A comparison of drug substance predicted chemical stability with ICH compliant stability studies

Williams, Helen; Bright, Jonathan; Roddy, Emily; Poulton, Andrew M.; Cosgrove, Steve; Turner, F; Harrison, Pamela; Brookes, Alan; MacDougall, E; Abbott, Alexander; Gordon, C

doi:10.1080/03639045.2018.1542707

Cited by 20 publications

(7 citation statements)

References 13 publications

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“…7E). Williams et al reported a similar conclusion in a study using ASAP for small chemicals drugs [27]. As illustrated in Fig.…”

Section: Comparison Between Stability Prediction and Long-term Stabil...supporting

confidence: 67%

“…Typically, during ASAP studies, the pharmaceutical product is exposed to different temperatures, typically between 50 °C and 80 °C, and various relative humidity levels for 3 to 4 weeks. ASAP studies have generally been used to predict the stability of small chemical drugs [27,28], and the approach has recently been used to predict the stability of peptides [29,30]. It has also been used in regulatory submissions for advanced shelf-life prediction in support of stability studies, especially for clinical trials [31].…”

Section: Introductionmentioning

confidence: 99%

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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

et al. 2022

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Monoclonal antibodies (mAbs) represent a dynamic class of biopharmaceutical products, as evidenced by an increasing number of market authorizations for mAb innovator and biosimilar products. Stability studies are commonly performed during product development, for instance, to exclude unstable molecules, optimize the formulation or determine the storage limit. Such studies are time-consuming, especially for mAbs, because of their structural complexity which requires multiple analytical techniques to achieve a detailed characterization. We report the implementation of a novel methodology based on the accelerated stability assessment program (ASAP) in order to model the long-term stability of mAbs in relation to different structural aspects. Stability studies of innovator infliximab and two different biosimilars were performed using forced degradation conditions alongside in-use administration conditions in order to investigate their similarity regarding stability. Thus, characterization of post-translational modifications was achieved using liquid-chromatography–tandem mass spectrometry (LC-MS/MS) analysis, and the formation of aggregates and free chain fragments was characterized using size-exclusion chromatography–multi-angle light scattering (SEC-MALS-UV/RI) analysis. Consequently, ASAP models were investigated with regard to free chain fragmentation of mAbs concomitantly with N57 deamidation, located in the hypervariable region. Comparison of ASAP models and the long-term stability data from samples stored in intravenous bags demonstrated a relevant correlation, indicating the stability of the mAbs. The developed methodology highlighted the particularities of ASAP modeling for mAbs and demonstrated the possibility to independently consider the different types of degradation pathways in order to provide accurate and appropriate prediction of the long-term stability of this type of biomolecule. Graphical abstract Supplementary Information The online version contains supplementary material available at 10.1007/s00216-022-04396-7.

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“…7E). Williams et al reported a similar conclusion in a study using ASAP for small chemicals drugs [27]. As illustrated in Fig.…”

Section: Comparison Between Stability Prediction and Long-term Stabil...supporting

confidence: 67%

Section: Introductionmentioning

confidence: 99%

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

et al. 2022

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“…Environmental stability studies were performed on drug loaded formulations over a period of 12 weeks utilizing selected settings that were intended to simulate everyday use. Generic protocols set by the International Conference on Harmonization (ICH) were considered for the environmental conditions used for this preliminary investigation [71,72]. Samples were kept in airtight, glass jars containing desiccant bags and stored: (a) in a dark enclosure (23 ± 3 • C/65 ± 5% RH), (b) refrigerator (4 ± 2 • C) and (c) under room conditions (24 ± 3 • C/70 ± 5% RH) and tested in triplicate.…”

Section: Stability Studiesmentioning

confidence: 99%

Optimal Design, Characterization and Preliminary Safety Evaluation of an Edible Orodispersible Formulation for Pediatric Tuberculosis Pharmacotherapy

Matawo

Adeleke

Wesley-Smith

2020

IJMS

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The severity of tuberculosis (TB) in children is considered a global crisis compounded by the scarcity of pharmaceutical formulations suitable for pediatric use. The purpose of this study was to optimally develop and evaluate a pyrazinamide containing edible orodispersible film formulation potentially suitable for use in pediatrics actively infected with TB. The formulation was prepared employing aqueous-particulate blending and solvent casting methods facilitated by a high performance Box Behnken experimental design template. The optimized orodispersible formulation was mechanically robust, flexible, easy to handle, exhibited rapid disintegration with initial matrix collapse occurring under 60 s (0.58 ± 0.05 min ≡ 34.98 ± 3.00 s) and pyrazinamide release was controlled by anomalous diffusion coupled with matrix disintegration and erosion mechanisms. It was microporous in nature, light weight (57.5 ± 0.5 mg) with an average diameter of 10.5 mm and uniformly distributed pyrazinamide load of 101.13 ± 2.03 %w/w. The formulation was physicochemically stable with no evidence of destructive drug–excipient interactions founded on outcomes of characterization and environmental stability investigations. Preliminary inquiries revealed that the orodispersible formulation was cytobiocompatible, palatable and remained intact under specific storage conditions. Summarily, an edible pyrazinamide containing orodispersible film formulation was optimally designed to potentially improve TB pharmacotherapy in children, particularly the under 5 year olds.

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“…Several approaches have been described that predict the shelf life of liquid dosage forms of biopharmaceutics based on accelerated stability studies [22][23][24][25][26][27][28][29][30]. These are generally performed at elevated temperatures (e.g., 25 and 40 • C), whereas the recommended temperature for long-term storage is usually between 2 and 8 • C for injectable biopharmaceutics.…”

Section: Introductionmentioning

confidence: 99%

Long-Term Stability Prediction for Developability Assessment of Biopharmaceutics Using Advanced Kinetic Modeling

2022

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A crucial aspect of pharmaceutical development is the demonstration of long-term stability of the drug product. Biopharmaceuticals, such as proteins or peptides in liquid formulation, are typically administered via parental routes and should be stable over the shelf life, which generally includes a storing period (e.g., two years at 5 °C) and optionally an in-use period (e.g., 28 days at 30 °C). Herein, we present a case study where chemical degradation of SAR441255, a therapeutic peptide, in different formulations in combination with primary packaging materials was analyzed under accelerated conditions to derive long-term stability predictions for the recommended storing conditions (two years at 5 °C plus 28 days at 30 °C) using advanced kinetic modeling. These predictions served as a crucial decision parameter for the entry into clinical development. Comparison with analytical data measured under long-term conditions during the subsequent development phase demonstrated a high prediction accuracy. These predictions provided stability insights within weeks that would otherwise take years using measurements under long-term stability conditions only. To our knowledge, such in silico studies on stability predictions of a therapeutic peptide using accelerated chemical degradation data and advanced kinetic modeling with comparisons to subsequently measured real-life long-term stability data have not been described in literature before.

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A comparison of drug substance predicted chemical stability with ICH compliant stability studies

Cited by 20 publications

References 13 publications

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

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

Optimal Design, Characterization and Preliminary Safety Evaluation of an Edible Orodispersible Formulation for Pediatric Tuberculosis Pharmacotherapy

Long-Term Stability Prediction for Developability Assessment of Biopharmaceutics Using Advanced Kinetic Modeling

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