Analytical

Using Technology to Overcome Bioprocessing Complexity: Advanced Concentration and Analytical Technologies Accelerate Development and Manufacture of mAbs, Vaccines, and Biosimilars

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Unlike chemically synthesized drugs, whose structure is known and reproducible, biological drugs are derived from living cells and are sensitive, complex mixtures requiring cutting-edge biological technologies for their production. The growing importance of biosimilars in recent years is reflected in a corresponding rise in market value. The value of the global biologic therapeutic drug market reached approximately US$230 billion in 2014 and, according to BCC Research, will increase to nearly $390 billion by the end of 2019. This corresponds to…

June 27, 2016

Quality By Design for Monoclonal Antibodies, Part 1: Establishing the Foundations for Process Development

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The quality by design (QbD) modernized approach to pharmaceutical development is intended to provide regulatory flexibility, increased development and manufacturing efficiency, and greater room to innovate as well as improve manufacturing processes within defined ranges without obtaining regulatory approval first. QbD is a systematic developmental approach that starts with a clear goal in mind and emphasizes understanding of how variability in both process and materials affects a final product (1). Historically, product quality has been assured either with end-product testing…

June 16, 2016

Osmolality Measurements for High-Concentration Protein–Polymer Solutions: Variation Based on Working Principles of Osmometers

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Osmolality is a critical attribute for injectable formulations. It is desirable to have products match physiological osmotic conditions. Furthermore, osmolality provides confirmation of soluble content in solution. Preventing injection of hypo- or hyperosmotic solutions is a key element of parenteral formulation development. Additionally, some investigators have explored correlations between injection pain and formulation osmolality, although no significant correlation has yet been observed (1–4). Osmolality is a valuable in-process test also because it provides a reliable and repeatable value that reflects…

June 15, 2016

Enhanced Biosimilar Product Characterization: A Case Study Using Raman Spectroscopy Combined with Dynamic Light Scattering

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Biophysical characterization has drawn great attention from the biopharmaceutical industry and regulatory agencies across the globe, especially for use in biosimilar drug product development. Currently available biophysical characterization tools can help in screening and optimizing better (more stable) formulations for such products. However, most tools cannot be used for head-to-head comparison of the biophysical properties of an optimized biosimilar formulation with those of an innovator product at higher concentrations. We developed and optimized a formulation for monoclonal antibody MAb B…

June 15, 2016

Ask the Expert Liposome and Viral Vector Characterization: Use of Electron Microscopy and Image Analysis

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with Dr. Josefina Nilsson For this webcast, Josefina Nilsson (EM Services business unit head) discussed Vironova’s work, including case studies. She focused on characterization of drug and gene delivery platforms with electron microscopy and image analysis, specifically for systems that use viral vectors or liposomes. Along with two colleagues — Gustaf Kylberg (image analysis expert) and Mathieu Colomb-Delsuc (electron microscopist) — she then answered questions from the audience. Nilsson’s Presentation Structural characterization provides important insights into the quality of development and…

June 15, 2016

Critical Factors for Fill–Finish Manufacturing of Biologics

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Over recent decades, protein-based therapeutics have emerged as key drivers of growth in the pharmaceutical industry. Drug development pipelines have filled with biologics, and a handful of monoclonal antibody (MAb) products have become some of the best-selling drugs around the world. Production of biotherapeutics is often challenging because of the inherent instability of these large, complex molecules. Their fragile nature has forced manufacturers to change how bulk drug substances (BDSs) are handled and final drug product is formulated, sterile filtered,…

May 17, 2016

Special Report on Continuous Bioprocessing: Upstream, Downstream, Ready for Prime Time?

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Once an engineering curiosity and smallscale laboratory technique, continuous bioprocessing has evolved in just a few short years to a topic of intense and increasing interest to most bioprocessors. Critics point to a steep learning/adoption curve, but that is nothing new in biomanufacturing.Andrew Zydney is a distinguished professor of chemical engineering at Pennsylvania State University. He has noted these challenges facing continuous processing: commercially unproven unit operations (especially downstream), a lack of equipment robustness, sterility concerns, and uncertain development timelines…

May 11, 2016

Clearance of Persistent Small-Molecule Impurities: Alternative Strategies

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Small-molecule impurities that bind to and copurify with protein biopharmaceuticals traditionally have been removed using bind-and-elute (BE) chromatography. However, that approach may be undesirable for a number of reasons. For instance, it may present a facility-fit challenge or provide a lower process yield than what is acceptable. A common scenario in which BE chromatography may be undesirable is in removal of unreacted conjugation reagents. Bioconjugates represent an important and growing class of pharmaceuticals that include PEGylated proteins, vaccines, and antibody–drug…

May 11, 2016

Best Practices for Critical Sterile Filter Operation: A Case Study

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A number of regulatory guidelines recommend preuse integrity testing of critical sterilizing liquid filters for aseptic processing (1–3). Before sterilization, a preuse test will confirm that a filter is installed properly and was not damaged during shipment or handling. Performing a preuse test after sterilization detects damage that may have occurred during the sterilization cycle. Testing after sterilization limits risk, so it is a practice applied based on risk assessment. Because it is perceived to reduce business loss risk, preuse…

May 11, 2016

Accelerated, Seamless Antibody Purification: Process Intensification with Continuous Disposable Technology

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Process intensification through continuous manufacturing has been practiced in the chemical, petrochemical, and food industries for years and has gained much interest among biopharmaceutical manufacturers (1). Key drivers encouraging biomanufacturers of therapeutic molecules to convert batch processes into continuous operation include flexibility, productivity, cost effectiveness, and product consistency. Continuous upstream processing has been demonstrated for the manufacture of a broad range of molecules, including complex/labile proteins such as enzymes (2) and monoclonal antibodies (3). Recent publications have reported successful application…

May 11, 2016