MAb

Introduction: Practicalities of Aseptic Processing for Modern Biological Drug Products

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With proliferating modalities entering and moving through the biopharmaceutical industry’s development pipeline, drug presentations are expanding and diversifying to accommodate. Even “traditional” biologics such as monoclonal antibodies (MAbs) have evolved in their formulation and packaging, with the emergence of highly concentrated drug products, prefilled syringes, and devices that enable patients to inject themselves at home rather than visiting a local clinic for drug infusion. Patients, clinicians, and payers are demanding convenience and cost-effectiveness as well as safety, quality, and efficacy…

March 21, 2023

Purification of Hepatitis B Virus Surface Antigen for Vaccine Products: Impact of Ligand Density on HBsAg Purification By Immunoaffinity Chromatography

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According to the World Health Organization (WHO), more than 350 million people worldwide are chronic carriers of hepatitis B virus (HBV) (1). Around 25% of carriers develop liver cirrhosis and/or carcinoma, making HBV responsible for the deaths of one million people annually (1). The virus has a spherical shape with a lipoprotein coating mostly of HBV surface antigen (HBsAg) (2). Knowing that, drug developers have created recombinant HBV vaccines based on HBsAg synthesized in yeast or mammalian cells (3, 4).…

March 21, 2023

Advances Toward Dry-Powder Formulations for Monoclonal Antibodies

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Therapies based on monoclonal antibodies (MAbs) and other recombinant proteins usually are formulated as aqueous solutions for subcutaneous injection or intravenous infusion. However, as the biopharmaceutical industry amasses manufacturing knowledge and experience with such products, interest is surging for alternative formulation methods. Aerosolizable dry powders for inhalable administration represent a particularly promising option, with potential advantages not only for drug delivery and dosing, but also for patient comfort and compliance with treatment regimens. Previous research into dry-powder biopharmaceutical formulation has…

March 21, 2023

eBook: Monoclonal Antibodies — Reviewing the Past Year in Design, Engineering, Characterization, Manufacturing, and Formulation

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Even as advanced therapies and new modalities grab headlines, the monoclonal antibody (MAb) segment of the biopharmaceutical industry continues to perform, bringing needed treatments for emergent infections, rare diseases, and widespread conditions to patients who need help around the world. In fact, MAbs are at the heart of many emerging therapeutics, including bispecifics/multispecifics, antibody fragments, and antibody–drug conjugates (ADCs). But the original molecular class itself still dominates the biopharmaceutical development pipeline and the interest of biotechnology suppliers around the world.…

February 23, 2023

Two-Step Monoclonal Antibody Purification Using a Multicolumn Continuous Chromatography Platform

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Biomanufacturers typically have relied on multistep processes for optimal removal of impurities such as host-cell proteins (HCPs), DNA, adventitious viruses, and aggregates. However, additional purification steps increase downstream expenses significantly, including costs of supplementary resin, hardware, and buffers. The substantial footprint required at a processing site and additional time needed to perform a complete multistep purification process also increase production costs and complicate process execution. Thus, it is imperative to design and test effective purification procedures for high-quality biotherapeutics, but…

October 20, 2022

Cell-Line Development for Expressing IgM Antibodies

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Immunoglobulin G (IgG) antibodies have been studied and applied as biopharmaceuticals for decades, and they remain dominant in the monoclonal antibody (MAb) pipeline. By contrast, immunoglobulin M (IgM) molecules are much larger and consequently more challenging for biomanufacturing and therapeutic application. Essentially, they appear as clusters of the familiar Y-shaped IgG molecules, joined at their bases in pentameric (Figure 1) or hexameric forms. That structure gives them 10 and 12 binding moieties, respectively, which translate to superior binding power (avidity)…

May 24, 2022

Managing Host-Cell Proteins: Robust Risk-Assessment Frameworks for Process-Related Impurities in Biological Products

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Although biomanufacturing processes are designed to generate highly pure drug substances, some host-cell proteins (HCPs) copurify with target proteins and thus remain in finished drug products. Biopharmaceutical developers are keenly aware that such impurities must be minimized to protect patients. HCPs can activate several kinds of immune responses in treated patients, including production of antidrug antibodies and induction of cross-reactivity with therapeutic proteins (1–5). HCPs also can diminish drug efficacy, potency, and/or stability (6, 7). Thus, regulatory guidances such as…

May 20, 2022

eBook: Intensifying Processes for Monoclonal Antibodies

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The commercial manufacturing success of monoclonal antibodies (MAbs) has become a touchstone of the biopharmaceutical industry. MAbs are so well established that they often are referred to as “traditional” biologics, and well-known MAb processing methods have become a model for processing of other “advanced” or “emerging” therapies. But MAb processing continues to advance as biomanufacturers seek ways to improve efficiencies, lower costs, and (most recently) increase sustainability of facilities. Drug makers are particularly interested in strategies for MAb process intensification.…

April 28, 2022

Antibody-Derivative Biotherapeutics: Fragments and Fusions Define the Future

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Monoclonal antibodies (MAbs) remain the dominant biopharmaceutical product class, but as biotechnologies have advanced in recent decades, developers have found ways to exploit their “magic-bullet” capabilities while putting aside their limitations. That has led to a new generation of antibody-related therapeutics created by cutting and pasting molecular domains. Researchers are mixing and matching functional moieties of antibodies and other molecules to create custom-designed proteins with powerful efficacy and tunable targeting. A simple search at Taylor & Francis Online (https://www.tandfonline.com), the…

February 9, 2022

Development and Manufacture of Therapeutic Bispecific Antibodies

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To meet the ongoing need for new and improved drugs, the biopharmaceutical community strives to create molecules with new functions. Bispecific antibodies (bsAbs), which can simultaneously home in on two different targets, illustrate the scientific ingenuity needed for this task. The basic proof of concept for these complex molecules was established in 1960 (1), and their application to the redirection of effector cells was reported in the mid-1980s (2–4), but producing them has proved to be challenging. Many technical advances,…

February 9, 2022