BLOOD PRODUCT SAFETY
Immediately preceding Transmissible Spongiform Encephalopathies  

Corporate Support:
Corporate Donor:

Sponsoring Publications:
American Journal of Hematology
IBPN
Intervirology

Sponsoring Association:
PPTA

Scientific Advisors
Dr. Nicola Boschetti, ZLB Bioplasma AG (Switzerland)
Dr. Larisa Cervenakova, American Red Cross
Dr. William N. Drohan, Clearant, Inc.
Dr. Bernard Horowitz, Horowitz Consultants, LLC
Dr. Thomas J. Lynch, Clearant, Inc.
Dr. Paul R. McCurdy, Consultant
Dr. Kathryn Martin Remington, Bayer Corporation
Dr. Hannelore Willkommen, Paul-Ehrlich-Institut (Germany)

Blood Product Safety Speakers
Dr. Leon E. Barstow, Protein Therapeutics
Dr. Jeri Ann Boose, BioReliance
Dr. Nicola Boschetti, ZLB Bioplasma AG (Switzerland)
Dr. Harvey J. Brandwein, Immuno-Rx, Inc.
Mr. Jan M. Bult, PPTA
Dr. Paul Coleman, Abbott Laboratories
Dr. Albert Farrugia, TGA Laboratories
Dr. Damon Getman, Gen-Probe Incorporated
Dr. Jonathan C. Goldsmith, Immune Deficiency Foundation
Dr. Chien Ho, Carnegie Mellon University
Dr. Yu-Wen Hu, University of Ottawa and Canadian Blood Service
Dr. Thomas Kreil, Baxter
Dr. Margot Kruskall, Beth-Israel Deaconess Medical Center
Dr. Nico Lelie, Sanquin-CLB Diagnostic Division (The Netherlands)
Dr. Keith McKenney, Clearant, Inc.
Dr. Judi Miller, Octapharma (Portugal)
Dr. Jerry Ortolano, Pall Corporation
Dr. Georg Pauli, Robert Koch-Institut (Germany)
Dr. James W. Polarek, FibroGen, Inc.
Dr. Howard E. Purdum, CryoFacets, Inc.
Dr. Charles Tackney, Ortho Clinical Diagnostics
Dr. Stefan Wildt, GlycoFi

Session Topics Include:
Policy and a Regulatory Case Study
Screening
Inactivation
New Applications
Emerging Issues

PROGRAM

Sunday, February 9

5:00-6:30pm Early Registration, Poster and Exhibit Setup

Monday, February 10

7:30am Registration, Poster and Exhibit Viewing, Light Continental Breakfast

 

POLICY AND A REGULATORY CASE STUDY

8:30 Welcome by Session Chairperson
Dr. William N. Drohan, President, Clearant, Inc.

8:45 Going the Extra Mile: Voluntary Safety Practices
Mr. Jan M. Bult, President, PPTA
This presentation will speak to the voluntary safety practices that industry has initiated that go beyond those required by regulatory agencies to detect and remove infectious agents and to ensure the flow of high quality plasma from collection to fractionation.

9:15 Current Issues in Blood Safety: The Haemophilia Community's Perspective
Dr. Albert Farrugia, Head, Blood and Tissue Products Group, TGA Laboratories
Continuing developments in donor selection, laboratory testing, and pathogen inactivation have ensured that plasma concentrates for the treatment of haemophilia are among the safest drugs. However, the emergence of new infectious agents such as vCJD and previously unrecognized viruses mandates constant vigilance. Furthermore, the impact of safety measures on product supply always has to be considered by the patient community dependent on these products. This presentation will review the current blood safety and supply environment from the perspective of the haemophilia community.

9:45 Recent Developments with Solvent Detergent Virus Inactivated Plasma: Politics or Product?
Dr. Judi Miller, Scientific Director, Octapharma
SD plasma was developed as a safer alternative to fresh frozen plasma. More than 7 million units have been used in Europe since its launch in 1991, where its clinical safety, efficacy, and tolerability have been well demonstrated and widely recognized. Conversely, SD plasma has been the subject of considerable controversy and concern in the U.S., since it became available in 1998. This case study will review the current issues, examine differences between the SD plasma products marketed in the U.S. and Europe, and suggest possible explanations for the above dichotomy.

