QA/QC

Mass Spectrometric Conjugate Characterization: Process Qualification of Recombinant Protein–Hapten Conjugation

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Conjugated protein biotherapeutics such as PEGylated proteins (with polyethylene glycol), antibody–drug conjugates (ADCs), and protein–haptens often present unique analytical challenges related to characterizing the conjugation aspect of their manufacturing processes. Analytical characterization of this class of proteins requires knowledge of the sites of conjugation, the degree of conjugation, and the drug-to-protein ratio. Here we present case studies in development of reliable methods based on mass spectrometry (MS) to characterize a protein–hapten drug substance during late-phase process validation. This protein is…

November 14, 2016

Providing Lipids Boosts Protein Productivity: Testing a Feed Supplement with Multiple Cell Clones and Media Formulations

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As the biologics (and now biosimilar) markets continue to grow, pressure increases on biomanufacturers to reduce cost of goods sold (CoGS). One way they can reduce cost is by increasing protein productivity in terms of protein titer per volume of culture. Media optimization is a key strategy for increasing protein productivity. In the past few decades, average titers across the industry have increased greatly — from <0.5 g/L in the 1980s to >3 g/L today, and it is not uncommon…

November 14, 2016

Advanced Protein Engineering Enhances Biopharmaceutical Manufacturing and Analytics

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Production of proteins for pharmaceutical use is a complex, multistep process that requires technologies for purifying such molecules from highly complex biological mixtures. It also calls for reliable, cost-effective, high-throughput analytical techniques to determine protein quality and functionality to ensure the safety and efficacy of end-products. Mistakes in product development and manufacturing not only are immensely costly, but they can also put patients at risk. Many well-established processes and analytical tools are available for use in manufacturing antibody drugs (e.g.,…

November 14, 2016

Special Report: A Strategy for Cost-Effective Capture Using Agarose-Based Protein A Resins

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It is well recognized that the cost of Protein A resins is substantial. If a developmental monoclonal antibody (MAb) makes it to marketing approval and manufacturing, the high cost of purification using a Protein A resin is amortized over a large number of purification cycles, and the contribution to cost of goods is reduced to acceptable levels. However, a high percentage of clinical projects will fail, and the Protein A resin will be used only for a small number of…

October 26, 2016

Progress Toward Commercial Scale and Efficiency in Cell Therapy Bioprocessing

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Regenerative medicine includes both cell and gene therapies. Currently 672 regenerative medicine companies operate around the world, and 20 products have been approved by the US Food and Drug Administration (FDA). Of 631 ongoing clinical trials by the end of 2015 (1), over 40% are in oncology, followed in prominence by cardiovascular and infectious diseases. Here I focus on gene and cell therapy bioprocessing in which the final products delivered to patients are cells. Cell therapies are either autologous (derived…

October 17, 2016

Viral Risk Evaluation of Raw Materials Used in Biopharmaceutical Production

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Ensuring a continuous supply of safe medicines to patients is a key objective for both health authorities and the pharmaceutical industry. A critical component to that end is maintaining a reliable supply of qualified raw materials (RMs). Manufacturers must ensure not only the suitability of RMs for their intended use in a manufacturing process, but also their highest attainable safety with regards to viruses and other adventitious agents. The need to apply a risk-based RM control strategy is in line…

October 14, 2016

Investigation of Foreign-Particle Contamination: Practical Application of FT-IR, Raman, and SEM-EDS Technologies

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The presence of visible foreign particulate matter is considered a critical defect in parenteral products and one of the main reasons they can be recalled (1). Foreign particles present during any stage of manufacturing are considered to be contaminants and can impose a risk to the control of the manufacturing processes (2). For those reasons, particle contamination arising in any manufacturing step initiates a nonconformance or out-of-specification observation. That requires an investigation to identify root cause so as to mitigate…

September 15, 2016

Science, Risks, and Regulations: Current Perspectives on Host Cell Protein Analysis and Control

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State-of-the-art analytics guide process development by providing companies with thorough understanding, effective removal, suitable control, and comparability assessment after process changes of host cell proteins (HCPs) in recombinant biotechnology products. An array of analytical techniques and approaches can be used to establish control strategies for host cell proteins. Techniques used for HCP characterization and comparability include two-dimensional (2D) gel electrophoresis with a range of stains, 2D immunoblotting, 2D high-performance liquid chromatography (HPLC), 2D difference gel electrophoresis (DIGE), and increasingly mass…

September 15, 2016

Regulating Quality in Continuous Processing

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Regardless of the industry and product being manufactured, continuous processing has demonstrated numerous benefits. In addition to smaller manufacturing footprints, reduced material consumption and waste generation, increased efficiencies, and lower capital and operating costs continuous manufacturing typically leads to more consistent processes and product quality. In the pharmaceutical industry, the latter two attributes align perfectly with FDA’s Quality by Design (QbD) and process analytical technology (PAT) initiatives. The challenge is determining how to apply these concepts in practice. Applying the…

June 27, 2016

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