Barrett P.N.,Biomedical Research Center |
Portsmouth D.,Biomedical Research Center |
Ehrlich H.J.,Baxter BioScience
Current Opinion in Molecular Therapeutics | Year: 2010
The growing prospect of avian influenza viruses achieving sustained interhuman transmission, combined with the recent emergence of a novel swine-origin A/H1N1 influenza strain, has brought the issue of influenza vaccine production capacity into sharp focus. It is becoming increasingly clear that traditional egg-based manufacturing processes may be insufficient to meet global vaccine demands in a pandemic situation that is caused by a highly pathogenic influenza virus. This review introduces the concepts of modern, cell culture-derived influenza vaccines and their manufacture, and explains the advantages of these vaccines in terms of both speed and efficiency of production as well as immunogenic efficacy. Vaccine production technologies using the mammalian cell lines Vero, MDCK and PER.C6, as well as the baculovirus/insect cell platform, are described in detail. Clinical data are provided from cell culture-derived vaccines that are at an advanced stage of development, and insights are provided into recent developments in the preclinical evaluation of more experimental technologies. © Thomson Reuters (Scientific) Ltd.
Windyga J.,Institute of Haematology and Transfusion Medicine |
Abbuehl B.E.,Baxter BioScience |
Hafeman A.E.,Baxter BioScience
Expert Review of Hematology | Year: 2014
Individuals with hemophilia B experience frequent and spontaneous bleeding episodes into joints and muscles that can lead to severe arthropathy, chronic pain, disability, and diminished quality of life (QoL). Prophylaxis with factor nine (FIX) concentrates may reduce the frequency of bleeding events and improve QoL. Recombinant FIX (rFIX) concentrates are a potentially safer treatment option than plasma-derived FIX products with respect to pathogen transmission risk, but until recently, only one licensed rFIX product was available. We describe a newly approved rFIX concentrate, BAX326 (RIXUBIS; Baxter Healthcare Corporation). Phase III studies of BAX326 demonstrated its efficacy and safety in prophylactic, on-demand, and surgical settings and showed that its pharmacokinetic properties were comparable to those of the licensed comparator. Importantly, prophylaxis with BAX326 significantly improved physical health-related QoL, demonstrating that this new rFIX treatment that has the potential to improve outcomes in hemophilia B patients. © 2014 Informa UK, Ltd.
Duncan N.,Indiana Hemophilia and Thrombosis Center |
Shapiro A.,Indiana Hemophilia and Thrombosis Center |
Ye X.,Baxter Bioscience |
Epstein J.,Baxter Bioscience |
Luo M.P.,Baxter Bioscience
Haemophilia | Year: 2012
Prophylaxis and adherence to prophylaxis are increasingly recognized as important factors for the health-related quality of life (HRQOL) of haemophilia patients. This study aims to assess treatment practices over time, HRQOL and adherence among severe haemophilia A patients in the US. Severe haemophilia A patients or their caregivers participated in a 2009 cross-sectional survey. HRQOL was measured using either PEDS-QL or SF-12; adherence was measured using the VERITAS-Pro. Student t-tests evaluated differences between children vs. adults and self-infusion status. A total of 117 respondents participated in the survey, capturing data for 64 adults (mean age=37.9years) and 53 children (mean age=10.5years). Although 96% of paediatric patients were currently receiving prophylaxis, only 32 (50%) adults reported receiving prophylaxis at some point in their life. Adults who have always been on prophylaxis reported better physical functioning and physical HRQOL (both P<0.05) than adults who had not. The paediatric group reported better adherence compared to the adult group on the total scale (38 vs. 45.8, P<0.05). Children <12years had higher adherence than adolescents 12-18years old (35.5 vs. 40.8; P<0.05). Paediatric patients infused by family members showed better adherence than paediatric self-infusers (P<0.05). This study showed different treatment patterns between paediatric and adult patients and how the patterns impacted HRQOL. It also provided the first standardized evaluation of adherence using the VERITAS-Pro in a US national sample. This study enhances understanding of treatment practices and adherence for the US haemophilia population and may offer insight into where adherence can be improved. © 2012 Blackwell Publishing Ltd.
Bowers D.,PPD Inc |
Fish T.,Baxter Bioscience
Drug Information Journal | Year: 2013
Today's medical information contact centers face a number of complex challenges. A recent survey of the DIA Medical Communications Special Interest Area Community (SIAC) members indicated that budgetary pressures, employee training, preparing for product launches, and ensuring business continuity are all concerns for the majority of contact centers. Additionally, more than one third of contact centers mentioned mergers and acquisitions. This article will review the results of the survey and discuss best practices for addressing the 3 most common topics noted in the survey: budget, training, and supporting product launches. The article is intended as a resource for contact center managers and to help encourage the sharing of best practices within the industry. © The Author(s) 2013.
Rabel P.O.,Baxter BioScience
Euro surveillance : bulletin européen sur les maladies transmissibles = European communicable disease bulletin | Year: 2011
We analysed by neutralisation assay 55 intravenous immunoglobulin preparations produced from human plasma collected in three central European countries, specifically Austria, Germany and the Czech Republic, from 2006 to 2010. The preparations from 2009 and 2010 contained increasing titres of neutralising antibodies against West Nile virus (WNV) in the absence of reported human WNV cases in these countries.
