Process for the large-scale production of a vaccine against poli

Drug – bio-affecting and body treating compositions – Lymphokine

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A61K 3913

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045253498

ABSTRACT:
A process for large-scale production of poliomyelitis vaccine separately entails, for each type of poliomyelitis virus used, the following steps. A cell strain, using a cell stock, is multiplied by culturing the same in a liquid nutritive medium on microcarriers in suspension and by successive passages into biogenerator of increasing volumes. The last biogenerator is one having a capacity of at least 150 liters and the nutritive medium contains serum. This operation is carried out with stirring at a rate not greater than 40 rpm. At the end of the final passage the liquid nutritive medium is withdrawn and replaced by one that is serum-free. The biogenerator used for the last passage is then inoculated with virus which is permitted to develop, again with stirring at a rate not greater than 40 rpm. After virus culture, the liquid suspension is withdrawn, filtered, concentrated at least 150 times by ultrafiltration, subjected first to gel filtration and then to ion exchange chromatography. The resulting concentrated suspension is diluted with a serum-free medium and then inactivated. The suspensions of the respective types used are mixed from which individual dosages are prepared.

REFERENCES:
Van Wezel et al., Developments in Biological Standardization, vol. 42: 65-69, (1979), Large-Scale Concentration and Purification of Virus Suspension from Microcarrier Culture for the Preparation of Inactivated Virus Vaccines, (248 liters).
Thilly et al., Microcarrier Culture: A Homogeneous Environment for Studies of Cellular Biochemistry, (1979), in Jakoby (ed.), Methods in Enzymology Cell Culture, vol. 58, pp. 184-194, Large-Scale Scale-Up Accomplished Easily: (1000 ml. volume bottles for Microcarrier work).
Meignier, Developments in Biological Standardization, 42: 141-145, (1979), Cell Culture on Beads Used for the Industrial Production of Foot-and-Mouth Disease Virus, (150 liter Roux flask).
Giard et al., Biotechnology and Bioengineering, 21: 433-442, (1979), Human Interferon Production with Diploid Fibroblast Cells Grown on Microcarriers, (3.times. greater yield than roller bottles).
Van Wezel et al., Developments in Biological Standardization, 41: 159-168, (1978), New Approach to the Production of Concentrated and Purified Inactivated Polio and Rabies Tissue Culture Vaccines, (125 liters), (250 liters), (260 liters).
Van Wezel et al., Process Biochemistry, 13: 6-8, (1978), "Large Scale Cultivation of Animal Cells in Micro Carrier Culture", (200 liters).
Van Wezel et al., Devel. Biol. Stand., 40: 69-75, (1977), Production of an Inactivated Rabies Vaccine in Primary Dog Kidney Cells, (250 liters).
Levine et al., Somatic Cell Genetics 3: 149-155, (1977), Microcarrier Cell Culture: New Methods for Research-Scale Application, (large-scale concns attained).
Giard et al., Appl. & Envir. Microbiol., 34: 668-672, (1977), Virus Production with a Newly Developed Microcarrier System, (great promise for large-scale prod'n), (100 liter scale-up).
Spier et al., Biotechnology and Bioengineering, 18: 659-667, (1976), The Production of FMD Virus from BHK21C13 Cells Grown on the Surface of Deae Sephadex A50 Beads, (1000 liter scale-up).
Van Wezel, Nature, 216: 64-65, (1967), Growth of Cell Strains and Primary Cells on Micro-Carriers in Homogeneous Culture.
A. L. Van Wezel, Develop. Biol. Standard, vol. 47, pp. 7-13, (1981).
B. Mered et al., Develop. Biol. Standard, vol. 47, pp. 41-53, (1981).
B. J. Montagnon et al., Develop. Biol. Standard, vol. 47, I, pp. 55-64, II, pp. 151-155, (1981).
Eagle, Science, vol. 130, pp. 432-433, (1959).
WHO Expert Committee on Biological Standardization, 32nd Report, Technical Report Series No. 673, WHO-Geneva, (1982).

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