Cell lines production

Cell Line Product Reactor Volume (L) Max. Perfusion Rate (d ) Cultivation Time (d) Centrifuge Type g-factor " Feed Flow Rate " (L min ) Max. Viable Cell Cone. (10 mL- ) Separation Efficiency (%) Reference... 

However, with careful QC of liquid handling and standardized cell line production parameters can be maintained at a steady level. Some cellular assays, which use harvested native cells, depend on large batches, often obtained from different donors or cadavers. It is important that these assays are recalibrated with new batches and the validation process repeated. 

Product Cell line production Company Therapeutic indication... 

Independent Assays for Provings Virus Removal. Retrovimses and vimses can also be present in culture fluids of mammalian cell lines (15,24). Certainly the absence of vims can be difficult to prove. Model vimses, eg, NIH Rausher leukemia vims and NZB Xenotropic vims, were spiked into fluids being purified, and their removal subsequently vaUdated when subjected to the same purification sequence as used for the product. 

The plaque assay is desirable because it is very sensitive and only detects infectious viral particles. However, there are viral agents which cannot be supported by cell lines. In these cases other methods must be used. The polymerase chain reaction (PGR), which amplifies DNA or RNA from viral agents, can be used to detect the presence and quantity of viral agents. The amount of RNA or DNA target in the initial sample can be determined by competitive PGR where the quantity of amplified product is compared to a control PGR product where the initial amount of target is known. Quantification is also possible by an end-point dilution method similar to that used to determine a tissue culture infections dose. PGR methods can be very sensitive however. 

In 1975, the first successful production of MAbs was reported (44). By fusing normal antibody-producing cells with a B-ceU tumor (myeloma), hybridoma cell lines resulted which produced antibodies having a specificity to only one deterrninant on an antigen ie, all the antibodies produced from the cell line are identical. These studies resulted in a standard approach to MAb production. In this approach, the hybridoma cells are produced in large quantities in culture and screened to select specific clones producing the desired MAb using an appropriate assay. The selected clones are then expanded in culture (or in animals), the cells are collected, and the MAbs are extracted and purified. 

Production of the vims in a bioreactor reactor, using a continuous cell line, has also been studied (85,86). This will reduce production costs and side effects. Both Madin-Darby canine kedney (MDCK) and Vero cell lines are being developed for production of the vaccine. 

Product Cell line Process Year introduced Reference... 

A wide variety of mammalian cells are used in industrial practice and to accommodate the diversity, a variety of cell culture technologies have evolved depending on the cell line and product characteristics. 

Rat Neuroblastoma N1E115 cell line Coupling to Gi, inhibition of cAMP production ... 

Q5A(R1) Viral Safety Evaluation of Biotechnology Products Derived from Cell Lines of Human or Animal Origin... 

In-vitro models can provide preliminary insights into some pharmacodynamic aspects. For example, cultured Caco 2 cell lines (derived from a human colorectal carcinoma) may be used to simulate intestinal absorption behaviour, while cultured hepatic cell lines are available for metabolic studies. However, a comprehensive understanding of the pharmacokinetic effects vfill require the use of in-vivo animal studies, where the drug levels in various tissues can be measured after different dosages and time intervals. Radioactively labelled drugs (carbon-14) may be used to facilitate detection. Animal model studies of human biopharmaceutical products may be compromised by immune responses that would not be expected when actually treating human subjects. 

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