Water for Injection
Water for Injection is sterile, nonpyrogenic, distilled water in a single-dose container for intravenous administration after the addition of a suitable solute. It may also be used as a dispensing container for diluent use. The pH is 5.5 (5.0 to 7.0)
Water for Injection is used as an excipient in the production of parenteral and other preparations where product endotoxin content must be controlled, and in other pharmaceutical applications, such as cleaning of certain equipment and parenteral product-contact components. The minimum quality of source or feed water for the generation of Water for Injection is Drinking Water as defined by the U.S. EPA, EU, Japan, or the WHO.
This source water may be pre-treated to render it suitable for subsequent distillation. The finished water must meet all of the chemical requirements for Purified Water as well as an additional bacterial endotoxin specification. Since endotoxins are produced by the kinds of microorganisms that are prone to inhabit water, the equipment and procedures used by the system to purify, store, and distribute Water for Injection must be designed to minimize or prevent microbial contamination as well as remove incoming endotoxin from the starting water. Water for Injection systems must be validated to reliably and consistently produce and distribute this quality of water.
The Water for Injection monograph also allows it to be packed in bulk for commercial use. Required specifications include the test for Bacterial endotoxins, and those of the packaged water Sterile Purified Water, except for Labeling. Bulk packaged Water for Injection is required to be sterile, thus eliminating microbial contamination quality
changes.
Manufacturing Procedure
1. Preparation of water.
a. Check the water for injection used for injection preparation and verify that it meets the conductivity limit of NMT
1.3 µS/cm, Bacterial Endotoxin less than 0.25 USP Endotoxin Unit per mL, and pH range of 5.0 to 7.0.
b. Test the rinsings from the container that are used during solution preparation for conductivity (limit NMT
1.0 S).
2. Preparation of water.
a. Add water for injection to the final volume in the preparation tank and transfer to a sterile mobile tank.
b. Transfer the mobile tank from the solution preparation area to the solution room.
3. Preparation of ampoules.
Use type I 10-mL clear glass ampoules, USP.
a. Wash the ampoules according to operating procedures.
b. Sterilize the ampoules by using a dry-heat tunnel.
c. Set the temperature as per the latest validation studies with revised cycle
4. Sterilization.
Sterilize the filtration assembly and ampoule filling machine parts at 122◦C for 30 minutes. Set parameters according to the current validated cycle.
5. Sterile filling.
a. Aseptically connect the N2 line through the sterile N2 filter to the inlet of the mobile holding tank as per SOPs.
b. Asepticallyconnectoneendofthepreviouslysterilized filtration assembly with a 0.22-m pore-size filtration
cartridge to the outlet of the mobile holding tank and the other end to the holding tank.
C. Before starting the sterile filtration, check the integrity of the filter cartridge according to SOPs.
d.Operate the ampoule-filling machine according to SOPs. Bleed the dosing system as described in the operating procedures. Adjust the fill volume to up to mark.
e. Sterile-fill sterile water for injection from the bulk into each sterile, dry clean ampoule and seal it.
6. Terminal sterilization.
Sterilize the filled ampoules in a Finn Aqua autoclave at the current validated cycle. Set the temperature at 121◦C for 20 minutes.
7. Ampoule leak test.
Perform the leak test according to SOPs and transfer to optical checking.
8. Optical checking.
Inspect the ampoules under the optical checking machine and record and transfer them to packaging.
Precaution: Store all bulk water in a tightly closed container. Avoid absorption of CO2 and other gases.