10:15 Poster and Exhibit Viewing, Refreshment Break

 

SCREENING

10:45 Performance of the Procleix Parvovirus B19/HAV Assay
Dr. Damon Getman, Staff Scientist, R&D, Gen-Probe Incorporated
We have recently assessed the performance of the Parvovirus B19/HAV Assay currently under development at Gen-Probe Incorporated using the WHO International Standard and the CBER Panel for parvovirus and the HLD-2 panel from CDC for HAV. These studies and those using in-house reproducibility panels indicate excellent analytical sensitivity for both analytes. In addition, 100% specificity was demonstrated by testing normal donor specimens provided by the Community Blood Center of Greater Kansa City. Testing of normal plasma spiked with other blood-borne pathogens indicated the absence of cross-reactivity. These data and the results of testing ~2000, 16-member pools from the American Red Cross will be discussed.

11:15 Detecting Potentially Fatal Bacteria in Donated Blood
Dr. Jerry Ortolano, Vice President, Scientific and Laboratory Services, Pall Corporation
A new technology for screening blood components for bacterial contamination will be discussed.

11:45 Sensitivity of HCV RNA and HIV RNA Blood Screening Assays
Dr. Nico Lelie, VQC Laboratory, Sanquin-CLB Diagnostic Division
This presentation will discuss data produced from the ongoing study of assay sensitivity by Sanguin-CLB Diagnostic Division
Summary unavailable at time of printing.

12:15 Lunch (on your own)

INACTIVATION

1:30 Comments by Session Chairperson
Dr. Bernard Horowitz, Horowitz Consultants, LLC

1:40 Emerging Technologies in Donor Screening
Dr. Charles Tackney, Scientific Director, Ortho Clinical Diagnostics

2:10 Design and Interpretation of Viral and TSE Cleaning Studies for Biopharmaceutical Products
Dr. Jeri Ann Boose, Senior Director, Analytical and Viral Clearance Services, BioReliance
Cleaning validation studies for viruses and agents causing the transmissible spongiform encephalopathies have recently become an integral part of the biosafety testing package for biopharmaceutical products. This presentation covers the key aspects in the design and interpretation of a cleaning validation study for adventitious agents.

2:40 Validation of Pathogen Inactivation by Using Nucleic Acid Testing
Dr. Keith McKenney, Director, Molecular Biology, Clearant, Inc.
Nucleic acid testing (NAT) is particularly sensitive for detecting and quantitating pathogens. However, many inactivation methods do not remove pathogen nucleic acid (NA), making ANT not well suited for validating the inactivation of pathogens in blood derived products. Gamma irradiation does not remove pathogen NA, but inactivates it by introducing strang breaks in viral pathogen NA. We demonstrate a new NAT method termed "analysis of large target amplicons" (ALTA) to detect and quantify viral inactivation. In conjunction with traditional NAT, viral pathogens can be detected, quantified and shown to be inactivated.

3:10 Poster and Exhibiting Viewing, Refreshment Break

3:40 Virus Safety of Allogeneic Avital Bone Tissue Transplants
Dr. Georg Pauli, Projektgruppen/Forschungskoordination, Robert Koch-Institut
Based on national and international guidelines, the antivirucidal effectiveness of a variety of virus inactivation procedures was investigated. Three enveloped viruses-human immunodeficiency virus type 2 (HIV-2), pseudorabies virus (PRV), and bovine virus diarrhoea virus (BVDV)-and three nonenveloped viruses-hepatitis A virus (HAV), poliovirus (PV-1), and porcine/bovine parvovirus (PPV, BPV)-were used. The following inactivation procedures were investigated: gamma irradiation (25 kGy), heat treatment (82.5°C/15 min.) and chemical sterilization, e.g., peracetic acid-ethanol treatment (PES, 2% peracetic acid, 96% ethanol, Aqua [2:1:1], 200 mbar, agitation, 4 hours).

4:10 Treatment of Fibrinogen with "Broad Spectrum Pulsed Light"
Dr. Nicola Boschetti, Senior Research Scientist, R&D, Virology, ZLB Bioplasma AG
Inactivation of enveloped and nonenveloped viruses in a fibrinogen preparation by Broad Spectrum Pulsed Light (BPSL, PureBright) is reported. Inactivation kinetics of model viruses as well as structural and functional data on fibrinogen, factor XIII, and fibronectin are presented. Robust inactivation for parvoviridae, picornaviridae, and herpesviridae was achieved. Coauthors: Bettina Bolliger, Thomas Hostettler, Anita Mischler, Peter Baillod, and Christoph Kempf).

4:40 UVC and Ozone Decontamination of Ultrasonically Degassed Plasma
Dr. Howard E. Purdum, President, CryoFacets, Inc.
UVC and ozone are both known to be effective decontamination agents of plasma and other biologicals. To improve these techniques, a new ultrasonic vacuum degassing system has been developed. For UVC treatment, degassing removes the dissolved oxygen that would otherwise form damaging free radicals during illumination. For ozone treatment, degassing removes the previously dissolved oxygen and nitrogen that would otherwise slow the absorption of the applied ozone. Because UVC and ozone act by separate mechanisms, their combination yields a highly effective, rapid decontamination system that requires no other agents to be added or removed.

