Protein particles: What we know and what we do not know

Ripple, Dean C.; Dimitrova, Mariana N.

doi:10.1002/jps.23242

Cited by 91 publications

(74 citation statements)

References 44 publications

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“…Such differences may originate from the different physical principles that some of the methods use, thus presenting inherent difficulties. Additional challenges may be posed by sample composition and the properties of the different types of particles present in the sample (for example, particles with refractive index values close to that of the medium may be difficult to detect accurately by either light obscuration or flow microscopy measurements (18,20,21)). As we develop comprehensive understanding of the analytical performance of the various techniques for particle characterization available today, it is essential that we strive to grasp the complex factors governing their operation.…”

Section: Discussionmentioning

confidence: 99%

Factors Governing the Precision of Subvisible Particle Measurement Methods – A Case Study with a Low-Concentration Therapeutic Protein Product in a Prefilled Syringe

et al. 2015

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Purpose The current study was performed to assess the precision of the principal subvisible particle measurement methods available today. Special attention was given to identifying the sources of error and the factors governing analytical performance. Methods The performance of individual techniques was evaluated using a commercial biologic drug product in a prefilled syringe container. In control experiments, latex spheres were used as standards and instrument calibration suspensions. ResultsThe results reported in this manuscript clearly demonstrated that the particle measurement techniques operating in the submicrometer range have much lower precision than the micrometer size-range methods. It was established that the main factor governing the relatively poor precision of submicrometer methods in general and inherently, is their low sampling volume and the corresponding large extrapolation factors for calculating final results. ConclusionsThe variety of new methods for submicrometer particle analysis may in the future support product characterization; however, the performance of the existing methods does not yet allow for their use in routine practice and quality control.KEY WORDS subvisible particles . precision . particle counting methods . protein particles ABBREVIATIONS CC Coulter counter CV Coefficient of variance ECD Equivalent circular diameter MFI Micro flow imaging LO Light obscuration NTA Nanoparticle tracking analysis PFS Pre-filled syringe r.h. Relative humidity RMM Resonant mass measurement RMM (+) Positively buoyant particles detected by RMM RMM (−) Negatively buoyant particles detected by RMM

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Section: Discussionmentioning

confidence: 99%

Factors Governing the Precision of Subvisible Particle Measurement Methods – A Case Study with a Low-Concentration Therapeutic Protein Product in a Prefilled Syringe

et al. 2015

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“…When comparing particle sizes and size distributions, it needs to be considered that the results depend on the type of instrument and measurement principle used to generate the data [8]. Even for the same measurement principle, this can differ for different instruments.…”

Section: General Recommendations and Pitfalls For Particle Analysismentioning

confidence: 99%

“…Another challenge for protein particle analysis is the lack of standards or surrogate particles that are representative for protein particles and their properties [8,33,53,79]. As an example, light obscuration, flow imaging, electric sensing zone, and resonant mass measurement are capable of analyzing micron particles, but with different measurement principles.…”

Section: General Recommendations and Pitfalls For Particle Analysismentioning

confidence: 99%

Subvisible and Visible Particle Analysis in Biopharmaceutical Research and Development

Hawe¹,

Zölls²,

Freitag³

et al. 2015

Biophysical Characterization of Proteins in Developing Biopharmaceuticals

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“…It is during the optimization of such formulations that careful attention must be paid to mitigating the formation of aggregates and particulates, which may arise via several destabilization processes. 2 Mechanisms leading to protein aggregation in bulk solution in the context of formulation have been widely reviewed. 3 Briefly, they include covalent changes such as oxidation and deamination, and physical changes arising from protein-protein interactions and surface adsorption-desorption.…”

Section: Introductionmentioning

confidence: 99%

Antibody adsorption on the surface of water studied by neutron reflection

Smith

Holman

et al. 2017

mAbs

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Surface and interfacial adsorption of antibody molecules could cause structural unfolding and desorbed molecules could trigger solution aggregation, resulting in the compromise of physical stability. Although antibody adsorption is important and its relevance to many mechanistic processes has been proposed, few techniques can offer direct structural information about antibody adsorption under different conditions. The main aim of this study was to demonstrate the power of neutron reflection to unravel the amount and structural conformation of the adsorbed antibody layers at the air/water interface with and without surfactant, using a monoclonal antibody 'COE-3 0 as the model. By selecting isotopic contrasts from different ratios of H 2 O and D 2 O, the adsorbed amount, thickness and extent of the immersion of the antibody layer could be determined unambiguously. Upon mixing with the commonly-used non-ionic surfactant Polysorbate 80 (Tween 80), the surfactant in the mixed layer could be distinguished from antibody by using both hydrogenated and deuterated surfactants. Neutron reflection measurements from the co-adsorbed layers in null reflecting water revealed that, although the surfactant started to remove antibody from the surface at 1/100 critical micelle concentration (CMC) of the surfactant, complete removal was not achieved until above 1/10 CMC. The neutron study also revealed that antibody molecules retained their globular structure when either adsorbed by themselves or co-adsorbed with the surfactant under the conditions studied.

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Protein particles: What we know and what we do not know

Cited by 91 publications

References 44 publications

Factors Governing the Precision of Subvisible Particle Measurement Methods – A Case Study with a Low-Concentration Therapeutic Protein Product in a Prefilled Syringe

Factors Governing the Precision of Subvisible Particle Measurement Methods – A Case Study with a Low-Concentration Therapeutic Protein Product in a Prefilled Syringe

Subvisible and Visible Particle Analysis in Biopharmaceutical Research and Development

Antibody adsorption on the surface of water studied by neutron reflection

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