Development of orthogonal NISTmAb size heterogeneity control methods

Turner, Abigail; Yandrofski, Katharina; Telikepalli, Srivalli; King, Jason; Heckert, Alan; Filliben, James J.; Ripple, Dean C.; Schiel, John E.

doi:10.1007/s00216-017-0819-3

Cited by 33 publications

(48 citation statements)

References 43 publications

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“…Capillary zone electrophoresis (CZE), size exclusion chromatography (SEC), reducing sodium dodecyl sulfate capillary electrophoresis (rCE-SDS), and non-reducing sodium dodecyl sulfate capillary electrophoresis (nrCE-SDS) were performed according to the qualified methods as described in publications 2 and 3 of this series [ 11 , 12 ]. To establish homogeneity and assign reference values, one 150 μL vial fraction (prepared as described in the ESM) was analyzed from three racks (racks 1, 50, 90) of each lot of RM 8671 ( n = 3 vials per lot).…”

Section: Methodsmentioning

confidence: 99%

“…The generic injection sequence was: Blank - IQ - PS 8670 - test samples (no more than 10) - IQ - PS 8670 – Blank, and was repeated as necessary to analyze all samples. Instrument qualification and system suitability controls were required to pass method performance criteria as outlined during method qualification [ 11 , 12 ]. Data analysis for each method was performed as described in the requisite qualification paper [ 9 , 11 , 12 ].…”

Section: Methodsmentioning

confidence: 99%

“…The most immediate utility of the NISTmAb is for physicochemical/biophysical analysis technology development, method control, and harmonization of best practices. An expansive and continuously growing historical characterization dataset has been compiled as a foundation for these intended uses [ 3 – 8 ], a subset of which has been refined and qualified for quality monitoring [ 9 – 12 ], and used herein for quality attribute value assignment as part of the NISTmAb lifecycle management plan.…”

Section: Introductionmentioning

confidence: 99%

“…Property values may be assigned to a given RM through a variety of measurement modes, the results of which influence the value designation (certified, reference, or informational as described in) [ 10 , 13 ]. A series of method-specific protocols, each of which has been recognized by the community as common measurement methods for mAbs, were qualified to be suitable for NISTmAb measurement in the preceding papers of this series using the in-house NISTmAb primary sample (PS 8670) [ 9 – 12 ]. The physicochemical property values were then assigned to each individual lot of RM 8671 using the qualified methods and a stratified sampling and analysis plan, thereby allowing simultaneous evaluation of intra-lot homogeneity.…”

Section: Introductionmentioning

confidence: 99%

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The NISTmAb Reference Material 8671 value assignment, homogeneity, and stability

et al. 2018

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The NISTmAb Reference Material (RM) 8671 is intended to be an industry standard monoclonal antibody for pre-competitive harmonization of best practices and designing next generation characterization technologies for identity, quality, and stability testing. It must therefore embody the quality and characteristics of a typical biopharmaceutical product and be available long-term in a stable format with consistent product quality attributes. A stratified sampling and analysis plan using a series of qualified analytical and biophysical methods is described that assures RM 8671 meets these criteria. Results for the first three lots of RM 8671 highlight the consistency of material attributes with respect to size, charge, and identity. RM 8671 was verified to be homogeneous both within and between vialing lots, demonstrating the robustness of the lifecycle management plan. It was analyzed in concert with the in-house primary sample 8670 (PS 8670) to provide a historical link to this seminal material. RM 8671 was verified to be fit for its intended purpose as a technology innovation tool, external system suitability control, and cross-industry harmonization platform. Graphical abstractThe NISTmAb Reference Material (RM) 8671 is intended to be an industry standard monoclonal antibody for pre-competitive harmonization of best practices and designing next generation characterization technologies for identity, quality, and stability testing. Electronic supplementary materialThe online version of this article (10.1007/s00216-017-0800-1) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The NISTmAb Reference Material 8671 value assignment, homogeneity, and stability

et al. 2018

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“…SEC uses porous stationary phase material wherein the size variants are separated based on the differential access to the pores of the SEC material resulting in different path lengths in relationship to the size [61,62]. SEC is effectively separating low molecular weight and high molecular weight species in mAbs [63]. SEC has found many applications like stability testing [64], quality control during manufacturing [65], in depth characterization of antibody-drug-conjugates (ADC's) [66] and assessing aggregate content in biosimilarity studies [67].…”