5:10 Panel Discussion

5:40-6:40pm Networking Reception

Tuesday, February 11

8:30am Poster and Exhibit Viewing, Light Continental Breakfast

 

NEW APPLICATIONS

9:00 Comments by Session Chairperson
Dr. Kathryn Martin Remington, Bayer Corporation

9:10 Design of Novel Recombinant Hemoglobins as Potential Hemoglobin-Based Oxygen Carriers
Dr. Chien Ho, Department of Biological Sciences, Carnegie Mellon University
We have developed an expression system to produce authentic human normal adult hemoglobin in Escherichia coli. Using this expression system we can design any mutant hemoglobin needed for our research. During the past few years, we have designed and expressed a number of recombinant hemoglobins with different oxygen affinities and cooperactivity, as well as varying degrees of oxidation toward methemoglobin formation. With these recombinant hemoglobins, we hope to design the next generation of hemoglobin based-oxygen carriers or hemoglobin therapeutics.

9:40 Production of Fully Human Blood Glycoproteins in Yeast
Dr. Stefan Wildt, GlycoFi
GlycoFi is developing technology to meet the biopharmaceutical industry's current need for vastly increased production capacity for the expression of therapeutic proteins. The company is focusing its cellular and metabolic engineering expertise on the development of genetically engineered yeast and fungi that are able to perform "human-like" glycosylation. Producing complex glycoproteins, similar in structure to their human counterparts, has been the premier challenge in biologics manufacturing. Yeast and fungi-based expression systems are capable of yielding titers in excess of 20 g/l, an order of magnitude higher than any titer that has been achieved in mammalian cells; and they are able to do this in a fraction of the time. Advances in the engineering of "humanized" yeast will be presented.

10:10 Conversion of Groups A, B, and AB Red Blood Cells to Enzyme Converted Group O Red Blood Cells
Dr. Margot Kruskall, Consultant, Clinical and Medical Affairs, Zymequest Inc., Director, Division of Laboratory and Transfusion Medicine, Beth-Israel Deaconess Medical Center
The need for blood which can be transfused into any recipient has been ongoing. This presentation will discuss a new method in which red blood cells of any type can be enzymatically converted to Group O red blood cells to allow universal transfusion.

10:40 Poster and Exhibit Viewing, Refreshment Break

11:10 Development of a Recombinant Gelatin Plasma Expander Engineered for Optimal Hemodynamic Performance
Dr. James W. Polarek, Vice President, Collagen and Gelatin Development, FibroGen Inc.
FibroGen, Inc. is developing novel gelatins, using a recombinant expression system, for use as a plasma expander to treat severe hypovolemia. We have engineered and expressed fragments of the human alpha 1 (I) collagen gene resulting in well-defined, fully-characterized products designed to attain the plasma persistence of human serum albumin, while maintaining beneficial diuretic effects observed with gelatin-based plasma expanders currently in use. Our recombinant plasma expanders have a superior safety profile due to their recombinant nature and lack of animal-derived and human plasma derived components. The economics of production of a recombinant plasma expander are estimated to be competitive with currently used albumin products.

11:40 Oral Gammaglobulin Treatment of Gastrointestinal Symptoms in Autistic Children
Dr. Leon E. Barstow, President and CEO, Protein Therapeutics, Inc.
Results from an open label pilot trial conducted with an oral formulation of human gammaglobulin (Oralgam™) in twelve children with chronic gastrointestinal (GI) disturbances and a diagnosis of Autistic Disorder will be presented. A Gastrointestinal Severity Index (GSI) was used to score symptoms. All children received a single daily dose of Oralgam™ before bedtime for eight weeks. Nine subjects completed eight weeks of treatment. Six of nine subjects (67%) met the definition of clinical response and five of nine (55%) met the definition of clinical remission in GI symptoms. There were modest improvements in behavioral scores. A larger multicenter dose-ranging placebo-controlled study is planned for 2003.

12:10 Leukocyte Derived Cytokines (IRX-2) for Cancer Immunotherapy
Dr. Harvey J. Brandwein, President, Immuno-Rx, Inc.
IRX-2 is a uniform, well-defined set of natural cytokines produced by human mononuclear cells in culture. The product is a potent stimulant for T cells and dendritic cells, and is being developed as an immunotherapy treatment for head and neck cancer. Various methods of viral removal or inactivation have been tested for inclusion in the IRX-2 manufacturing process, and these results will be presented.

