Formulation

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

Container Materials for Biopharmaceuticals: A Comparative Small-Scale Case Study of Stainless Steel and a Proprietary Nickel-Based Alloy

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Evaluating compatibility of a drug substance with all surfaces that it might come into contact with during drug product manufacturing is essential to ensure product quality. Proteins can adsorb to contact surfaces, form aggregates, and desorb into a drug-substance solution. Proteins also can degrade in presence of leachables generated from contact surfaces during manufacturing. Containers and vessels used during manufacturing are single-use disposable components or metal tanks, primarily either 316L stainless steel (SS) or C-276 Hastelloy nickel-based alloy (HLY). Researchers…

December 12, 2022

Rapid Screening of Bioavailability: Enhancing Technologies to Accelerate Time to Clinic

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Jesus Rosales, senior scientist in oral formulation development, Catalent. Rosales highlighted efforts to accelerate small-molecule products into clinical development. His company uses rapid formulation prototyping and both in silico and in vitro tools for technology selection. Early phase development is a tortuous path for every drug type, from identifying and validating targets and leads to optimization of drug products. Many options are available for oral solid-dose products: basic powder forms that are reconstituted in a clinic, capsules containing only the…

August 24, 2022

Nonideal Colligative Properties in High-Concentration MAb Solutions

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Injectable-drug formulations for both subcutaneous and intravenous administration are designed to be consistent with the number of solutes present in human tissue. Such consistency with physiological conditions is achieved by adding an appropriate amount of salt and/or sugar to attain the desired tonicity. Care must be taken to prevent exposure of cells to either hypotonic or hypertonic formulations that could cause lysis or shrinking, respectively (1). Injection of formulations that deviate from human-plasma osmolality (295 mOsm) can cause pain upon…

December 8, 2021

Formulation, Fill and Finish of Lentiviral Vectors: Part 1 — Case Study in Facility and Process Design

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Over the past few years, Oxford Biomedica Ltd. (OXB) has developed and implemented a fill–finish platform (“Oxbox,” Figure 1) at its viral vector processing facility in the United Kingdom. The facility includes four segregated bulk viral-vector drug substance (VS) suites, where closed systems and bioburden control processes apply, and two viral-vector drug product (VP) fill–finish suites that apply aseptic processing, with space for expansion by scale-out as product output demand increases. Segregated suites enable the facility to process different viral…

October 29, 2021

Spurring on Innovation in Gene Therapy Development

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Gene therapies based on adenoassociated virus (AAV) vectors hold promise for treating myriad conditions. Immunogenicity remains a challenge for such products, however. With support from PerkinElmer, Roland W. Herzog (professor of pediatrics and Riley Children’s Foundation professor of immunology at the Indiana University School of Medicine) joined Nagendra Venkata Chemuturi (scientific director of global research for drug metabolism and pharmacokinetics, DMPK, at Takeda Pharmaceuticals) to deliver a BPI “Ask the Expert” presentation exploring strategies for minimizing immune responses to AAV-based…

October 29, 2021

Aseptic Considerations in Formulation, Fill and Finish: Choosing Between Barrier and Isolator Technologies

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Biological drug substances are constituent in a wide range of medicinal products with an even broader spectrum of applications. Those include autoimmune-disease treatments (e.g., for arthritis), vaccines, and recombinant therapeutic proteins (e.g., for cancer treatment). What such products all have in common is that they are manufactured using biotechnology and other cutting-edge technologies. Biologics are not as physically robust as their small-molecule counterparts. Hence, during biomanufacturing processes, these complex molecules present a number of challenges. Some of the typical shared…

September 30, 2021

Creative Formulation: A Useful Approach to Patient-Centered Drug Development

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The development of new medicines is a highly regulated process focused on demonstrating efficacy and safety of new products. Although such qualities always will remain the primary focus of drug development, the biopharmaceutical industry gradually has adopted additional design aspects. New approaches can help meet patients’ divergent needs to improve their lives in meaningful ways. Often referred to as “patient-centered” or “patient-focused” drug-product design, such considerations are expected by many experts to become an increasingly dominant part of future drug…

September 30, 2021

Analysis of Trace-Level, High-Risk HCPs: Proteomics Advances for Preventing Degradation of Polysorbates in Biotherapeutic Formulations

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Polysorbate-80 (PS-80) and polysorbate-20 (PS-20) are used widely in formulation of biotherapeutic products for preventing surface adsorption and as stabilizers against protein aggregation (1). Degradation of polysorbates can cause turbidity and potential formation of subvisible particles mainly consisting of poorly soluble hydrophobic free fatty acids (1). Polysorbate degradation is an industry-wide challenge both in biotherapeutics processing and formulation development. The risk of such degradation increases with higher cell densities and greater expression titers in bioprocessing, as well as with higher…

September 30, 2021

Single-Use Technology for Formulation and Filling: A Case Study from Swissfillon AG and Pall Corporation

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Swissfillon AG is a contract manufacturing organization (CMO) based in Switzerland. Fully compliant with current good manufacturing practice (CGMP) regulations, it provides state-of-the-art aseptic filling for pharmaceutical and biotechnology companies, from clinical-phase materials to commercial quantities. This CMO specializes in high-value, difficult-to-fill products. Swissfillon recognized that adoption of single-use systems (SUS) on a commercial scale required major improvements in consistency and reliability compared to manual operations at pilot and clinical-trial scale. The single-use formulation and filling process, which includes an…

September 30, 2021