2023

The Rise of Antibody–Drug Conjugates and Related Modalities: Innovations and Partnerships Lead the Way

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Antibody–drug conjugates (ADCs) are straightforward as a concept. When a cytotoxic small-molecule drug is attached to an antibody raised against a specific molecular receptor, it theoretically creates a highly targeted and effective therapy. And the ability to target cells precisely has obvious applications for indications such as cancer. However, in practice, developing and manufacturing ADCs has proven difficult, said Janice M. Reichert, chief operating officer of The Antibody Society, which is an international nonprofit organization that supports antibody-related research and…

Developers Work To Refine Platforms for the Best Results

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Antibody-conjugate technologies have been pushed out of the limelight somewhat in recent years by mRNA/oligonucleotides and cell/gene therapies. Yet while many people were talking about the “next big thing” — and remember, the next big thing in cancer treatment not so long ago was antibody–drug conjugate (ADC) therapy — this now-maturing segment of the biopharmaceutical industry has begun proving its worth. As of November 2022, the US Food and Drug Administration (FDA) had approved 14 different ADCs for cancer indications.…

Manufacturing Challenges of Therapeutic Antibody–Drug Conjugates

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The pharmaceutical industry has come a long way since 1907, when Paul Ehrlich coined the term “magic bullet” for treatments that could target disease-causing cells while sparing normal, healthy cells (1, 2). Researchers began investigating targeted cytotoxins as therapeutic bioconjugates in the late 1980s. Groups led by Ellen Vitetta at the University of Texas Southwestern Medical Center (3), Ira Pastan at the US National Institutes of Health (4), and John R. Murphy at Boston University (5) fused truncated Pseudomonas exotoxin…

September 2023: From the Editor

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With another September comes another collective sprint to the end of the year. Because of our three-month minimum span from receipt of a manuscript to its publication, we already are planning our January–February issue. But between now and then, we have plenty to do. The publication’s editors, Dan Stanton’s BioProcess Insider team, and our conference colleagues are gathering up ideas, comparing notes, evaluating trends, and creating editorial and conference calendars for 2024. The BPI conference and colocated meetings are coming…

Cell Culture Media Fingerprinting: A Three-Tiered Approach

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Cell culture media range from simple components to complex chemically defined mixtures. They may contain a number of chemical components, each with individual chemical properties — and any variation in which ingredients can affect cell culture processes and biological products being manufactured. Although simple substances can be identified easily using well-known classical methods such as Fourier-transform infrared spectroscopy (FTIR), analysis becomes more challenging when dealing with complex mixtures. Section VII-3-C of the Q7A guidance from the International Council for Harmonisation…

Engineering the Future: Cell-Line Development Discussions at BPI West

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Big data, next-generation sequencing (NGS), automation, and powerful analytical technologies are helping biopharmaceutical companies achieve the parallel goals of cell-line development: precise integration of transgenes into production cells with documented monoclonality, shortening timelines and increasing productivity. Presentations in the most recent Biotech Week Boston (BWB) and the BPI Conference US West (BPI West) programs have demonstrated that there is no one way to accomplish those goals. Combining several of the approaches highlighted herein just might take biopharmaceutical production to new…

Establishing Microbiological and Particulate Controls When Reworking a Sterile Drug Product

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Reworking of finished sterile-product batches requires particular attention to maintaining microbial and particulate control. The strategy is permitted with regulatory agreement and observation of regulations such as 21 CFR 820 (1). Note that reworking is distinct from reprocessing. Under ICH Q7, reprocessing is confined to intermediates, whereas reworking is reserved for finished products (2). Reworking includes steps that were not part of an initial biomanufacturing process. The reworked steps are process elements that are designed either to bring an out-of-specification…

Validating Prefiltration Dirty-Hold Times for Upstream Media and Feed Solutions: Implications for Establishing In-Process Microbial Control

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Biopharmaceutical manufacturing processes require that prepared raw materials and product intermediates be held at different stages. During hold times, however, process and product intermediates are susceptible to microbial risks from bioburden, endotoxins, and exotoxins. Such risks arise from multiple sources, including bioproduction facilities, equipment, operations, and raw materials. Even a prepared intermediate can help microbes to grow. The US Food and Drug Administration’s (FDA’s) guidance on Sterile Drug Products Produced By Aseptic Processing states that “the time limits established for…

Advancing Vaccine Development with Novel Chromatography Solutions

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The rise of new diseases and infections has increased the need for accelerated development of safe and effective vaccines. In addition, the search for vaccines continues for long-known pandemic diseases such as acquired immunodeficiency syndrome (AIDS) and malaria, for which effective vaccines currently do not exist. To address the difficulties of vaccine development for such indications, scientists are researching new modalities including viral vectors, recombinant proteins, and nucleic acids. However, each vaccine production process is unique and will have its…

Advances in Bioanalytical Tools for the Characterization of In-Process Viral Samples

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The best bioanalytic tools support bioprocess development by enabling scientists to measure and monitor samples throughout an entire bioprocess quickly and efficiently. Sofia Carvalho is a senior research associate at Portugal’s Instituto de Biologia Experimental e Tecnológica (iBET, https://ibet.pt), a nonprofit biotechnology research organization that works to advance biologicals and biotherapeutics research and development by connecting academia and industry. In an April 2023 webinar, she discussed how advances in bioanalytical tools for viral and viral-like sample characterization can improve the…