12:40 Luncheon

 

EMERGING ISSUES

1:50 Comments by Session Chairperson
Dr. Bernard Horowitz

2:00 West Nile Virus: how to address the virus d’jour
Dr. Thomas Kreil, Director, Viral Safety, Baxter
West Nile Virus (WNV), initially identified in 1937, attracted increased publicity after its first appearance on the East Coast of the USA in 1999, which was further elevated by the magnitude of the 2002 epidemic in the USA which resulted in more than 200 fatalities. With the reported transmission of WNV through solid organ transplants and blood donations the virus then challenged the established structures which ensure the safety of blood components and plasma-derivatives.

After consultations between primarily the CDC and the FDA, the competent authority issued a Guidance for Industry, to assess donor suitability and the safety of blood and blood derivatives in cases of known or suspected cases of WNV infection. In addition, the authority invited all the involved stake-holders, i.e. scientific institutions, patient organizations and the sourcing as well as the fractionating industry, to discuss any potential implications during a two day workshop hosted by the agency.

At this meeting, the agencies supposition of uncompromised safety margins for plasma derivatives, which had been based on extrapolations from “model” virus data, was verified by Baxters investigations using a 1999 New York WNV isolate, testing key virus inactivation processes used during the manufacture of their products. These “verification studies” confirmed that WNV, like other flaviviruses, was readily inactivated by these processes, and also supported the validity of the model virus concept. 

In addition, several diagnostics manufacturers had undertaken initial steps toward developing either serological or PCR-based WNV tests, and other presentations indicated that dedicated virus inactivation technologies which could be used during the preparation of blood components for transfusion are effective against WNV.

Altogether, the US outbreak of WNV has thus established a successful precedent for how the parties concerned with the safety of the blood supply, i.e. authorities, scientific institutions, patient organizations and industry, can collaborate to make productive use of available resources, while avoiding unnecessary constraints, both to the ultimate benefit of the patient.

2:30 TT Virus (TTV) and TTV-like Viruses (TTLVs) in Different Population and Blood Transfusion Dependent Patients
Dr. Yu-Wen Hu, Adjunct Professor, Faculty of Medicine, University of Ottawa, Scientist, R&D, Canadian Blood Services
The prevalence of TTV and TTV-like viruses in different populations is varied, depending on style of living and health care. One hundred percent of the blood transfusion dependent patients carry the viruses and more than 80% of them are infected with more than one genotype of the viruses. The clinical consequence of mixed genotype infections will be discussed.

3:00 Poster and Exhibit Viewing, Refreshment Break

3:30 HBsAg Mutants: A Strategy to Evade and Conquer
Dr. Paul Coleman, Abbott Laboratories
Mutations in the antigenic domain of HBsAg can be shown to alter or eliminate antibody binding sites. This capacity for immunoevasion affects the host's ability to neutralize viral mutant infection, and also affects the detection of these mutants by HBsAg immunoscreening assays. The potential impact on blood safety will be discussed.

4:00 Transmission of Viral Infection in IVIG
Dr. Jonathan C. Goldsmith, Vice President, Medical Affairs, Immune Deficiency Foundation
Data will be presented relating to the transmission of viral infection via IVIG.

4:30 Panel Discussion with All Afternoon Speakers

4:45 Close of Conference

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Hotel Information
Washington Marriott Hotel
1221 22nd Street, N.W.
Washington, DC 20037
T: 202-872-1500
F: 202-872-1424
Room Rate: $175 S/D
Cut-off Date: January 16, 2003
Please call the hotel directly to make your room reservation. Identify yourself as a Cambridge Healthtech Institute conference attendee to receive the reduced room rate. Reservations made after the cut-off date or after the group room block has been filled (whichever comes first) will be accepted on a space-and-rate-availability basis. Rooms are limited, so please book early.

Travel Information
Special Zone and Discount Fares have been established for this conference with United Airlines. Please call United Airlines Meeting Reservation Desk at 800-521-4041 and reference ID #579YS.

Call for Posters
Cambridge Healthtech Institute encourages attendees to gain further exposure by presenting their work in the poster sessions. Please fill out the registration form, with the poster title and primary author. To ensure inclusion in the conference CD, a one-page summary must be submitted and registration must be paid in full by January 10, 2002.   Click here for poster instructions

Call for Sponsors and Exhibitors
This multi-conference meeting provides excellent venues for companies wishing to target the leading researchers active in developing and implementing the latest advances and new strategies for the inactivation and removal of infectious agents in whole blood, cord blood, component concentrates, and plasma. CHI strongly encourages any company with new techniques, services, or products related to blood product safety and screening to consider sponsoring and/or exhibiting at this event. For additional information please contact Deborah Brooks (617) 630-1312, via email at dbrooks@healthtech.com or Angela Parsons (617) 630-1367, via email at aparsons@healthtech.com.