Investigation of a Degradant in a Biologics Formulation Buffer Containing L-Histidine

Wang, Chunlei; Yamniuk, Aaron P.; Dai, Jun; Chen, Sike; Stetsko, Paul; Ditto, Noah T; Zhang, Yingru

doi:10.1007/s11095-015-1648-8

Cited by 5 publications

(3 citation statements)

References 25 publications

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“…Wang and colleagues report the investigation of a degradant in a biologics formulation buffer containing L-histidine. 90 , 91 As described in this study, histidine can degrade to urocanic acid. Histidine degradation was slightly increased by Mn +2 .…”

Section: Review Of Hcapsmentioning

confidence: 66%

A systematic review of commercial high concentration antibody drug products approved in the US: formulation composition, dosage form design and primary packaging considerations

Ghosh,

Gutka,

Krause

et al. 2023

mAbs

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Three critical aspects that define high concentration antibody products (HCAPs) are as follows: 1) formulation composition, 2) dosage form, and 3) primary packaging configuration. HCAPs have become successful in the therapeutic sector due to their unique advantage of allowing subcutaneous self-administration. Technical challenges, such as physical and chemical instability, viscosity, delivery volume limitations, and product immunogenicity, can hinder successful development and commercialization of HCAPs. Such challenges can be overcome by robust formulation and process development strategies, as well as rational selection of excipients and packaging components. We compiled and analyzed data from US Food and Drug Administration-approved and marketed HCAPs that are ≥100 mg/mL to identify trends in formulation composition and quality target product profile. This review presents our findings and discusses novel formulation and processing technologies that enable the development of improved HCAPs at ≥200 mg/mL. The observed trends can be used as a guide for further advancements in the development of HCAPs as more complex antibody-based modalities enter biologics product development.

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Section: Review Of Hcapsmentioning

confidence: 66%

A systematic review of commercial high concentration antibody drug products approved in the US: formulation composition, dosage form design and primary packaging considerations

Ghosh,

Gutka,

Krause

et al. 2023

mAbs

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show abstract

“…Sample color has also been correlated with enrichment in acidic species of mAbs (Butko, Pallat, Cordoba, & Yu, 2014). Use of chelators, antioxidants, or radical scavengers, such as EDTA or diethylene triamine pentaactic acid, have proven successful in mitigating the catalytic activities of degrading enzymes and oxidative stresses (Lam, Yang, & Cleland, 1997; Wang et al, 2015). Photo‐induced degradation could be mitigated through reducing unnecessary light exposure during manufacturing and storage (Du et al, 2019).…”

Section: Appearance Attributesmentioning

confidence: 99%

Strategies for high‐concentration drug substance manufacturing to facilitate subcutaneous administration: A review

Holstein

Hung

Feroz

et al. 2020

Biotech & Bioengineering

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To achieve the high protein concentrations required for subcutaneous administration of biologic therapeutics, numerous manufacturing process challenges are often encountered. From an operational perspective, high protein concentrations result in highly viscous solutions, which can cause pressure increases during ultrafiltration. This can also lead to low flux during ultrafiltration and sterile filtration, resulting in long processing times. In addition, there is a greater risk of product loss from the holdup volumes during filtration operations. From a formulation perspective, higher protein concentrations present the risk of higher aggregation rates as the closer proximity of the constituent species results in stronger attractive intermolecular interactions and higher frequency of self-association events. There are also challenges in achieving pH and excipient concentration targets in the ultrafiltration/ diafiltration (UF/DF) step due to volume exclusion and Donnan equilibrium effects, which are exacerbated at higher protein concentrations. This paper highlights strategies to address these challenges, including the use of viscosity-lowering excipients, appropriate selection of UF/DF cassettes with modified membranes and/or improved flow channel design, and increased understanding of pH and excipient behavior during UF/DF. Additional considerations for high-concentration drug substance manufacturing, such as appearance attributes, stability, and freezing and handling are also discussed. These strategies can be employed to overcome the manufacturing process challenges and streamline process development efforts for high-concentration drug substance manufacturing.

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“…HILIC columns have been used for released glycans characterization and biologics formulation excipients characterization. 17,18 On ERLIC, the column stationary phase is positively charged and repulses basic peptides back to the mobile phase. Meanwhile, the mobile phase contains a high percentage of organic solvents, resulting in a water layer formed on the stationary phase, which would retain the polar peptides through hydrophilic interaction.…”

Section: Introductionmentioning

confidence: 99%

Antibody characterization using novel ERLIC-MS/MS-based peptide mapping

Jing

Kim²,

Zhou³

et al. 2018

mAbs

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Electrostatic repulsion hydrophilic interaction chromatography (ERLIC) coupled with mass spectrometry (MS) is a technique that is increasingly being used as a trapping/enrichment tool for glycopeptides/phosphorylated peptides or sample fractionation in proteomics research. Here, we describe a novel ERLIC-MS/MS-based peptide mapping method that was successfully used for the characterization of denosumab, in particular the analysis of sequence coverage, terminal peptides, methionine oxidation, asparagine deamidation and glycopeptides. Compared to reversed phase liquid chromatography (RPLC)-MS/MS methods, ERLIC demonstrated unique advantages in the retention of small peptides, resulting in 100% sequence coverage for both the light and heavy chains. It also demonstrated superior performance in the separation and characterization of asparagine deamidated peptides, which is known to be challenging by RPLC-MS/MS. The developed method can be used alone for peptide mapping-based characterization of monoclonal antibodies, or as an orthogonal method to complement the RPLC-MS/MS method. This study extends the applications of ERLIC from that of a trapping/fractioning column to biologic therapeutics characterization. The ERLIC-MS/MS method can enhance biologic therapeutics analysis with more reliability and confidence for bottom-up peptide mapping-based characterization.

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Investigation of a Degradant in a Biologics Formulation Buffer Containing L-Histidine

Abstract: L-histidine formulation buffer can be contaminated to induce histidine degradation to trans-urocanic acid, which shows a large UV 280 nm absorbing peak at the total permeation volume under SEC conditions. Amino acids alanine and cysteine effectively inhibit this histidine degradation.

Cited by 5 publications

References 25 publications

A systematic review of commercial high concentration antibody drug products approved in the US: formulation composition, dosage form design and primary packaging considerations

A systematic review of commercial high concentration antibody drug products approved in the US: formulation composition, dosage form design and primary packaging considerations

Strategies for high‐concentration drug substance manufacturing to facilitate subcutaneous administration: A review

Antibody characterization using novel ERLIC-MS/MS-based peptide mapping

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