Analytical

Innovation in Biopharmaceutical Manufacture

The following is a report from a workshop on innovation in biopharmaceutical manufacturing held at the Annual bioProcessUK Conference in Bristol on 29 November 2012. The aim of the workshop was to access the experience of practitioners in the United Kingdom so as to understand better the challenges and opportunities for innovation in this sector. The workshop addressed the drivers that influence the implementation of process improvements and novel technologies in biopharmaceutical manufacture from the perspective of both manufacturers and…

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…

Mathematical Model for Production of Recombinant Antibody 14D9 By Nicotiana tabacum Cell Suspension Batch Culture

Transgenic plants are increasingly considered a competing system for producing high-value recombinant proteins for biomedical and industrial purposes at affordable costs (1). Researchers have shown that molecular farming (or biopharming) is a secure technology that is capable of rendering valuable recombinant proteins free of toxins and animal pathogens in a relatively short time (2,3,4,5,6). Scientists have also demonstrated that most recombinant antibodies produced in plants maintain their functional properties (substantial bioequivalence) as well as do those produced in mammalian cell…

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…

How to Hit a Moving Target

Although multiple factors can compromise the drug-like properties of biological molecules, we are still at a very early stage in learning how to assess them. This is despite — or perhaps more correctly, because of — the pharmaceutical industry’s accelerating drive to develop biological molecules as therapeutic agents. And I say “we” because this applies not only to the biopharmaceutical industry itself and the analytical instrument companies that serve it, but also those charged with regulating it. We are all…

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…

Robots in the Laboratory

Whether cell-based or molecular biology focused, most assays performed in biopharmaceutical laboratories involve liquid solutions. Increasingly, automated liquid handlers (laboratory robotics) are demonstrating utility in these labs, especially for high-throughput screening and optimization of cell culture media, chromatography conditions, formulations, and so on. Some experts say that screening 100,000 samples/day will soon become routine. But the robots haven’t condemned all manual pipettes to the trash heap — far from it. With multichannel and electronic pipettes improving throughput and reproducibility of…

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…