ImageVerifierCode 换一换
格式:PDF , 页数:2 ,大小:56.05KB ,
资源ID:532057      下载积分:5000 积分
快捷下载
登录下载
邮箱/手机:
温馨提示:
如需开发票,请勿充值!快捷下载时,用户名和密码都是您填写的邮箱或者手机号,方便查询和重复下载(系统自动生成)。
如填写123,账号就是123,密码也是123。
特别说明:
请自助下载,系统不会自动发送文件的哦; 如果您已付费,想二次下载,请登录后访问:我的下载记录
支付方式: 支付宝扫码支付 微信扫码支付   
注意:如需开发票,请勿充值!
验证码:   换一换

加入VIP,免费下载
 

温馨提示:由于个人手机设置不同,如果发现不能下载,请复制以下地址【http://www.mydoc123.com/d-532057.html】到电脑端继续下载(重复下载不扣费)。

已注册用户请登录:
账号:
密码:
验证码:   换一换
  忘记密码?
三方登录: 微信登录  

下载须知

1: 本站所有资源如无特殊说明,都需要本地电脑安装OFFICE2007和PDF阅读器。
2: 试题试卷类文档,如果标题没有明确说明有答案则都视为没有答案,请知晓。
3: 文件的所有权益归上传用户所有。
4. 未经权益所有人同意不得将文件中的内容挪作商业或盈利用途。
5. 本站仅提供交流平台,并不能对任何下载内容负责。
6. 下载文件中如有侵权或不适当内容,请与我们联系,我们立即纠正。
7. 本站不保证下载资源的准确性、安全性和完整性, 同时也不承担用户因使用这些下载资源对自己和他人造成任何形式的伤害或损失。

版权提示 | 免责声明

本文(ASTM E2888-2012 Standard Practice for Process for Inactivation of Rodent Retrovirus by pH《使用pH进行逆转录病毒灭活过程的标准实施规程》.pdf)为本站会员(confusegate185)主动上传,麦多课文库仅提供信息存储空间,仅对用户上传内容的表现方式做保护处理,对上载内容本身不做任何修改或编辑。 若此文所含内容侵犯了您的版权或隐私,请立即通知麦多课文库(发送邮件至master@mydoc123.com或直接QQ联系客服),我们立即给予删除!

ASTM E2888-2012 Standard Practice for Process for Inactivation of Rodent Retrovirus by pH《使用pH进行逆转录病毒灭活过程的标准实施规程》.pdf

1、Designation: E2888 12Standard Practice forProcess for Inactivation of Rodent Retrovirus by pH1This standard is issued under the fixed designation E2888; the number immediately following the designation indicates the year oforiginal adoption or, in the case of revision, the year of last revision. A n

2、umber in parentheses indicates the year of last reapproval. Asuperscript epsilon () indicates an editorial change since the last revision or reapproval.1. Scope1.1 This practice assures 5 log10 inactivation of non-defective C-type retroviruses, which are endogenous to murinehybridoma and CHO cells a

3、nd are potentially present in theproduction stream of biopharmaceutical processes that userodent derived cell culture.1.2 The process parameters specified in this practice con-sistently assure 5 log10 inactivation of murine retrovirus byadjusting the pH of a process solution after initial affinityca

4、pture chromatography purification.1.3 This practice is applicable to mAb, IgG fusion, or otherrecombinant proteins produced from rodent cell lines (forexample, CHO or murine hybridoma), which do not targetretroviral proteins. Additionally, the low pH step is performedon a cell-free intermediate, pos

5、t initial capture using protein Achromatography.1.4 The 5 log10 inactivation of murine retrovirus claimedby using this practice will be utilized in conjunction with otherclearance unit operations (for example, chromatography andvirus retentive filtration) to assure sufficient total processclearance

6、of murine retroviruses, which will be supportive ofearly phase regulatory filings.1.5 The values stated in SI units are to be regarded asstandard. No other units of measurement are included in thisstandard.2. Terminology2.1 Definitions of Terms Specific to This Standard:2.1.1 IgG fusion proteina dim

