Aluminum Phosphate Vaccine Adjuvant: Analysis of Composition and Size Using Off-Line and In-Line Tools
| Autor: | Ulrich Schacht, Carmen Mei, Liliana M. Sampaleanu, Nicole Lazaris, Marina Kirkitadze, Shuxin Cong, James Cronin, Matthew Balmer, Sylvie Morin, Daniel Chapman, Sasmit S. Deshmukh, Katherine Drolet-Vives, Moriam O. Ore, Bruce Carpick |
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| Rok vydání: | 2019 |
| Předmět: |
Materials science
lcsh:Biotechnology Process analytical technology medicine.medical_treatment Biophysics Infrared spectroscopy Raw material Focused beam reflectance measurement (FBRM®) Biochemistry 03 medical and health sciences 0302 clinical medicine Structural Biology lcsh:TP248.13-248.65 Genetics medicine Advanced manufacturing 030304 developmental biology Process analytical technology (PAT) 0303 health sciences Fourier transform infrared spectroscopy (FTIR) Final product X-ray photoelectron spectroscopy (XPS) Laser diffraction (LD) Particle size distribution 3. Good health Computer Science Applications Chemical engineering 030220 oncology & carcinogenesis Attenuated total reflection Aluminum phosphate adjuvant (AlPO4) Raman spectroscopy Particle size Adjuvant Research Article Biotechnology |
| Zdroj: | Computational and Structural Biotechnology Journal Computational and Structural Biotechnology Journal, Vol 17, Iss, Pp 1184-1194 (2019) |
| ISSN: | 2001-0370 |
| DOI: | 10.1016/j.csbj.2019.08.003 |
| Popis: | Purpose Aluminum-based adjuvants including aluminum phosphate (AlPO4) are commonly used in many human vaccines to enhance immune response. The interaction between the antigen and adjuvant, including the physical adsorption of antigen, may play a role in vaccine immunogenicity and is a useful marker of vaccine product quality and consistency. Thus, it is important to study the physicochemical properties of AlPO4, such as particle size and chemical composition. Control of the vaccine adjuvant throughout the manufacturing process, including raw materials and the intermediate and final product stages, can be effectively achieved through monitoring of such key product attributes to help ensure product quality. Methods This study focuses on the compositional analysis of AlPO4 adjuvant at the intermediate and final manufacturing stages using the off-line methods Fourier-Transform Infrared (FTIR) and Raman spectroscopy, X-ray Photoelectron Spectroscopy (XPS), and the in-line method Attenuated Total Reflectance (ATR). Particle size distribution of AlPO4 was measured off-line using Laser diffraction (LD) and in-line using Focused Beam Reflectance Measurement (FBRM®). Results There was no observable difference in size distribution between the intermediate and final stage AlPO4 by off-line and in-line analysis, in both small- or large-scale production samples. Consistent peak shifts were observed in off-line and in-line infrared (IR) spectroscopy as well as off-line XPS for both small- and large-scale AlPO4 manufacturing runs. Additionally, IR spectroscopy and FBRM® for size distribution were used as in-line process analytical technology (PAT) to monitor reaction progress in real-time during small-scale AlPO4 manufacturing from raw materials. The small-scale adsorption process of a model protein antigen (Tetanus toxoid) to AlPO4 adjuvant was also monitored by in-line ReactIR probe. Conclusion This study demonstrated that in-line PAT can be used to monitor particle size and chemical composition for the various stages of adjuvant manufacturing from raw materials through intermediate to final adjuvant product stage. Similar approaches can be utilized to help assess lot-to-lot consistency during adjuvant manufacturing and vaccine product development. Moreover, the use of in-line PAT is highly conductive to advanced manufacturing strategies such as real-time product release testing and automated processes of the future. Graphical Abstract Unlabelled Image |
| Databáze: | OpenAIRE |
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