2022

Deriving Mesenchymal Stromal Cells from Umbilical Cord Lining and Wharton’s Jelly: A Comparative Study of Extraction Methods and Culture Media

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Mesenchymal stromal cells (MSCs) are multipotent, self-renewing progenitor cells that can differentiate into adipocytes, chondrocytes, and osteocytes (1). Cultured MSCs are plastic-adherent and spindle-shaped, and they express cell-surface markers CD44, CD73, CD90, and CD105, but not CD14, CD34, CD45, CD11b, CD79a, CD19, or HLA-DR (2, 3). First isolated from bone marrow (BM), human MSCs have been investigated extensively in clinical studies. MSCs also have been isolated from adipose tissue (4) and peripheral blood (5). Perinatal organs and tissues such as…

September 28, 2022

Opportunities in the Field of Host-Cell Proteins Part 1: Their Sources and Implications for Protein-Drug Efficacy

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Biopharmaceuticals are produced in genetically modified cells; thus, they contain process-and product-related impurities. Those deriving from manufacturing processes include host cell DNA/RNA, viral DNA/RNA, cellular debris, lipids, and host-cell proteins (HCPs) (1). Mammalian, bacterial, fungal, insect, and plant cell lines have been used to overexpress recombinant proteins. Currently, the most frequently used hosts for biomolecule synthesis are Escherichia coli and Chinese hamster ovary (CHO) cells. E. coli has been used to produce heterologous proteins since the beginning of the biotechnology…

September 28, 2022

A Plug-and-Produce GMP Plant for Cell and Gene Therapy — Part 1: Case Study in Modular Facility Design and Deployment

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The use of approved advanced therapy medicinal products (ATMPs) remains limited despite their potential to address unmet medical needs. One example uses chimeric antigen receptor (CAR) T cells for treatment of refractory lymphoma (1). Typically, such medicinal products begin with cells that are harvested from a patient and genetically programmed to recognize and eliminate tumor cells upon reinfusion. Several cell therapies based on this and other technologies are approved for use in the United States, Europe, and China (2). Given…

September 28, 2022

Overcoming Challenges in Viral Vector Production for Gene Therapy Using HEK Cell Cultures

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An estimated 300 million people worldwide live with rare diseases, and over 70% of such disorders are caused by genetic mutations (1, 2). Cell and gene therapies offer hope and potential cures for many previously untreatable diseases. Accordingly, the global gene therapy market is expected to be worth USD 5.02 billion by 2028, a significant growth from USD 1.46 billion in 2020 (3). Manufacturing gene therapies will be a key challenge over the next two decades. But just a few…

September 28, 2022

Twenty Years of Innovation: Reflections on the Industry’s Past and Future

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In honor of BPI’s 20th anniversary as a publication, the editors invited authors to reflect on the industry’s past, present, and future. Below, the chief operating officer of Selexis offers her perspectives along with responses to questions from the editorial team. Significant Scientific and Technological Innovations One of the most important innovations in bioprocessing has been the combination of next-generation sequencing with bioinformatics. The ability to sequence a host cell-line genome and transcriptome rapidly and cost-effectively and the development of…

September 28, 2022

Comprehensive Virus Clearance Evaluation Using Microscale Membrane Adsorbers

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Membrane adsorbers can be a simple and effective choice for anion-exchange (AEX) purification of biopharmaceuticals. However, as Sherri Dolan (global technology consultant for virus clearance at Sartorius) explained during a May 2022 presentation, biomanufacturers generally do not leverage their membranes’ full loading capacities. Doing so could improve process economics and decrease costs for several downstream applications. Dolan’s Presentation Membrane adsorbers are ideal for flow-through AEX applications (e.g., secondary purification and polishing) because they can be used at high flow rates…

September 28, 2022

Analytical Tools for Improving Up- and Downstream AAV Process Development

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During a May 2022 Ask the Expert presentation, Ivana Petrović Koshmak (head of upstream process development at BIA Separations, part of Sartorius) highlighted the gene- therapy industry’s need for fast, reliable analytics that work with both up- and downstream samples. High-performance liquid chromatography (HPLC) methods can fulfill that need, but process development (PD) scientists would need to account for the complexity of bioreactor samples to make such methods feasible for end-to-end analytics. Koshmak described a novel instrument that is designed…

September 28, 2022

Next-Generation Software Solutions for Analytical Chromatography Processes

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High-performance liquid chromatography (HPLC) has become a leading analytical method for biopharmaceutical process development and optimization, particularly for therapies that leverage plasmid DNA (pDNA), messenger RNA (mRNA), and viral vectors. In July 2022, Blaž Goričar (manager of process analytics development at BIA Separations, a Sartorius company) demonstrated the features of his company’s PATfix software for HPLC data processing and analytics. He described how the program can simplify method execution and enhance evaluation of resulting data. Goričar’s Presentation PATfix software is…

September 28, 2022

Leveraging Prior Knowledge to Demonstrate Analytical Competency

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Analytical groups are developing more methods than ever to address mounting demand for biopharmaceuticals. Still, such teams need to work within tight timelines to help candidate therapies advance quickly through clinical trials. During a May 2022 presentation, Rajgopal Rudrarapu (senior scientist at the Almac Group) pointed out that regulatory agencies allow biomanufacturers to apply prior knowledge to facilitate analytical development and validation. He described how his company leveraged prior knowledge to develop and validate a capillary isoelectric focusing (cIEF) method…

September 28, 2022

Bringing Gene-Therapy Product Quality Into Focus

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Regulatory agencies are scrutinizing gene-therapy product quality more closely than ever, yet such therapies still are produced in small batches and at high costs. Thus, drug companies are struggling to make safe and efficacious gene therapies available to patients. In an April 2022 presentation, Tim Kelly (chief executive officer of Oxford Biomedica Solutions, OXB Solutions) emphasized the importance of addressing both process output and product quality when manufacturing adenoassociated virus (AAV)-based gene therapies. Such an approach requires deep expertise and…

September 28, 2022