New version of GMP requires pharmaceutical water to be at least drinking water quality. The design, installation, operation and maintenance of water treatment equipment and conveying systems should ensure that pharmaceutical water meets the set quality standards. The operation of water treatment equipment should not exceed its design capacity.
The refined segment of pharmaceutical water generally uses purified water. There are usually three processes for the production of purified water, which can also be determined according to the requirements of pharmaceutical enterprises:
Raw water, raw water tank, raw water pump, multimedia filter, activated carbon filter, softener, primary precision filter, primary reverse osmosis, secondary reverse osmosis, ozone generator, purified water tank, ultraviolet sterilizer, pure water pump, and water outlet.
Raw water, raw water tank, raw water pump, multimedia filter, activated carbon filter, softener, primary precision filter, primary reverse osmosis, mixed ion exchanger, ozone generator, purified water tank, ultraviolet sterilizer, pure water pump, and water outlet.
Raw water, raw water tank, raw water pump, multimedia filter, activated carbon filter, softener, primary precision filter, primary reverse osmosis, EDI electronic deionization device, ozone generator, purified water tank, ultraviolet sterilizer, pure water pump, and water outlet.
The main difference between the above processes is the equipment after the primary reverse osmosis: secondary reverse osmosis, mixed ion exchanger, EDI electronic deionization device.
Purified water pipeline
The purified water pipeline must not be buried underground, firstly, the drainage at the lowest point cannot be completed, and secondly, leakage will not be detected in time, which will cause water system pollution.
Disinfection and sterilization
The common disinfection methods for water system in pharma are: pure steam method, pasteurization method, ozone method, ultraviolet method, and chemical disinfectant method.
Enterprises can choose the sterilization method according to the purification water system of the enterprise: Pure steam sterilization is suitable for pressure-resistant containers and pipelines. Pure steam high temperature and pressure (121℃, 0.2Mpa) can kill all surviving microorganisms.
Pasteurization method, low-temperature sterilization method (> 80℃) is suitable for activated carbon filter, softener, and storage circulation pipeline.
Ozone sterilization method is suitable for the sterilization of purified water pipelines, and ozone is a strong oxidant that does not produce by-products and residues.
Ultraviolet sterilization method can be used in combination with hot sterilization or chemical sterilization.
In the chemical disinfectant method, residual disinfectants need to be monitored after disinfection is completed.
The commonly used disinfectants are sodium hypochlorite, hydrogen peroxide, peracetic acid, formaldehyde, and isothiazolones.
The tank is placed in the water production room to avoid multi-tank design. The tank should be equipped with sterilizing air filters, and an appropriate number of spray balls should be installed on the tank top. The valve at the bottom of the tank should be able to drain residual water.
Select hydrophobic filter elements made of PTFE or PVDF materials and steam-heated or electrically heated filter housings. The integrity of the air filter needs to be tested.
Preferentially choose double-tube plate structure heat exchangers or tube-tube heat exchangers. If this type of structure is not selected, ensure that the clean side pressure is higher than the unclean side.
The sanitary pump has a reasonable structure, reasonable material selection, easy to clean and maintain, and is compatible with the selected sterilization method.
Butterfly valves and diaphragm valves can be selected for purified water and injection water; sanitary ball valves can be selected for pure steam; ball valves cannot be used in water system in pharma because when the valve is closed, the dead water in the valve will pollute the entire water system when the valve is opened again, which poses a greater risk.
Blind pipes/dead corners
There should be no dead corners in the purified water system, and the L/d ratio of blind pipes should be less than 3.
Maintain positive pressure system
Determine the system capacity, tank capacity, and pump flow rate according to the water consumption; the combination of the tank and water-making equipment can meet the peak water consumption, and the water-making capacity can meet the normal water consumption. The maximum flow rate of the pump can meet the peak water consumption + return flow.
Automatic welding (such as argon arc welding), followed by quick coupling, and then sanitary flange connection should be preferred for pipeline welding, and threaded connections should not be used.
The instruments ensure accuracy and reliability throughout the range and have been calibrated. Instrument selection and installation should reduce potential contamination, with a hygienic structure and materials that are compatible with the water system.
The control system is managed according to computerized requirements, with a hierarchical password for the human-machine interface, the tank liquid level is connected to the water system, and the data control system should comply with FDA electronic record management.
The water system in pharma is an important public system in pharmaceutical enterprises and is also the focus of daily inspections, customer audits, and official inspections. By explaining the composition and inspection points of the water system, we hope to help everyone manage the purified water system well.