Simultano določanje izbranih kritičnih atributov (CQA) pri razvoju bioloških zdravil s pomočjo FTIR tehnike

Stevanović, Sofija (author), Kolar, Mitja (mentor)

Diplomsko delo predstavlja možnost uporabe spektroskopije FTIR za razvoj bioloških zdravil. Osnovni koncepti spektroskopije FTIR sta interakcija med infrardečo svetlobo in snovjo ter princip Fouriereve transformacije. Analizator MIRA pa predstavlja najsodobnejši in visoko zmogljiv instrument, ki temelji na spektroskopiji FTIR in lahko meri tekoče vzorce. Poudarek eksperimentalnega dela so prednosti in izzivi spektroskopije FTIR, kot so kvalitativna in kvantitativna karakterizacija kompleksnih bioloških vzorcev, napoved sekundarne strukture beljakovin ter zaznavanje agregacije in glikozilacije beljakovin. Pri tem sta analizirana različna vzorca (F1 in F3) s terapevtskimi proteini. Glede na rezultate in dobljene FTIR spektre so ocenjeni učinkovitost, občutljivost in natančnost tehnike FTIR za zaznavanje sprememb v pH, koncentraciji in agregaciji proteinskih vzorcev končnih farmacevtskih izdelkov. Ugotovljeno je bilo, da je tehnika FTIR primerna za določanje pH, sestavin raztopine s kvalitativnega in kvantitativnega vidika, vendar ni primerna za analize vzorcev z nedefinirano sestavo. Ključne so tudi ugotovitve, da tehnika FTIR ni najbolj primerna in učinkovita za vse vrste vzorcev, ker ima nekatere omejitve, kot sta nelinearnost v širšem merilnem območju in občutljivost glede sestave vzorcev. Predlagano je, da so potrebne nadaljnje raziskave tehnike FTIR za potrebe analitike bioloških zdravil.

• Language: Slovenian
• Keywords: FTIR spektroskopija, kritični atributi kakovosti, biofarmacevtika
• Work type: Bachelor thesis/paper
• Organization: FKKT - Faculty of Chemistry and Chemical Technology
• Year: 2024
• PID: 20.500.12556/RUL-161305
• Publication date in RUL: 09.09.2024

Secondary language

• Language: English
• Title: Simultaneous determination of selected critical attributes (CQA) in biosimilar drug development using FTIR technique

Abstract

This thesis presents the possibility of using FTIR spectroscopy for the development of biological drugs. The basic concepts of FTIR spectroscopy are the interaction between infrared light and matter and the Fourier transform principle. The MIRA analyser is a state-of-the-art, high-performance instrument based on FTIR spectroscopy that can measure liquid samples. The experimental work focuses on the benefits and challenges of FTIR spectroscopy, such as qualitative and quantitative characterisation of complex biological samples, protein secondary structure prediction, and detection of protein aggregation and glycosylation. Here, different samples (F1 and F3) with therapeutic proteins are analysed. The performance, sensitivity and accuracy of the FTIR technique for the detection of changes in pH, concentration and aggregation of protein samples of finished pharmaceutical products were evaluated in the light of the results and the FTIR spectra obtained. It was found that the FTIR technique is suitable for the determination of pH, solution constituents from a qualitative and quantitative point of view, but not suitable for the analysis of samples with undefined composition. The key findings are also that the FTIR technique is not the most suitable and efficient for all types of samples because it has some limitations, such as non-linearity over a wider measurement range and sensitivity with respect to the composition of the samples. It is suggested that further research on the FTIR technique for the analysis of biological medicinal products is needed.

• Keywords: FTIR spectroscopy, critical quality attributes, biopharmaceuticals