2022

Building Manufacturing Capabilities for Adenoassociated Virus Vectors: Key Considerations for Facility Design and Operations

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Demand for gene therapies based on adenoassociated virus (AAV) vectors continues to exceed manufacturing capacity. Part of the imbalance stems from the growing number of AAV-based candidates that are advancing through clinical studies. Zhao et al. report that, in September 2021, researchers were enrolling participants for and/or conducting 137 trials for such products (1). As of August 2022, three AAV-based therapies have received commercial authorization in the United States and/or European Union, and other products have received conditional approval (2–5).…

October 20, 2022

Effective Processing of Lentiviral Vectors: Introducing a Paradigm-Shifting Technology

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Therapeutic developers face significant challenges in purifying cell and gene therapies (CGTs). Current technologies for laboratory-scale lentivirus (LV) feedstock preparation are inefficient and not fit for purpose. From the benchtop to the clinic, all stages of CGT development require new solutions that break away from the current paradigm of biopharmaceutical manufacturing. Nereus LentiHERO nanofiber-based technology can address difficulties associated with purifying large and fragile modalities. Here, experts from the viral vector team at Astrea Bioseparations discuss how Nereus LentiHERO technology…

October 20, 2022

Statistical Method for Establishing Control Limits for Nonnormal Data Distribution: Focus on Continued Process Verification Monitoring

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According to the US Food and Drug Administration’s (FDA’s) process validation guidance, critical quality attributes (CQAs) and critical process parameters (CPPs) are used to assess the statistical stability of a bioprocess and its ability to meet acceptable criteria as a part of a continued process verification (CPV) program using control charts (1). For those control charts, control limits are used to assess the statistical stability of process parameters and attributes. When data are normally distributed, control limits are established straightforwardly…

October 20, 2022

October 2022: From the Editor

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Happy autumn! I am writing this a few days before the editors head to Biotech Week Boston and the BPI conference. This is my first travel since January of 2020, and I am eager to see everyone again. As usual, the fall months coincide with our finalizing next year’s editorial calendar. I will be able to share those details (and other BPI news) with you in our next issue. One major project that came our way a few months ago…

October 20, 2022

Why Cell Manufacturing Matters: How Bioprocess Innovations Have Laid the Foundation for a Cell-Based Products Revolution

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In the first cell therapy special issue of BioProcess International back in 2011, members of the International Society for Cell and Gene Therapy’s (ISCT’s) commercialization committee highlighted the need for cell-processing professionals who prepare bone-marrow and cord-blood products to collaborate with bioprocess engineers in establishing commercially-relevant manufacturing processes for a new wave of cell-based therapies (1). The emerging field of cell and gene therapy presented unique challenges for creating scalable bioprocesses under current good manufacturing practices (CGMPs) to accommodate primary…

October 20, 2022

US Patent Law: A 20-Year Retrospective

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The past 20 years have been extraordinary for intellectual property law. Most of the transformations can be attributed to changes in the statute, US Supreme Court jurisprudence, almost complete turnover in judges in the Court of Appeals for the Federal Circuit (“Federal Circuit,” below), and advances in technology that could not have been anticipated in 2002. An understanding of those changes requires a retrospective of patent law over those 20 years. At that time, the Federal Circuit was 20 years…

October 20, 2022

Expanding Considerations in Cleaning Validation: Risks Posed By Indirect Product-Contact Surfaces on Pharmaceutical Equipment

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Cleaning validation receives a great deal of attention within the biopharmaceutical industry, not least because of the risks of product adulteration and hence patient harm from improperly cleaned surfaces (notwithstanding additional concerns such as operator protection). Traditionally, cleaning validation efforts focus on direct product-contact surfaces. However, the hazard and resultant risk posed from indirect product-contact surfaces should not be underestimated. Consideration of the risks presented by indirect surfaces should figure into every contamination-control strategy. Understanding of these risks cannot be…

October 20, 2022

Using 3D Imaging To Understand Sterilizing-Grade Filtration of Liposomes

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Sterilizing-grade filtration is an essential operation for biomanufacturing. It ensures that drug substances are free from microorganisms at the end of a downstream process. The COVID-19 pandemic has highlighted the need for high-quality therapies to be manufactured efficiently at scale, with particular focus on the need for multiple vaccines to be developed, produced, and distributed globally (1). Some vaccines have used lipid nanoparticle encapsulation technology, which also has potential for use in gene therapy development in the near future. Lipid…

October 20, 2022

Optimizing and Intensifying ADC Aggregate Removal: A DoE Approach to Membrane Chromatography and Rapid Cycling

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Antibody–drug conjugates (ADCs) represent a growing therapeutic segment of the oncology field. Five such treatments received market approval from the US Food and Drug Administration (FDA) between 2008 and 2018, whereas three were approved in 2019 and two each were approved in 2020 and 2021 (1). This disruptive technology combines highly potent small-molecule payloads with monoclonal antibodies (MAbs) to improve their specificity as cancer treatment. The antibodies deliver those toxic compounds directly to cancer cells but not to healthy cells,…

October 20, 2022

Opportunities in the Field of Host Cell Proteins: Part 2: Ensuring Patient Safety

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Process-related impurities such as host cell proteins (HCPs) can raise concerns about biological product efficacy, quality, safety depending on their properties and levels. In the first part of this series, we surveyed relevant regulatory frameworks and detailed potential effects of HCPs on biologic efficacy. Here in part 2, we review available literature on HCPs and patient safety, including information about HCP-related immune responses and adverse clinical events. HCP Effects on Patient Safety At least five HCP-induced factors can influence a…

October 20, 2022