7、eric protein comprised oftwo monomers, each monomer consisting of a peptide se-quence (usually a human receptor-like protein or proteinfragment) fused to the carboxyl-terminal of the Fc-domain of ahuman IgG antibody.2.1.1.1 DiscussionDimerization occurs by way of the Fcdomain.2.1.2 immunoglobulin G

8、(IgG)an antibody molecule com-posed of four peptide chains two heavy chains and twolight chains.2.1.2.1 DiscussionEach IgG has two antigen bindingsites. IgG constitutes 75 % of serum immunoglobulins inhumans. IgG molecules are synthesized and secreted by plasmaB cells. There are four IgG subclasses

9、(IgG1, 2, 3, and 4) inhumans, named in order of their abundance in serum (IgG1being the most abundant). Only human IgG1, IgG2, and IgG4show significant affinity to protein A.2.1.3 log10 reduction value (LRV)typically used to de-scribe the degree of reduction of a population, in this caserodent retro

10、virus, by the treatment process.2.1.3.1 DiscussionEach log reduction (10-1) represents a90 % reduction in the population. So a process shown toachieve a 6-log reduction (10-6) will reduce a population froma million (106)to1.2.1.4 monoclonal antibody (mAb)monospecific antibodieswhich have affinity fo

11、r the same antigen and are made from amaster cell bank, cloned from a parent cell.2.1.5 murine leukemia virus (MuLV)retroviruses namedfor their ability to cause cancer in murine (mouse) hosts.2.1.5.1 DiscussionMuLV is a member of the genus Gam-maretrovirus. MuLV is an enveloped spherical RNA viruswh

12、ich has a diameter of 80110 nm and has low chemicalresistance. MuLV is used as a model for non-defective C-typeendogenous retrovirus or retrovirus like particles produced bymurine hybridoma and CHO cell lines. MuLV is used to assessrodent retrovirus clearance of protein purification processesthat us

13、e rodent cells for production.2.1.6 recombinant proteinproduced from the expressionof recombinant DNA within living cells.2.1.6.1 DiscussionRecombinant DNA is genetically engi-neered by inserting foreign DNA into the DNA of an appro-priate host so that the foreign DNA is replicated along with thehos

14、t DNA.2.1.7 retrovirusan RNA virus that is propagated in a hostcell using the reverse transcriptase enzyme to produce DNAfrom its RNA genome.2.1.7.1 DiscussionDNA is then incorporated into thehosts genome by an integrase enzyme. The virus is thereafterreplicated as part of the host cells DNA. Retrov

15、iruses areenveloped viruses that belong to the viral family Retroviridae.1This practice is under the jurisdiction of ASTM Committee E55 on Manufac-ture of Pharmaceutical Products and is the direct responsibility of SubcommitteeE55.04 on General Biopharmaceutical Standards.Current edition approved Au

16、g. 1, 2012. Published September 2012. DOI:10.1520/E2888-12.Copyright ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959. United States12.1.8 modular validationa modular clearance study is onethat demonstrates virus removal or inactivation at individualsteps duri

17、ng the purification process (column chromatography,filtration, heat treatment, solvent/detergent treatment, low pHtreatment, etc.).2.1.8.1 DiscussionEach module, or unit operation, in thepurification scheme may be studied independently of the othermodules. Different model mAb may be used to demonstr

18、ateviral clearance in different modules, if necessary. If thepurification process of a product mAb differs at any of the virusremoval or inactivation modules from the model mAb, thismodule must be studied independently from the model. Theother, identical modules in the procedure may be extrapolatedt

19、o the product mAb. The total LRV of a purification processcan be obtained by adding the LRVs of the individual mod-ules.23. Significance and Use3.1 Rodent cell lines are widely used in the production ofbiological therapeutics such as monoclonal antibodies andrecombinant proteins. These cell lines ar

20、e known to containgenes encoding endogenous retroviral-like particles or toproduce infectious endogenous retrovirus. Despite the lack ofevidence for an association between such rodent retrovirusesand disease in man, the potential contamination of humantherapeutics poses patient safety concerns.Addit

21、ionally, adven-titious agents such as viruses can be introduced into a drugsubstance manufacturing process from other sources such asraw materials. Potential safety issues can be attributed to thesebiosafety testing for products made using rodent cell lines.33.2 Low pH inactivates retroviruses by de

