2022

DNA to IND in 13 Months: A CMC Strategy for Bispecifics

Multichain protein biotherapeutics such as bispecific molecules have been developed to treat cancer, neurological and ophthalmic disorders, and autoimmune and inflammatory diseases. Early successes now are driving greater numbers of such molecules toward clinical evaluation and commercial approval. However, the complexity of bispecific development and manufacture calls for innovative tools and technologies to facilitate the clinical journeys of such products and prevent costly setbacks for their sponsors. In its commitment to fostering novel biomolecular formats, Lonza has designed a chemistry,…

Harnessing the Untapped Power of the Human Commensal Virome

Viruses are ubiquitous members of every ecosystem, including the human body (1). A common misconception is that all viruses are harmful. In fact, their relationships to human hosts can be pathogenetic, symbiotic, or commensal. In the latter case, a virus benefits from but neither harms nor helps its host (2). Commensal viruses are as abundant as human cells, and their coexistence has persisted for millennia, permitting our immune systems to recognize them as part of us. Among the most abundant…

Optimize Your Early Preclinical Process for Gene Therapy Success

Early decisions can impact the success of a novel gene therapy, so how can therapeutics companies make sure to set off on the right track? In this article, drug developers will learn some things that they should consider at the start of their therapeutic journey. We explore the impact of early technical decisions, including the importance of seeking high-yielding plasmids and a well-validated cell line. We cover logistical considerations, such as plasmid supply chain challenges and how to avoid them.…

Addressing Unwanted Immunogenicity in Gene Therapies

Immunogenicity is the ability of a substance, such as a foreign and/or potentially dangerous protein, to provoke an antigen-specific immune response. However, some immune responses can be detrimental, such as in autoimmune diseases and unwanted reactions to biological therapeutics. The latter case can compromise biopharmaceutical safety and efficacy, and preexisting immunity against biologic components can preclude patients from receiving life-changing treatments, perhaps most notably in gene therapy (1). Gene therapies are designed to target the root cause of a genetic…

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

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).…

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

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…

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

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 2022: From the Editor

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…

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

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…

US Patent Law: A 20-Year Retrospective

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…