20.500.12556/DKUM-85587 A comparison of analytical techniques for the determination and monitoring of charge variants in therapeutic proteins master's thesis Primerjava analitskih tehnik za določevanje in spremljanje nabitih oblik terapevtskih proteinov Charge variants of therapeutic proteins are considered to be drug product variants and process-related impurities. To monitor charge heterogeneity, the development of a new analytical method is needed. Imaged capillary isoelectric focusing, capillary zone electrophoresis, and cation exchange chromatography assays were evaluated as candidate assays to support the early development of two new biological drug candidates. These are the analytical techniques most frequently used in the pharmaceutical industry for monitoring charge heterogeneity. We compared the advantages and disadvantages of these analytical techniques for monitoring charge variants in two innovative monoclonal antibodies. The results obtained revealed similarities and differences in the various analytical techniques. However, there is only a short time-frame dedicated to analytical method development when developing new biological drugs. With this in mind, imaged capillary isoelectric focusing showed a perfect balance between the quality and speed of analysis. Nabite oblike terapevtskih proteinov so definirane kot različice produkta in nečistoče vezane na proces. Za spremljanje heterogenosti naboja je potreben razvoj analitske metode. Za zgodnji razvoj analitske metode za podporo razvoja dveh inovativnih bioloških zdravil so bile ovrednotene naslednje analitske tehnike: kapilarno izoelektrično fokusiranje, kapilarna conska elektroforeza in kationska izmenjevalna kromatografija. To so najpogosteje uporabljene tehnike za spremljanje heterogenosti naboja proteinov v farmacevtski industriji. Primerjali smo prednosti in slabosti analitskih tehnik ter uspešno določili ustrezne metode za spremljanje nabitih različic obeh monoklonskih protiteles. Rezultati so razkrili podobnosti in razlike analitskih tehnik. Pri izbiri najprimernejše analitske tehnike smo upoštevali, da je v okviru razvoja novih bioloških zdravil, razvoju analitskih metod namenjeno kratko časovno obdobje, zato so imele prednost metode s kratkim analiznim časom in metode, ki ne potrebujejo optimizacije. Z obzirom na to, kapilarno izoelektrično fokusiranje izkazuje popolno ravnovesje med kakovostjo in hitrostjo analize. Imaged capillary isoelectric focusing capillary zone electrophoresis cation exchange chromatography charge variants biological drug kapilarno izoelektrično fokusiranje kapilarna conska elektroforeza kationska izmenjevalna kromatografija nabite oblike terapevtskih proteinov biološka zdravila true true false [E. Kropušek] Angleški jezik Slovenski jezik Magistrsko delo/naloga 2023-09-03 16:55:00 2023-10-03 13:12:55 2023-11-09 03:05:56 0000-00-00 00:00:00 2023 0 Maribor 0 Maribor 1 spletni vir (1 datoteka PDF (XII, 61 f.)) 0000-00-00 NiDoloceno NiDoloceno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 543.54:547.96(043.2) 171233795 MAG_Kropusek_Eva_2023.pdf MAG_Kropusek_Eva_2023.pdf 1 1F2DE87A8D0498694D6BAFF465824C83 976764f566a2e97a336c87f03f81fcb5198e456b24a3f71c098c19a2f4d55a64 3ef62590-5c77-11ee-972e-00155d000105 https://dk.um.si/Dokument.php?lang=slv&id=173015 Fakulteta za kemijo in kemijsko tehnologijo 0 0 0