工艺开发与质量控制

We have measured solutions of lysozyme under conditions known to effect its physical state in order to investigate the potential of Raman spectroscopy as a non-invasive and label-free tool to assess protein formulation stability. Results from this study identified specific Raman signature bands in this protein that can be used to identify individual amino acid residues that are reflect structural changes in proteins.

Recently, nitrosamines, which are likely carcinogenic to humans, have been detected globally in the Sartan class of drugs, Ranitidine and Nizatidine. Medicines regulatory authorities, including the European Medicines Agency (EMA), the U.S. Food and Drug Administration (FDA), and the Japanese Ministry of Health and Welfare (MHLW), have issued notices and guidance to pharmaceutical manufacturers and distributors, requesting self-inspection and assessment regarding the risk of nitrosamine contamination.

医用气体受美国药典(USP)、欧洲药典(EP)和日本药典(JP)的监管，这些药典为所有医用气体制定了标准，包括涉及质量、浓度、纯度、包装、标签和识别的规范。HORIBA 在此领域通过提供多种高精度的分析与测量解决方案为医用气体生产过程的品质控制做出贡献。

监测培养基的条件对促进再生药物和蛋白质合成等过程中的细胞增殖非常重要。由于培养基介质组份复杂，且荧光成份多样，因此需要荧光激发发射三维矩阵(EEM)来同时全面展现发光信息。本篇报告主要通过测量 EEM 来监测细胞增殖过程中的细胞培养基组份的变化。

本应用说明重点展示了 Duetta 荧光分光光度计在极低浓度下测量转铁蛋白的高灵敏度。该仪器可同步进行荧光和吸光度测量，为蛋白质分析提供了关键优势。同时，我们将 Duetta 获得的荧光检测结果与专用低容量台式分光光度计的吸光度检测结果进行了对比分析。

The complexity of viral particles remains one of the biggest hurdles in the development process. In this note, the upstream process of analyzing viral preparations is addressed, as well as the use of multi-laser nanoparticle tracking analysis (NTA) as a cost and time efficient method to measure size, count virus particles, and correlate to infectious titer.

Protein aggregation is an important concern when developing and manufacturing biotherapeutics since these subvisible aggregate particles have been associated with the adverse drug reactions. Protein aggregates may provoke adverse events through an unwanted immune response. And, regardless of mechanism of reaction, subvisible particle contamination has been a concern for manufacturers and regulators.

Size matters in vaccine delivery systems. Nanoparticles smaller than 200 nm generally present a greater immunogenic response than micro-particles larger than 1 micron. This rather simple statement is based on the common understanding that particles with sizes resembling the dimensions of viruses are treated like viruses by the body.

The study of protein aggregation encompasses a broad range of interactions and mechanisms. Many studies into this subject area investigate the aggregation of misfolded proteins, which is thought to be responsible for many degenerative diseases. Since aggregation typically leads to a physical change in protein size, particle size analysis has proven to be a useful experimental technique in this field.

The ViewSizer 3000 enables scientists to visualize and quantify the kinetics of protein aggregation in real-time for biologic therapeutics under a variety of stress conditions including agitation, temperature and the addition of contaminants. The case study featured here validates these capabilities for agitation and temperature stress conditions with the 100 mg/mL mAb A.

Protein scientists typically discuss “protein size” or molecular weight, as opposed to using the phrase “particle size”, but particle size analyzers are often used in their studies. There is also interest in the surface charge or valence of proteins, so zeta potential is another measurement used by protein chemists.

Zeta potential is a key physical parameter that describes surface charge on proteins. Although there has been interest in measuring the zeta potential of proteins for many years, the measurements were often difficult due to a variety of reasons including the “cooking” of proteins on the cell electrodes when using light scattering techniques.

Join Dr. Kevin Dahl of Particlese LLC and Dr. Linda Kidder of HORIBA Scientific provide tips and alternative solutions for better vaccine development and quality. They will discuss the application of multi-laser nanoparticle analysis (NTA) in determining vaccine degradation and total particle count. They will also present a new analytical approach, fluorescence A-TEEM method for rapid screening of similar but different vaccine final formulations.