DOCSLIB.ORG

Recombinant Factor VIII: Past, Present and Future of Treatment of Hemophilia A

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Recombinant Factor VIII: Past, Present and Future of Treatment of Hemophilia A Drugs of Today 2018, 54(4): 269-281 Copyright © 2018 Clarivate Analytics CCC: 1699-3993/2018 DOI: 10�1358/dot�2018�54�4� 2800622 Review Article Recombinant factor VIII: past, present and future of treatment of hemophilia A S. Raso1, 2 and C. Hermans2 1Azienda Ospedaliera Universitaria Policlinico, Division of Haematology, Department of Surgical, Oncological and Stomatological Disciplines, Palermo, Sicilia, Italy; 2Division of Adult Haematology, St-Luc University Hospital, Brussels, Belgium Contents Summary � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � 269 Introduction � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � 270 History of rFVIII products � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � 270 Main features of rFVIII � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � 270 Generations of rFVIII � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � 271 Standard half-life rFVIII products � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � 272 Extended half-life rFVIII products � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � 274 Current challenges and perspectives � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � 276 Conclusions � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � 278 References � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � 278 Summary the manufacturing process, so that patients would not be exposed to known or emerging pathogens. The development of recombinant factor VIII (rFVIII) was Recent efforts have concentrated on improving the initially driven by the necessity to treat hemophilia A expression of rFVIII, reducing its immunogenicity and (HA) patients with FVIII concentrates without the risk enhancing its pharmacokinetic (PK) behavior. These of transmitting infectious agents. Over the last three new goals have been possible thanks to the develop- decades the safety of rFVIII has been further improved by ment of biotechnology and a better knowledge of the completely removing animal or human proteins from function and structure of FVIII. Several approaches such as deletion of the B-domain, expression of FVIII by human cell lines, sequence modification, struc- Correspondence: Cedric Hermans, MD, PhD, FRCP, Division of Adult Haematology, St-Luc University Hospital, Avenue Hippocrate tural modification, coexpression with other proteins, 10, 1200 Brussels, Belgium� E-mail: cedric�hermans@uclouvain�be� fusion with the Fc fragment of immunoglobulins 269 Recombinant factor VIII for hemophilia A S. Raso and C. Hermans and PEGylation have been utilized. As a result of these a fraction cryoprecipitated from plasma contained efforts, different rFVIII products have been validated large amounts of FVIII (6)� Purified plasma-derived in terms of efficacy, immunogenicity and PK profile. (pd)FVIII concentrates have been available since the Other technologies are currently being explored to 1970s, and in the following 10 years fractionation improve the PK of FVIII and allow its subcutaneous and purification processes evolved making plasma- administration. Although nonreplacement therapies derived concentrates available and allowing home and HA gene therapy appear to be promising alter- replacement therapy (5)� natives for HA, rFVIII will very likely remain as a crit- ical component for the treatment of HA because of During the first part of the 1980s, the HIV epidemic its physiological activity and mode of action, as well devastated the hemophilia community, and in the as its unique ability to induce or restore tolerance to late 1990s over 95% of severe HA patients had been exogenous FVIII. This review summarizes the principal infected by hepatitis C virus through pdFVIII (5)� As a features of past, current and emerging rFVIII products consequence, many measures including enhanced for HA. donor screening tests and the introduction of viral inactivation have been implemented to improve the Key words: Hemophilia A – Coagulation factor disorders – infectious safety of plasma-derived concentrates� Recombinant FVIII – Standard half-life FVIII – Extended Nevertheless, the fear of transmitting other unknown, half-life