UPDATE Editorial: Ready-to-Use Cells: a major advance in technology for cell-based bioassays
C Jane Robinson, PhD; Scientific Liaison, Biopharmaceutical Emerging Best Practices Association; Email:
Jane.Robinson@
bebpa.org
Jane Robinson is Scientific Liaison for the Biopharmaceutical Emerging Best Practices Association (CA, USA) a non-profit organization for the presentation and discussion of scientific issues to facilitate safer and faster biopharmaceutical product development. She has a particular interest in the development of in vitro bioassays. Previously, she worked for 25 years at the National Institute for Biological Standardization and Control (UK) where she was responsible for the establishment of a laboratory for the standardization and control of polypeptide growth factors and related molecules of therapeutic and diagnostic potential.
Keywords: ready-to-use cells, thaw-and-use cells, cell-based bioassay
Introduction In the biopharmaceutical industry, cell-based bioassays are used for characterization and potency measurement throughout the drug development and production process. Until a few years ago, the only options for preparation of cells for the majority of assays were either continuous culture or fresh preparation of primary cells. For assays in immortalized cell lines, this entails a frozen aliquot of cells being thawed and cultured through sufficient passages to allow the cells to stabilize, and then cells being harvested as required from the continuous culture, up to a specified passage limit. Maintenance of a continuous culture requires considerable resources and also increases the risk of variability and contamination. Moreover, the need to plan stabilization and expansion of the culture places constraints on assay scheduling. For primary cells, variability in the source tissue and the isolation procedure contribute to variability in the assay results, and availability of the source tissue and length of the isolation procedure can constrain assay scheduling.
Ready-to-use, thaw-and-use
Te limitations and problems of deriving cells for bioassays by continuous culture or fresh preparation from source tissue have driven the development of ‘ready-to-use’ cells, which can be used directly in an assay or with only minimal preparation, such as dilution into appropriate medium [1,2,3]. In most cases, ready-to-use cells are stored as a bank of frozen aliquots and so are also termed ‘thaw-and-use’ cells. Tere are commercial sources of some ready-to-use cells supplied as growing cultures, some of these ready-plated in kits or matrices. Growing cultures can offer a solution for certain cell types and requirements, but various advantages of frozen cell aliquots, including convenience of handling and scheduling, make thaw-and-use cells the more widely used.
One advantage of using a bank of frozen aliquots of thaw-and-use cells is in permitting much of the quality control testing, such as sterility, post-thaw viability and functional performance and intra- and inter-lot variability, to be performed on sample vials ahead of, and independent of, assay scheduling. Utilizing a vial of cells directly from the bank provides less opportunity for variability to arise within the cells before their addition to the assay system, compared with cells undergoing lengthy culture. It avoids the problem of cells being used from successive harvests, thus having different passage histories. To benefit from such improved consistency of the cells at the point of addition to the assay, robustness of the protocol for thawing cells and for any preparation steps is crucial.
Increasing commercial availability Many biopharmaceutical companies develop banks of their own proprietary
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The Collectables: Year in Bioanalysis
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