate antibody specificities for potency testing of immune globulins for treatment of PIDD; and, finally, on the second day, our goal was to address approaches to diminishing measles antibody levels in currently licensed products.

            So on the first day of the workshop, our goal was to identify the most clinically relevant antibody specificities for PIDD patients.  Epidemiology and surveillance data was reviewed and there was a description of patient registries in Europe and the United States.  The registries which are supported by the European Society for Immunodeficiencies and, the United States, Immunodeficiency Network, have the potential to gather long-term perspective clinical data on these patients.  We then reviewed data on antibody levels in currently licensed products and both of these datasets were taken to then address the question of which antibody specificities would be useful and relevant to measure with respect to clinical importance and to assure lot to lot manufacturing consistency.

            The first question we addressed to the panel of experts and the workshop audience was which pathogens are of greatest concern in immune globulin treated and untreated patients.  And to address this question, data on infectious diseases and PIDD, both patients with humeral and cellular immunodeficiencies was presented by clinicians.

            The workshop participants identified Strep pneumococcus and Haemophiles influenzae as the most important bacterial infections for this patient population.  Several viral infections were also mentioned as pathogens of concern including Epstein-Barr Virus, Cytomegalovirus, echoviruses, Varicella Zoster, adenovirus and Coxsackie.

            Representatives from the FDA, the Paul-Ehrlich-Institut in Germany and two IGIV fractionaters then presented data on antibody levels in currently licensed products.  The presentations revealed that multiple antibody specificities have been studied, trends in antibody levels over time, across products and variations with the plasma source whether recovered or source were observed and regarding emerging diseases, West Nile Virus antibody titers, have been measured in U.S. products, although as one would expect both seasonal and locational variations are observed.

            So at the end of the first day of the workshop, it was proposed that pilot testing of immune globulins for Strep pneumonia and H. influenza should be conducted and we believe this type of study is feasible since assays have been validated for the specificities in serum and who reference labs already exist to which samples could be sent for testing.

            In the proposed studies, manufacturers would voluntarily send blinded samples to their reference lab for testing antibody levels to determine the feasibility, antibody levels and function, and several manufacturers have expressed their willingness to send samples.  And finally, we would like to measure the trough titer level antibodies to these bacterial pathogens in patients receiving the product to determine the relationship between in vitro potency and in vivo levels.  And we anticipate that by working with manufacturers, samples from clinical studies would be available for this type of testing.

            On the second day of the workshop, we discussed the current lot release tests for measles antibodies and measles antibody levels are a standard lot release measure of potency in the United States products and this was a historically important specificity due to measles epidemics.  There has been declining antibody levels observed in products over the past several years and this is attributed to the decline of titers in the donor population.

            The regulatory impact of declining measles titers is that the product could fail the lot release specification and the specific lots must be rejected and rejection of lots could lead to an obvious negative impact on the availability of the product for the primary immune deficient patients.

            Presentations at the workshop revealed data on the measles epidemiology in the United States,  decreasing measles titers in the donor population, immune globulin products and primary immune deficient patients and the estimated protective level of antibody in these patients.  I won't expand on these presentations since the data will be presented to the Committee later this afternoon.

            Following those presentations, we asked the following questions to the expert panel and the audience:  is measles infection of current clinical concern for primary immune deficient patients, how much measles antibody is needed to attenuate or prevent measles in this patient population; what is the potential clinical impact of diminishing anti-measles titers in immune globulin products; and finally, what are the possible approaches to address the decline of anti-measles antibodies in immune globulins with respect to clinical efficacy in prevention of measles infection as well as with respect to utility of a test for lot-to-lot consistency.

            So the possible approaches identified by the discussants at the workshop included: (1) gathering relevant data relating product titers to patient trough levels and estimated protective levels and (2) the option that CBER can potentially change the recommendation on antibody potency, however, this change in level must be scientifically and clinically justifiable and this is the issue that will be before the Committee today.

            So in summary, the next steps identified at the workshop are to (1) design and implement testing protocols to assess levels of antibodies in immune globulins to H. Influenza and Strep pneumonia pathogens commonly associated with infection in primary immunodeficient patients and the study will evaluate the feasibility of using these specificities as potency tests; (2) implement a study to measure measles antibody trough levels by neutralization assays in patients to better ascertain the relationship between product dose and trough level; and finally, CBER will deliberate on solutions to address the diminishing measles antibodies titers and immune globulins weighing, of course, the scientific, clinical and supply considerations.

            And finally, information is available on the CBER website including the transcript and all of the workshop presentations.  Thank you for your attention.

            CHAIRMAN SIEGAL:  Thank you, Dr. Scharpf.  Are there questions from the Committee?  I actually do have a question which is that since we will discuss this later but is it feasible to change the licensure requirements entirely so that measles antibody which may not really be relevant is simply not part of the criteria for approval of the product.

            DR. SCHARPF:  I think we can look at examining changing the titer and that's what we will present later this afternoon to the Committee.

            CHAIRMAN SIEGAL:  Because it certainly would be more relevant to look at representative pneumococcal antibody titers for the PIDD population.

            DR. SCHARPF:  And that was some of the conclusions of the workshop.