FVIII not yet identified and emerging infectious diseases and the desire for safer and more convenient thera- Introduction pies have led to an increasing interest in recombinant DNA technology (7, 8)� Hemophilia A (HA) and B are congenital X-linked bleeding disorders resulting from a deficiency of In 1984 the FVIII gene was cloned and led to the clotting factor VIII (FVIII) and IX (FIX), respectively (1)� licensure of rFVIII in 1992 (5)� rFVIII products, which HA affects 1 in 5,000 male births and it is charac- are derived through heterologous transfection of terized, according to the basal FVIII level, by spon- rFVIII DNA plasmids into a nonhuman mammalian taneous or traumatic bleeding episodes, which can cell line, virtually eliminated blood-borne pathogen progress to debilitating arthropathy and signifi- transmission (9)� The introduction of rFVIII concen- cantly impact patients’ quality of life (1)� trates nearly 20 years ago represented a significant The primary aim of care is to prevent and treat hem- advance in the treatment of HA� The most challeng- orrhagic episodes using replacement therapy with ing aspects of HA management today are the occur- FVIII concentrates, given on demand or prophylac- rence of FVIII inhibitors and the burden of frequent tically (2)� Recombinant FVIII (rFVIII) products repre- intravenous infusions required for prophylactic sent a major advance over the past century for the replacement therapy (5)� treatment of HA in terms of safety, hemostatic effi- cacy and manufacturing� The development of neu- Main Features of rFVIII tralizing antibodies, or inhibitors, against exogenous FVIII and the limited half-life (~12 hours) of many The human FVIII (hFVIII) gene is localized on the long available products remain major challenges (3, 4)� arm of the X chromosome and its expression is pre- dominantly in sinusoidal and vascular endothelial cells in the liver and the lungs (10, 11)� After trans- History of rFVIII Products lation, the protein undergoes further processing FVIII replacement therapy has been the cornerstone of N-linked glycans, sulfation of specific tyrosine in the treatment of hemophilia and has made major residues, copper binding, O-linked glycosylation advances over the past century from the adminis- and intracellular proteolysis within the Golgi appa- tration of blood transfusions to the use of recombi- ratus and endoplasmic reticulum prior to secretion nant products in 1992 (5)� Prior to the 1950s, whole into plasma (12, 13)� The mature FVIII is a complex blood transfusion was the only possible therapy� 300-kD heterodimeric glycoprotein consisting of six Subsequently, in the 1960s it was discovered that structural domains and three acidic subdomains, 270 Drugs of Today 2018, 54(4) S. Raso and C. Hermans Recombinant factor VIII for hemophilia A organized in a heavy chain [A1(a1)A2(a2)B] and a embryonic kidney (HEK) cells (13)� This HEK-derived light chain [(a3)A3C1C2] (12)� rFVIII product (human-cl rhFVIII) does not contain Gal 1 3Gal and Neu5Gc epitope (19)� rFVIII is one of the largest and most complex proteins manufactured commercially to date (14)� Because Sulfationα → is another post-translational modification of its structure and post-translational modification important for the function of FVIII (20)� Six active sul- requirements, production of rFVIII depends on the fation sites of tyrosine residues have been identified use of mammalian cell lines, and either Chinese in hFVIII and all six sulfation sites are necessary for hamster ovary (CHO) or baby hamster kidney (BHK) the full procoagulant activity of FVIII� Sulfation of the cells were initially used� In fact, both the CHO and residue Y1680 (Tyr 1680) is considered crucial for the BHK cell lines have demonstrated their capacity to stability of FVIII and its binding to von Willebrand synthesize rFVIII that includes all of the post- factor (VWF) (13)� The proportion of Tyr 1680 is high translational modifications necessary for its hemo- in BHK-derived rFVIII products as well as in other static activity (9, 14)� rFVIII products made from different cell lines, rang- ing from 1% to 6�5% for second-generation rFVIII to The expressed proteins are secreted into a culture up to 15% for third-generation rFVIII (21)� medium, resulting in a large-scale production of rFVIII products, which in some cases contain human and animal proteins for stabilization (15, 16)� The Generations of rFVIII purification process of rFVIII involves many steps, Several preparations of rFVIII are currently avail- such as multiple chromatography columns, includ- able for patients
