000			03315cam a2200349 a 4500
003			EG-GiCUC
005			20250223031513.0
008			160524s2015 ua d f m 000 0 eng d
040			_aEG-GiCUC _beng _cEG-GiCUC
041	0		_aeng
049			_aDeposite
097			_aM.Sc
099			_aCai01.08.03.M.Sc.2015.Em.Q
100	0		_aEman Lotfi Shaltout
245	1	0	_aQuality assessment of biosimilars relative to innovator products using instrumental methods of analysis / _cEman Lotfi Shaltout ; Supervised Maissa Yacoub Salem , Medhat Ahmed Alghobashy , Faten Abdelaziz Fathalla
246	1	5	_aتحديد جودة المنتجات الحيوية المماثلة نسبة إلى منتجات المبتكر باستخدام طرق التحليل الآلى
260			_aCairo : _bEman Lotfi Shaltout , _c2015
300			_a116 P. : _bcharts ; _c25cm
502			_aThesis (M.Sc.) - Cairo University - Faculty of Pharmacy - Department of Analytical Chemistry
520			_aBiosimilars are biotechnology-derived products that are biologically similar but not identical to an authorized innovator product. Extensive comparability study for the biosimilar product and the reference product is commonly required. An orthogonal testing protocol was developed and validated to assess the quality of Filgrastim biosimilars. Initial screening was carried out using gel electrophoresis and peptide mapping to confirm the product primary structure. CIEF was used to detect the charged impurities. It was optimized using neutrally coated capillaries over a wide-range pH gradient (pH 3.0{u2013}10.0). Impurities above the acceptable limits were detected in both biosimilar products. CIEF also revealed heterogeneity in the active ingredient that has not been investigated by the manufacturers. RP-HPLC was employed for the determination of Filgrastim in the presence of its oxidative degradation products. The assay was accurate and precise over a linear concentration range of 9.38{u2013}300.00 æg/mL. SE-HPLC was carried out over a molecular weight range of 5{u2013}150 kDa to reveal impurities with high molecular weight. The assay was found accurate and precise over a linear concentration range of 20.00{u2013}400.00 æg/mL.Filgrastim oxidized forms and higher molecular weight impurities were detected in the biosimilars. Immunoassay was carried out to determine the protein content and to predict the tertiary structural confirmation. Antigen- antibody reaction was very low in the two biosimilars. Inability to bind could be due to some degree of protein deformation. Finally; spectrophotometric techniques were used to determine the total protein content. Results confirmed the need for in-house validated orthogonal testing protocols to be developed by local regulatory authorities. This should prevent access of substandard biosimilars to price-sensitive markets
530			_aIssued also as CD
653		4	_aBiosimilars relative
653		4	_aInnovator products
653		4	_aInstrumental methods of analysis
700	0		_aFaten Abdelaziz Fathalla , _eSupervisor
700	0		_aMaissa Yacoub Salem, _eSupervisor
700	0		_aMedhat Ahmed Alghobashy , _eSupervisor
856			_uhttp://172.23.153.220/th.pdf
905			_aAml _eCataloger
905			_aNazla _eRevisor
942			_2ddc _cTH
999			_c56623 _d56623