magistrsko delo
Barbara Jeras (Author), Aleš Podgornik (Mentor), Marjan Marinšek (Thesis defence commission member), Matevž Pompe (Thesis defence commission member)

Abstract

Področje bioloških zdravil predstavlja najhitreje rastoč del farmacevtske industrije, monoklonska protitelesa (mAb) pa največjo skupino bioloških zdravil. Zaradi velike kompleksnosti samih bioloških molekul in tudi zahtevnosti njihove priprave je proizvodnja bioloških zdravil zelo draga, zato niso dostopna vsem, ki bi jih potrebovali. Posledično je trenutno ena glavnih usmeritev farmacevtske industrije razvoj novih, učinkovitejših in cenejših postopkov proizvodnje. Najpogosteje uporabljena tehnika pri čiščenju in izolaciji bioloških zdravil je kromatografija. Za razliko od veliko pogosteje uporabljenih šaržnih kromatografij je v industrijskem merilu ekonomičnejša in produktivnejša kontinuirna kromatografija. Namen magistrskega dela je razvoj učinkovitejše in cenejše prve stopnje procesa za čiščenje ter izolacijo monoklonskih protiteles, torej kromatografske stopnje na protein A nosilcu. V preliminarnih študijah smo ovrednotili različne protein A kromatografske nosilce, sledila je optimizacija kromatografskega procesa, kjer pa smo upoštevali učinkovito odstranjevanje nečistoč. Proces smo izvedli na sistemu BioSMB z vpeljavo kontinuirne kromatografije na treh kolonah, pri čemer smo določili najbolj optimalne parametre tega procesa. Na izbranih nosilcih smo naredili še dodatne poskuse z uporabo različnih monoklonskih protiteles, s čimer smo pokazali robustnost razvitega procesa. Ker so trendi biotehnologije v čim bolj kontinuirnem delovanju in povezovanju posameznih stopenj, smo povezali bioproces s prvim kromatografskim korakom. V zaključni fazi smo naredili ekonomsko primerjavo šaržnega in kontinuirnega procesa ter potrdili prednosti novega procesa.

Keywords

proteini;protein A;monoklonska protitelesa;kontinuirna kromatografija;kromatografski nosilci;kontinuirni sistemi PCC;biološka zdravila;magistrska dela;

Data

Language: Slovenian
Year of publishing:
Typology: 2.09 - Master's Thesis
Organization: UL FKKT - Faculty of Chemistry and Chemical Technology
Publisher: [B. Jeras]
UDC: 66.081.3(043.2)
COBISS: 1538512579 Link will open in a new window
Views: 777
Downloads: 210
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Other data

Secondary language: English
Secondary title: Development of continuous chromatography for monoclonal antibodies
Secondary abstract: Monoclonal antibodies (mAb) represent the main group of biologics, which are the fastest growing part in pharmaceutical industry. Production of biologics is very expensive due to its complexity and demanding manufacturing processes. For that reason they remain unaffordable to many patients. The main focus of the pharmaceutical industry is therefore the development of new, cost effective and more efficient preparation processes. Chromatography is most commonly used technicque for purification and isolation of biologics. Nowadays, batch chromatography still has important role but especially for large scale, continuous chromatography shows better economical results and productivity. The main purpose of master thesis is development of more efficient and cost effective first chromatography step for purification and isolation of monoclonal antibodies, which is chromatography on protein A resins. In preliminary studies we evaluated different protein A resins and optimized existing length of sequence, where we focused on efficient impurity removal. We developed continuous chromatography step on 3 columns using BioSMB system, where we determined the most optimal parameters. Additional experiments on two additional monoclonal antibodies were done, to show robustness of the developed process. Since trends in industry are going towards a more connected processes, we also connected bioprocess part with protein A chromatography step as first process step of protein purification and isolation. The last part of this thesis was economical evaluation between batch and continuous chromatography, where we confirmed benefits of newly developed process.
Secondary keywords: monoclonal antibodies;continuous chromatography;protein A resins;continuous systems PCC;
Type (COBISS): Master's thesis/paper
Study programme: 1000376
Embargo end date (OpenAIRE): 1970-01-01
Thesis comment: Univ. v Ljubljani, Fak. za kemijo in kemijsko tehnologijo
Pages: XI f., 63 str.
ID: 11364493