An ultimate interpretation to a new version of GMP (a)


Cold water’s consuming points are needed to use when injecting water in the circulation line. As for whether the water consuming points are universally set for using a cooler, or must be a single point of configuration cooler, Is there a specific requirement? (FL1)

Explanation: The specific setting scheme can be determined by the enterprise according to their own actual situation. Here, ISPE have some principles that must be followed. When there are multiple points using cold water for injection and universally using the set heat transfer, after the last water consuming point , a centralized heat transfer is usually adopted, then the water is heated to above 70 ℃ in the pipe, thus the microbial control measures are strengthened. It can be seen in ISPE 2001 volume 4 of water and steam system.

(The exiting of ISPE is single tank, the WFI figure of binary circuits with cold water’s use)

When water is purified by using loop, water injection system to reduce microbial contamination, what method should be adopted when processing?

Explanation: Purified water use loop cycle and keep a certain velocity. Generally, the ultraviolet lamp can be used to UV sterilization on-line , but the intensity of the ultraviolet shall be calculated according to the flow. 30 mj/cm2 is usually taken as dose values of irradiation. In addition, according to the change of the microbial contamination, pasteurization disinfection can be regularly used for sterilizing. For example, when the temperature is above 80 ℃, it should cycle for 1 to 2 hours. While in the process of injecting water, microbial is more than rectifying limit or stop overhaul, which is caused for some reason, then pure steam sterilization should be adopted.

Injection of water and pure steam system will often appear red rust. Is it necessary to inactivate like initial equipment every year? Or put the system inactivate regularly? (FL1)

Explanation: In many water system, it is usually a high temperature of injection water and pure steam system that we can see the red rust. It is not limited to storage and distribution system, and it also exists in distilled water and pure steam generator. In some cases, the water system will appear red rust for working 1 to 2 months . In other cases, red rust might be observed for several years. The red rust is a common phenomenon in this industry.Under special circumstances, after inactivating and removing red rust for a week, it will appear red rust again in the injection for cold water of an enterprise. System has inactivated and removed red rust for 3 times, and every time after a week’s processing, the whole system appear red rust again.The FDA has not put forward written opinions for the problem of red rust to describe phenomenon of red rust in high pure water and pure steam. " The standard of red rust" is still in accordance with the United States pharmacopoeia on the basis of the water quality standards. It is understandable that red rust in the system of serious part should be put in the system of high temperature and the soda separation area, and it is impossible for average companies to initial inactivation of these areas.

The produce of red rust is inevitable and repeatable. As long as it does not affect the water quality, there is no need to treating the system by using the method of initial inactivation. Because inactivation can not completely solve the problem of red rust, excessive inactivation will increase workload, and it may damage the system. When necessary, filters and regular cleaning can be used in the system of consuming points. It can also use phosphoric acid, citric acid, oxalic acid and citric acid ammonium to deal with according to the severity of the problem , and finally rinse.