Load more

Recommended publications
  • Clinical Commissioning Policy: Susoctocog Alfa for Treating Bleeding Episodes in People with Acquired Haemophilia a (All Ages)
    Clinical Commissioning Policy: Susoctocog alfa for treating bleeding episodes in people with acquired haemophilia A (all ages) NHS England Reference: 170061P 1 NHS England INFORMATION READER BOX Directorate Medical Operations and Information Specialised Commissioning Nursing Trans. & Corp. Ops. Commissioning Strategy Finance Publications Gateway Reference: 07603 Document Purpose Policy Clinical commissioning policy: Susoctocog alfa for treating bleeding Document Name episodes in people with acquired haemophilia A (all ages) Author Specialised Commissioning Team Publication Date 29 June 2018 Target Audience CCG Clinical Leaders, Care Trust CEs, Foundation Trust CEs , Medical Directors, Directors of PH, Directors of Nursing, NHS England Regional Directors, NHS England Directors of Commissioning Operations, Directors of Finance, NHS Trust CEs Additional Circulation #VALUE! List Description Routinely Commissioned - NHS England will routinely commission this specialised treatment in accordance with the criteria described in this policy. Cross Reference 0 Superseded Docs 0 (if applicable) Action Required 0 Timing / Deadlines By 00 January 1900 (if applicable) Contact Details for [email protected] further information 0 0 0 0 0 0 Document Status This is a controlled document. Whilst this document may be printed, the electronic version posted on the intranet is the controlled copy. Any printed copies of this document are not controlled. As a controlled document, this document should not be saved onto local or network drives but should always be accessed from the intranet. 2 Standard Operating Procedure: Clinical Commissioning Policy: Susoctocog alfa for treating bleeding episodes in people with acquired haemophilia A (all ages) First published: June 2018 Prepared by the National Institute for Health and Care Excellence (NICE) Commissioning Support Programme Published by NHS England, in electronic format only.
    [Show full text]
  • Australian Public Assessment for Efmoroctocog Alfa (Rhu)
    Australian Public Assessment Report 1 for efmoroctocog alfa (rhu) Proprietary Product Name: Eloctate Sponsor: Biogen Idec Australia Pty Ltd January 2015 1 The non-proprietary name has changed post registration from efraloctocog alfa to efmoroctocog afla to harmonise with the International Non-proprietary Name. Therapeutic Goods Administration About the Therapeutic Goods Administration (TGA) · The Therapeutic Goods Administration (TGA) is part of the Australian Government Department of Health and is responsible for regulating medicines and medical devices. · The TGA administers the Therapeutic Goods Act 1989 (the Act), applying a risk management approach designed to ensure therapeutic goods supplied in Australia meet acceptable standards of quality, safety and efficacy (performance), when necessary. · The work of the TGA is based on applying scientific and clinical expertise to decision- making, to ensure that the benefits to consumers outweigh any risks associated with the use of medicines and medical devices. · The TGA relies on the public, healthcare professionals and industry to report problems with medicines or medical devices. TGA investigates reports received by it to determine any necessary regulatory action. · To report a problem with a medicine or medical device, please see the information on the TGA website <http://www.tga.gov.au>. About AusPARs · An Australian Public Assessment Record (AusPAR) provides information about the evaluation of a prescription medicine and the considerations that led the TGA to approve or not approve a prescription medicine submission. · AusPARs are prepared and published by the TGA. · An AusPAR is prepared for submissions that relate to new chemical entities, generic medicines, major variations, and extensions of indications. · An AusPAR is a static document, in that it will provide information that relates to a submission at a particular point in time.
