重组单抗药物质控中物理检查的有关问题探讨

重组单抗药物的物理检查是其质量控制的必要环节,对于评价制品的功能非常重要,对单抗药物安全、有效、质量可控具有重要意义。本文通过阐述物理检查项目中澄清度、浊度、不溶性微粒、澄明度、可见异物和颜色等关键概念及其部分概念表述变化的历史沿革、相似概念的理解和辨析,探讨了中国药典、欧洲药典在上述试验方法的差异,进一步解决了注册检验中物理检查遇到的常见问题,为国内外单抗制品注册检验的相关工作提供参考。

Physical tests of Mabs are essential for the quality control,which are very important for the evaluation of functions,safety,effectiveness,and controllable quality.In this paper,the key concepts such as clarity,turbidity,particulate matter,visible particles and coloration of physical tests were stated.Development of the concepts was also elaborated,as well as similarity and difference in the understanding of the methods between Chinese pharmacopoeia(ChP)and European pharmacopoeia(EP).Common problems of physical tests for registration were solved further,providing reference for the domestic and foreign registration tests.

[1] GUO W(郭玮),WANG WB(王文波),YU CF(于传飞),et al.Comparative study of size and charge heterogeneities of anti-TNF-α antibodies by high performance liquid chromatography(TNF-α单抗分子大小变异体与电荷变异体色谱行为的比较研究)[J].Chin J Microbiol Immu(中华微生物学和免疫学杂志),2014,34(9):723
[2] ChP 2010.Vol Ⅲ(中国药典2010年版.三部)[S].2010:314
[3] ICH Guidelines:Quality Guidelines.5C[S].1995:4
[4] ICH Guidelines:Quality Guidelines.6B[S].1999:9
[5] SARMA VR,SILÜERTO EW,DAVIES DR,et al.An electron microscopic study of human γ Gl immunoglobulin crystals[J].J Biol Chem,1971,246(11):3760
[6] ChP 2010.Vol Ⅱ(中国药典2010年版.二部)[S].2010:Appendix(附录)76
[7] EP 7.0[S].2011:Methods of analysis 2.2.1
[8] ChP 2010.Vol Ⅱ(中国药典2010年版.二部)[S].2010:Appendix(附录)71
[9] ChP 1963(中国药典1963年版)[S].1963:Appendix(附录)4
[10] ChP 2005.Vol Ⅱ(中国药典2005年版.二部)[S].2005:Appendix(附录)66
[11] RIPPLE DC,DIMITROVA MN.Protein particles:what we know and what we do not know[J].J Pharm Sci,2012,101(10):3568
[12] BEE JS,GOLETZ TJ,RAGHEB JA.The future of protein particle characterization and understanding its potential to diminish the immunogenicity of biopharmaceuticals:a shared perspective[J].J Pharm Sci,2012,101(10):3580
[13] DOESSEGGER L,MAHLER HC,SZCZESNY P,et al.The potential clinical relevance of visible particles in parenteral drugs[J].J Pharm Sci,2012,101(8):2635
[14] ChP 2010.Vol Ⅲ(中国药典2010年版.三部)[S].2010:Appendix(附录)31
[15] EP 7.0[S].2011:Methods of analysis 2.9.19
[16] LED SE.New aspects of the Maillard reaction in foods and the human body,Angew[J].Chem Int Ed Engl,1990,29(6):565
[17] BELL L N,TOUMA D E,WHITE K L,et al.Glycine loss and Maillard browning as related to the glass transition in a model food system[J].Food Sci,1998,63(10):625
[18] SCHEBOR C,KAREL M,CHIRIFE J.Color formation due to non-enzymatic browning in amorphous,glassy,anhydrous,model systems[J].Food Chem,2000,65(4):427
[19] DYER JM,BRINGANS SD,BRYSON WG.Characterisation of photooxidation products within photoyellowed wool proteins:tryptophan and tyrosine derived chromophores[J].Photochem Photobiol Sci,2006,5(7):698
[20] ChP 2010.Vol Ⅱ(中国药典2010年版.二部)[S].2010:Appendix(附录)68
[21] EP 7.0[S].2011:Methods of analysis 2.2.2
[22] CHEN LY(陈立亚),YU BZ(于宝珠),GAO YC(高玉成),et al.Issues of light obscuration used in sub-visible particle testing of injetions(光阻法在注射液不溶性微粒检查中应用的几个技术问题)[J].Chin J Pharm Anal(药物分析杂志),2002,22(2):158
[23] WANG ML(王敏丽),XIAO L(肖林),HOU JF(侯继峰).Quality investigation of human albumin and analysis tendency of content insoluble particles(人血白蛋白中不溶性微粒的检测及制品质量考察趋势分析)[J].Chin J Pharm Anal(药物分析杂志),2012,32(4):725