Polymerases are natural enzymes that are vital to nucleic acid synthesis: DNA polymerase for replication of deoxyribonucleic acid and RNA polymerase for replication of ribonucleic acid. Thus all living things make and use polymerases of their own. But in 1969, the University of Wisconsin’s Thomas D. Brock and Hudson Freeze identified a new species of extremophilic bacterium thriving at 160 °F (70 °C) in a hot spring in Yellowstone National Park. In time, heat-tolerant polymerase isolated from Thermus aquaticus (Taq)…
Laboratory Equipment
Characterization of Human Mesenchymal Stem Cells
Human mesenchymal stem cells (hMSCs) are a self-renewing population of adherent, multipotent progenitor cells that can differentiate into several lineages. The current definition of MSCs includes adherence to standard tissue culture plastic ware, expression of various surface antigens, and multilineage in vitro differentiation potential (osteogenic, chondrogenic, and adipogenic). hMSCs hold great promise as therapeutic agents because of their potential ability to replace damaged tissue and their immunomodulatory properties. Consequently, many clinical trials using hMSCs are currently under way in a…
Automation of Cell Therapy Biomanufacturing
Biomanufacturing automation is an established mission-critical step in the commercialization pathway for conventional therapeutics, including small molecules and monoclonal antibodies (MAbs) (1). The prospect of a potential biologic progressing into late-stage clinical trials without a robust biomanufacturing strategy to support at least pilot-plant scale bioprocessing is simply unthinkable. Conversely, the cell therapy industry (or at least a significant proportion of it) regard this as a trend that is unlikely to be mirrored as the industry develops. The aim of this…
A Powerful Pairing
Biological product and process characterization are not new to this quality by design (QbD) and process analytical technology (PAT) era. In the 1990s we saw the FDA introduce the concept of well-characterized biologics: an acknowledgment that analytical technology had advanced to the point where the bioprocess did not necessarily (or not fully, anyway) define a biopharmaceutical product. That ultimately led to the regulation of some types of products within the United States moving from the purview of FDA’s Center for…
2012 in Review
As children growing up, we could barely contain our anticipation for those banner, milestone years: entering first grade, becoming a teenager, turning 16 and then 18, high-school graduation. But even the most innocuous “in-between” years saw notable change and maturation, and 2012 was just such a year for the growing cell therapy sector. Although it is not likely to be noted as a pivotal or breakthrough year, 2012 nonetheless delivered some significant and welcome signposts of continued sector maturation. Here…
Antibodies, Bioassays, and Cells
It’s no surprise that immunochemistry forms a broad and solid basis of biopharmaceutical analytical laboratory work. Immunochemicals include antibiotics and antigens, nucleic acids and nucleotides, enzymes, lipids, antioxidants, probes and dyes, and proteins and peptides. Available from companies such as Advanced Immunochemical, Immundiagnostik, Lampire Biological Laboratories, and Rockland Antibodies and Assays, their many uses include antibody isotyping and fragmentation. Adjuvants, buffers, assay kits, target biomolecules, and phage-display systems support those applications. Because background and off-target effects complicate the study of…
Protein Scaffolds
The recent success of monoclonal antibodies (MAbs) as therapeutic agents to treat cancer, multiple sclerosis, rheumatoid arthritis, and other chronic inflammatory and autoimmune disorders (Table 1) has catapulted these once difficult-to-develop molecules to the forefront of modern molecular medicine (1, 2). The size of the global MAb market in 2008 was valued at almost US$28 billion. Industry analysts predict that the size of the MAb market will grow to almost $68 billion by 2015, with the largest growth occurring in…
Biophysical Analysis of Living Cells
Adecades-old technology is finally emerging from clinical laboratories and demonstrating its utility in drug discovery and development. Cell therapy researchers bring their laboratory experiences with them as their science is commercialized. And as biopharmaceutical production engineers incorporate quality by design (QbD) and process analytical technology (PAT) into their work, they find that a method for monitoring the state and distribution of living cells can help build valuable upstream process knowledge. In flow cytometry, cells are suspended in fluid to flow…
Rapid Detection of Pandemics
A Coronavirus — like severe acute respiratory syndrome (SARS) — is back in the headlines. On returning from a trip to Saudi Arabia in summer 2012, a Qatari national was struck down by a mystery respiratory illness. Because of inadequate diagnostic capabilities, the patient was transferred from Qatar to London for intensive-care treatment and diagnosis. The UK Health Protection Agency (HPA) confirmed infection with the same Coronavirus strain discovered by a Dutch team following the death of a Saudi national…
Noninvasive Optical Sensor Technology in Shake Flasks
In process development, appropriate scaling is important to achieve acceptable product quality without compromising titer (1). Scale-down approaches involve matching the oxygen transfer coefficient (kLa) value, impeller tip speed, power per unit volume, or mixing time to those of a bioreactor (2). Bench-top bioreactors are typically used in bioprocess engineering as scale-down models of commercial units in fermentation and cell culture because of their similarity in geometry (H/D ratio) and mechanical properties (agitation type and sparging). By contrast, shaking culture…