    [Show full text]
  • Human and Recombinat Coagulation Factor VIII
    08 July 2016 EMA/PRAC/471535/2016 PRAC List of questions To be addressed by the marketing authorisation holder(s) for human and recombinant coagulation factor VIII containing medicinal products Referral under Article 31 of Directive 2001/83/EC resulting from pharmacovigilance data Procedure number: EMEA/H/A-31/1448 Advate EMEA/H/C/0520/A31/0078 Elocta EMEA/H/C/3964/A31/0006 Helixate Nexgen EMEA/H/C/0276/A31/0178 Iblias EMEA/H/C/4147/A31/0002 Kogenate EMEA/H/C/0275/A31/0185 Kovaltry EMEA/H/C/3825/A31/0004 Novoeight EMEA/H/C/2719/A31/0014 Nuwiq EMEA/H/C/2813/A31/0015 Obizur EMEA/H/C/2792/A31/0003 Refacto AF EMEA/H/C/0232/A31/0134 Voncento EMEA/H/C/2493/A31/0022 Active substances: human coagulation factor VIII; efmoroctocog alfa; moroctocog alfa; octocog alfa; simoctocog alfa; susoctocog alfa; turoctocog alfa 30 Churchill Place ● Canary Wharf ● London E14 5EU ● United Kingdom Telephone +44 (0)20 3660 6000 Facsimile +44 (0)20 3660 5555 Send a question via our website www.ema.europa.eu/contact An agency of the European Union © European Medicines Agency, 2016. Reproduction is authorised provided the source is acknowledged. 1. Background Today’s standard treatment of congenital haemophilia (and acquired haemophilia A) is based on prophylactic or on-demand replacement therapy with coagulation factor VIII (FVIII), either with plasma derived or with recombinant FVIII products. Principally both substance classes may be used for prophylactic treatment as well as for therapeutic treatment in case of spontaneous bleedings. Inhibitor development in haemophilia A patients receiving FVIII products mostly occurs in previously untreated or minimally treated patients (PUPs), who are still within the first 50 days of exposure to the treatment.
    [Show full text]
  • PRESS RELEASE Stockholm, Sweden, 8 July 2020
    PRESS RELEASE Stockholm, Sweden, 8 July 2020 Data to be presented at ISTH Virtual Congress highlights Sobi´s commitment to advancing rare haematology treatments Sobi™ will present data at the ISTH Virtual Congress (International Society on Thrombosis and Haemostasis), 12 – 14 July 2020, strengthening evidence for the efficacy and safety of Elocta® (efmoroctocog alfa) and Alprolix® (eftrenonacog alfa), for haemophilia A and B respectively, as well as pharmacokinetic data on BIVV001 (rFVIIIFc-VWF-XTEN). Data for Doptelet® (avatrombopag) in treatment for thrombocytopenia within Chronic Liver Disease (CLD) and Chronic Immune Thrombocytopenia (ITP) will be presented. Final data in previously untreated patients with haemophilia Final data from the long-term studies: PUPs A-LONG and PUPs B-LONG in previously untreated patients (PUP) with haemophilia A and B, treated with Elocta and Alprolix will be presented in collaboration with Sanofi. Factor replacement therapy remains a cornerstone of haemophilia management and data shared in presentations will add to a growing body of clinical evidence for rFVIIIFc and rFIXFc, extended half-life factor therapies for haemophilia A and B, respectively. Oral Communication • Final results of the PUPs A-LONG Study: Evaluating Safety and Efficacy of rFVIIIFc in Previously Untreated Patients with Haemophilia A. Oral communication #OC 03.2. Sunday, July 12, 2020 from 10:15 – 11:30 EDT (16.15-17.30 CET) (Joint with Sanofi) Abstracts • Final Results of PUPs B-LONG Study: Evaluating Safety and Efficacy of rFIXFc in Previously Untreated Patients with Haemophilia B. Poster presentation # PB0956. (Joint with Sanofi) • A French Multicentre Prospective, Non-Interventional Study (B-SURE) Evaluating Real-World Usage and Effectiveness of Recombinant Factor IX Fc Fusion Protein (rFIXFc) in People with Haemophilia B: Baseline Data.
