Downstream Processing

Advancing Vaccine Development with Novel Chromatography Solutions

The rise of new diseases and infections has increased the need for accelerated development of safe and effective vaccines. In addition, the search for vaccines continues for long-known pandemic diseases such as acquired immunodeficiency syndrome (AIDS) and malaria, for which effective vaccines currently do not exist. To address the difficulties of vaccine development for such indications, scientists are researching new modalities including viral vectors, recombinant proteins, and nucleic acids. However, each vaccine production process is unique and will have its…

Viral Clearance in the Age of Q5A(R2) and the Case for Using Noninfectious Spiking Agents

As viruses can arise during the manufacture of biopharmaceuticals, regulatory agencies require “viral clearance” validation studies for each biopharmaceutical prior to approval. For example, Type C Retrovirus-Like Particles (RVLP) are endogenously produced during CHO cell expression. As such, regulatory agencies require proof that downstream process steps can effectively remove or inactivate retrovirus. A model mammalian virus, Xenotropic Murine Leukemia Virus (XMuLV) is typically used to demonstrate RVLP clearance. However, the establishment of RVLP quantification methods has made it possible to…

Advances in Protein A Chromatography Resins

Aaron Moulin, field application scientist, Purolite (North America). Aaron Moulin spoke about Purolite’s patented jetting technology, highlighting the performance of Praesto Jetted A50 and Praesto Jetted A50 HipH protein A affinity resins. He began by describing the traditional way to produce agarose beads through batch emulsification, which takes six to eight weeks. Manufacturers perform solubilization, emulsification (with a nonpolar atrophic solvent, usually toluene), crosslinking, screening (sieving), functionalizing, and final testing for quality attributes. The sieving step alone takes three to…

BioProcess Insider Interview: Hayley Crowe, Senior Vice President, Purolite

Purolite has manufactured chromatography resin technologies for over 40 years. According to Crowe, the company ventured into producing a jetted agarose resin specifically for protein purification in 2016 by combining in-house knowledge with that of experts from around the world. Purolite’s patented jetting process creates beads of uniform size. Customers benefit for several reasons: Manufacturing processes can be made faster because users don’t have to waste time disposing of particles that are too small. The uniform bead size facilitates column…

Deep Roots: A Journey Through the Influence of Chromatography on the Biopharmaceutical Industry

The biopharmaceutical industry as we know it today dates back to the late 19th century. Emil von Behring and Paul Ehrlich, among other scientists, were pioneers in the industry. Their work on serum therapy laid a foundation for the development of vaccines and immunotherapies. The modern biopharmaceuticals emerged in 1973 with the advent of recombinant DNA technology. That groundbreaking discovery opened doors to new frontiers, enabling scientists to manipulate an organism’s DNA for manufacturing novel biological products. The fruits of…

Shaping the Future of Viral Clearance: Analyzing ICH Q5A(R2) and Its Impacts

In October 2022, a new draft of ICH Q5A (R2) was released, the first such update in more than 20 years. This draft revision was necessary to reflect current scientific knowledge and biotechnology advances such as new product types that are amenable to viral clearance and alternative virus clearance validation strategies. In this report, we delve into the evolving landscape of viral clearance practices, focusing on the implementation of continuous manufacturing, advancements in study design, and the implications for cell…

Chromatographic Purification: Data Science, Chemistry, and Process Engineering Are Driving Bioprocess Innovation Forward

When people decry “the lack of innovation” in biomanufacturing, I often find myself scratching my head. Maybe we’re working from different angles on the concept — for some, it might mean only those advances that are truly disruptive and replace a previous paradigm completely. But what I see in the biopharmaceutical industry currently is an explosion of new ideas, fresh approaches to established technologies, and incremental improvements that all add up to paint a dynamic picture of innovation indeed. “Creativity…

Demystifying Mixed-Mode Chromatography Resins: Emerging Applications for Purification of Non-MAb Protein Therapeutics

Although monoclonal antibodies (MAbs) still represent the most common and most lucrative drug class in the biopharmaceutical industry, enthusiasm is growing for other recombinant-protein products. Clinical pipelines and even commercial portfolios are beginning to feature a breadth of nonantibody proteins and fragments as well as variations on the conventional-antibody theme: e.g., single-chain variable fragments (scFvs), fragment antigen-binding (Fab) products, and single-domain antibody fragments (also called nanobodies). By exploring such formats, drug developers hope to continue leveraging the efficacy advantages of…

Platform Optimization for Efficient AAV Purification: Insights from a CDMO

The number of clinical studies continues to increase for candidate gene therapies based on adenoassociated virus (AAV) vectors. Application of different AAV serotypes has enabled drug developers to target a large panel of tissues and to address a breadth of diseases — but with the drawback that each serotype necessitates a distinctive purification process. Such development work requires considerable resources and results in long process-development timelines, which can cause significant delays to entering clinical trials. Thus, gene-therapy companies and contract…

Intensification of Fab-Fragment Purification: Multicolumn Chromatography Using Prepacked Protein L Columns

Antibody fragments — such as fragment antigen-binding (Fab) domains, single-chain variable fragments (ScFvs), and heavy-chain variable domains (nanobodies) — have emerged as increasingly important therapeutic and diagnostic alternatives to full-length monoclonal antibodies (MAbs) for a multitude of diseases. Whereas MAb downstream processing is well established and easy to scale based on protein A capture, the purification of antibody fragments is just on the verge of standardized processing. The most promising candidate for effective capture of those containing a kappa light…