A universal tool for stability predictions of biotherapeutics, vaccines and in vitro diagnostic products

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: June 21, 2023

Abstract It is of particular interest for biopharmaceutical companies developing and distributing fragile biomolecules to warrant the stability activity their products during long-term storage shipment. In accordance with quality by design principles, advanced kinetic modeling (AKM) has been successfully used predict product shelf-life relies on data from short-term accelerated studies that are generate Arrhenius-based models can, in turn, be exploited forecasts. The AKM methodology was evaluated through a cross-company perspective key indicating attributes different types biotherapeutics, vaccines combined vitro diagnostic kits. demonstrated predictions up 3 years maintained under recommended conditions (2–8 °C) or have experienced temperature excursions outside cold-chain show excellent agreement experimental real-time data, thus confirming as universal reliable tool wide range types.

Language: Английский

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Prediction of long-term stability of high-concentration formulations to support rapid development of antibodies against SARS-CoV-2

mAbs, Journal Year: 2025, Volume and Issue: 17(1)

Published: Feb. 28, 2025

Long-term stability of antibody therapeutics is required to ensure their safety and efficacy when administered patients. However, obtaining shelf life supporting, long-term data are often a limiting factor for new drug candidates starting clinical trials. Predictive stability, which uses short-term accelerated kinetic modeling forecast storage has the potential provide justification support establishing life, although its application biologics only recently gained traction. We have developed empirical models key stability-indicating quality attributes high-concentration IgG1 liquid formulations. Using Arrhenius-based approaches, including Arrhenius plotting global fitting, we applied kinetics predict seven anti-SARS-CoV-2 antibodies. determines by reaction rate logarithm against inverse temperature, while fitting simultaneously fits model with at multiple temperatures comprehensively understand kinetics. These approaches were used fit leveraging collected conditions (5°C) least 1 month three within 25–40°C. Model accuracy was demonstrated using (up 36 months) 5°C. The approach successfully in development enable rapid regulatory Investigational New Drug Medicinal Product Dossier filings where limited available time filing. Our results show that successful predictions estimation can be achieved high data, may especially beneficial response programs severely constrained timelines. Thus, described demonstrates how predictive can, addition enabling earlier decision-making development, also justify product submissions, faster patient access life-saving products.

Language: Английский

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Investigating in-vitro functionality and in-vivo taste assessment of eco-friendly Tadalafil Pastilles

Heliyon, Journal Year: 2024, Volume and Issue: 10(8), P. e29543 - e29543

Published: April 1, 2024

Tadalafil (TDL) has poor bioavailability due to the less aqueous solubility and bitter taste. Oral solid dosage forms, especially tablets, have a broad market worldwide. Constraints of tablets are long process, pollution, high processing cost, requiring more excipient. The research was performed optimize an eco-friendly immediate-acting pastille TDL put forward alternate formulation tablet using advanced data mining tools. Another objective is assess taste masking Brief Access Taste Aversion

Language: Английский

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Predicting the Long-Term Stability of Biologics with Short-Term Data

Molecular Pharmaceutics, Journal Year: 2024, Volume and Issue: 21(9), P. 4673 - 4687

Published: Aug. 9, 2024

Understanding the long-term stability of biologics is crucial to ensure safe, effective, and cost-efficient life-saving therapeutics. Current industry regulatory practices require arduous real-time data collection over three years; thus, reducing this bottleneck while still ensuring product quality would enhance speed medicine patients. We developed a parallel-pathway kinetic model, combined with Monte Carlo simulations for prediction intervals, predict (2+ years) biotherapeutic critical attributes (aggregates, fragments, charge variants, purity, potency) short-term (3-6 months) from intended, accelerated, stressed temperatures. rigorously validated model 18 drug products, composed IgG1 IgG4 monoclonal antibodies, antibody-drug conjugates, dual protein coformulations, fusion protein, including high concentration (≥100 mg/mL) formulations, in liquid lyophilized presentations. For each product, we accurately predicted trends multiple using just 6 months data. Further, demonstrated superior via our methods compared industry-standard linear regression methods. The robust repeatable results work across an unprecedented suite compounds suggest that models simulation can

Language: Английский

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Shelf-life prediction and storage stability of Aeromonas bacteriophage vB_AsM_ZHF

Virus Research, Journal Year: 2022, Volume and Issue: 323, P. 198997 - 198997

Published: Nov. 10, 2022

Phage therapy is a potential alternative to antibiotics for the treatment of bacterial infections. Due good antibacterial and therapeutic effects phages, phage has received attention demand clinical applications gradually increased. storage stability shelf life are key aspects biopharmaceutical development registration. In this study, Aeromonas salmonicida was stored at different temperatures 12 months. We found that 4 °C optimal temperature. case cryopreservation, 10% dimethyl sulfoxide (DMSO) more effective protecting -20 -80 than 30% glycerin. Indeed, titer decreased by only one order magnitude within year when DMSO added. Hydroxyapatite (HAP) reduced inactivation phages six orders during 28ºC 1 year, significantly lower in SM buffer. addition, excipients lyophilization, tryptic soy broth (TSB) tryptone or skim milk powder (SMP) combination with trehalose alleviated lyophilization subsequent 28 °C. Furthermore, model predicting shelf-life established Accelerated Stability Assessment Program (ASAP) based on Arrhenius equation. The error less 15% comparing predicted value actual °C, indicating high accuracy. study demonstrated first time, which provided theoretical basis application products.

