2021

Evaluation of a Novel Peptide-Based Affinity Ligand for Human IgM Purification: Use of an Automated Liquid-Handling System for Rapid Assessment of Binding Kinetics and Capacity

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One-step affinity purification of antibodies is a powerful and widely used tool in the biopharmaceutical industry. Although different strategies can be used to purify immunoglobulin isotype G (IgG), the larger antibody isotype IgM has limited options. Human IgM is the largest antibody and primarily exists as a pentamer in the bloodstream (1). IgM molecules exhibit higher avidity than other antibodies do and serve as essential activators for the complement cascade (1–3). Approaches to IgM purification with hydroxyapatite and ion-exchange (IEX)…

February 4, 2021

Bioreactor Automation Driven by Real-Time Sensing: Enhancing Productivity Through Accurate, Efficient Glucose Control

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In the quest for improved quality and productivity in drug manufacturing, the industry is moving toward increasing use of bioreactor systems with real-time integrated monitoring and advanced analytics that can enable automation, drive performance, and improve data-rich quality control. However, there are multiple options for sensors and technologies that monitor important cell-culture variables or critical process parameters (CPPs). Furthermore, cell culture vessels can be disposable single-use bioreactors (SUB) or reusable glass or stainless-steel models. They can operate in stirred tanks,…

February 4, 2021

Silicone Tubing for Biopharmaceutical Applications: Particulates, Endotoxins, and Bioburden Characterization

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Adoption of single-use systems (SUS) has increased steadily over the past few years driven by an increased focus on manufacturing biologics that require smaller scales than blockbuster drugs. Although SUS provide many benefits, some factors need to be considered when implementing them in biopharmaceutical production. With the regulatory landscape intensifying worldwide, drug manufacturers are expecting more data from suppliers to support the purity claims of supplied products, especially related to the purity of their product-contact surfaces. In this article, we…

February 3, 2021

A Universal Assay Determination Method for Antisense Oligonucleotides: A New Slope Spectroscopy Method

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Antisense oligonucleotides (ASOs) are short, synthetic, single-stranded oligodeoxynucleotides that can alter RNA and reduce, restore, or modify protein expression through several distinct mechanisms. ASO technology has become an important drug discovery platform for most major pharmaceutical companies. To date, six antisense drugs have been approved by regulatory agencies to treat diseases spanning viral infections, hyperlipidemias, and neurological diseases. More than 50 additional ASO drugs are in clinical trials. For an ASO drug product, an assay of its active pharmaceutical ingredient…

February 3, 2021

Ask the Expert: Enabling Digital Chromatogram Review to Streamline Column Evaluations

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Chromatogram review enables evaluation of packed-bed chromatography processes. Typically, that method entails paper-based, qualitative comparison of a profile obtained during a run with another from a reference batch. Such a protocol can be time consuming, resource intensive, and susceptible to operator error. Martin D. Jensen (senior engineer at Fujifilm Diosynth Biotechnologies, FDB) delivered an “Ask the Expert†presentation on 20 October 2020 to describe advantages that his company gained by transitioning from paper-based to digital chromatogram review. Jensen’s Presentation Chromatogram…

February 3, 2021

Ask the Expert: Revealing Cell Secrets Using Optical Sensors in Upstream Processing

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Upstream operations can benefit significantly from real-time, in-line testing of cell-culture conditions. Yet as Jake Boy (senior application scientist at Scientific Bioprocessing Inc., SBI) observed in his 5 November 2020 “Ask the Expert†webcast, traditional electrochemical probe sensors do not perform well in T-flasks, shake flasks, Petri dishes, and microfluidics devices. Boy described how fluorescence-based optical sensors can glean valuable data from small culture devices, assisting with research into cellular growth. SBI’s Presentation Boy began by highlighting successful applications of…

February 3, 2021

Ask the Expert: Derisking INDs with Unrivaled Monoclonality Assurance in Cell-Line Development

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On 1 December 2020, BPI presented an “Ask the Expert†webinar with Tanner Nevill (vice president of program management at Berkeley Lights). Monoclonality assurance is a central regulatory requirement for all cell lines producing biologic therapies. Well-plate imaging is the “gold standard†for confirming that a cell line originates from a single cell, but it is labor intensive and prone to errors in the form of “ghost cells†and debris that look like cells. Using the Berkeley Lights Beacon system, cells…

February 3, 2021

Therapeutics Innovation in a Pandemic Era

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Biopharmaceutical companies have demonstrated a rapid and powerful response to the COVID-19 pandemic, with innovators leading the way. A rush of investor money has been pouring into companies with the best odds of making it to the vaccine finish line. But such heavy investments in one sector lead some industry experts to wonder about the financial support of research into cure pathways for other serious diseases such as cancer, multiple sclerosis, and Alzheimer’s disease. When the pandemic abates with vaccines…

February 3, 2021

eBook: Formulation, Fill–Finish — Biopharmaceutical Drug-Product Trends and Technologies

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As with many other aspects of biopharmaceutical development, evolving technologies are transforming drug-product development and manufacturing. In a November 2020 report on the Informa Connect “Drug Delivery Partnerships†meeting, BPI senior technical editor Cheryl Scott reviewed how new delivery-device technologies are bringing together companies with disparate expertise to serve patients with chronic conditions better than ever before. The ever-increasing capabilities of electronics and information technology (IT) not only are enabling development of “smart†delivery devices, but also improving the potential…

January 29, 2021

Nontargeted HCP Monitoring in Downstream Process Samples: Combining Micro Pillar Array Columns with Mass Spectrometry

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Protein biopharmaceuticals have emerged as important treatments for diseases with otherwise unmet medical needs. These biologics are produced by recombinant mammalian, yeast, or bacterial expression systems. Along with therapeutic proteins, those cells produce endogenous host-cell proteins (HCPs) that can contaminate biopharmaceutical products despite multiple purification steps in downstream processing. Because such process-related impurities can affect product safety and efficacy, they need to be monitored closely. Multicomponent enzyme-lined immunosorbent assays (ELISAs) presently are the workhorse method for HCP testing, with high…

December 18, 2020