Factors Governing the Accuracy of Subvisible Particle Counting Methods

Quiroz, Anacelia Ríos; Finkler, Christof; Huwyler, Jörg; Mahler, Hanns‐Christian; Schmidt, Roland; Koulov, Atanas V.

doi:10.1016/j.xphs.2016.03.044

Cited by 19 publications

(14 citation statements)

References 36 publications

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“…3). Similar to literature reports on SMPs 28,46 and as discussed earlier for the shared protein control, NTA resulted in overall higher particle concentration than RMM. Although the particle concentration between the methods were orders of magnitude different, a weak positive correlation exists between the 2 techniques (Pearson correlation coefficient of 0.39, p ¼ 0.006, Table 1), indicating a link between the outcomes from these 2 techniques.…”

Section: Submicron Particle Analysis On Late-phase Clinical and Commesupporting

confidence: 88%

“…29 However, significant differences (approximately 2 orders of magnitude) were observed in the protein control particle concentration between the 2 techniques (Figs. 2c vs. 2d) that is consistent with the published results for a low-concentration therapeutic protein product, 28 suggesting that the observed difference is not sample-related but likely arises from the particle counting technology. The higher particle concentration by NTA can partly be explained by differences in the particle size limits of the 2 techniques, that is, the mean particle size measured by RMM was greater than that by NTA (a difference of >200 nm, Appendix E-2).…”

Section: System Suitability Standards: Polystyrene Beads For Size Andsupporting

confidence: 88%

“…For "clean" samples with low particle concentration, a sufficient sample volume should be measured to ensure an adequate number of detected particles. 27,28 For this benchmarking study, no minimal volume was specified as it was the participant's responsibility to ensure sufficient volume was used. For robust and reproducible data, it was recommended to perform triplicate measurements by loading a fresh sample aliquot for every replicate.…”

Section: Rmm: Concentration Range Dilution and Methods For Samples/mentioning

confidence: 99%

See 2 more Smart Citations

A Multicompany Assessment of Submicron Particle Levels by NTA and RMM in a Wide Range of Late-Phase Clinical and Commercial Biotechnology-Derived Protein Products

Hubert¹,

Yang

Kwok

et al. 2020

Journal of Pharmaceutical Sciences

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One of the major product quality challenges for injectable biologics is controlling the amount of protein aggregates and particles present in the final drug product. This article focuses on particles in the submicron range (<2 mm). A cross-industry collaboration was undertaken to address some of the analytical gaps in measuring submicron particles (SMPs), developing best practices, and surveying the concentration of these particles present in 52 unique clinical and commercial protein therapeutics covering 62 dosage forms. Measured particle concentrations spanned a range of 4 orders of magnitude for nanoparticle tracking analysis and 3 orders of magnitude for resonant mass measurement. The particle concentrations determined by the 2 techniques differed significantly for both control and actual product. In addition, results suggest that these techniques exhibit higher variability compared to well-established subvisible particle characterization techniques (e.g., flow-imaging or light obscuration). Therefore, in their current states, nanoparticle tracking analysis and resonant mass measurementebased techniques can be used during product and process characterization, contributing information on the nature and propensity for formation of submicron particles and what is normal for the product, but may not be suitable for release or quality control testing. Evaluating the level of SMPs to which humans have been routinely exposed during the administration of several commercial and late-phase clinical products adds critical knowledge to our understanding of SMP levels that may be considered acceptable from a safety point of view. This article also discusses dependence of submicron particle size and concentration on the dosage form attributes such as physical state, primary packaging, dose strength, etc. To the best of our knowledge, this is the largest study ever conducted to characterize SMPs in late-phase and commercial products.

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Section: Submicron Particle Analysis On Late-phase Clinical and Commesupporting

confidence: 88%

Section: System Suitability Standards: Polystyrene Beads For Size Andsupporting

confidence: 88%

Section: Rmm: Concentration Range Dilution and Methods For Samples/mentioning

confidence: 99%

See 1 more Smart Citation

A Multicompany Assessment of Submicron Particle Levels by NTA and RMM in a Wide Range of Late-Phase Clinical and Commercial Biotechnology-Derived Protein Products

Hubert¹,

Yang

Kwok

et al. 2020

Journal of Pharmaceutical Sciences

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“…Using the flow imaging microscopy method, we found that SvP contaminationsdand cell debrisdcan be differentiated from actual cells in cell therapy products by the analyst. While the flow imaging microscopy method is currently not suggested for quality control purposes for traditional drug products, 17,22 the method may offer value in a process assessment related to minimizing potential particulate contaminations and support product development and the particle control strategy for cell therapy products.…”

Section: Resultsmentioning

confidence: 99%

“…[13][14][15][16] Even though MFI and FlowCAM are based on the same measurement principle, they differ in resolution and particle parameters. 17 However, in some cases, MFI may provide more accurate particle determinations. 15,16,18 Flow imaging methods also provide the benefit of morphological assessments; hence, the differentiation of different particle species may be achievable.…”

Section: Introductionmentioning

confidence: 99%

Subvisible Particulate Contamination in Cell Therapy Products—Can We Distinguish?

Vollrath

Mathaes

Sediq

et al. 2020

Journal of Pharmaceutical Sciences

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Cell therapy products represent an exciting new class of medicinal products, which must be parenterally administered. Thus, compliance with parenteral preparation guidelines is required. One requirement for parenteral products is the characterization of particle contaminations. As cell-based products are turbid suspensions, containing particles, the cells, characterization and control of foreign particle impurities remain a challenge. Within this study, we evaluated a flow imaging microscopy method for the detection and characterization of subvisible particle contaminations in cell-based products. We found that flow imaging microscopy is a potential method where subvisible particle contaminations can be differentiated from the cells in cell therapy products.

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Process Development of Protein Therapeutics

Huang¹,

Bowes²,

Yang³

et al. 2021

Burger's Medicinal Chemistry and Drug Discovery

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The application of recombinant DNA technology to the production of protein therapeutics has undergone tremendous progress over the past decades. Considerable scientific effort has been devoted to developing robust processes that produce large amounts of complex proteins with the desired product quality attributes. An overview of the contributions from the four major disciplines working in concert to deliver these processes and methods will be covered. This article will discuss some of the tools, methods, and approaches used to produce, purify, formulate, and analyze the drugs of modern biotechnology. Future trends in each of the disciplines will also be presented.

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Factors Governing the Accuracy of Subvisible Particle Counting Methods

Cited by 19 publications

References 36 publications

A Multicompany Assessment of Submicron Particle Levels by NTA and RMM in a Wide Range of Late-Phase Clinical and Commercial Biotechnology-Derived Protein Products

A Multicompany Assessment of Submicron Particle Levels by NTA and RMM in a Wide Range of Late-Phase Clinical and Commercial Biotechnology-Derived Protein Products

Subvisible Particulate Contamination in Cell Therapy Products—Can We Distinguish?

Process Development of Protein Therapeutics

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