<b>Formulation concerns of protein drugs</b>

Chen, Tracy

doi:10.3109/03639049209046331

Cited by 49 publications

(25 citation statements)

References 131 publications

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“…It was shown that a highly conserved histidyl residue in the center of the Protein A binding site of IgGs faces a complementary histidyl residue on Protein A (Chen, 1992). These residues have a positive charge at low pH, thus repelling each other and dissociating the Protein A-IgG hydrophilic interaction.…”

Section: Exposure To Low Ph Conditionmentioning

confidence: 99%

“…As a result, operating conditions for Protein A columns typically require the use of low pH conditions (between pH 3 and 4). At this low pH proteins might undergo structural changes that could contribute to product aggregation (Chen, 1992;Krishnamurthy and Manning, 2002). In the preparation of CamPath-1H 1 (Alemtuzumab), which elutes from the Protein A column with 0.1 M Sodium Citrate, pH 3.2, the eluate contained approximately 25% aggregated mAb (Phillips et al, 2001).…”

Section: Exposure To Low Ph Conditionmentioning

confidence: 99%

“…In the preparation of CamPath-1H 1 (Alemtuzumab), which elutes from the Protein A column with 0.1 M Sodium Citrate, pH 3.2, the eluate contained approximately 25% aggregated mAb (Phillips et al, 2001). Strategies to minimize aggregate formation during Protein A chromatography have been considered and include the use of urea-a chaotropic agent-at moderate concentrations (<2 M) as an effective stabilizer or to carry out the separation under low temperature conditions (Chen, 1992).…”

Section: Exposure To Low Ph Conditionmentioning

confidence: 99%

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Aggregates in monoclonal antibody manufacturing processes

Vázquez-Rey¹,

Lang

2011

Biotech & Bioengineering

417

304

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Monoclonal antibodies have proved to be a highly successful class of therapeutic products. Large-scale manufacturing of pharmaceutical antibodies is a complex activity that requires considerable effort in both process and analytical development. If a therapeutic protein cannot be stabilized adequately, it will lose partially or totally its therapeutic properties or even cause immunogenic reactions thus potentially further endangering the patients' health. The phenomenon of protein aggregation is a common issue that compromises the quality, safety, and efficacy of antibodies and can happen at different steps of the manufacturing process, including fermentation, purification, final formulation, and storage. Aggregate levels in drug substance and final drug product are a key factor when assessing quality attributes of the molecule, since aggregation might impact biological activity of the biopharmaceutical. In this review it is analyzed how aggregates are formed during monoclonal antibody industrial production, why they have to be removed and the manufacturing process steps that are designed to either minimize or remove aggregates in the final product.

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Section: Exposure To Low Ph Conditionmentioning

confidence: 99%

Section: Exposure To Low Ph Conditionmentioning

confidence: 99%

Section: Exposure To Low Ph Conditionmentioning

confidence: 99%

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Aggregates in monoclonal antibody manufacturing processes

Vázquez-Rey¹,

Lang

2011

Biotech & Bioengineering

417

304

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“…One is to increase the conformational stability of proteins and reduce unfolding (e.g., through the mechanism proposed by Timasheff. 3,[13][14][15][16] Another possibility is to reduce the irreversible degradation of unfolded species and thus increase the apparent reversibility of thermal unfolding. 17,18 This article suggests the use of detergents to increase protein stability by means of the second mechanism.…”

Section: Effect Of Tween 80 On Unfolding and Aggregation At 60°cmentioning

confidence: 99%

Protection of Bovine Serum Albumin from Aggregation by Tween 80

Arakawa

Kita

2000

Journal of Pharmaceutical Sciences

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“…DSC has been used to probe energetics of protein folding/unfolding transitions and thermodynamic mechanisms 49,50 . The melting point of a protein can be used as an indicator of its relative thermal stability.…”

Section: Impact Of Iron On Mab Thermal Stability Analyzed By Dscmentioning

confidence: 99%