The content we introduce in this issue is as follows:

1. Verification of non-pharmacopoeial water-the verification principle of non-pharmacopoeial water. For pharmaceutical water that is higher than the pharmacopoeial standard, more stringent verification is required; for the water that is lower than the requirement of the pharmacopoeia, risk assessment needs to be carried out according to the process requirements , And then determine the depth and scope of verification.

2. Daily monitoring-In daily sampling monitoring, for the water injection system, it is necessary to ensure that all points of use are detected every week. Under this condition, the number of samples taken every day is evaluated, and the key sampling points need to be performed according to the process Daily monitoring. The quality of the water system should be reviewed at least once a year, and the main content of the retrospective verification should be listed.

3. Regular maintenance-should include system maintenance frequency, maintenance methods of different components, maintenance records, control of qualified spare parts, etc. And listed the specific content of the maintenance work.

4. Periodic verification-including the results of periodic performance evaluation of the use of the system, the nature and extent of system changes, and the expected future use of the system. It also lists the items that should be considered in the verification plan.

13.2.7 Verification of non-pharmacopoeial water

Non-pharmacopoeia water refers to the types of water that are not specified in the pharmacopoeia, such as deionized water, reverse osmosis water and laboratory water. There are many types of these waters. According to the different needs of various factories or laboratories, the quality standards of these waters may be lower or higher than the requirements of the pharmacopoeia. For example, the production of a special product requires the use of water to have chemical indicators It is the same as purified water, but requires endotoxin control. This is equivalent to using a non-pharmacopoeial water that is higher than the requirements of the pharmacopoeia purified water for production. This non-pharmacopoeial water must fully comply with the verification requirements mentioned above, even according to the product The characteristics and requirements are more stringent verification. Although there is no clear quality standard for non-pharmacopoeial water, for pharmaceutical companies, the quality of non-pharmacopoeial water used should generally not be lower than that of drinking water.

Some other process water, such as deionized water, is generally lower in quality than pharmacopoeia water, but it is also used in the early stages of some processes, so simple verification is required. These need to carry out risk assessment according to process requirements, and then determine the depth and scope of verification. Part of the laboratory water used in the research and development stage may need to comply with GMP requirements, and it is necessary to decide which pharmacopoeial water to use according to the requirements of GMP management and conduct corresponding verification. In accordance with GMP management requirements, there is no need to use pharmacopoeial water or water required for laboratory testing, and these need to be replaced by appropriate non-pharmacopoeial water. Due to the particularity of laboratory tests, such as endotoxin test water and non-pharmacopoeial water with low endotoxin levels, these special non-pharmacopoeial waters need reasonable purification measures and means to monitor their quality, which need to be determined by the user after risk assessment The depth and scope of verification.

13.2.8 Daily monitoring

After the performance confirmation is completed, the system should be comprehensively evaluated and a daily monitoring plan should be established based on the results of the third stage. In daily sampling monitoring, the sampling frequency of the point of use (usually some minimum frequency) is less than the sampling frequency determined in the performance verification. For the water injection system, it is necessary to ensure that all points of use are detected every week. Under this condition, the number of samples taken per day is kept evaluated, and the key sampling points need to be monitored daily according to the process. In this way, for larger distribution systems, sampling can be taken in turn to ensure that each sampling point can be collected once a week. For purified water and pure steam systems, the risk of system impact is low, and the frequency of routine monitoring of water for injection can be appropriately reduced. All these and daily monitoring sampling plans need to be recorded in the SOP.

A water system quality review should be conducted at least once a year. The annual system audit helps users understand the trend of the system over time, and can also adjust the alarm limits and action limits set by the system based on data analysis, and even related SOPs. System quality review should not be limited to the results of water quality sampling, it should be a comprehensive review of the system, including:

① System drawing review and related SOP review.

② Audit of the status of system confirmation and verification.

③ Audit of system preventive maintenance and troubleshooting records.

④ Review of critical system deviations and alarms.

⑤ Audit the results and trends of the daily monitoring data of the system.

⑥ Review of system disinfection procedures.

⑦ Audit of system related training records.

13.2.9 Regular maintenance

The pharmaceutical water system should be maintained according to the system maintenance procedures, which should include the maintenance frequency of the system, the maintenance methods of different components, the maintenance records, and the control of qualified spare parts. After regular maintenance of the system, there is no need for re-verification, and only continuous water quality testing if necessary. Typical maintenance tasks for pharmaceutical water systems are as follows.

① Regular cleaning of storage tanks.

② Regular replacement of vulnerable parts such as valves, gaskets, and respirators.

③ Pressure test, cleaning and passivation of piping system.

④ Thorough cleaning and replacement of water machine multi-media filters, activated carbon filters, and RO reverse osmosis membranes.

⑤ Inspection, inspection and replacement of instruments.

13.2.10 Periodic verification

To ensure that the pharmaceutical water system operates well throughout the life cycle, it needs to be re-verified regularly after a certain period of operation. This should include the results of the regular performance evaluation of the use of the system, the nature and extent of system changes, and the expected future use of the system. And the company's appropriate quality system. The items that should be considered in the plan are as follows.

① Maintenance. Routine maintenance of the system, such as replacement of parts, cleaning, etc. generally do not need to be verified again.

② Transformation. Transformation generally includes replacing "different" components, changing system configuration or changing control procedures, operating parameters, etc. If the retrofit does not change the purpose of the initial system design, it may not require complete repeated verification. The degree of revalidation depends on the potential impact of the transformation on the system.

③ Design changes. Design changes represent major changes to the initial design and require re-verification of the system. For example, adding a deionization device to a purified water production line will change the final treatment effect, which requires more complicated re-verification.

④ System performance is unstable and major deviations occur. Deviations need to be investigated and the system re-verified if necessary.

Source: GMP Industry News