Cover -- Contents -- Abbreviations -- 1. Introduction -- 2. General -- 2.1 Current directions -- 2.1.1 Strategic directions in biological standardization -- 2.1.2 Vaccines and biological therapeutics: recent and planned activities in biological standardization -- 2.1.3 Blood products and related in vitro diagnostics: recent and planned activities in biological standardization -- 2.2 Reports -- 2.2.1 Report of the WHO Blood Regulators Network -- 2.2.2 Reports from international laboratories and WHO collaborating centres for biological standards -- 2.3 Issues -- 2.3.1 Scientific issues identified by users of WHO biological Reference Preparations -- 2.3.2 Issues shared with the WHO Expert Committee on Specifications for Pharmaceutical Preparations -- 3. International Recommendations, Guidelines and other matters related to the manufacture and quality control of biologicals -- 3.1 Vaccines and related substances -- 3.1.1 Guidelines on the quality, safety and efficacy of dengue tetravalent vaccines (live, attenuated) -- 3.1.2 Recommendations to assure the quality, safety and efficacy of BCG vaccines -- 3.1.3 Recommendations to assure the quality, safety and efficacy of acellular pertussis vaccines -- 3.1.4 Assessing risk when a potential adventitious agent is found -- 3.1.5 Calibration of seasonal and pandemic influenza antigen working reagents by WHO essential regulatory laboratories -- 3.1.6 Proposed new projects for developing or updating written standards -- 3.2 Blood products and related substances -- 3.2.1 Guidelines for thromboplastins and plasma used to control oral anticoagulant therapy with vitamin K antagonists -- 3.2.2 Assessment criteria for national blood regulatory systems -- 4. International reference materials - vaccines and related substances -- 4.1 WHO International Standards and Reference Reagents - vaccines and related substances.

4.1.1 First WHO International Standard for meningococcal serogroup C polysaccharide -- 4.1.2 First WHO International Standard for anti-pneumococcal antibodies in serum -- 4.1.3 Third WHO International Standard for trivalent inactivated polio vaccine -- 4.2 Proposed new projects - vaccines and related substances -- 4.2.1 Replacement of the First WHO International Standard for antibody to influenza A virus subtype H1N1pdm -- 4.3 Ongoing stability monitoring - vaccines and related substances -- 4.3.1 Inactivated hepatitis A vaccine -- 4.4 Progress reports - vaccines and related substances -- 4.4.1 Characteristics of an improved potency assay for inactivated influenza vaccines -- 4.4.2 Hepatitis B vaccine -- 5. International reference materials - blood products and related substances -- 5.1 WHO International Standards and Reference Reagents - blood products and related substances -- 5.1.1 Assignment of a value for von Willebrand factor propeptide to the Sixth WHO International Standard for factor VIII/VWF plasma -- 5.1.2 Third WHO International Standard for fibrinogen (plasma) -- 5.1.3 First WHO International Reference Reagent for anti-human neutrophil antigen-1a antibody -- 5.1.4 First WHO International Reference Reagents for blood group genotyping -- 5.1.5 Revision of the instructions for use of the First WHO International Reference Repository for platelet transfusion relevant bacterial strains -- 5.1.6 Apolipoprotein B -- 5.2 Proposed new projects - blood products and related substances -- 5.2.1 Replacement of the Second WHO International Reference Preparation for serum IgE -- 5.2.2 Replacement of the Third WHO International Standard for plasmin -- 5.2.3 Haemoglobin A2 -- 6. International reference materials - in vitro diagnostic device reagents -- 6.1 WHO International Standards and Reference Reagents - in vitro diagnostic device reagents.

6.1.1 Third WHO International Standard for HIV-1 for NAT-based assays -- 6.1.2 Third WHO International Standard for hepatitis B virus for NAT-based assays -- 6.1.3 First WHO International Reference Panel for hepatitis B virus genotype for HBsAg assays -- 6.1.4 Fourth WHO International Standard for hepatitis C virus for NAT-based assays -- 6.1.5 First WHO International Standard for hepatitis E virus for NAT-based assays -- 6.1.6 First WHO International Reference Standard for anti-Trypanosoma cruzi antibodies -- 6.1.7 First WHO International Standard for Epstein-Barr virus for NAT-based assays -- 6.2 Proposed new projects - in vitro diagnostic device reagents -- 6.2.1 Third Meeting of WHO Collaborating Centres for Biological Standards -- 6.2.2 Replacement of the First WHO International Standard for hepatitis A virus for NAT-based assays -- 6.2.3 Replacement WHO International Standard for hepatitis B e-antigen -- 6.2.4 Replacement WHO International Standard for hepatitis B e-antibodies -- 6.2.5 First WHO International Reference Panel for hepatitis E virus genotypes for NAT-based assays -- 6.2.6 Replacement of the First WHO International Reference Panel for HIV-1 subtypes -- 6.2.7 First WHO International Reference Panel for HIV-1 circulating recombinant forms -- 6.3 Ongoing stability monitoring -- 6.3.1 Prostate-specific antigen -- 7. International reference materials - biotherapeutics other than blood products -- 7.1 WHO International Standards and Reference Reagents - biotherapeutics other than blood products -- 7.1.1 First WHO International Standard for transforming growth factor beta-3 -- 7.2 Proposed new projects - biotherapeutics other than blood products -- 7.2.1 Replacement of the First WHO International Standard for interleukin-2 -- 7.2.2 Replacement of the Second WHO International Standard for recombinant human erythropoietin.

7.2.3 Replacement of the Fourth WHO International Standard for urinary follicle-stimulating hormone and urinary luteinizing hormone -- 7.2.4 Replacement of the Second WHO International Standard for luteinizing hormone (human, pituitary) -- 8. International reference materials - antibiotics -- 8.1 WHO International Standards and Reference Reagents - antibiotics -- 8.1.1 Third WHO International Standard for dihydrostreptomycin -- 8.2 Proposed new projects - antibiotics -- 8.2.1 Replacement of the First WHO International Standard for neomycin B -- 8.2.2 Replacement of the Second WHO International Standard for neomycin -- Annex 1 WHO Recommendations, Guidelines and other documents related to the manufacture and quality control of biological substances used in medicine -- Annex 2 Guidelines on the quality, safety and efficacy of dengue tetravalent vaccines (live, attenuated) -- Annex 3 Recommendations to assure the quality, safety and efficacy of BCG vaccines -- Annex 4 Recommendations to assure the quality, safety and efficacy of acellular pertussis vaccines -- Annex 5 Generic protocol for the calibration of seasonal and pandemic influenza antigen working reagents by WHO essential regulatory laboratories -- Annex 6 Guidelines for thromboplastins and plasma used to control oral anticoagulant therapy with vitamin K antagonists -- Annex 7 Assessment criteria for national blood regulatory systems -- Annex 8 Biological substances: WHO International Standards and Reference Reagents.