April 2023

April 2023: From the Editor

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The biopharmaceutical industry is continually reinventing itself. It evolved from a science-driven entrepreneurial approach and has worked over five decades to weave its network of business, regulatory, and process-development modes somewhat after the fact. The origin of so many bioprocesses in academic research laboratories prompted some of us in the editorial world to propose article series on “biobusiness 101 for scientists” back even in the early 1990s. Much of the industry’s progress toward its current form depended on adapting processes…

April 20, 2023

Using Regulatory T Cells for Treatment of Type 1 Diabetes, Part 1

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During the January 2023 Advanced Therapies Week in Miami, FL, Leonardo Ferreira, an assistant professor from the Medical University of South Carolina, spoke about his team’s work in developing chimeric antigen receptor (CAR) regulatory T cells (Tregs) as living therapeutics for type 1 diabetes. Ferreira has focused on type 1 diabetes since 2016, when he undertook postdoctoral work at the University of California at San Francisco under Qizhi Tang and Jeff Bluestone before continuing his research at his own laboratory…

April 20, 2023

Leveraging Material-Binding Recombinant Proteins: A Novel Approach to Tissue Regeneration

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In March 2023, I took the opportunity to speak with Luis Alvarez about the founding of Theradaptive. The company specializes in engineering recombinant proteins, with an initial focus on developing therapeutics for regeneration of soft, vascular, and bone tissue. “Theradaptive grew out of my thinking about combat injuries,” Alvarez told me. Before earning a doctoral degree in biomedical engineering from the Massachusetts Institute of Technology and working as cofounding deputy director of the US Department of Defense’s regenerative medicine program,…

April 20, 2023

Overcoming the Digital Divide: Leveraging Intelligent Automation and Informatics Expertise

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Shifting to a digital regulatory environment is forcing pharmaceutical companies to confront knowledge gaps across key research and development (R&D) functions. As health authorities streamline information exchange through data standardization, the separation between regulatory operations and other functions within the pharmaceutical industry begins to blur. By advancing implementation of ISO identification of medicinal product (IDMP) standards, companies are improving interoperability and information sharing among key clinical, pharmacovigilance, quality, manufacturing, and supply-chain–logistics teams. However, a company’s important regulatory and strategic planning…

April 20, 2023

Biopharma 4.0 — the Talent Evolution

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Biopharma 4.0 refers to applications of data and digital technologies to biotherapeutic manufacturing. Technological advances now enable the internet and its embedded systems to serve as a nucleus through which biomanufacturers can integrate production lines and processes across organizational boundaries, thereby forming a networked and agile value chain. Solutions under the industry 4.0 umbrella include • platforms for “smart” manufacturing made possible by the internet of things (IoT) • artificial intelligence (AI) • systems for process automation • technologies for…

April 20, 2023

Large-Scale AAV Production: Advantages of an Insect-Cell Baculovirus Expression Vector Platform

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Adenoassociated viruses (AAVs) have been the center of intensive research since their fortuitous (incidental) discovery in 1965 as a contaminant in a simian adenovirus preparation (1). Initial scientific interest primarily focused on understanding the fundamental biology of this virus type, but later it was harnessed to serve as a genetic vector for use in treating or even curing certain genetic diseases (2). Many distinct characteristics make AAVs a versatile tool for development of clinical candidates, exemplified currently by more than…

April 20, 2023

Quantitative Risk Assessment of Limits for Residual Host-Cell DNA: Ensuring Patient Safety for In Vitro Gene Therapies Produced Using Human-Derived Cell Lines

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Viral-vector gene therapies (GTs) manufactured from cell-substrate production systems can contain residual amounts of host-cell DNA (hcDNA), which in a final product presents safety risks to treated patients. Therefore, drug manufacturers monitor and control residual hcDNA levels in purified products (1, 2). The US Food and Drug Administration (FDA) and other global regulatory agencies recommend tight, quantifiable limits for hcDNA levels: 10 ng/dose, with DNA fragments smaller than the functional gene size of 200 base pairs (bp) (3). However, because…

April 20, 2023

Going Big in Cold-Chain Management: Anticipating Challenges and Finding Solutions for Large Volumes

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Bulk drug substances (BDS) often require frozen storage to preserve the integrity of biological material. Cold-chain management is particularly important given recent trends toward increasing globalization and decentralization and diversifying modalities. A secure cold chain is essential for maintaining a product’s critical quality attributes (CQAs) — such as drug product stability, integrity, and purity — and to prevent costly product losses. Scaling Up the Cold Chain Frozen storage at commercial scale presents its own challenges; facilities must be able to…

April 20, 2023

Strengthening Data Management and Integrity for CGT Applications

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The specialized nature of cell and gene therapies (CGTs) requires that they be delivered to single patients or in low batch numbers. Manufacturing CGTs at scale is critical to industry success, but doing so at an economically viable cost is a key obstacle. Today’s therapies cost between US$400,000 and $3.5 million per patient, largely because of the need for highly skilled workers to deliver those innovative drugs. The CGT industry has innovated across all areas of production, from collection of…

April 20, 2023