Language: Английский

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Effects of the COVID-19 pandemic: new approaches for accelerated delivery of gene to first-in-human CMC data for recombinant proteins

mAbs, Journal Year: 2023, Volume and Issue: 15(1)

Published: June 6, 2023

The COVID-19 pandemic highlighted the urgent need for life-saving treatments, including vaccines, drugs, and therapeutic antibodies, delivered at unprecedented speed. During this period, recombinant antibody research development cycle times were substantially shortened without compromising quality safety, thanks to prior knowledge of Chemistry, Manufacturing Controls (CMC) integration new acceleration concepts discussed below. Early product knowledge, selection a parental cell line with appropriate characteristics, application efficient approaches generating manufacturing lines drug substance from non-clonal cells preclinical first-in-human studies are key elements success. Prioritization established analytical platforms, implementation advanced methods, consideration adventitious agent testing viral clearance studies, establishing stability claim less real-time data additional components that enable an accelerated successful gene clinical-grade material strategy.

Language: Английский

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Science- and Risk-Based Stability Strategies to Support Product Lifecycle Changes

The AAPS Journal, Journal Year: 2024, Volume and Issue: 26(2)

Published: March 14, 2024

Language: Английский

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A thermodynamic investigation into protein–excipient interactions involving different grades of polysorbate 20 and 80

Journal of Thermal Analysis and Calorimetry, Journal Year: 2024, Volume and Issue: 149(23), P. 13941 - 13951

Published: Aug. 25, 2024

Abstract Developing stable biopharmaceutical formulations is of paramount importance and typically achieved by incorporating surfactants as stabilising agents, such polysorbate 20 80. However, little known about the effect surfactant grade has on formulation stability. This study evaluates regular Super-refined™ polysorbates 80 their interaction with model proteins, namely β-lactoglobulin (β-Ig), human serum albumin (HSA) immunoglobulin gamma (IgG), using isothermal titration calorimetry (ITC) differential scanning (DSC). ITC results indicated that all four underwent binding interactions β-Ig HSA, yet no was observed IgG this postulated to be a consequence differences in secondary structure composition. Surfactant occurred at ratios ~ 3:2 regardless used dissociation constants ranging from 284 388 µM, whereas HSA bound 3:1 429 653 µM. Changes enthalpy were larger for compared implying former produced greater than latter. DSC facilitated measurement temperature unfolding each protein presence where further confirmed had an increased between 4 6 K improved stability, again, IgG. thermodynamically characterised role stabilisation formulations.

Language: Английский

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Stability Modeling Methodologies to Enable Earlier Patient Access

Journal of Pharmaceutical Sciences, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 1, 2024

Language: Английский

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Modeling study of long-term stability of the monoclonal antibody infliximab and biosimilars using liquid-chromatography–tandem mass spectrometry and size-exclusion chromatography–multi-angle light scattering

Analytical and Bioanalytical Chemistry, Journal Year: 2022, Volume and Issue: 415(1), P. 179 - 192

Published: Nov. 30, 2022

Monoclonal antibodies (mAbs) represent a dynamic class of biopharmaceutical products, as evidenced by an increasing number market authorizations for mAb innovator and biosimilar products. Stability studies are commonly performed during product development, instance, to exclude unstable molecules, optimize the formulation or determine storage limit. Such time-consuming, especially mAbs, because their structural complexity which requires multiple analytical techniques achieve detailed characterization. We report implementation novel methodology based on accelerated stability assessment program (ASAP) in order model long-term mAbs relation different aspects. infliximab two biosimilars were using forced degradation conditions alongside in-use administration investigate similarity regarding stability. Thus, characterization post-translational modifications was achieved liquid-chromatography–tandem mass spectrometry (LC-MS/MS) analysis, formation aggregates free chain fragments characterized size-exclusion chromatography–multi-angle light scattering (SEC-MALS-UV/RI) analysis. Consequently, ASAP models investigated with regard fragmentation concomitantly N57 deamidation, located hypervariable region. Comparison data from samples stored intravenous bags demonstrated relevant correlation, indicating mAbs. The developed highlighted particularities modeling possibility independently consider types pathways provide accurate appropriate prediction this type biomolecule.

Language: Английский

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