According to the FDA Water for Injection is a non-pyrogenic and sterile water used for intravenous injection after addition of a suitable solute.
Its pH value ranges from 5.0 to 7.0 usually maintained at 5.5. Its osmolarity is 0.
As it is used intravenously and must be sterile at all times, it demands absolute precision in preparation. The USP and FDA allow two methods for preparing water for Injection, they are:
1. Distillation
2. Reverse Osmosis
But before getting into any of these processes, the water goes through pretreatment. Pretreatment includes removal of chlorine using activated carbon beds and removal of residual ionic compounds through percolation of water through ion exchange resins.
Most of the organic contaminants are removed during this process. The FDA allows less than 500 ppb of total organic compounds in Water for Injection.
After pretreatment, one of the two processes has opted.
1. Distillation:
After pretreatment, the water is heated in a still until it is vaporized. The water vapor is re-condensed in condensation tubes using flowing cold water. The obtained distilled water can be used as Water for Injection. Distillation leaves behind heavy ions, particulates and endotoxins from the water. It is a slow process compared to Reverse Osmosis.
2. Reverse osmosis (RO)
RO takes filtration to a molecular and ionic level. The pre-treated water is passed through a semi-permeable membrane capable of retaining dissolved ions, salts and organic compounds. RO is used industrially for preparing the water in bulk. They are equipped with booster pumps and sophisticated storage system to ensure the quality of the final product obtained. RO machines should be constantly maintained as it can be easily corrupted due to varying temperatures, pressure and pH of the water. RO is more efficient than distillation in the sense that it can produce up to 190,000 liters sterile water in a day.
Storage of sterile water is critical because microbial growth in water can occur at rapid speeds. To prevent this, Water for Injection is maintained at 90 degree Celsius and kept in motion inside a distribution loop in a velocity of 5 feet per second.
Due to the low conductivity of the Water for Injection, they have high affinity towards ions and dissolve ions from surfaces they come in contact to easily. Hence, silicon carbide or tungsten carbide mechanical seals are used for storage.
After its production and before its use, Water for Injection should go through validation to ensure its quality. There are three stages in WFI water system validation:
1. Installation qualification: Monitoring that the system follows design drawings, specifications and manufacturer’s recommendation.
2. Operational qualification: It is the operational phase where the system and equipment must operate as specified by the manufacturer.
3. Performance qualification: Under stimulated conditions and after installation and operational qualification, the system must meet all the conditions that it is required to as specified by the manufacturer.
Any design changes that take place after the use of the system must go through the validation process. Hence preparing Water for Injection in a quite intricate and tedious process.
Hence, by Water for Injection can be prepared by these two processes and should only be used by going through the validation.