22、naturing the viralenvelope proteins. Similar to all chemical reactions, thisdepends on reactant concentration (that is, H+ ion concentra-tion as measured by pH), time of reaction and temperature ofreaction. Implementing the parameters that give robust andeffective rodent retrovirus inactivation esta

23、blished by thispratice, in conjunction with other clearance unit operations (forexample, chromatography, virus retentive filtration) can assuresufficient purification process clearance of rodent retroviruses.43.3 This practice incorporates parameters that give robustand effective rodent retrovirus i

24、nactivation, which can be usedas modular validation for the low pH viral clearance moduleusing MuLV, the model non-defective C-type retrovirus endog-enous to murine hybridoma and CHO cells.4. Procedure4.1 For this practice, the primary variables specified are theconcentration range of buffer composi

25、tion elements, pH,temperature, protein concentration, and time during hold con-ditions.4.2 This practice will be applicable to mAb, IgG fusion, orother recombinant proteins, produced from rodent (forexample, CHO or murine hybridoma) cell lines, which do nottarget retroviral proteins.4.3 The low pH v

26、iral inactivation step must be performed ona cell-free intermediate, post initial capture using protein Achromatography.4.4 The inactivation process and the corresponding log10reduction of 5.0 are as follows:54.4.1 The hold temperature is 15C,4.4.2 The hold time is 30 minutes,4.4.3 The hold pH is 3.

27、6 throughout the course of the holdtime, and4.4.4 The buffer matrix will be glycine, citrate, or acetatebased, and the concentration of components will be in thefollowing ranges:4.4.4.1 If utilized, sodium chloride will be 500 mM inconcentration, and4.4.4.2 The protein concentration is 25 g/L.5. Key

28、words5.1 inactivation; retrovirus; rodentASTM International takes no position respecting the validity of any patent rights asserted in connection with any item mentionedin this standard. Users of this standard are expressly advised that determination of the validity of any such patent rights, and th

29、e riskof infringement of such rights, are entirely their own responsibility.This standard is subject to revision at any time by the responsible technical committee and must be reviewed every five years andif not revised, either reapproved or withdrawn. Your comments are invited either for revision o

30、f this standard or for additional standardsand should be addressed to ASTM International Headquarters. Your comments will receive careful consideration at a meeting of theresponsible technical committee, which you may attend. If you feel that your comments have not received a fair hearing you should

31、make your views known to the ASTM Committee on Standards, at the address shown below.This standard is copyrighted by ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959,United States. Individual reprints (single or multiple copies) of this standard may be obtaine

32、d by contacting ASTM at the aboveaddress or at 610-832-9585 (phone), 610-832-9555 (fax), or serviceastm.org (e-mail); or through the ASTM website(www.astm.org). Permission rights to photocopy the standard may also be secured from the ASTM website (www.astm.org/COPYRIGHT/).2U.S. Food and Drug Adminis

33、tration (FDA), Points to Consider in theManufacture and Testing of Monoclonal Antibody Products for Human Use, 1997,Department of Health and Human Services, Food and Drug Administration,Rockville, MD.3The International Conference on Harmonisation of Technical Requirements forRegistration of Pharmace

34、uticals for Human Use (ICH), Viral Safety Evaluation ofBiotechnology Products Derived from Cell Lines of Human or Animal Origin, Q5A,1999, Geneva, Switzerland.4Brorson, K., Krejci, S., Lee, K., Hamilton, E., Stein, K., et al., “BracketedGeneric Inactivation of Rodent Retroviruses by Low pH Treatment

35、 for MonoclonalAntibodies and Recombinant Proteins,” Biotechnology and Bioengineering , Vol 82,No. 3, 2003, pp. 321329.5Miesegaes, G., Bailey, M., Wilkommen, H., Chen, Q., Roush, D., et al.,“Proceedings of the 2009 Viral Clearance Symposium,” Journal of DevelopmentalBiology (Basel), Basel, Karger, Vol 133, 2010, pp. 2542.E2888 122

copyright@ 2008-2019 麦多课文库(www.mydoc123.com)网站版权所有
备案/许可证编号:苏ICP备17064731号-1