Wroblewska A.,Sanquin AMC Landsteiner Laboratory and van Creveld Laboratory |
Reipert B.M.,Baxter BioScience |
Pratt K.P.,University of Washington |
Voorberg J.,Sanquin AMC Landsteiner Laboratory and van Creveld Laboratory
Journal of Thrombosis and Haemostasis | Year: 2013
Only a fraction of patients with hemophilia A develop a neutralizing antibody (inhibitor) response to therapeutic infusions of factor VIII. Our present understanding of the underlying causes of the immunogenicity of this protein is limited. In the past few years, insights into the uptake and processing of FVIII by antigen-presenting cells (APCs) have expanded significantly. Although the mechanism of endocytosis remains unclear, current data indicate that FVIII enters APCs via its C1 domain. Its subsequent processing within endolysosomes allows for presentation of a heterogeneous collection of FVIII-derived peptides on major histocompatibility complex (MHC) class II, and this peptide-MHC class II complex may then be recognized by cognate effector CD4+ T cells, leading to anti-FVIII antibody production. Here we aim to summarize recent knowledge gained about FVIII processing and presentation by APCs, as well as the diversity of the FVIII-specific T-cell repertoire in mice and humans. Moreover, we discuss possible factors that can drive FVIII immunogenicity. We believe that increasing understanding of the immune recognition of FVIII and the cellular mechanisms of anti-FVIII antibody production will lead to novel therapeutic approaches to prevent inhibitor formation in patients with hemophilia A. © 2012 International Society on Thrombosis and Haemostasis.
Saint-Remy J.-M.,Catholic University of Leuven |
Reipert B.M.,Baxter BioScience |
Monroe D.M.,University of North Carolina at Chapel Hill
Haemophilia | Year: 2012
Inhibitor development remains a challenge to appropriate haemophilia treatment. This challenge is being addressed, in part, by an expanding knowledge of the mechanisms that drive inhibitor development including how elements of the innate immune response play a role in inhibitor development. There are promising therapies that may suppress an active immune response. Models to assess the immune responses are becoming ever more sophisticated. Newer models can be used at the preclinical level to evaluate the role of MHC-class II presentation of antigens in both in vitro cell culture studies and in vivo in transgenic mice that express either the protein to be studied or that express human MHC-class II proteins. Parallel to work designed to reduce or reverse inhibitors is development of improved therapies including bypassing agents to treat patients with inhibitors. With these new treatment modalities comes the problem of assessing efficacy at the preclinical level. Models to evaluate bleeding are being developed that may give a more subtle assessment of bypassing agents. These models represent in part an attempt to incorporate the role of ongoing bleeding into the evaluation. Overall, these newer models have great potential in preclinical studies to evaluate the risk of inhibitor development of new therapeutics and to assess the functionality of these new therapeutics. © 2012 Blackwell Publishing Ltd.
Mohamed A.F.,Rti International |
Epstein J.D.,Baxter BioScience |
Li-Mcleod J.M.,Baxter BioScience
Haemophilia | Year: 2011
Little is known about the relative importance of factor VIII (FVIII) treatment attributes to haemophilia A patients and their willingness to accept trade-offs among these attributes. To quantify patient and parent preferences for FVIII treatments and compare the relative importance of treatment attributes. Adult patients and parents of children with severe haemophilia A in the US completed a web-enabled, choice-format conjoint survey that presented a series of 12 trade-off questions, each including a pair of hypothetical treatment profiles. Each profile was defined by percent of bleeds stopped with one or two infusions, chance of developing an inhibitor, risk of viral infection, preparation volume, dosage strengths available, and history of supply shortage. Trade-off questions were based on a D-optimal experimental design. Preference weights for attribute levels were estimated using random-parameters logit. One hundred and forty seven subjects completed the survey. Over the ranges of attribute levels included in the study, risk of viral infection was the most important attribute. Remaining attributes were ranked in decreasing order of importance as follows: chance of developing an inhibitor, dosage strengths available, percent of bleeds stopped with one or two infusions, history of supply shortage, and preparation volume. Risk of viral infection was 6.0 times as important as percent of bleeds stopped with one or two infusions and 2.7 times as important as the chance of developing an inhibitor. While risk of viral infection was the most important attribute, this research demonstrates that many FVIII treatment attributes are important in the decision-making process. © 2010 Blackwell Publishing Ltd.
Reipert B.M.,Baxter Bioscience
Hematology | Year: 2014
The development of neutralizing antibodies against factor VIII (FVIII inhibitors) and factor IX (FIX inhibitors) is the major complication in hemophilia care today. The antibodies neutralize the biological activity of FVIII and FIX and render replacement therapies ineffective. Antibodies are generated as a result of a cascade of tightly regulated interactions between different cells of the innate and the adaptive immune system located in distinct compartments. Any event that modulates the repertoire of specific B or T cells, the activation state of the innate and adaptive immune system, or the migration pattern of immune cells will therefore potentially influence the risk for patients to develop inhibitors. This chapter reviews our current understanding of different pathways of antibody development that result in different qualities of antibodies. Potential differences in differentiation pathways leading to high-affinity neutralizing or low-affinity non-neutralizing antibodies and the potential influence of gene polymorphisms such as HLA haplotype, FVIII haplotype, and polymorphisms of immunoregulatory genes are discussed.
Reipert B.,Baxter Bioscience |
Arruda V.,Children's Hospital of Philadelphia |
Lillicrap D.,Queen's University
Haemophilia | Year: 2010
Antibody responses to clotting factor concentrates remain a major treatment limitation. In conjucation with ongoing clinical studies, the pathogenesis and potential treatment of clotting factor immune responses is being evaluated in a variety of animal models. © 2010 The Authors. Journal compilation © 2010 Blackwell Publishing Ltd.