2021

A Strategic Approach to Selecting the Optimal Process Intensification Scenario

Current demands placed on the biopharmaceutical industry are pushing manufacturers toward process intensification, an approach that modifies unit operations or an entire manufacturing process to optimize efficiency. Three common intensification scenarios in upstream processing are seed-train intensification (usually at the n – 1 stage), concentrated fed-batch production, and dynamic perfusion (at the production bioreactor stage). In downstream processes, intensification strategies typically involve moving from single- to multicolumn chromatography. Biomanufacturers can realize several kinds of improvements from intensified processing, including reductions…

Comparing Single-Use Multicycle Cake Filtration with Depth Filtration: Eliminating the Downstream Bottleneck

Over the past few decades, single-use (SU) technology has increased bioproduction efficiency significantly, especially with the introduction of disposable bioreactors in upstream processing. To keep pace with major developments and increases in upstream capacity, downstream processes also must increase capacity and efficiency. However, cell harvesting and downstream processing continue to present bottlenecks in manufacturing (1). Typical clarification processes are composed of primary and secondary clarification steps, such as centrifugation followed by depth filtration, respectively (1). Two sets of SU depth…

Transfection Best Practices for AAV Gene Therapy Programs

As viral vectors continue to push gene therapy innovations closer to market, many researchers are setting their sights on optimizing transfection, the process of delivering corrective genetic material into cells. It’s not just a question of how to transfect them, but also how to do so efficiently and at high volumes. Approaches that work for one cell line might not perform well for others, and transfection protocols can have different implications for scalability and cost during production for clinical trials.…

Focusing on the Patient Journey Can Increase Access to Lifesaving Therapies

Cell and gene therapies (CGTs) are positioned currently as last-chance, “miracle” cures for patients who have severe illnesses. Such promises require innovation. Despite the cutting-edge science and significant investment that goes into CGT development, fundamental challenges remain, including patient access. The highly personalized nature of autologous-therapy development presents myriad logistical, financial, and manufacturing challenges to ensuring global access to treatment. Understanding a patient’s journey to treatment is vitally important to achieving that goal. Barriers to Cell and Gene Therapy Access…

Recombinant Proteins for Cell and Gene Therapy Research: A Conversation with Shenandoah Biotechnology

Recombinant proteins such as growth factors and cytokines are essential for cell therapy, gene therapy and regenerative medicine research, development and manufacturing. These proteins are critical in the production of desired cell types and subsequent differentiation of cells, to deliver the desired effect. Founded 15 years ago, Shenandoah Biotechnology applies a proprietary method of folding and purifying recombinant proteins from both bacterial and mammalian systems to enable cost-effective, large-scale production of Cell Therapy Grade proteins to support these groundbreaking treatments.…

Aseptic Considerations in Formulation, Fill and Finish: Choosing Between Barrier and Isolator Technologies

Biological drug substances are constituent in a wide range of medicinal products with an even broader spectrum of applications. Those include autoimmune-disease treatments (e.g., for arthritis), vaccines, and recombinant therapeutic proteins (e.g., for cancer treatment). What such products all have in common is that they are manufactured using biotechnology and other cutting-edge technologies. Biologics are not as physically robust as their small-molecule counterparts. Hence, during biomanufacturing processes, these complex molecules present a number of challenges. Some of the typical shared…

Creative Formulation: A Useful Approach to Patient-Centered Drug Development

The development of new medicines is a highly regulated process focused on demonstrating efficacy and safety of new products. Although such qualities always will remain the primary focus of drug development, the biopharmaceutical industry gradually has adopted additional design aspects. New approaches can help meet patients’ divergent needs to improve their lives in meaningful ways. Often referred to as “patient-centered” or “patient-focused” drug-product design, such considerations are expected by many experts to become an increasingly dominant part of future drug…

Analysis of Trace-Level, High-Risk HCPs: Proteomics Advances for Preventing Degradation of Polysorbates in Biotherapeutic Formulations

Polysorbate-80 (PS-80) and polysorbate-20 (PS-20) are used widely in formulation of biotherapeutic products for preventing surface adsorption and as stabilizers against protein aggregation (1). Degradation of polysorbates can cause turbidity and potential formation of subvisible particles mainly consisting of poorly soluble hydrophobic free fatty acids (1). Polysorbate degradation is an industry-wide challenge both in biotherapeutics processing and formulation development. The risk of such degradation increases with higher cell densities and greater expression titers in bioprocessing, as well as with higher…

A Holistic Approach: Bridging the Gap Between Suppliers and Biomanufacturers

How can biopharmaceutical manufacturers expect their suppliers to deliver what the industry wants and needs if it doesn’t communicate those desires? Without industry input, biotechnology suppliers are developing technologies “blindly.” Despite their having delivered great value over the years, together the greater community can do better. Aligned industry input is a vital element in the development process. Here we describe how two BioPhorum workstreams focused on drug-product development have worked to facilitate these communications. Last summer, the container–closure integrity (CCI)…

Closed-System Transfer Devices: Collaboration Provides Tools to Guide Compatibility and Stability Testing Strategy

Ever since the first biopharmaceutical product (biologic) was approved in the 1980s, companies have developed protocols and tests to ensure that such products are safe and effective. Biologics are very different from traditional small-molecule drugs, with unique risks inherent to their manufacturing processes. Biopharmaceutical formulations often present as complex mixtures that can be sensitive to heat, light, and many other factors, all of which must be monitored and assessed. However, until recently, developers worked mostly independently, with only their own…