Manufacturing of High-Concentration Monoclonal Antibody Formulations via Spray Drying--the Road to Manufacturing Scale

Gikanga, Benson; Turok, Robert; Hui, Ada; Bowen, Mayumi; Stauch, Oliver B.; Maa, Yuh‐Fun

doi:10.5731/pdajpst.2015.01003

Cited by 44 publications

(22 citation statements)

References 22 publications

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“…The preparation of biologics solutions at a concentration of > 100 mg/ml is generally feasible today [ 60 ], which is a major step towards reducing the dosing volume. However, the development of such high-concentration dosing solutions remains a challenge for many reasons, including the high viscosities involved, limitations in protein solubility, protein degradation and aggregation, protein stability in long-term storage, and the difficulty of achieving mAb concentrations > 500 mg/ml [ 17 ].…”

Section: The Complexities and Improvements For Subcutaneous Administrmentioning

confidence: 99%

Subcutaneous Administration of Biotherapeutics: An Overview of Current Challenges and Opportunities

2018

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Subcutaneous delivery of biotherapeutics has become a valuable alternative to intravenous administration across many disease areas. Although the pharmacokinetic profiles of subcutaneous and intravenous formulations differ, subcutaneous administration has proven effective, safe, well-tolerated, generally preferred by patients and healthcare providers and to result in reduced drug delivery-related healthcare costs and resource use. The aim of this article is to discuss the differences between subcutaneous and intravenous dosing from both health-economic and scientific perspectives. The article covers different indications, treatment settings, administration volumes, and injection devices. We focus on biotherapeutics in rheumatoid arthritis (RA), immunoglobulin-replacement therapy in primary immunodeficiency (PI), beta interferons in multiple sclerosis (MS), and monoclonal antibodies (mAbs) in oncology. While most subcutaneous biotherapeutics in RA, PI, and MS are self-administered at home, mAbs for oncology are still only approved for administration in a healthcare setting. Beside concerns around the safety of biotherapeutics in oncology, a key challenge for self-administration in this area is that doses and dosing volumes can be comparatively large; however, this difficulty has recently been overcome to some extent by the development of high-concentration solutions, the use of infusion pumps, and the coadministration of the dispersion enhancer hyaluronidase. Furthermore, given the increasing number of biotherapeutics being considered for combination therapy and the high dosing complexity associated with these, especially when administered intravenously, subcutaneous delivery of fixed-dose combinations might be an alternative that will diminish these burdens on healthcare systems.

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Section: The Complexities and Improvements For Subcutaneous Administrmentioning

confidence: 99%

Subcutaneous Administration of Biotherapeutics: An Overview of Current Challenges and Opportunities

2018

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“…In these types of formulations, arginine has shown viscosity lowering abilities and expedite powder reconstitution. [36,162] Its superior stabilizing ability is proposed to be associated to its side chain ability to form H-bonds with proteins. [23] However, in aerosolisable formulations of IgG, arginine was not successful in maintaining long-term stability.…”

Section: Polysaccharidesmentioning

confidence: 99%

“…Nonetheless, it is important to understand if the processes developed at smaller scales are transferable to larger ones. Obviously, the commercialization of products such as Exubera V R , Trelstar V R LA, Somatuline V R LA, and Raplixa V R , as well as other additional evidence in literature show that dry powder inhalers, wound therapies, vaccines [124,144] and injectables [34,36,82] of proteins can be successfully produced at larger scales. A potential difference between spraydryers across scales, due to differences in equipment and throughput, is the particle size of the obtained powders.…”

Section: Spray-drying Scalesmentioning

confidence: 99%

Progress in spray-drying of protein pharmaceuticals: Literature analysis of trends in formulation and process attributes

et al. 2021

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Spray-drying is an inherently continuous and well-established industrial drying process. It can accelerate manufacturing of biopharmaceuticals and vaccine products, resulting in both an economic and health benefit. In this review, we cover a systematic assessment and discuss the spray-drying of diverse protein pharmaceuticals and excipients included therein, solvent systems applicable to these formulations, equipment used and, respective process parameters. Further, key quality aspects of spray-dried protein solids are discussed. Based on the overall trends, we present a concise perspective into the future of protein pharmaceuticals spray-drying.

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“…In the follow-up study, Gikanga et al [9] evaluated the Furthermore, the activity of mAb formulations postspray drying was reported to be comparable to those prior to spray drying using an in vitro potency assay.…”

Section: Spray Dryingmentioning

confidence: 99%

Drying of Biopharmaceuticals: Recent Developments, New Technologies and Future Direction

et al. 2018

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The dehydration of biopharmaceutical products through dr ying provides numerous benefits, including ease of handling and storage, reduction in transportation costs, and improved stability. Typically, the drying of biotherapeutics is accomplished through freeze-drying, however, the removal of water by lyophilization possesses several drawbacks, including lengthy drying times, low energy efficiency, and the high cost of purchasing and maintaining the equipment. Furthermore, freezedr ying is a batch process which may be challenging to adapt and implement with the recent push for continuous manufacturing. These limitations have led to the search for next-generation drying technologies that can be applied to the manufacture of biotherapeutic products. Several alternative dr ying methods to freeze-dr ying have been developed and implemented in industries outside of pharmaceuticals, such as food and agriculture, and some are at an advanced state. With the aim of applying lessons learned from technologies in various industries, herein, we review several processing technologies with particular emphasis on the advantages and disadvantages of each in comparison to lyophilization and their potential to be adapted and utilized for drying biotherapeutic compounds.

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Manufacturing of High-Concentration Monoclonal Antibody Formulations via Spray Drying--the Road to Manufacturing Scale

Cited by 44 publications

References 22 publications

Subcutaneous Administration of Biotherapeutics: An Overview of Current Challenges and Opportunities

Subcutaneous Administration of Biotherapeutics: An Overview of Current Challenges and Opportunities

Progress in spray-drying of protein pharmaceuticals: Literature analysis of trends in formulation and process attributes

Drying of Biopharmaceuticals: Recent Developments, New Technologies and Future Direction

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