A comparison of analytical techniques for the determination and monitoring of charge variants in therapeutic proteins

master's thesis

Eva Kropušek (Author), Matjaž Finšgar (Mentor), David Majer (Co-mentor), Matej Birk (Co-mentor)

Abstract

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.

Keywords

Imaged capillary isoelectric focusing;capillary zone electrophoresis;cation exchange chromatography;charge variants;biological drug;

Data

Language:	English
Year of publishing:	2023
Typology:	2.09 - Master's Thesis
Organization:	UM FKKT - Faculty of Chemistry and Chemical Engineering
Publisher:	[E. Kropušek]
UDC:	543.54:547.96(043.2)
COBISS:	171233795
Views:	131
Downloads:	21
Average score:	0 (0 votes)
Metadata:

Other data

Secondary language:	Slovenian
Secondary title:	Primerjava analitskih tehnik za določevanje in spremljanje nabitih oblik terapevtskih proteinov
Secondary abstract:	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.
Secondary keywords:	kapilarno izoelektrično fokusiranje;kapilarna conska elektroforeza;kationska izmenjevalna kromatografija;nabite oblike terapevtskih proteinov;biološka zdravila;magistrske naloge;
Type (COBISS):	Master's thesis/paper
Thesis comment:	Univ. v Mariboru, Fak. za kemijo in kemijsko tehnologijo
Pages:	1 spletni vir (1 datoteka PDF (XII, 61 f.))
ID:	19882406