Razvoj i validacija spektroskopijske metode bliskoga infracrvenoga zračenja za određivanje udjela vode u cjepivu protiv meningokoka serogrupa A i C

doctoral thesis

• Title (english): Development and validation of a near-infrared spectroscopic method for water content determination in meningococcal vaccine serogroups A and C
• Author: Ines Fabijanić; MBZ: 257081
• Mentor: Anita Slavica (mentor)
• Committee member: Jagoda Šušković (član povjerenstva)
• Granter: University of Zagreb; Faculty of Food Technology and Biotechnology; (Department of Biochemical Engineering); (Laboratory for Biochemical Engineering, Industrial Microbiology and Malting and Brewing Technology); Zagreb
• Defense date and country: 2021-07-07, Croatia
• Scientific / art field, discipline and subdiscipline: BIOTECHNICAL SCIENCES; Biotechnology
• Universal decimal classification (UDC): 615 - Pharmacology. Therapeutics. Toxicology

Abstract

Cilj ovog rada je bio razviti i validirati nove spektroskopijske metode bliskoga infracrvenoga zračenja (NIR) za određivanje udjela vode u liofiliziranom cjepivu protiv meningokoka serogrupa A i C i pročišćenim meningokoknim polisaharidima serogrupe (PMPS) A i C prema sustavnom pristupu procesne analitičke tehnologije (PAT). Novi eksperimetalni dizajn temeljen na metodi standardnog dodavanja u liofilizirana cjepiva omogućio je procjenu točnosti predikcije NIR modela, obuhvativši mjerne nesigurnosti NIR modela i sustavnu pogrešku referentne Karl-Fischer metode. Utvrđeno je da na rezultate određivanja ostatne vode u liofiliziranom cjepivu standardnom Karl-Fischer metodom utječe atmosferska vlaga te je osmišljena Karl-Fischer metoda koja udovoljava kriterijima za referentnu metodu. Profil točnosti potvrdio je da NIR model točno određuje udjel vode u liofiliziranom cjepivu u rasponu od 1,0 - 6,7 %. Izvedbene karakteristike optimalnih NIR modela za određivanje udjela vode u djelatnim tvarima, PMPS A i PMPS C procijenjene su na temelju kemometrijskih parametara. Rezultati ovog rada upućuju na potencijal primjene novih NIR metoda u praćenju kritičnog parametra kvalitete - udjela vode u stvarnom vremenu u svim fazama proizvodnje liofiliziranog cjepiva protiv meningokoka serogrupa A i C prema sustavnom PAT pristupu skraćujući vrijeme za puštanje serije lijeka u promet.

Abstract (english)

The aim of the present study was to develop and validate near-infrared (NIR) spectroscopic methods for water content determination in freeze-dried meningococcal vaccine serogroups A and C and purified meningococcal polysaccharides serogroups (PMPS) A and C in accordance with Process Analytical Technology (PAT). A novel approach based on the standard addition method in freeze-dried vaccines is proposed to clearly demonstrate the NIR model’s ability to give accurate predictions, by evaluating not only uncertainties associated with the NIR calibration model, but also systematic error arising from the reference Karl-Fischer method. However, results for water content in freeze-dried vaccine obtained by standard Karl-Fischer method were influenced by atmospheric moisture. Consequently, the suitability of the newly proposed Karl-Fischer for a reference method was confirmed. The accuracy profile showed that the NIR model successfully determined water content over the 1.0–6.7 % range. In addition, the best NIR models for drug substances, PMPS A and PMPS C were evaluated based on chemometric parameters. The present study confirmed that NIR methods could be used in the PAT concept for monitoring of critical quality parameter - water content in all production phases of freeze-dried meningococcal vaccine serogroups A and C in a timely manner therefore reducing a batch release time.

• Keywords: Karl-Fischer titracija; liofilizirano cjepivo protiv meningokoka serogrupa A i C; NIR spektroskopija; određivanje udjela vode; profil točnosti
• Keywords (english): Karl-Fischer titration; freeze-dried meningococcal vaccine; NIR spectroscopy; water content determination; accuracy profile
• Language: croatian
• URN:NBN: urn:nbn:hr:159:333906
• Promotion: 2021
• Study programme: Title: Postgraduate PhD Study in Nutrition; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje biotehničkih znanosti, polje nutricionizam (doktor/doktorica znanosti, područje biotehničkih znanosti, polje nutricionizam)
• Type of resource: Text
• Extent: 171 str. : 30 cm
• File origin: Born digital
• Access conditions: Open access
• Created on: 2021-11-23 13:04:22