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September 2013
Cell- and tissue-based therapies are being used increasingly to treat many diseases for which currently no other adequate treatment options are available. These products contain human or animal cells that can replace, regenerate, or augment a recipient’s diseased, dysfunctional, or injured cells, tissues, or organs. Cells or tissues might be unmanipulated, or their biological characteristics can be altered ex vivo before administration of the final product to patients. Examples of cell therapies range from traditional blood transfusions to recent approaches in autologous stem cell transplants and allogeneic engineered tissue substitutes.
Components used to make a cell-or tissue-based product can vary greatly in their sources, complexity, and manufacturing processes. Because such materials can profoundly affect the expansion, differentiation, and activity of a processed cell or tissue product, they can in turn have a significant impact on final product quality attributes. In addition, the biological comple...
+1
Separating
spectroscopy
from
spectrometry
is not as straightforward as it might seem. Spectroscopy is the science of the interactions between matter and radiated energy, and spectrometry is the technology that applies that science (
1
). The former generates no results on its own. It is concerned with spectra produced when matter interacts with or emits electromagnetic radiation, including all methods of producing and analyzing light spectra using spectroscopes, spectrographs, spectrometers, and spectrophotometers.
The distinction should come from the meanings of the suffixes –
scope
(seeing), and –
meter
(measuring). The first instruments used to observe spectra were only visual, so they were properly called
spectroscopes
. Once spectra could be recorded photographically, the related instruments were called
spectrographs
. They did not measure anything, however, only produced images. Instruments that make direct electronic measurements through digital technology are rightly called
spectrometers
The number of blockbuster monoclonal antibody (MAb) drugs continues to grow. In 2008, MAbs generated revenues in excess of US$15 billion (
1
), making them the highest-earning category of all biotherapeutics. The world MAb market will reach $62.3 billion in 2015, with next-generation therapeutic antibody revenues reaching $2.3 billion in 2015 according to Visiongain reports published in September and November 2011 (
2
,
3
). Biosimilar antibodies will also begin to enter established markets as regulatory authorities clear approval pathways for them. Most antibody drugs treat cancer and autoimmune diseases, and many of the rest are used to treat orphan and infectious diseases. Unfortunately, antibodies are complex proteins in many ways, which complicates their purification and characterization, making it difficult for their developers to meet the rigid requirements for therapeutics.
Because of the inherent and engineered variations in therapeutic antibody structures, there is no “one-size-fits-all” when i...
The quality by design (QbD) and process analytical technology (PAT) approaches have shown significant benefit in the classical pharmaceutical industry and are now strongly influencing bioprocessing. Monitoring critical process parameters (CPPs) during biotechnological cell cultivations is essential to maintaining high efficiencies and quality. Commercial sensor systems for real-time inline monitoring are available for some parameters, such as pH or the concentration of dissolved oxygen (DO). For others such as glucose concentration, total cell count (TCC), and viability no robust online prediction is yet possible for most applications. This gap may be closed with the help of near-infrared spectroscopy (NIRS), which can provide quantitative prediction of single analytes with real-time measurement.
PRODUCT FOCUS: RECOMBINANTproteins
PROCESS FOCUS: Production
WHO SHOULD READ: QA/QC, process development, and manufacturing
KEYWORDS: Quality by design, process analytical technology, statistical analysis, robust...
+4
Biologic drugs are subject to unique regulatory and technical requirements because of their origin and expression in genetically engineered host cells, as well as their underlying physicochemical properties and elaborate purification processes. One such requirement is the accurate monitoring and effective removal of process-derived impurities such as host-cell proteins (HCPs) and DNA/RNA, viruses, cell culture media, chromatographic leachates, and so on (
1
). Of those impurities, HCPs are perhaps the most challenging to accurately monitor. Each expression system’s proteome consists of thousands of different proteins, some of which can copurify with a biological drug. So the HCP monitoring method must be a multianalyte assay that can detect a great majority of the protein impurities that could be present in a batch of drug substance (
2
,
3
).
One of the most widely used methods for monitoring HCPs is the enzyme-linked immunosorbent assay (ELISA) due to its high sensitivity (low ppm) and potential for br...
+2
Cell line selection is important to any pharmaceutical company’s development pathway for biological compounds (
1
). In cell-line selection laboratories, many different, slightly variable cell lines are tested in parallel for desired characteristics. Candidate cell lines are chosen for further development on the basis of their performance in basic tests of critical quality attributes (CQAs).
Historically, such cell lines were selected in large-volume containers because it was necessary to have sufficient volume in culture to allow repeated sampling without damaging the culture (
2
). In new, small-scale bioreactors with 10-mL total culture volumes, removing even half a milliliter five times for parameter testing represents a total loss of 25% of culture volume. Such a change will dramatically affect the behavior of cells in culture (
2
).
Traditional Methods
Use of fluorescent tests has been a standard in the hospital diagnostic market for many years. The system was adopted in hospitals because of its acc...
Current methodologies in genetics and microbiology enable researchers to influence metabolic pathways of microbial cells in many directions. Beside the academic interest in investigating fundamental functions in metabolic pathways, commercial production of valuable compounds by microbial hosts is state of the art. For example, such products include enzymes (lipases, proteases, phytases), therapeutic agents (insulin, antibodies), bulk chemicals (lysine, glutamate, citric acid), or the microbial cells themselves (used in brewing or milk processing), with therapeutic agents probably the fastest growing market.
Reducing cost is a driving interest in commercial bioprocesses. Therefore, genetic manipulations can provoke the transformation of low- into high-producing strains. Such work can generate a huge number of candidates to be screened for higher productivity, as shown by Brockmeier et al., who generated a library of 148 signal peptides in
Bacillus subtilis
to enhance secretion of heterologous expressed p...
A cocktail of three specific genes can reprogram cells in the scars caused by heart attacks into functioning muscle cells. Adding a gene that stimulates the growth of blood vessels enhances that effect, say researchers from Weill Cornell Medical College, Baylor College of Medicine, and Stony Brook University Medical Center in a report that appears online in the
Journal of the American Heart Association
(
1
).
“The idea of reprogramming scar tissue in the heart into functioning heart muscle was exciting,” said Todd K. Rosengart, chair of the Michael E. DeBakey Department of Surgery at BCM and the report’s corresponding author. “The theory is that if you have a big heart attack, your doctor can just inject these three genes into the scar tissue during surgery and change it back into heart muscle. However, in these animal studies, we found that the effect is enhanced when combined with the VEGF [vascular endothelial growth factor] gene.”
“This experiment is a proof of principle,” said Ronald G. Crystal, ch...
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