血液的体积及组成

按一下以編輯母片標題樣式,按一下以編輯母片,第二層,第三層,第四層,第五層,*,*,血液的體積及組成,70公斤重的成年男子含有5公升的血量。,含紅血球、白血球及血小板。,成年人血漿(,plasma),佔全身血液總量的5060%。,血漿的大部分是水，水主要作為溶劑。血漿呈淡黃色，其中含有數百種血漿蛋白，包括白蛋白(,albumin)、,球蛋白(,globulins),及纖維蛋白原(,fibrinogen)。,1,人類血漿之特異性,是一種非常豐富及複雜之生物來源物質。,含超過100200種以上不同的（醣）蛋白（包括凝血因子，蛋白分解酵素抑制劑，蛋白分解酵素，免疫球蛋白），白蛋白，,peptide，,生長因子.。,約1720種血漿成分已建立治療價值。,是一人類治療所必需的兵工廠。,2,血漿來源,Source Plasma (from,plasmapheresis,),Recovered Plasma (from whole blood donations),3,血液的功能,運送細胞的產物及廢物，並將養分及氧氣送到細胞。,血液內吞噬細胞的功用除了如清道夫外，並且能抵抗外來的感染。,為運輸激素的途徑。,平衡穩定體內的,pH,值。,將體熱帶到皮膚發散以維持體溫恆定。,4,5,6,7,Take a break,!,8,9,10,11,12,Viruses transmissible via blood and plasma products,13,Human Viruses of ConcernWith Respect to Plasma Derivatives,Enveloped Viruses,Human Immune Deficiency Virus (HIV),Hepatitis B (HBV),Hepatitis C (HCV),Non-Enveloped Viruses,Human,Parvovirus,B19 (B19),Hepatitis A (HAV),Not,Significient,Risks,Human T-,lymphotrophic,virus (HTLV I & II),Cytomegalovirus,(CMV),Epstein Barr Virus (EBV),Unmeasurable,Risks,Transmissible,Spongioform Encephalopathies,(TSE, esp. CJD),Unidentified and /or emerging agents,14,Significance of Viral Envelope,Protein necessary for attachment and penetration of host cells are on the surfaces of viruses.,Non-enveloped viruses tend to be more resistant to,physico,-chemical conditions (heat, solvent-detergent).,The smallest viruses are non-enveloped.,15,Donor Screening for Viral Contamination,16,General Safety Measures,Screening donors,Maintaining donor deferral registries to eliminate unsuitable donors from the rolls,Testing blood and plasma donations,Testing pools, intermediates, and/or final containers,Viral clearance steps in manufacturing,Monitoring and investigating adverse incidents to ensure that deficiencies are corrected,17,What is a,Prion,?,proteinaceous,infectious agent,resists treatments that destroy nucleic acids,destroyed by treatments that degrade protein,derived from the,prion,protein (,PrP,),isoform,of,PrP,c,/,subfraction,of,PrP,sc,partially resistant to,proteinases,18,19,Viral elimination treatments of plasma products,Specific,Nanofiltration,: filtration of a protein through a membrane/hollow fiber with a nominal pore size of a few nanometers (in the range of 15 to 40 nm) in conditions where proteins migrate through the,nanofilter,while viruses are retained,Non specific:,Chromatography, Precipitation,Ultrafiltration,20,Most frequently used specific viral inactivation treatments of plasma products,Acid pH (,IgG,),Incubation of the protein solution (,IgG,) at pH 4, with or without the presence of traces of pepsin, at 37,o,C for 22 hours or more.,21,Most frequently used specific viral inactivation treatments of plasma products,Solvent-Detergent,Incubation of an homogeneous plasma protein solution in the presence of an organic solvent (tri n-butyl phosphate) and a detergent (Tween 80; Triton X-100) for 4-6 hours at 25 to 35,o,C.,22,Most frequently used specific viral inactivation treatments of plasma products,Dry Heat Treatment,Heat-treatment of a,lyophilised,protein product or fraction (dry state) from several minutes to several days at temperatures from 60 to 100,o,C,23,Most frequently used specific viral inactivation treatments of plasma products,Pasteurization,Heat-treatment of an homogeneous protein solution (,liquid state,) for 10 hours at 60,o,C, generally in the presence of stabilizers (sugars, amino-acids,polyols,.),24,Viral Clearance,Clearance= Inactivation and/or Removal,Individual manufacturing steps:,-specifically designed for viral clearance,-intended primarily for purification,Each clearance step is separately validated,Production methods and practices must conform to validated methods,25,Viral Clearance Validation I: Scale-down,Necessity:,-Undesirable to introduce viruses into production facilities;,-Limited ability to produce large amounts of high titer virus preparations;,-Risk to laboratory workers.,Requirements,-Lab process mimics production scale (relative geometries, volumes, flow rates, etc.),-Lab process performs like production process (relative capacity, yield, purification, etc.),26,Viral Clearance Validation II:,Selection of relevant and model viruses,Typically, several viruses are selected to encompass the anticipated risks.,Relevant,=a virus that may be found in the blood or plasma.,Model,=a laboratory strain of a virus not necessarily found in the blood or plasma.,27,Classification for biological products,Class I,Products derived from human tissues or fluids:(plasma derivatives, hormones from urine, placental derivatives, etc.),Risk encountered: no species barrier, unknown viruses.,Viral safety: screening of the donors and the capacity of the process to eliminate and/or inactivate viruses.,28,Classification for biological products,Class II,Viral vaccines: killed (inactivated) and live attenuated vaccines,Risk encountered,: Presence of residual active virus in killed vaccines (Cutter incident-1953); reversion to virulence of the attenuated strains or a failure in GMP.,Viral safety,: Control of the inactivation procedure and genetic stability of the attenuated viruses.,29,Classification for biological products,Class III,Products derived from animal tissues and fluids: collagen, heparins, animal,immunoglobulins, monoclonal antibodies produced in,ascites, etc.,Risk encountered,: Presence of viruses in the starting material; the screening for viral markers of the source material is not feasible.,Viral safety,: There is the species barrier. Viral safety is based solely on the capacity of the process to remove and/or inactive viruses.,30,Classification for biological products,Class IV,Products derived from animal cell cultures: proteins obtained by,rDNA, monoclonal antibodies, cytokines.,Risk encountered,: Presence of viruses in the cells used in production and/or contamination of the product by viruses present in the reagent used in the process or a breakthrough in SMP.,Viral safety,: Characterization and control of the cell banks and of the reagents used in production; process capable of generating highly purified products.,31,Classification for biological products,Class V,Bacterial vaccines,toxoides,and,rDNA,proteins expressed in bacteria or yeast.,Risk encountered,: Residual live bacteria in vaccines and the potential presence of viruses in the reagents of animal origin used for some bacteriological media (theoretical risk).,32,33,