Orkambi

Krogmeier, Stephanie; Pritchard, Justin R.; Dokou, Eleni; Miles, Sue; Connelly, Gregory; Medendorp, Joseph; Bourland, Michael; Swinney, Kelly

doi:10.1016/b978-0-12-813479-5.00003-3

Cited by 2 publications

(1 citation statement)

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“…Thus, CM can enable rapid development of robust tablets and capsules in a cost-efficient manner . As a result, over the past decade, CM has gained widespread attention, leading to the approval of several new commercial drug products, including Orkambi (lumacaftor/ivacaftor), Verzenio (abemaciclib), , Daurismo (glasdegib maleate), Duvroq (daprodustat), , and Cibinqo (abrocitinib) . Advancements in technology have also led to the development of several platform technologies based on CM …”

Section: Introductionmentioning

confidence: 99%

Drug Phase Transformation and Water Redistribution during Continuous Tablet Manufacturing: A Case Study of Carbamazepine Dihydrate

et al. 2023

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In recent years, continuous tablet manufacturing technology has been used to obtain regulatory approval of several new drug products. While a significant fraction of active pharmaceutical ingredients exists as hydrates (wherein water is incorporated stoichiometrically in the crystal lattice), the impact of processing conditions and formulation composition on the dehydration behavior of hydrates during continuous manufacturing has not been investigated. Using powder X-ray diffractometry, we monitored the dehydration kinetics of carbamazepine dihydrate in formulations containing dibasic calcium phosphate, anhydrous (DCPA), mannitol, or microcrystalline cellulose. The combined effect of nitrogen flow and vigorous mixing during the continuous mixing stage of tablet manufacture facilitated API dehydration. Dehydration was rapid and most pronounced in the presence of DCPA. The dehydration product, amorphous anhydrous carbamazepine, sorbed a significant fraction of the water released by dehydration. Thus, the dehydration process resulted in a redistribution of water in the powder blend. The unintended formation of an amorphous dehydrated phase, which tends to be much more reactive than its crystalline counterparts, is of concern and warrants further investigation.

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Section: Introductionmentioning

confidence: 99%

Drug Phase Transformation and Water Redistribution during Continuous Tablet Manufacturing: A Case Study of Carbamazepine Dihydrate

et al. 2023

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Raman spectroscopy as an alternative rapid microbial bioburden test method for continuous, automated detection of contamination in biopharmaceutical drug substance manufacturing

Masucci,

Hauschild,

Gisler

et al. 2024

Journal of Applied Microbiology

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Aims To investigate an in-line Raman method capable of detecting accidental microbial contamination in pharmaceutical vessels, such as bioreactors producing monoclonal antibodies via cell culture. Methods and results The Raman method consists of a multivariate model built from Raman spectra collected in-line during reduced-scale bioreactor batches producing a monoclonal antibody, as well as a reduced-scale process with intentional spiking of representative compendial method microorganisms (n = 4). The orthogonal partial least squares regression discriminant analysis model (OPLS-DA) Area Under the Curve (AUC), specificity and sensitivity were 0.96, 0.99 and 0.95, respectively. Furthermore, the model successfully detected contamination in an accidentally contaminated manufacturing-scale batch. In all cases, the time to detection (TTD) for Raman was superior compared to offline, traditional microbiological culturing. Conclusions The Raman OPLS-DA method met acceptance criteria for equivalent decision making to be considered a viable alternative to the compendial method for in-process bioburden testing. The in-line method is automated, non-destructive, and provides a continuous assessment of bioburden compared to an offline compendial method, which is manual, results in loss of product, and in practice is only collected once daily and requires 3–5 days for enumeration.

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Orkambi

Cited by 2 publications

References 0 publications

Drug Phase Transformation and Water Redistribution during Continuous Tablet Manufacturing: A Case Study of Carbamazepine Dihydrate

Drug Phase Transformation and Water Redistribution during Continuous Tablet Manufacturing: A Case Study of Carbamazepine Dihydrate

Raman spectroscopy as an alternative rapid microbial bioburden test method for continuous, automated detection of contamination in biopharmaceutical drug substance manufacturing

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