            CHAIRMAN SIEGAL:  Anybody else?

            DR. GOLDING:  Yes, I'll just help to answer that question.  I mean we are looking very actively at changing this, the relevant titers, and what Jennifer mentioned is that we're looking at H. influenzae and also at Strep pneumoniae as being much more important and relevant pathogens.  But I don't think we have any plans in the near future to drop measles because as you will hear later, we still think this is a pathogen we need to worry about even though it's much rarer these days.  But also in terms of consistency of lot-to-lot testing, it's important to have tests in place that have the history and the ability to show differences between batches.

            CHAIRMAN SIEGAL:  Okay.  Let's move on.  Finally, Lore Fields from FDA is going to summarize the FDA workshop just yesterday on licensure of apheresis blood products.

            MS. FIELDS:  Good morning.  Yesterday we had a workshop on the licensure of aphersis blood products at Lister Hill Auditorium at NIH.

            In keeping with the vision of CBER to protect and improve public health and to approve safe and effective blood products, we planned a workshop to help educate industry on how we approve apheresis submissions at the Blood and Plasma branch.  We estimate that currently appropriately 40 percent of the submissions coming into the Blood and Plasma branch are on apheresis products.  We did have 175 places available yesterday for the workshop and we did fill the entire auditorium.

            The goals and objectives for the workshop were to educate industry on the licensure process for apheresis platelets, red blood cells and plasma for transfusion.  We wanted to discuss the managed review process as it applies to the Blood and Plasma branch, discuss and review the required documents needed for submission, review the comparability protocol and what is required to obtain one and review the requirements for an apheresis instrument.  Additionally, we asked speakers from industry to give examples on how they successfully submit their FDA's licensure submissions. We also asked Dr. Katz from the Mississippi Valley Regional Blood Center to talk on his recently published paper, "Frequent Platelet Apheresis Does Not Clinically Significantly Decrease the Platelet Counts in Donors" by Dr. Katz, et al.

            The workshop was developed and cosponsored by CBER, the Department of Health and Human Services, AABB and America's Blood Centers and we would like to thank AABB, ABC and HHS for their contributions to the workshop.

            During the workshop, we had several presentations.  I'm going to go over just very brief overviews of what was discussed.  Dr. Goodman did open the workshop for us.

            Dr. Williams provided an informative presentation on the statutes and regulations that we use to do licensure submissions.  Dr. Williams also covered licensing, changes to an approved application, alternative procedures and how managed review is applied to the Blood and Plasma branch.

            Ms. Ciaraldi did a comprehensive presentation that described how we perform reviews.  This presentation included the documents, regulations, guidance and operators' manuals references that we frequently use when we are doing our reviews.

            Ms. Nesbitt did a top ten pitfalls with submissions presentation and what we did with this was he got together in the Blood and Plasma branch and we came up with the top ten reasons that we find errors in submissions and she went through them.  Hopefully, the blood centers will then be able to apply this to their submissions before they send them in and it will facilitate the process of getting licensure done in  a timely manner.

            The next two presentations were given by representatives of the American Red Cross and Blood Systems.  We are always being asked for examples of acceptable submissions.  So we asked these two blood centers to provide the attendees with an overview of their processes.

            Steve Kassapian who is the Director of Regulatory Affairs at American Red Cross reviewed his processes and included some of the examples and forms that his group has put together over the last couple of years that they use to facilitate their process.

            Ms. Kathleen Hopping from BSI reviewed how they have standardized their platelet Apheresis licensure process.  She also provided the attendees with timetables on how the process improvement has reduced the time of the licensure or the approval for licensure at their blood centers.

            I went over a brief review of the current guidance for platelet Apheresis and the 2005 draft guidance.

            We did have an unexpected presentation yesterday that is unfortunately not on your slides.  A direct final rule was actually displayed yesterday as well.  So we had a surprise presentation by Ms. Elizabeth Callahan who is the Acting Director of the Division of Blood Applications and in this is the changes that will allow a storage period of seven days for platelet Apheresis and also the increase for the minimum pH from 6.0 to 6.2 for platelet Apheresis quality control.

            Dr. Katz put on a presentation based on the comments to the 2005 draft guidance.  His group did a study to determine what the impact is on platelet counts and donation intervals.  This is the data that was previously presented to you in March of 2006.  The paper was recently published and so we asked him to present the data to the attendees.

            The failure investigation presentations covered the regulations behind the investigations by Ms. Hoi-may Wong and also one example of how a structured investigation process is working at a major blood center.

            Ms. Faye Kugele described how the ARC has standardized their failure investigation processes and how the standardized procedures have improved their investigation of failed products.

            We did something a little different at our workshop and one of the things is we spent a lot of time talking to the regulatory people at the blood centers, but they never actually see our faces.  So we spent about 30 minutes at our afternoon break kind of introducing ourselves to them so they had a face to go with the person that they talked to.

            The Device Manufacturers Forum was an opportunity for the manufacturers to provide the attendees with pertinent information from their operators' manuals, package inserts and other documents that should be included with their submission.  They also provided updates on recent changes on their cleared devices and this was done by Merilyn Wiler from Gambro, Dr. Orton from Fenwal and Sue Finneran from Haemonetics.