Cell cultures quality control

Halton DM, Peterson WD Hukku B (1983) Cell culture quality control by rapid isoenzymatic characterisation. In Vitro 19 16-24. 

Using an inverted microscope, equipped with phase contrast optics if possible, examine cell culture vessels individually. Scrutiny should be especially rigorous in cases in which large-scale production is involved. Check each culture first using low power. The suppliers listed provide the specific media required but other suitable vendors exist. Batches of media should be tested for optimal growth promotion before use in cell culture quality control. 

Analytical scientists will provide support for many of the activities in a biopharmaceutical company. They are responsible for characterizing the molecules in development, establishing and performing assays that aid in optimization and reproducibility of the purification schemes, and optimizing conditions for fermentation or cell culture to include product yields. Some of the characterization techniques will eventually be used in quality control to establish purity, potency, and identity of the final formulation. The techniques described here should provide the beginning of a palette from which to develop analytical solutions. 

Quality Controls During Cell Culture (In-Process Controls) and Final Product Release Criteria... 

Change control Complaints and recalls Contract manufacturers and laboratories Agents, distributors, repackers, and relabelers Specific guidance for API manufacture by cell culture or fermentation APIs for use in clinical trials (quality, equipment, facilities, control of raw materials, production, validation, change control, laboratory controls, and documentation)... 

As a quality control, some flasks of this bank (about two or three) should be used to confirm that the cell bank concentration and viability are satisfactory and free of contaminants. Then, a flask of the bank should be thawed and the cells cultured to obtain a working bank. The size of this bank will depend on the future demand. At this stage it is important to confirm that the master and the work banks are genetically identical. 

Cell culture practice requires rigorous control with respect to the quality of material and reagents, the origin and integrity of the cell lines, and the absence of microbial contamination. 

While some culture media are formulated to promote cell multiplication (growth media), others only maintain cell structural and metabolic integrity (maintenance media), but do not stimulate cell division. Media prepared with highly purified compounds and with known composition are designated chemically defined media. These are particularly attractive for biopharmaceutical production, because they are less vulnerable to contamination and quality control is easier. Nevertheless, these media can be expensive. 

Several modifications of the method are described in the literature (Artursson and Karlsson 1991 Hidalgo and Borchardt 1989 and many others). Modifications include cell culture medium, time of cultivation and frequence of medium change, variations of trypsinization methods and others. In an industrial environment cell cultivation methods are maintained over many years constant to reduce variability and ensure constant results in quality assessment protocols. Additionally to quality control parameters like TEER and permeability markers expression levels of major enzymes and transporters are checked. 

Cells in primary culture Phase I and II present, whole metabolic expensive, batch variability, quality control, com-... 

Jones, A. J. S., and Garnick, R. L. (1990). Quality control of rDNA-derived human tissue-type plasminogen activator. In Large Scale Mammalian Cell Culture Technology (A. S. Lubiniecki, ed.), pp. 543-566. Dekker, New York. 

Many other tests could have been included to demonstrate the value of in vitro tests in quality control. Some, such as multistage impingers for aerosols, can be predictive of in vivo behaviour, or at least give an assurance of consistency of effect. An interesting test system for evaluating inhaled nasal delivery systems (Fig. 12.18) combines a physical device with cultured cells so that the interaction of microparticles with living cells can be studied directly. As new delivery systems appear, new tests will be required - as will ingenuity. 

Doyle A Bolton BJ (1994), The quality control of cell lines and the prevention, detection and cure of contamination. In Basic Cell Culture a Practical Approach, pp. 243-271. IRL Press, Oxford. 

Stacey, GN, Parodi, B Doyle, AJ (1995) The European Tissue Culture Society (ETCS) initiative on quality control of cell lines. Experiments in Clinical Cancer Research 4 210-211. 

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