Section: Separation Of Proteoforms Of Therapeutic Proteins 41 Separamentioning

confidence: 99%

Preparing Proteoforms of Therapeutic Proteins for Top-Down Mass Spectrometry

Hidayah¹,

Gaikwad²,

Heikaus³

et al. 2020

Proteoforms - Concept and Applications in Medical Sciences

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A characteristic of many proteoforms, derived from a single gene, is their similarity regarding the composition of atoms, making their analysis very challenging. Many overexpressed recombinant proteins are strongly associated with this problem, especially recombinant therapeutic glycoproteins from large-scale productions. In contrast to small molecule drugs, which consist of a single defined molecule, therapeutic protein preparations are heterogenous mixtures of dozens or even hundreds of very similar species. With mass spectrometry, currently highquality spectra of intact proteoforms can be obtained only, if the complexity of the mixture of individual proteoform-ions, entering the gas phase at the same time is low. Thus, prior to mass spectrometric analysis, an effective separation is required for getting fractions with a low number of individual proteoforms. This is especially true not only for recombinant therapeutic proteins, because of their huge heterogeneity, but also relevant for top-down proteomics. Purification of proteoforms is the bottleneck in analyzing intact proteoforms with mass spectrometry. This review is focusing on the current state of the art, especially of liquid chromatography for preparing proteoforms for mass spectrometric top-down analysis. The topic of therapeutic proteins has been chosen, because this group of proteins is most challenging regarding their proteoform analysis.

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Automatic Continuous Online Monitoring and Control of Polymerization Reactions and Related Methods

Reed

2019

Encyclopedia of Analytical Chemistry

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Automatic continuous online monitoring and control of polymerization (ACOMP) is a widely applicable platform for monitoring and controlling polymerization reactions. It relies on the continuous extraction, dilution, and conditioning of a small sample stream from the reactor on which measurements by various combinations of detectors are made. By combining simultaneous data from multiple detectors continuous monitoring of salient reaction characteristics can be made, such as kinetics, conversion of comonomers, composition drift, evolution of molecular mass and intrinsic viscosity, and detection of unusual phenomena, such as microgelation and runaway reactions. A growing area for ACOMP is its integration into predictive and closed‐loop reaction control with intriguing possibilities for enhancement by machine learning and artificial intelligence. Typical detectors include light scattering (LS), ultraviolet (UV)/visible spectrophotometry, viscometry, refractivity, and polarimetry, while NMR, dynamic light scattering (DLS), Mie scattering, conductivity, and near infrared (IR) and Fourier‐transform infrared (FTIR) are also used. Recent additions to ACOMP include the ability to use multiple similar sensors to detect the onset and evolution of polymer stimuli responsive behavior during synthesis; for example copolymer compositions at which a lower critical solution temperature (LCST) occurs. ACOMP has been applied to free radical, controlled free radical, and condensation reactions, to micellar, emulsion, and inverse emulsion polymerization, to post‐polymerization and derivatization reactions, and to batch, semi‐batch, and continuous reactors. While ACOMP is not inherently a chromatographic method, its continuous stream can be used in automatic conjunction with gel permeation and other separation chromatographies. Recently, ACOMP has been deployed in full‐scale industrial polymerization reactors to optimize efficiency and product quality.

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Development of orthogonal NISTmAb size heterogeneity control methods

Cited by 33 publications

References 43 publications

The NISTmAb Reference Material 8671 value assignment, homogeneity, and stability

The NISTmAb Reference Material 8671 value assignment, homogeneity, and stability

Preparing Proteoforms of Therapeutic Proteins for Top-Down Mass Spectrometry

Automatic Continuous Online Monitoring and Control of Polymerization Reactions and Related Methods

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