    [Show full text]
  • Annual Report 2016
    Annexes to the annual report of the European Medicines Agency 2016 Annex 1 – Members of the Management Board ............................................................... 2 Annex 2 - Members of the Committee for Medicinal Products for Human Use ...................... 4 Annex 3 – Members of the Pharmacovigilance Risk Assessment Committee ........................ 6 Annex 4 – Members of the Committee for Medicinal Products for Veterinary Use ................. 8 Annex 5 – Members of the Committee on Orphan Medicinal Products .............................. 10 Annex 6 – Members of the Committee on Herbal Medicinal Products ................................ 12 Annex 7 – Committee for Advanced Therapies .............................................................. 14 Annex 8 – Members of the Paediatric Committee .......................................................... 16 Annex 9 – Working parties and working groups ............................................................ 18 Annex 10 – CHMP opinions: initial evaluations and extensions of therapeutic indication ..... 24 Annex 10a – Guidelines and concept papers adopted by CHMP in 2016 ............................ 25 Annex 11 – CVMP opinions in 2016 on medicinal products for veterinary use .................... 33 Annex 11a – 2016 CVMP opinions on extensions of indication for medicinal products for veterinary use .......................................................................................................... 39 Annex 11b – Guidelines and concept papers adopted by CVMP in 2016 ...........................
    [Show full text]
  • Therapeutics Advisory Group
    Therapeutics Advisory Group CCG and NHS Trusts in Norfolk and Waveney Index of TAG recommendations Generic name Indication BNFclass Trafficlight IQoro euromuscular training Hiatus hernia - improving symptoms No BNF entry - device Double Red Not recommended for device routine use / Not commissioned (L-) Carnitine Carnitine Deficiency 9.8.1 Drugs used in Red Hospital / Specialist metabolic disorders only (Para-)aminosalicylic acid Tuberculosis 5.1.9 Antituberculosis Double Red Not recommended for drugs - routine use / Not Antimycobacterials commissioned 5-fluorouracil + salicyclic acid Hyperkeratotic actinic keratosis 13.8.1 Photodamage Double-GreenSuitable for GPs to topical solution initiate and prescribe 5-fluorouracil 5% w/w cream Non-hypertrophic actinic keratosis 13.8.1 Photodamage Double-GreenSuitable for GPs to initiate and prescribe Abacavir HIV infection in combination with other 5.3.1 HIV Infection Red Hospital / Specialist antiretroviral drugs only Abacavir + dolutegravir + HIV infection in combination with other 5.3.1 HIV Infection Red Hospital / Specialist lamivudine antiretroviral drugs only Abacavir and lamivudine HIV infection in combination with other 5.3.1 HIV Infection Red Hospital / Specialist antiretroviral drugs only Abaloparatide Male and juvenile osteoporosis 6.6.1 Calcitonin and Double Red Not recommended for Calcitonin and routine use / Not parathyroid hormone commissioned Abatacept Rheumatoid arthritis - 1st line biologic 10.1.3 Drugs that suppress Red Hospital / Specialist after failure of non-biologic DMARDs
    [Show full text]
  • Australian Public Assessment Report for Lonoctocog Alfa (Rch)
    Australian Public Assessment Report for lonoctocog alfa (rch) Proprietary Product Name: Afstyla Sponsor: CSL Behring Australia Pty Ltd January 2018 Therapeutic Goods Administration About the Therapeutic Goods Administration (TGA) · The Therapeutic Goods Administration (TGA) is part of the Australian Government Department of Health and is responsible for regulating medicines and medical devices. · The TGA administers the Therapeutic Goods Act 1989 (the Act), applying a risk management approach designed to ensure therapeutic goods supplied in Australia meet acceptable standards of quality, safety and efficacy (performance) when necessary. · The work of the TGA is based on applying scientific and clinical expertise to decision- making, to ensure that the benefits to consumers outweigh any risks associated with the use of medicines and medical devices. · The TGA relies on the public, healthcare professionals and industry to report problems with medicines or medical devices. TGA investigates reports received by it to determine any necessary regulatory action. · To report a problem with a medicine or medical device, please see the information on the TGA website <https://www.tga.gov.au>. About AusPARs · An Australian Public Assessment Report (AusPAR) provides information about the evaluation of a prescription medicine and the considerations that led the TGA to approve or not approve a prescription medicine submission. · AusPARs are prepared and published by the TGA. · An AusPAR is prepared for submissions that relate to new chemical entities, generic medicines, major variations and extensions of indications. · An AusPAR is a static document; it provides information that relates to a submission at a particular point in time. · A new AusPAR will be developed to reflect changes to indications and/or major variations to a prescription medicine subject to evaluation by the TGA.
