Molecule and Manufacturability Assessment Leading to Robust Commercial Formulation for Therapeutic Proteins

Ramachander, Ranjini; Rathore, Nitin

doi:10.1007/978-1-4614-7978-9_2

Cited by 5 publications

(3 citation statements)

References 11 publications

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“…Consequently, biologic stability is generally more nuanced than that of small molecules and is more prone to incompatibility with conventional physical and chemical processing used in the fabrication of drug delivery devices. For any given biologic, physical and chemical stability, tendency for aggregation, or freeze–thaw behavior must all be investigated and may require formulation optimization to mitigate any shortcomings . Processes of denaturing, fragmentation, and aggregation can be impacted by protein concentrations, solution pH or osmolarity, solvent–protein interactions, or even physical pressure. , Whether administered by injection, with a metered pump, or a permanent implant, delivery of biologics commonly relies on aqueous formulations of drug, where preparation of the administered drug is separated from its mode of delivery.…”

Section: Introductionmentioning

confidence: 99%

Injectable Devices for Delivery of Liquid or Solid Protein Formulations

et al. 2023

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Sustained delivery of protein therapeutics remains a largely unsolved problem across anatomic locations. Miniaturized devices that can provide sustained delivery of protein formulations have the potential to address this challenge via minimally invasive administration. In particular, methodologies that can optimize protein formulation independent of device manufacture have the greatest potential to provide a platform suitable for wide applications. The techniques developed here demonstrate the fabrication of tubular devices for sustained release of protein therapeutics. Utilizing a dip-casting process, fine-scale tubes can be reliably produced with wall thickness down to 30 μm. Techniques were developed that enabled effective loading of either solid or liquid formulations, while maintaining a cylindrical form-factor compatible with placement in a 22-gauge needle. Further, highly compacted protein pellets that approach the expected density of the raw materials were produced with a diameter (∼300 μm) suitable for miniaturized devices. Release from a solid-loaded device was capable of sustaining release of a model protein in excess of 400 days. Given significant interest in ocular applications, intravitreal injection was demonstrated in a rabbit model with these devices. In addition, to simulate repeated injections in ocular applications, serial intravitreal injection of two devices in a rabbit model demonstrated acceptable ocular safety without significant intraocular inflammation from clinical exam and histology.

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Section: Introductionmentioning

confidence: 99%

Injectable Devices for Delivery of Liquid or Solid Protein Formulations

et al. 2023

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“…During protein therapeutics development, a potential product will go through many processing and storage steps (e.g., extreme pH, elevated temperature) exerting stresses that may lead to changes in protein structure. To ensure the selection of the optimal molecule for commercialization, candidate screening is carried out by biopharmaceutical companies . Characterization of HOS, along with other analyses, provides enhanced insight into structure and stability, which can often differentiate one candidate from another.…”

Section: Introductionmentioning

confidence: 99%

“…To ensure the selection of the optimal molecule for commercialization, candidate screening is carried out by biopharmaceutical companies. [13][14][15] Characterization of HOS, along with other analyses, provides enhanced insight into structure and stability, which can often differentiate one candidate from another.…”

Section: Introductionmentioning

confidence: 99%