The Quality Control Of Fermentation System And Effects On E. Coli Fermentation Process Of Typhoid Vaccine

In recent years, GMP, GLP, and related ideas penetrated into the quality control of biological products and experimental procedure.Lanzhou Institute of biological products developed by the Research Office of the first tyPhoid Vi polysaccharide-protein conjugate vaccines with recombinant Pseudomonas aeruginosa Exotoxin a(rEPA) as the protein carrier,expressed by Escherichia coli, the host Escherichia coli bacteria directly affects the production of tyPhoid Vi polysaccharide-protein conjugate vaccines.The test is based on the GMP quality control requirements, applying quality management methods and tools, the host Escherichia coli fermentation process and its related system implementation of quality control, the results were as follows:1. Laboratory system of impact assessment.The stage of the assessment results:(1) directly affect the systems for air purification systems, process water systems, gas systems,fermentation system, dry heat sterilization, autoclave systems systems, laboratory accreditation systems, biological safety cabinets, hollow fiber system, tomograPhy, 37 ℃culture, weighbridge, Pharmaceutical refrigerator, 37 ℃ Shaker-incubator;(2) indirect effects system for refrigerator, electrical power distribution system;(3) without affecting the system for fire-fighting system, laundry facilities.2. Fermentation system key components of the evaluation.The stage assessment results for:(1) fermentation system of key component, including: tank body, and pH sensor, and DO sensor, and temperature sensor, and computer control unit, and Blender, and speed sensor, and elimination bubble pulp, and elimination bubble sensor, and flowmeter, and pressure table,and CIP control unit(2) fermentation system of non-key component, including: clip sets, and into material mouth, and out material mouth, and people hole, and motor, and control valve,and circuit.3. Risk management.The stages of risk identification, risk analysis, risk assessment, and ultimately determine the risk level of each component in the experiment: pH, DO,temperature, pressure and aseptic fermentation system for fermentation process of high risk,the need for risk control.4. High risk points of control.The stage is divided into validation and measurement of two parts:(1) a certification section: directly affects the system of pulsant vacuum sterilizer,biological safety cabinets and fermentation tanks are verified, validated found temperature drift of pulsating vacuum sterilizer, after repair and adjust again, and its sterilizing ability comply with the GMP requirements.(2) the measurement part: according to the results of the key components in assessment and risk management, pH sensor, DO sensors, temperature sensors, the system pressure gauge, flow meter, speed sensors and laboratory accreditation system in the spectro Photometer, pH meters, electronic scales, electroPhoresis, gel imaging systems and measuring equipment such as a microscope, to replace the failed pressure gauge.5. The host Escherichia coli fermentation.Respectively before and after the implementation of quality control on three consecutive batch fermentation of Escherichia coli host, through the development of results, quality control of fermentation before the results are superior quality control, three significantly higher yields, increased success rate of fermentation.Obviously, good test in quality control systems on the host Escherichia coli fermentation culture played a role in promoting.To sum up, quality management methods and tools used in the lab can help research the problems of and records and solved in a documented manner, this experiment for improving work efficiency, accuracy, reproducibility, reliability is of great practical significance.