    [Show full text]
  • Justification
    Justification to the Resolution of the Federal Joint Committee (G-BA) on an Amendment of the Pharmaceuticals Directive (AM ‑ RL): Annex XII – Resolutions on the Benefit Assessment of Medicinal Products with New Active Ingredients in Accordance with Section 35a SGB V Damoctocog alfa pegol From 20 June 2019 Contents 1. Legal basis ................................................................................................................ 2 2. Key points of the resolution ..................................................................................... 2 2.1 Additional benefit of the medicinal product in relation to the appropriate comparator therapy ..................................................................................................... 3 2.1.1 Approved therapeutic indication of damoctocog alfa pegol (Jivi®) in accordance with the summary of product characteristics ............................................ 3 2.1.2 Appropriate comparator therapy ................................................................... 3 2.1.3 Extent and probability of the additional benefit .............................................. 5 2.1.4 Summary of the assessment ........................................................................ 6 2.2 Number of patients or demarcation of patient groups eligible for treatment ...... 6 2.3 Requirements for a quality-assured application ................................................ 7 2.4 Treatment costs ..............................................................................................
    [Show full text]
  • Dossier Zur Nutzenbewertung Gemäß § 35A SGB V
    Dokumentvorlage, Version vom 16.08.2018 Dossier zur Nutzenbewertung gemäß § 35a SGB V Turoctocog alfa pegol (Esperoct®) Novo Nordisk Pharma GmbH Modul 3 A Behandlung und Prophylaxe von Blutungen bei Patienten im Alter von 12 Jahren und älter mit Hämophilie A (angeborener Faktor VIII-Mangel). Zweckmäßige Vergleichstherapie, Anzahl der Patienten mit therapeutisch bedeutsamem Zusatznutzen, Kosten der Therapie für die GKV, Anforderungen an eine qualitätsgesicherte Anwendung Stand: 30.07.2019 Dossier zur Nutzenbewertung – Modul 3 A Stand: 30.07.2019 Vergleichstherapie, Patienten mit therap. bedeutsamem Zusatznutzen, Kosten, qualitätsgesicherte Anwendung Inhaltsverzeichnis Seite Tabellenverzeichnis .................................................................................................................. 2 Abbildungsverzeichnis ............................................................................................................. 4 Abkürzungsverzeichnis ............................................................................................................ 5 3 Modul 3 – allgemeine Informationen ............................................................................ 7 3.1 Bestimmung der zweckmäßigen Vergleichstherapie .................................................... 8 3.1.1 Benennung der zweckmäßigen Vergleichstherapie ................................................ 9 3.1.2 Begründung für die Wahl der zweckmäßigen Vergleichstherapie .......................... 9 3.1.3 Beschreibung der Informationsbeschaffung für Abschnitt
    [Show full text]
  • Australian PI
    AUSTRALIAN PRODUCT INFORMATION OBIZUR® (susoctocog alfa) 1 NAME OF THE MEDICINE Susoctocog alfa (bhk). 2 QUALITATIVE AND QUANTITATIVE COMPOSITION Each OBIZUR vial contains nominally 500 units (U) of susoctocog alfa, which is a B domain deleted recombinant derived antihaemophilic factor VIII (rpFVIII), porcine sequence. After reconstitution, OBIZUR contains nominally 500 U/mL susoctocog alfa. Each vial of OBIZUR is labelled with the actual rpFVIII activity expressed in units determined by a one-stage clotting assay, using a reference rpFVIII material calibrated against the World Health Organization (WHO) 8th International Standard for human factor VIII concentrates. The specific activity of OBIZUR is in the range of 11000 - 18000 Units per milligram of protein. The potency values of OBIZUR determined by the chromogenic assay vary and are approximately 20-50 % lower than those of the one-stage clotting assay. Susoctocog alfa is expressed in a genetically engineered baby hamster kidney (BHK) cell line and secreted into the cell culture medium, and the protein is purified using a series of chromatography and filtration steps. The production process includes two dedicated viral clearance steps - a solvent/detergent treatment step for viral inactivation and a nanofiltration step through a series of two 15-nm filters for removal of viruses. No additives of human or animal origin are used in the formulation of OBIZUR. Excipient(s) with known effect Each vial of OBIZUR contains maximally 4.4 mg (198 mM) sodium per mL of reconstituted solution (see Section 4.4 SPECIAL WARNINGS AND PRECAUTIONS FOR USE). For the full list of excipients, see Section 6.1 LIST OF EXCIPIENTS.
