生物分离工程-双语版-8资料讲解.ppt

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1、生物分离工程-双语版-8Downstream processing equipmentv1 20%of equipments grow per year(1.0 billion$v (1991)to 5.2 billion$(2000)v2 Key to cutting production cost:v(1)Improvement in bioseparation equipmentsv(2)Upstream processv A minor changes in upstream significantlyv impact economic or otherwisev B purifica

2、tion process must consider upstream Bring a drug to market v1 Cost:$100 million to$300 million(1985-v 1992),350$to 400 million(1995)v2 Time:7 to 10 years v3 Research-focused companies combined with v drug development,manufacturing and marketing v resources v(1)1 to 3 fully integrated biopharmaceutic

3、al companies,v(2)10-15 platform companiesv(3)50-100 successful boutiques(小商店，小公司）v4 Allergan($1 billion in annual sales)combining Ligand(13 v million in annual research revenues）.Development time of biopharmaceuticals from FDAv1 Development time of drugsv (1)4-10 years(7 years),large part of drugsv

4、(2)7-23 years(12 years),small part of drugsv2 Risks and financial supportv (1)Few biotechnology companies were profitable in v 1993v (2)Considerable effort on developing credibility,and v appealing to investors to attract capital.v3 Very little effort on consumer needs and marketsBiotechnological pr

5、oduct ready for marketv1 conform to FDA standardv2 safe,potent and purev3 stable in injectable formv4 minimize the number of steps while v maintaining high yields and product purity,v quality and activityv A reduce the opportunity of product loss v B minimize product contamination.Process developmen

6、t consideratonv1 purpose v2 goalsv3 standardsv4 propertiesv5 native environmentv6 sourcev7 Prevent unnecessary and unexpected v loss of activity Downstream processing costs play a major rolev1 many academic and laboratory efforts are v focused on the isolation of a particular productv2 scant attenti

7、on is paid to the economics of v processv3 operational data from laboratory and pilot plant v are rarely reported Difficulties1 Not all the variables are completely known as the process is scaled-up.2 There should be enough flexibility in the process to take care of the unexpected needs.Centrifugati

8、on1 In biotechnology,centrifugation is effectively used to separate products that exhibit very small differences in specific gravity.2 Compactly designed centrifuges have efficient economies of scale.3 Costs Economic considerations are a key factor in utilizing centrifuges.They can be broken down in

9、to 4 categories:1.Capital costs The capital costs of centrifuges runs from$50,000 to$500,000 depending on the size and configuration selected.Often the cost is strongly dependent on the specification required of the centrifuges.2.Operating costs Include utility,chemical and labor requirements.Produc

10、t recovery specification significantly influence the operating costs.4.Nontangible（不确定性的）costs Often neglected when purchasing a centrifuge pact centrifuge may save or make available floor space on the shop floormicrobial cells have a disposal cost associated with them,the drier the cake is,the less

11、 is the disposal cost 3.Maintenance It runs from 5 to 10%of the total labor costsThe improvements in the processI.Switching（转换）host cells from E.coli.to Chinese hamster cells.II.Changing the roller process to suspension-culture process.III.The costs per gram fell by about 100-fold.Example 8.2 The do

12、sage for tPA increased by two orders of magnitude to 100 mg which was expected to be 1 mg.In designing a process,the objectives should be clearly statedMany of the process variables change from the laboratory scale to the pilot plant scale.The time of transferring the purification process from the l

13、aboratory scale to the pilot plant scale is important.Emphasized 1only chromatography offers the high resolution required 2 to obtain a very pure product.2 Initial volume reduction steps may require clarification.3 The chromatography steps may be required.4 The sequence of purification steps is larg

14、ely dependent on the product to be purified.Scale-up should be attempted only when:a)a suitable processing strategy in accord with the product to be purified has been developed b)The process has been optimized on the laboratory scaleThe parameters that are perhaps easily controlled at the laboratory

15、 scale may be different and unpredictable at the pilot plant scale.Adjustments are often required.The modifications:Process optimization needs to be carries out continuously to improve the economics of the modified process.Example 8.3At the larger scale there was compression of particles in the colu

16、mn that decreased flow rate and caused significant back pressure.Silica was suitable.Three ways to change a chromatographic columnMaintaining a constant column areaextremely long columnsIncrease column diameter while holding the bed height constant:Perfusion chromatographyv110 times faster than conv

17、entional liquid chromatographyCost function vThe cost of the activated column per unit volume labor maintenance utilities depreciation（折旧）This is a profit function,not include investment cost,(i.e.research).Development of nondeformable gel materials Cost in running separationsvCost structureOperating cost(solvent cost)Column packing costCapital costs(columns,pumps,etc)Conclusionsv1 Data are scarcely availablev2 Economics determine bioseparation processv3 Meet the market demands and the government v standards 此课件下载可自行编辑修改，仅供参考！此课件下载可自行编辑修改，仅供参考！感谢您的支持，我们努力做得更好！谢谢感谢您的支持，我们努力做得更好！谢谢