Cell Line Development

Essentials in Quality By Design

Quality by design (QbD) is a systematic approach to drug development. It begins with predefined objectives and emphasizes product and process understanding and process control, all based on sound science, data-based decision making, and quality risk management (QRM). As introduced by the US Food and Drug Administration (FDA), QbD brings modern drug development methodologies to chemistry, manufacturing, and control (CMC) teams working on biologics, pharmaceuticals, and vaccines. The innovations associated with QbD are not so much the development concepts (which…

Cell Therapy Bioprocessing Technologies and Indicators of Technological Convergence

The cell therapy industry is undergoing a natural evolution from scientific curiosity into a commercially and clinically attractive opportunity (1). This evolution is by no means complete, and growing evidence suggests that its progression is driving significant developments in cell therapy bioprocessing — notably, convergence. Table 1:&#8 194; () Progressively, bioprocessing technologies primarily used in production of noncell-based products are being evaluated for cell therapy bioprocessing applications (2). Consequently, this process of convergence is leading to an increasing proportion of…

Effective Cryopreservation and Recovery of Human Regulatory T Cells

The list of conditions being targeted by cell therapies is rapidly growing, but commercializing cells for widespread medical use will require standardized laboratory practices. Development processes must be adapted specifically for cell-based drug products. Regulatory T-cell therapy represents a promising new frontier in the immunotherapy of autoimmune disorders, especially for patients who have been refractory to available treatments. Because of intrinsic fragility, cell therapy products can be highly sensitive to variations in manufacturing procedures. Standardization of drug-product cryopreservation and storage…

Assessing Flange Strength and Dimensional Variability

Plastic syringes are viable alternatives to glass syringes in the biopharmaceutical market. They have two main advantages over glass syringes: their break resistance (specifically on the finger flange) and their ability to maintain tighter dimensional tolerances and less variability (because of the flexible molding process). Both attributes are critical when a 1-mL long prefilled syringe is used with an autoinjector device. The high break resistance of plastic syringes can reduce the number of rejected units during a fill–finish process. And…

North, South, East, and West

Electrophoresis is the basis of all blotting methods, and BPI Lab covered it last month (1). Electroblotting is a method for transferring electrophoretically separated proteins or nucleic acids onto a polyvinylidene fluoride (PVDF) or nitrocellulose membrane for permanence using electric current and a transfer buffer solution. This allows for analysts to further study them using probes, ligands, or stains. Capillary blotting is a variation designed to work with capillary electrophoresis. After electrophoresis the following are stacked in cathode-to-anode order: a…

Enabling Technologies

Many technological advancements in recent years have enabled companies to shorten time to market, to better understand their manufacturing processes, and to characterize their products well. In BPI’s December 2013 issue (pages 47–50), I reported on the first half of an informal reader survey about those technologies, with commentary from some survey participants and others. This month concludes with my examination of analytical, formulation/fill–finish, and facilities technologies. Analytical Technologies After writing several installments of our new “BPI Lab” series this…

Analysis By Size and Charge

An early BPI Lab article addressed the power of liquid chromatographic separations for biopharmaceutical laboratory use (1). Such techniques separate biomolecules based on a number of different properties: size, solubility, hydrophobicity/-philicity, binding affinity. The next most powerful means of separation — and thus high-resolution identification — of nucleic acids and proteins/peptides is based primarily on electrostatic properties: electrophoresis. Although it doesn’t really work in a process or preparative setting, it is a fundamental technique in modern biopharmaceutical laboratories, where it…

Assay Acceptance Criteria for Multiwell-Plate–Based Biological Potency Assays

For most biopharmaceuticals, potency is assessed in a bioassay by comparing dose–response curves of the test material and a reference standard. As with all analytical techniques, such assays require criteria by which their execution can be judged objectively to be valid, regardless of whether the desired or expected result is obtained for the test sample. PRODUCT FOCUS: BIOLOGICSPROCESSFOCUS: R&D, QCWHO SHOULD READ: PRODUCT AND PROCESS DEVELOPMENT, ANALYTICAL, QCKEYWORDS: IMMUNOASSAYS, POTENCY ASSAYS, PRODUCT RELEASE, REFERENCE STANDARDS, CONTROL SAMPLES, SAMPLE ACCEPTANCELEVEL: ADVANCED…

Design of Experiments for Fed-Batch Process Development in Shaken Cultures

When designing a recombinant protein production process, a high number of parallel cultivations must be carried out. That task is typically performed using batch cultures in shake flasks or microwell plates, in which fermentation conditions are not monitored. To overcome that limitation, we combined the SensorDish Reader and Shake Flask Reader systems (from PreSens) with an enzymatic glucose delivery system (EnBase technology from BioSilta Oy) for Escherichia coli cultivations. Our objective was to determine whether SensorDish reader cultures would yield…

Responding to Life Sciences Manufacturing Industry Guidance

Increasingly, life science manufacturing companies are applying technology to meet quality by design (QbD) goals. Organizations collect overflowing volumes of process data as part of programs designed to improve manufacturing variability and outcomes. Collecting valuable data is now an everyday task thanks to available software and process analytical technology (PAT) tools. The industry today, in fact, has focused so much on gathering data that it often has lost sight of an important fact: Data collection systems are valuable only if…