A systematic review of commercial high concentration antibody drug products approved in the US: formulation composition, dosage form design and primary packaging considerations

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

Published: May 27, 2023

Three critical aspects that define high concentration antibody products (HCAPs) are as follows: 1) formulation composition, 2) dosage form, and 3) primary packaging configuration. HCAPs have become successful in the therapeutic sector due to their unique advantage of allowing subcutaneous self-administration. Technical challenges, such physical chemical instability, viscosity, delivery volume limitations, product immunogenicity, can hinder development commercialization HCAPs. Such challenges be overcome by robust process strategies, well rational selection excipients components. We compiled analyzed data from US Food Drug Administration-approved marketed ≥100 mg/mL identify trends composition quality target profile. This review presents our findings discusses novel processing technologies enable improved at ≥200 mg/mL. The observed used a guide for further advancements more complex antibody-based modalities enter biologics development.

Language: Английский

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Blueprint for antibody biologics developability

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

Published: March 7, 2023

Large-molecule antibody biologics have revolutionized medicine owing to their superior target specificity, pharmacokinetic and pharmacodynamic properties, safety toxicity profiles, amenability versatile engineering. In this review, we focus on preclinical developability, including its definition, scope, key activities from hit lead optimization selection. This includes generation, computational in silico approaches, molecular engineering, production, analytical biophysical characterization, stability forced degradation studies, process formulation assessments. More recently, it is apparent these not only affect selection manufacturability, but ultimately correlate with clinical progression success. Emerging developability workflows strategies are explored as part of a blueprint for success that an overview the four major properties all outcomes: 1) conformational, 2) chemical, 3) colloidal, 4) other interactions. We also examine risk assessment mitigation increase likelihood moving right candidate into clinic.

Language: Английский

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Recent Progress in Development and Application of DNA, Protein, Peptide, Glycan, Antibody, and Aptamer Microarrays

Biomolecules, Journal Year: 2023, Volume and Issue: 13(4), P. 602 - 602

Published: March 27, 2023

Microarrays are one of the trailblazing technologies last two decades and have displayed their importance in all associated fields biology. They widely explored to screen, identify, gain insights on characteristics traits biomolecules (individually or complex solutions). A wide variety biomolecule-based microarrays (DNA microarrays, protein glycan antibody peptide aptamer microarrays) either commercially available fabricated in-house by researchers explore diverse substrates, surface coating, immobilization techniques, detection strategies. The aim this review is development microarray applications since 2018 onwards. Here, we covered a different array printing strategies, substrate modification, biomolecule applications. period 2018-2022 focused using for identification biomarkers, viruses, differentiation multiple pathogens, etc. few potential future could be personalized medicine, vaccine candidate screening, toxin pathogen identification, posttranslational modifications.

Language: Английский

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Effects of arginine in therapeutic protein formulations: a decade review and perspectives

Antibody Therapeutics, Journal Year: 2023, Volume and Issue: 6(4), P. 265 - 276

Published: Oct. 1, 2023

Abstract Arginine (Arg) is a natural amino acid with an acceptable safety profile and unique chemical structure. Arg its salts are highly effective in enhancing protein refolding solubilization, suppressing protein–protein interaction aggregation reducing viscosity of high concentration formulations. have been used research 20 approved injectables. This review summarizes the effects as excipient therapeutic formulations focus on physicochemical properties, safety, applications products, beneficial detrimental liquid lyophilized when combined different counterions mechanism stabilization destabilization. The decade literature indicates that benefits overweigh risks it appropriately. It recommended to add along glutamate counterion top sugars or polyols counterbalance negative hydrochloride. use reducer stabilizer will be inevitable future trend biopharmaceutical industry for subcutaneous administration.

Language: Английский

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Molecular and functional insight into anti-EGFR nanobody: Theranostic implications for malignancies

Life Sciences, Journal Year: 2024, Volume and Issue: 345, P. 122593 - 122593

Published: March 28, 2024

Language: Английский

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Alternative Excipients for Protein Stabilization in Protein Therapeutics: Overcoming the Limitations of Polysorbates

Pharmaceutics, Journal Year: 2022, Volume and Issue: 14(12), P. 2575 - 2575

Published: Nov. 23, 2022

Given their safety and efficiency in protecting protein integrity, polysorbates (PSs) have been the most widely used excipients for stabilization of therapeutics years. In recent decades, however, there numerous reports about visible or sub-visible particles PS-containing biotherapeutic products, which is a major quality concern parenteral drugs. Alternative that are safe administration, efficient different drugs against various stress conditions, effective high-concentrated liquid formulations, stable under storage conditions duration product's shelf-life, compatible with other formulation components primary packaging highly sought after. The aim this paper to review potential alternative from families, including surfactants, carbohydrate- amino acid-based excipients, synthetic amphiphilic polymers, ionic liquids enable stabilization. For each category, important characteristics such as ability stabilize proteins thermal mechanical stresses, current knowledge related profile interactions components, debated. Based on provided information detailed discussion thereof, may pave way identification development

Language: Английский

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The Evolution of Commercial Antibody Formulations

Journal of Pharmaceutical Sciences, Journal Year: 2023, Volume and Issue: 112(7), P. 1801 - 1810

Published: April 8, 2023

Language: Английский

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Molecular Farming of Pembrolizumab and Nivolumab

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(12), P. 10045 - 10045

Published: June 12, 2023

Immune checkpoint inhibitors (ICIs) are a class of immunotherapy agents capable alleviating the immunosuppressive effects exerted by tumorigenic cells. The programmed cell death protein 1 (PD-1)/programmed death-ligand (PD-L1) immune is one most ubiquitous checkpoints utilized cells for evasion inducing apoptosis and inhibiting proliferation cytokine production T lymphocytes. Currently, frequently used ICIs targeting PD-1/PD-L1 include monoclonal antibodies (mAbs) pembrolizumab nivolumab that bind to PD-1 on lymphocytes inhibit interaction with PD-L1 However, costly, thus their accessibility limited in low- middle-income countries (LMICs). Therefore, it essential develop novel biomanufacturing platforms reducing cost these two therapies. Molecular farming such platform utilizing plants mAb production, has been demonstrated be rapid, low-cost, scalable can potentially implemented LMICs diminish exorbitant prices, ultimately leading significant reduction cancer-related mortalities within countries.

Language: Английский

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Histidine as a versatile excipient in the protein-based biopharmaceutical formulations

International Journal of Pharmaceutics, Journal Year: 2024, Volume and Issue: 662, P. 124472 - 124472

Published: July 14, 2024

Language: Английский

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A Comprehensive Review of Monoclonal Antibodies in Modern Medicine: Tracing the Evolution of a Revolutionary Therapeutic Approach

Cureus, Journal Year: 2024, Volume and Issue: unknown

Published: June 9, 2024

Monoclonal antibodies (mAbs) have emerged as potent therapeutic agents, revolutionizing the landscape of modern medicine. This comprehensive review traces evolution mAbs from their inception to current prominence, highlighting key milestones in development and exploring diverse applications. Beginning with an overview molecular structure mechanisms action, we delve into production engineering mAbs, including hybridoma technology recombinant DNA techniques. Therapeutic applications across various medical disciplines, cancer treatment, autoimmune diseases, infectious are examined detail, showcasing significant clinical successes mAbs. Furthermore, this discusses challenges opportunities manufacturing scalability, cost-effectiveness, access therapies. Looking ahead, implications future research practice explored, emphasizing potential for next-generation personalized medicine, integration emerging modalities such immunotherapy gene therapy. In conclusion, monoclonal underscores transformative impact on healthcare continued promise advance frontiers

Language: Английский

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