Vaccine production

• US 3,959,074 A
• Filed: 12/06/1974
• Issued: 05/25/1976
• Est. Priority Date: 06/14/1972
• Status: Expired due to Term

• Current Assignee: Merck & Co., Inc.
• Original Assignee: Merck & Co., Inc.
• Inventors: Miller, William J., McAleer, William J., Spier, Raymond E.
• Primary Examiner(s): Rosen, Sam
• Application Number:
  US05/530,109
• Time in Patent Office: 536 Days
• Field of Search: 195/1.7, 195/1.8, 195/1.4, 195/1.1, 424/89
• US Class Current: 435/3
• CPC Class Codes: C12N 5/0018 Culture media for cell or tissue culture media for specific animal cell type C12N5/06

Abstract

A process for the controlled manufacture of cells and vaccines in which reproducable real time quantitative assays are utilized to ascertain the physical and chemical state of the system, in order to more efficiently manage the system, so that cell sheet formation may be determined and the vaccine may be harvested at its maximum titre, thereby resulting in significantly increased yields and decreased production costs.

Claims

1. In a process for the controlled manufacture of vaccines wherein cells are grown in a glucose containing nutrient medium and infected with a virus, isocitric dehydrogenase is released from the cells, the improvement which comprises harvesting the virus when the increase of concentration of isocitric dehydrogenase undergoes a maximum rate of change whereby production of the virus is optimized, thereby resulting in greatly increased yields and substantially decreased production costs.

2. A process according to claim 1 wherein the cells are infected with the virus when the glucose consumption after about 80 hours is at least about 40 mg/100 cc.

3. A process for the controlled manufacture of human and animal vaccines on an industrial scale whereby the production cycle is optimized, thereby resulting in greatly increased yields and substantially decreased production costs, which comprises charging a cell propagator with cells and a nutrient containing fluid in which glucose is present in a concentration of about 100-150 mg/100 cc of the nutrient medium and operating said propagator to cause growth and propagation of said cells, during operation of said cell propagator performing real time assays to monitor glucose concentration in the nutrient medium, and, when the thus monitored glucose concentration reaches about 20-60 mg/100 cc of the nutrient medium, infecting the cell sheet with a virus capable of effecting the release from said cells, isocitricdehydrogenase, maintaining conditions in said propagator to propagate said virus and, during propagation of said virus, performing real time assays to monitor said enzyme concentration in the propagator and harvesting the resulting vaccine when the monitored enzyme concentration undergoes a maximum rate of change.

4. A process as in claim 3 wherein the system is infected with the desired virus when the glucose concentration has decreased to a level of 40-60 mg/100 cc. of fluid.