Subvisible Particulate Matter in Therapeutic Protein Injections

Новик, Е. С.; Dorenskaya, A. V.; Борисова, Н. А.; Гунар, О. В.

doi:10.1007/s11094-019-02005-z

Cited by 6 publications

(4 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The close agreement between the two curves confirms the reliability of the LO measurement. improve the accuracy in particle sizing by Light Obscuration measurements in several fields [5,6].…”

Section: Jinst 19 P04035mentioning

confidence: 99%

See 1 more Smart Citation

DEDALO: Device for Enhanced Dust Analyses with Light Obscuration sensors

Teruzzi,

Cremonesi,

Potenza

2024

J. Inst.

View full text Add to dashboard Cite

Instruments based on light obscuration sensors are widely used for measuring the size distribution of insoluble sub-visible particles in liquid suspensions, being fast and suitable for in situ and real-time measurements. Such instruments are typically calibrated by means of reference polystyrene spherical particles with a specific refractive index, which unavoidably leads to systematic errors when determining the size of particles of different materials. In this paper, we propose a reliable and consistent method to overcome this limitation by setting the refractive index value according to the sample, thus achieving an improved particle size distribution (PSD) measurement. An ad hoc, ready-to-use, open source code with a graphical interface able to drive an in-line instrument and obtain a real-time correction to the PSD has been developed. The method has been extensively validated with several oil emulsions characterized by different refractive index values and the results have been compared with an independent optical method. As an example of application, we have adopted this approach for the analysis of dust suspended in meltwater of an ice core from a glacier in the Aosta Valley (Italy). We believe that our approach will strongly improve the accuracy in characterizing liquid suspensions and reduce discrepancies between data obtained with different methods. The code has been made publicly available at: https://instrumentaloptics.fisica.unimi.it/dedalo/ and on the GitHub page of the corresponding author (https://github.com/LucaTeruzzi/DEDALO).

show abstract

Section: Jinst 19 P04035mentioning

confidence: 99%

“…Additionally, they are fast, easy to use, and can be used in situ or with minimal sample preparation. Therefore, they are suitable for real-time monitoring and process control applications [5,6]. They provide results within seconds, which is crucial for industrial use, including pharmaceuticals and electronics applications.…”

Section: Introductionmentioning

confidence: 99%

DEDALO: Device for Enhanced Dust Analyses with Light Obscuration sensors

Teruzzi,

Cremonesi,

Potenza

2024

J. Inst.

View full text Add to dashboard Cite

show abstract

“…Denatured proteins or proteins that maintain a structurally altered conformation are more prone to protein aggregation. , The aggregated proteins can form a distribution of particle ensembles from a nanometer to micrometer size . Of particular concern are subvisible particles (SVPs) with dimensions approximately between 1 and 100 μm because of the increased scrutiny from regulatory agencies such as the U.S. Food and Drug Administration. − These particles may increase the risk of immunogenicity relative to the same monomeric protein, as demonstrated by various in vitro and animal models. − Whether SVP-mediated immunogenicity occurs or not seems to depend on the size and concentration of aggregates, the stress condition used to generate the aggregates, the protein itself, and the model used in the study (e.g., in vitro or mouse-based models). The relationship between these studies and immunogenicity in the clinic remains poorly understood.…”

Section: Introductionmentioning

confidence: 99%

“…The relationship between these studies and immunogenicity in the clinic remains poorly understood. It is also critical to note that the amount of aggregates/SVPs used in such studies is typically much higher than what is normally found in commercial biotherapeutic products, which are expected to comply with limits set in the United States and European Pharmacopeias. , Currently, there are safe, marketed products that were approved prior to the routine monitoring and control of SVPs. Nevertheless, there is a need to better understand the subvisible particle (SVP) formation to more effectively identify and disrupt potential particle formation pathways to ensure product quality, safety, and regulatory expectations …”

Section: Introductionmentioning

confidence: 99%

The Impact of the Metal Interface on the Stability and Quality of a Therapeutic Fusion Protein

et al. 2020

View full text Add to dashboard Cite

Subvisible particle formation, which occurs after the sterile filtration step of the fill/finish process, is a challenge that may occur during the development of biotherapeutics with complex molecular structures. Here, we show that a stainless steel pump head from a rotary piston pump produces more protein aggregates, past the limit of the acceptable quality range for subvisible particle counts, in comparison to a ceramic pump head. The quartz crystal microbalance was used to quantify the primary layer, proteins irreversibly adsorbed at the solid–liquid interface, and the secondary diffuse gel-like layer interacting on top of the primary layer. The results showed that the mass of protein irreversibly adsorbed onto stainless steel sensors is greater than on an aluminum oxide surface (ceramic pump mimic). This suggests that the amount of adsorbed protein plays a role in surface-induced protein aggregation at the solid–liquid interface.

show abstract