Downstream Processing

Predictive Algorithm Modeling for Early Assessments in Downstream Processing: Using Direct Transition and Moment Analysis To Assess Chromatography Column Integrity at Production Scale

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Failure to detect breaches in chromatography column performance can be disastrous during large-scale commercial manufacturing. Our company uses algorithm modeling for near–real-time monitoring of column packing quality and sensitive detection of column-integrity breaches. The approach enables us to mitigate risks early on, save cost and time, and thereby deliver consistent product quality and purity during manufacturing. Here we discuss three case studies in which predictive algorithm modeling using moment analysis and direct transition analysis (DTA) helped us monitor column integrity…

Purification of Hepatitis B Virus Surface Antigen for Vaccine Products: Impact of Ligand Density on HBsAg Purification By Immunoaffinity Chromatography

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According to the World Health Organization (WHO), more than 350 million people worldwide are chronic carriers of hepatitis B virus (HBV) (1). Around 25% of carriers develop liver cirrhosis and/or carcinoma, making HBV responsible for the deaths of one million people annually (1). The virus has a spherical shape with a lipoprotein coating mostly of HBV surface antigen (HBsAg) (2). Knowing that, drug developers have created recombinant HBV vaccines based on HBsAg synthesized in yeast or mammalian cells (3, 4).…

Application of an Effective In-Line Analytical Instrument for Biopharmaceutical Development and Manufacture

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The rapid advancement and competitiveenvironment of the modern biopharmaceutical industry, accompanied by the need for continuous quality improvement, demand robust analytical instruments. Analytical technology is one key factor contributing to the quality and safety of finished products. Ongoing improvements in analytical instruments are needed to address new challenges, including specificity of target substances, high complexity of matrices, and multiple production stages with a number of input and output parameters and peculiarities. Those factors point to the demand for a versatile…

March 2, 2023

Production and Purification of Newcastle Disease Virus: A High-Yield Platform Process Based on a Novel Avian Cell Line and Monolith Chromatography

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Newcastle disease is an extremely infectious condition among domesticated poultry and other avian species. Its high morbidity and mortality rates among infected birds give the disease significant economic importance. Thus, many commercially available vaccines based on live or inactivated virions are used globally to protect against Newcastle disease infection. The causative agent is Newcastle disease virus (NDV), which belongs to the Paramyxoviridae family. NDV is a single-stranded, negative-sense, enveloped RNA virus of avian origin that is highly attenuated in humans…

February 9, 2023

Opportunities in the Field of Host Cell Proteins — Part 4: The Future of Immunogenicity Prediction

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Available literature abounds with case studies describing detection and identification of host cell proteins (HCPs) and other process-related impurities. In the previous installment of our review, we analyzed noteworthy studies, highlighting what they revealed about HCP immunogenicity and calling attention to topics that require further investigation. In this final installment of our four-part study, we focus on HCP risk assessment. We explore current and emerging strategies for immunogenicity prediction, then draw out key insights from the past 40 years of…

February 9, 2023

Save Valuable Facility Time with Single-Use TFF

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Biopharmaceutical developers and manufacturers are part of a global, dynamic, and highly competitive market. They face constant pressure to produce high-quality products within relatively short time frames and at reduced costs. Process-intensification strategies and single-use (SU) solutions are popular approaches to maximizing productivity and promoting fast, efficient, and lean processing — the pillars of next-generation facilities. Filtration is an integral part of all bioprocesses and is applied to many up- and downstream steps, including harvest, clarification, and concentration/diafiltration. Tangential-flow filtration…

February 9, 2023

Introduction: Viral Clearance and Inactivation in Downstream Processing

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Viral safety in the biopharmaceutical industry is both an upstream-production and downstream-processing concern. Companies must take a multipronged approach using orthogonal methods that are validated to prevent viral contamination or to remove it from biologic drug products. On the upstream side, the focus is on prevention through risk assessment and mitigation. That begins with environmental control of facilities and includes both careful selection of raw materials and cell lines and preparatory filtration of culture media components. In downstream processing of…

December 12, 2022

Triton X-100 Elimination: The Road Ahead for Viral Inactivation

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The nonionic surfactant Triton X-100 (C14H22O(C2H4O)n) is a key chemical used in ensuring the viral safety of biological medicinal products. Two pharmaceutical sectors share an extensive historical background with it: biopharmaceuticals and plasma-derived products, for which it is used to inactivate lipid-enveloped viruses. Recently, environmental regulations in the European Union have encouraged or mandated a phase-out of this surfactant (1). The goal of the ruling is to protect aquatic ecosystems from potential Triton X-100 degradation products that can function as…

December 12, 2022

Worst-Case Conditions for Viral Clearance

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As described in ICH Q5A on virus safety of biotechnological products (1) and the European guideline on virus safety of biotechnological products, EMEA 398498 (2), viral clearance studies are mandated as part of the viral safety evaluation of products derived from human or other mammalian cell lines. When acceptable ranges of process parameters are known, both guidelines recommend that scale-down models be evaluated under worst-case conditions for viral clearance. The BioPhorum Development Group’s viral clearance workstream performed a benchmarking survey…

December 12, 2022

Hollow-Fiber Nanofiltration for Robust Viral Clearance of Non-MAb Biologics

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Monoclonal antibody (MAb) and other therapeutic biologics produced by mammalian cells have the potential to introduce endogenous retroviruses and can be infected with adventitious viruses through raw materials or other parts of the biomanufacturing process (1–3). Based on regulatory guidelines, products derived from mammalian cells must contain less than one virus particle per million doses, which requires purification processes to demonstrate virus removal capabilities of about 12–18 log10 clearance of endogenous retroviruses and 6 log10 clearance for adventitious viruses (4).…

December 12, 2022