ArticlePharmaceutical research2011
Frozen state storage instability of a monoclonal antibody: aggregation as a consequence of trehalose crystallization and protein unfolding.
Article in Pharmaceutical research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pooled it
- Frozen storage of mAbs at elevated temperatures: Balancing stability and sustainability.International journal of pharmaceutics: X · 2026Article
- Development of a rapid calcium testing strip with metal-enhanced fluorescence for early detection of hypocalcemia in dairy cattle.Mikrochimica acta · 2026Article
- Antibody Aggregation: A Problem Within the Biopharmaceutical Industry and Its Role in AL Amyloidosis Disease.The protein journal · 2025Review
- Characterization of Freezing Processes in Drug Substance Bottles by Ice Core Sampling.AAPS PharmSciTech · 2024Article
- Enabling Efficient Design of Biological Formulations Through Advanced Characterization.Pharmaceutical research · 2023Review
- The effect of mAb and excipient cryoconcentration on long-term frozen storage stability - part 2: Aggregate formation and oxidation.International journal of pharmaceutics: X · 2022Article
- The effect of mAb and excipient cryoconcentration on long-term frozen storage stability - Part 1: Higher molecular weight species and subvisible particle formation.International journal of pharmaceutics: X · 2022Article
- A novel method for the storage and transport of biological samples of therapeutic proteins prior to the detection of analytes using ELISA.Scientific reports · 2021Article
- Advances in Cryochemistry: Mechanisms, Reactions and Applications.Molecules (Basel, Switzerland) · 2021Review
- Cryoconcentration and 3D Temperature Profiles During Freezing of mAb Solutions in Large-Scale PET Bottles and a Novel Scale-Down Device.Pharmaceutical research · 2020Article
- Investigation of the reversibility of freeze/thaw stress-induced protein instability using heat cycling as a function of different cryoprotectants.Bioprocess and biosystems engineering · 2020Article
- Sustained Release of Vascular Endothelial Growth Factor from Poly(ε-caprolactone-PEG-ε-caprolactone)-ACS omega · 2019Article
- Interfacial Stress in the Development of Biologics: Fundamental Understanding, Current Practice, and Future Perspective.The AAPS journal · 2019Article
- Distribution of Protein Content and Number of Aggregates in Monoclonal Antibody Formulation After Large-Scale Freezing.AAPS PharmSciTech · 2019Article
- Osmolyte-Induced Folding and Stability of Proteins: Concepts and Characterization.Iranian journal of pharmaceutical research : IJPR · 2019Review
- Pharmaceutical Development of AAV-Based Gene Therapy Products for the Eye.Pharmaceutical research · 2018Review
- Article
- Metal-Organic Framework Encapsulation Preserves the Bioactivity of Protein Therapeutics.Advanced healthcare materials · 2018Article
- Impact of Buffer, Protein Concentration and Sucrose Addition on the Aggregation and Particle Formation during Freezing and Thawing.Pharmaceutical research · 2018Article
Corrections and comments
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeTo investigate the cause of unexpected and erratic increase in aggregation during long-term storage of an IgG2 monoclonal antibody in a trehalose formulation at -20°C.
methodsFrozen matrix was sampled, stored frozen at various temperatures and analyzed by SEC over time.
resultsAggregation increased with time at -20°C but not at -40°C or -10°C. The cause of the instability was the crystallization of freeze-concentrated trehalose from the frozen solute when the storage temperature exceeds the glass transition temperature of the matrix (-29°C). Crystallization at -20°C deprives the protein of the cryoprotectant, leading to a slow increase in aggregation. Storage at -10°C also leads to crystallization of trehalose but no increase in aggregation. It is hypothesized that significantly higher mobility in the matrix at -10°C allows protein molecules that are unfolded at the ice interface on freezing to refold back before significant aggregation can occur. In contrast, lack of mobility at -40°C prevents crystallization, refolding, and aggregation.
conclusionsAggregation in the frozen state when stored above the glass transition temperature is a consequence of balance between rate of crystallization leading to loss of cryoprotectant, rate of aggregation of the unfolded protein molecules, and rate of refolding that prevents aggregation.
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21213025What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.