Downstream Development

Accelerating the Development and Manufacture of Therapeutics Using the Octet Platform

The high costs of therapeutic discovery, development, and manufacture require improved process efficiencies and economics. Analytical tools that eliminate the need for reagent labeling and enable real-time data visualization save development time and improve efficiencies during process development. The Octet biolayer interferometry (BLI) platform and assays can be used throughout process development and manufacturing, including cell-line development, clone selection, and dynamic binding capacity (DBC) determination for affinity purification columns. The ability of the Octet BLI platform to monitor binding interactions…

Your Partner for Host Cell Protein Analytics for Over 25 Years

Cygnus Technologies, part of Maravai LifeSciences, is the biopharmaceutical industry’s partner in host cell protein (HCP) and other process-related impurity detection and analytics. In addition, Cygnus now provides innovative viral clearance solutions. Cygnus helps companies developing therapeutic proteins, vaccines, antibodies, plasma derivatives, and gene therapies ensure the safety of their biotherapeutics before human trials, regulatory approval, and commercial release. Cygnus provides analytical tools and solutions for improving bioprocess development for faster regulatory approval and better clinical outcomes. Cygnus is an…

Ask the Expert: Considerations for Mass Spectrometric HCP Analysis During Process Development

Host-cell proteins (HCPs) must be assessed early in biopharmaceutical product development to establish the efficiency of a purification process. Liquid chromatography coupled with mass spectrometry (LC-MS) is a strong orthogonal method for HCP identification and quantitation. During an 18 March 2021 “Ask the Expert” presentation, Christina Morris (senior scientist at BioPharmaSpec) explained how MS analyses can enhance process development (PD), then presented considerations for generating spectral libraries, selecting samples for quantitation, and reviewing data. Morris’s Presentation Spectral Libraries: A typical…

Endotoxin Questions and Answers

Endotoxin — also known as lipopolysaccharide (LPS) — is a large molecule made up of a lipid and a polysaccharide portion found in the outer membrane of each Gram-negative bacterial cell. Examination of endotoxins is necessary for microbial and animal cell-culture operations that produce active pharmaceutical ingredients (APIs) and vaccines. If a cell culture is contaminated with endotoxins, it could affect cell growth and function (thus potentially affecting product quality). Biopharmaceutical companies need to understand the endotoxin levels within their…

challenges with exosome therapy

eBook: Challenges in Industrial Process Development of Exosome-Based Therapies: Characterizing and Managing Diversity

The traditional classification of extracellular vesicles (EVs) includes three types: exosomes, microvesicles, and apoptotic vesicles. Each type arises from a distinct origin and exhibits distinct characteristics. The problem is that their size ranges overlap and that the major surface proteins presented by exosomes also are present on the surfaces of microvesicles and apoptotic bodies. This makes it a challenge for process developers to identify the vesicle fraction that best serves a particular exosome therapy. Anion-exchange chromatography (AEC) can fractionate EVs…

The Downstream Perspective: Putting Product Knowledge to Work Using Technological Innovations

After over a quarter century in the industry — including downstream processing (DSP) and manufacturing directorships at Boehringer Ingelheim and leadership roles in technology development, quality, and manufacturing at Novasep — European consultant Margit Holzer is a recognized expert in downstream processing of biopharmaceutical products. Holding a doctorate in biotechnology from the University of Natural Resources and Applied Life Sciences in Austria, Holzer is familiar to BPI readers as both an author and conference participant (1, 2). And in May…

Ask the Expert: Highly Sensitive Host-Cell Protein Analyses Using Novel Chromatography Technology

Geert Van Raemdonck (global field support expert at PharmaFluidics) and Koen Sandra (scientific director of the Research Institution for Chromatography, RIC) teamed up for a 10 October 2019 “Ask the Expert” webinar to introduce micro Pillar Array Column (μPAC™) technology for liquid chromatography–mass spectrometry (LC–MS) for host-cell protein (HCP) detection. Van Raemdonck explained that μPAC technology approaches chromatography differently than does packed-bed technology. Microfluidic channels with arrays of free-standing pillars are etched lithographically into a silicon wafer. The resulting permeability…

Host-Cell Protein Analysis to Support Downstream Process Development: A High-Throughput Platform with Automated Sample Preparation

In the past few years, increasing numbers of biotherapeutics have been approved for market (1). Among all the regulatory concerns for commercial biotherapeutics, host-cell proteins (HCPs) are a major class of process-related impurities that remains a critical quality attribute (CQA) for bioprocess development because of associated risks to product quality, safety, and efficacy. HCP identification, clearance, assay setup, and process control are critical points for health authorities, and many guidelines aim for better control of HCP content in final biologic…

Viral Nanofilter Integrity: Using Variable-Pathlength UV-Vis Spectroscopy for the Gold Nanoparticle Test

Viral filtration (VF) using nanofilters removes endogenous and/or adventitious viruses from biologic drug-substance manufacturing processes (1). The gold particle test (GPT) is performed as part of postuse integrity testing — to complement postuse leakage testing — for cellulose filters such as Planova 20N filters from Asahi Kasei Corporation. First, a proprietary gold-colloid solution matched to the filter type (e.g., 20N) is filtered through the test article. That filter’s pore-size distribution can be assessed using spectrophotometric absorbance readings of the integrity-test…

Adenovirus Downstream Process Intensification: Implementation of a Membrane Adsorber

Historically, companies developing vaccines have used attenuated pathogens, inactivated infectious agents, or antigenic constituents purified from pathogenic sources. In the past 20 years, technological advances such as recombination and viral vectors, have enabled development of vaccines against diseases with previously no available treatments (1). Viral vectors have become one of the most rapidly evolving and promising fields in vaccinology and regenerative medicine. In addition to preventing infectious disease, they have a broad range of potential applications, including treatment of hereditary…