【Three Answers to Questions on GMP Implementation Details】—Pharmaceutical Water Systems

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This post was last edited by adminzou on 2016-10-27 at 15:55. Water systems for pharmaceutical use: 1. How are the purified water storage tanks and the circuits that use purified water sterilized? How should water for injection storage tanks and their associated pipelines be handled? Answer: The routine control of microorganisms in the purified water treatment circuit is typically achieved using medium-pressure ultraviolet lamps. The irradiation dose recommended in ISPE Volume 4 is 22 mj/cm2; companies may choose a dose of 30 mj/cm2 instead. Medium-pressure ultraviolet lamps are effective in destroying microbial cells, including proteins, deoxyribonucleic acid, and enzymes. They also have a good bactericidal effect on certain bacteria that are not sensitive to 254 nm light. In addition, these lamps can destroy photoactive enzymes, thereby reducing the ability of damaged microorganisms to carry out photosynthesis. The selection of ultraviolet radiation, pipe diameter changes, and flow rate must all be addressed in the design in order to ensure the quality of the purified water. Purified water storage tanks are usually pasteurized by circulating water at 85°C for more than 1 hour. The water for injection system is sterilized using pure steam. 2. What verifications should be carried out after restarting a water system that was shut down due to shutdown operations? Answer: This depends on the maintenance work and other changes that took place during the shutdown period, as well as the impact of such changes on the system; a decision should be made based on the results of the risk assessment. Major changes require verification. Article 2 of the General Principles of WHO guidelines states: „...After installation, commissioning, verification, and unplanned maintenance or modifications, water systems must be approved by the Quality Assurance (QA) department before they can be put into use.“ After performing preventive maintenance according to the pre-approved plan, it can be used without further approval.” (See WHO Guidelines for Water Systems for Pharmaceutical Use 2007) 3. During the validation of the water system, if all usage points were tested in full and the results were stable, is it then sufficient to monitor only endotoxins, microorganisms (for water for injection), or microorganisms (for purified water) during routine monitoring? Answer: To ensure that the system remains in good controlled condition, both water for injection and purified water should be subject to regular full inspections; a stable system typically requires a full inspection once a month. For water for injection, in addition to bacterial endotoxins and microorganisms, the conductivity and total organic carbon of water for injection should also be included as items for routine monitoring. These items are specified in the pharmacopoeia and can be regarded as a supplement to GMP ； For purified water, routine monitoring only tests microbial indicators.