Dizajn i konzistentnost industrijske proizvodnje proteinskih lijekova

professional thesis

• Author: Nikolina Gračić
• Mentor: Gordana Maravić Vlahoviček (mentor)
• Committee member: Jasmina Lovrić (predsjednik povjerenstva)
• Committee member: Gordana Maravić Vlahoviček (član povjerenstva)
• Committee member: Vesna Eraković Haber (član povjerenstva); MBZ: 215124
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; Zagreb
• Defense date and country: 2017, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Cilj ovog istraživanja bio je napraviti pregled trenutno dostupnih postupaka u industrijskoj proizvodnji proteinskih lijekova i definirati čimbenike koje je potrebno razmotriti prilikom postavljanja ponovljivog proizvodnog procesa. Postavljene su hipoteze da se odgovarajuće postavljenim proizvodnim procesom dobivaju željeni produkti proizvodnje proteinskih lijekova koji su prikladni za kliničku primjenu te da se odgovarajuće nadziranim i kontroliranim proizvodnim procesom kontinuirano dobivaju konzistentni produkti proizvodnje proteinskih lijekova koji su prikladni za kliničku primjenu.
Dostupna literatura pregledana je u širokom opsegu te su u radu sistematično iznesene opisane mogućnosti pojedinih procesa. Izneseni su i čimbenici za koje je opisano da imaju ili mogu imati utjecaj na ishod procesa. Utvrđeno je da je industrijska proizvodnja proteinskih lijekova složen proces koji je potrebno dizajnirati na način da se u svakom koraku procesa proizvodnje dobije produkt željenih karakteristika bez prisutnih onečišćenja ili s vrstom i količinom onečišćenja unutar definiranih zahtjeva. Dizajniranje proizvodnog procesa uglavnom podrazumijeva individualan pristup proizvodnji različitih proteina. Pritom se, osim karakteristika proteina i onečišćenja, u obzir uzimaju i željeni prinos procesa i troškovi proizvodnje. Pristup odabiru svakog koraka procesa, posebno koracima pročišćavanja, treba biti takav da se u obzir uzimaju drugi koraci procesa te upotrijebljena oprema i materijali. Veći broj koraka u procesu proizvodnje i korištenje sofisticiranih metoda analize čine proces proizvodnje proteinskih lijekova složenijim i skupljim od procesa proizvodnje lijekova malih molekula.
Zaključeno je da se odgovarajuće postavljenim, nadziranim i kontroliranim proizvodnim procesom dobivaju proteinski lijekovi prikladni za kliničku primjenu.

Abstract (english)

The objective of this work was to provide an overview of currently available manufacturing possibilities in industrial protein production and an overview of parameters that should be taken into account when designing a repeatable production process. It was hypothesized that with appropriately designed production process it is possible to obtain products that are adequate for clinical application and that by using appropriately monitored and controlled process it is possible to continuously obtain consistent products that are adequate for clinical application.
Available literature was reviewed in broad extent and described possibilities were systematically presented in this work. Parameters with possible effect on process outcome were also described. It was found that industrial protein production is a complex process that has to be designed in a way that a product with defined characteristics is obtained at each step of production with type and content of impurities within defined limits. Design of production process usually means individual approach to production of different proteins. Characteristics of protein and impurities, required process yield and cost of production have to be taken into account during the design of protein production process. Other production steps and material and equipment used have to be taken into account when deciding on methods that will be used for production and purification. More production steps and use of sophisticated analytical methods makes protein production process more complex and costly than production of small molecule drugs.
In conclusion, appropriately designed, monitored and controlled production process continuously results with protein drug products adequate for clinical application.

• Keywords: proteinski lijekovi; proizvodni proces; onečišćenja u lijekovima
• Keywords (english): protein drugs; production process; drug impurities
• Language: croatian
• URN:NBN: urn:nbn:hr:163:046610
• Study programme: Title: Drug development; Study programme type: university; Study level: postgraduate specialist; Academic / professional title: sveučilišni magistar/sveučilišna magistra razvoja lijekova (sveučilišni magistar/sveučilišna magistra razvoja lijekova)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2017-09-15 12:26:16