October 2015

Spotlight

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Niche Disease: Legionnaires’ Disease by Cheryl Scott Gram-negative, aerobic Legionella pneumophila bacteria were first identified as the cause of an outbreak of severe pneumonia at an American Legion Convention in a Philadelphia convention center in 1976. Since then (and probably long before), it has been responsible for occasional such outbreaks around the world. For example, an epidemic of the disease probably occurred in Minnesota in 1957. Such incidents are usually associated with poorly maintained artificial water systems (e.g., cooling towers…

October 15, 2015

Effective Management of Contract Organizations: Keeping the Product Pipeline Moving, Compliant, and Available

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Both small and large biopharmaceutical companies are increasingly pursuing the outsourcing of manufacturing and testing throughout the product lifecycle. The growing use of contract manufacturing organizations (CMOs) and contract testing organizations (CTOs) has led to increasing complexity within the biopharmaceutical industry as more third-party sites are leveraged to support global markets. To address those issues, a CASSS Chemistry, Manufacturing, and Controls (CMC) Strategy Forum was held in Washington, DC, 27–28 July 2014. The title was “Effective Management of Contract Organizations: Sponsors, Contract Organizations, Health Authorities and Patients — Keeping the Product Pipeline Moving, Compliant, and Available.” The CMC Strategy Forum is…

October 15, 2015

Management, Notification, and Documentation of Single-Use Systems Change Orders: Challenges and Opportunities

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Single-use systems (SUS) consist of numerous plastic components derived from different suppliers. As such, they are prone to changes, including alterations in construction materials or modifications in manufacturing processes. Such changes may originate at the immediate supplier or farther back in the supply chain as a result of product improvements, process improvements, part discontinuation, or even business decisions such as manufacturing site relocation. Whether those changes are major or minor, managing their impact on biopharmaceutial processes and product quality often…

October 15, 2015

Special Report: Turning Discoveries into Products — Developability Assessments and Highly Efficient Process Design

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High costs and long timelines for biopharmaceutical development are cause for reflecting on how best to allocate resources from the earliest discovery stage through critical go–no-go junctures. With inputs ranging from science, engineering, and economics, the coined term developability becomes the synthesis of answers to such questions as How well does the target represent a disease state? Does manipulating that state bring about improvement? Does the molecule behave as expected in living systems? What can be done about the emergence of independent safety, toxicology, and/or immunogenicity warning signs? Can the molecule…

October 15, 2015

The Secret Life of Protein A

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Affinity chromatography with protein A has become the foundation for purification of nearly every therapeutic IgG in commercial production. One of the features most responsible for its success has been its compelling simplicity. IgG binds. Contaminants do not. Load, wash, and elute pure IgG. In the real world, however, protein A does not elute pure IgG. It typically contains several hundred to a few thousand parts per million (ppm) contamination by host-cell proteins (HCPs) and other contaminants. Numerous studies demonstrate…

October 15, 2015

Identification and Quantification of Heat-Shock Protein 70: A Major Host-Cell Protein Contaminant from HEK Host Cells

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Recombinant therapeutic proteins are commonly produced by cell lines such as Chinese hamster ovary (CHO), human embryonic kidney (HEK) 293, murine myeloma (NS0), and Escherichia coli bacterial cells. Host-cell proteins (HCPs) are indigenous proteins produced by those expression hosts and considered to be process-related impurities generated from the cell culture process (1). HCPs are potentially harmful and immunogenic to patients, and they can compromise the stability of protein drugs (2–4). For those reasons, HCPs must be consistently removed or reduced…

October 15, 2015

Comparison of Concentration Measurement Technologies in Bioprocess Solutions

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Biopharmaceutical manufacturing involves complex process steps. Exacting production conditions are typically required to maximize the yield, purity, and quality of biological products. In recent years, process analytical technology (PAT) has been increasingly used to monitor key process and performance parameters in real time. That has enabled better control of production conditions. An important parameter required to achieve consistent results in many bioprocessing steps is solute concentration in process fluids. The Critical Need for Concentration Measurement Many biopharmaceutical manufacturing process steps require measuring…

October 15, 2015

Compatibility Assessment of a Model Monoclonal Antibody Formulation in Glass and Blow–Fill–Seal Plastic Vials

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Blow–fill–seal (BFS) technology has been recognized by the industry as an advanced aseptic solution (1–3). Catalent Pharma Solutions has been commercially supplying sterile BFS products to the pharmaceutical industry for decades, primarily in the respiratory and topical ophthalmic markets. Such product formulations range from simple solutions to emulsions with drug substances from classical small molecules to large complex proteins such as biologics. The company also has optimized BFS processes and its Advasept plastic container system for the manufacture of sterile…

October 15, 2015

Elucidation on India and China: Powerhouses of Asia 2015 Reports Assess Their Pharmaceutical Markets

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In the past year, CPhI Worldwide (a division of UBM EMEA) has released reports on both the Indian and Chinese pharmaceutical markets, findings of which were presented at CPhI India in Mumbai in early December 2014 and shortly after CPhI China in August 2015. India Looking Outward to Innovate The Indian report, CPhI India Pharmaceuticals 2015: Industry Explorations, was developed by CPhI in partnership with Global Business Reports (GBR) to provide a comprehensive analysis of the country’s pharmaceutical market. Overall, Indian companies…

October 15, 2015

Ask the Expert: Simulation and Optimization Software for Continuous Chromatography

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with Thomas Flouquet (Novasep) The first simulation and optimization software for chromatography process development in biopharmaceutical purification, the BioSC Predict program from Novasep received an 2015 Achema award for Pharmaceutical Engineering. Driven by user objectives, it can define practical constraints and desired strategies. Optimization algorithms provide the most adapted operational conditions for a BioSC system. In a webcast on 17 September 2015, Novasep’s Thomas Flouquet demonstrated the software’s functionality and customizability. He presented optimized recipes taking into account parameters such…

October 15, 2015