    [Show full text]
  • Medicines/Pharmaceuticals of Animal Origin V3.0 November 2020
    Medicines/pharmaceuticals of animal origin V3.0 November 2020 Medicines/pharmaceuticals of animal origin - This guideline provides information for all clinical staff within Hospital and Health Services (HHS) on best practice for avoidance of issues related to animal products. Medicines/pharmaceuticals of animal origin - V3.0 November 2020 Published by the State of Queensland (Queensland Health), November 2020 This document is licensed under a Creative Commons Attribution 3.0 Australia licence. To view a copy of this licence, visit creativecommons.org/licenses/by/3.0/au © State of Queensland (Queensland Health) 2020 You are free to copy, communicate and adapt the work, as long as you attribute the State of Queensland (Queensland Health). For more information contact: Medication Services Queensland, Queensland Health, GPO Box 48, Brisbane QLD 4001, email [email protected] An electronic version of this document is available at https://www.health.qld.gov.au/__data/assets/pdf_file/0024/147507/qh-gdl-954.pdf Disclaimer: The content presented in this publication is distributed by the Queensland Government as an information source only. The State of Queensland makes no statements, representations or warranties about the accuracy, completeness or reliability of any information contained in this publication. The State of Queensland disclaims all responsibility and all liability (including without limitation for liability in negligence) for all expenses, losses, damages and costs you might incur as a result of the information being inaccurate
    [Show full text]
  • A Practical Approach to the Patient with Acquired Haemophilia a in Poland
    Journal of Transfusion Medicine 2020, tom 13, nr 3, 186–194 DOI:10.5603/JTM.2020.0007 REVIEW ARTICLE Copyright © 2020 Via Medica ISSN 1689–6017 A practical approach to the patient with acquired haemophilia A in Poland Magdalena Górska-Kosicka1 , Michał Wójciak2 , Jerzy Windyga1, 3 1Department of Disorders of Hemostasis and Internal Diseases, Institute of Hematology and Transfusion Medicine in Warsaw 2Faculty of Medicine, Medical University of Warsaw 3Department of Hemostasis and Metabolic Diseases, Institute of Hematology and Transfusion Medicine, Warsaw Summary Acquired haemophilia (AHA) is a severe acquired bleeding disorder that develops due to circu- lating autoantibodies directed against coagulation factor VIII (FVIII). These antibodies inhibit the coagulation activity of FVIII in patient’s plasma. AHA is mainly diagnosed in the elderly and more than half of the cases are idiopathic. Underlying conditions which favor AHA oc- currence are — among others — autoimmune diseases, neoplasms, pregnancy and 12-month post-partum period. The clinical picture is dominated by extensive ecchymosis, less often by intramuscular and retroperitoneal haematomas or hemorrhages to the central nervous system. Laboratory findings include isolated prolonged activated partial thromboplastin time (APTT), decreased FVIII activity and the presence of a FVIII inhibitor. Although patients with AHA usually present with severe hemorrhagic disorders, asymptomatic forms may also occur, with accidentally detected prolonged APTT as the only abnormality. The aim of AHA management is bleeding control and eradication of inhibitor. Key words: acquired haemophilia A, factor VIII, bypassing agents, inhibitor, bleeding J Transf Med 2020; 13: 186–194 Introduction data however may be underestimated due to mis- diagnosis [2].
    [Show full text]