QA/QC

Reference Standards for Therapeutic Proteins: Current Regulatory and Scientific Best Practices

Sponsors developing and manufacturing protein therapeutic products use a variety of analytical tests (e.g., cell-based potency and chromatographic assays) to assess quality attributes of their active ingredients and drug products. Those tests are used to assess product quality in a number of activities, including characterization, comparability, lot release, and confirmation product quality and stability. Reference standards play a critical role in calibrating and confirming the suitability of such tests and in helping analysts to draw scientifically sound conclusions from data…

Cell Therapy Manufacturing

Fueled by a recent resurgence in public financing and compelling clinical data for indications as diverse as acute macular degeneration and pancreatic cancer, a growing number of cell therapies are driving toward pivotal clinical studies and commercialization. Although regulatory precedents have been set for various autologous and allogeneic products in the United States, Asia, and the European Union, regulatory guidance continues to evolve for a widening array of cell products. Adult stem cells (e.g., mesenchymal stem cells), embryonic stem cells,…

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…

Ready-to-Use Cryopreserved Primary Cells

Abiological measurement of drug activity is perhaps the most critical step in the series of tests required for product release both for clinical trials and the market. This evaluation plays an important role in the stability assessment of drug candidates. According to the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) Q6B document, measurements of biological activity can be performed in defined animal models that demonstrate a measurable physiological change in response to…

Nucleic Acid Impurity Reduction in Viral Vaccine Manufacturing

Commercial-scale viral vaccine manufacturing requires production of large quantities of virus as an antigenic source. To deliver those quantities, a number of systems are used for viral replication based on mammalian, avian, or insect cells. To overcome the inherent limitations in production outputs with serial propagation of cells, mammalian cells can be immortalized, which increases the number of times they can divide in culture. Modifications that immortalize cells are typically accomplished through mechanisms similar to those converting normal cells to…

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…

Quality Risk Assessment and Management Strategies for Biopharmaceutical Companies

You’ve probably been hearing a lot about risk assessment in recent months. Indeed, some 15 times more articles have been printed referencing the concept over the past year relative to a 12-month period just three years ago. That truly represents a geometric progression. Unfortunately, very few authors have been able to disambiguate the different methods or provide insight into this time-tested, multiple-industry philosophy that at its core uses good science to make better decisions. When we undertake the challenge to…

Process Improvements Increase Production Capacity of a Legacy Product

Implementation of postlicensure process improvements in the biopharmaceutical industry can benefit patients and drug manufacturers alike. Here we demonstrate through a case study how a change to the cell culture medium and process can be taken from proof of concept through scale-up to demonstration of feasibility. We further illustrate the scope and complexity of implementing a change in commercial manufacturing to realize significant benefits such as increased production capacity over an existing legacy process. The Importance of Postapproval Improvements Drug…