PHARMACEUTICAL INDUSTRY REQUIREMENTS

USP XXIII

The United States Pharmacopeia XXIII was put partially into effect in January 1995 and has requirements somewhat different than its predecessor which specified that water for injection be produced by distillation or reverse osmosis.  The new specifications omit any reference to the method of production but rely upon the integrity of the operator to conform to validation guidelines and protocol that had been established to ensure the purity of water produced meets its end requirements.  Reverse osmosis will produce water to meet all of the specifications both in the new and the old regulations.  A typical water for injection system will consist of pretreatment, reverse osmosis, ion exchange, and membrane filtration.  The new specifications could mean a conversion of many systems back to use of one of the several ion exchange processes both as pretreatment and after treatment to membrane processes. The choice between some of the ion exchange processes and RO or distillation will be a simple economic decision.

The new USP XXIII regulations focus on the contaminants of greatest concern in pharmaceutical-grade water (Figure PH-1). USP-grade water now has a limit of 100 cfu/ml (colony-forming units per milliliter).  Specifications for Water for Injection (WFI) are even more stringent, requiring less than 0.25 EU/ml (endotoxin units per milliliter). For existing systems, compliance may mean a simple upgrade or the entire revamping of a system and its components.  The new regulations should increase the use of several emerging technologies that have not been extensively used until now. For instance, while distillation, followed by double-pass reverse osmosis, is the most common method for producing WFI, recent tests have shown that the use of ceramic ultrafiltration membranes may also be a viable treatment method. 

Verity C. Smith of Veritec Consultants writing in UltraPure Water, advises the producer of pharmaceutical-grade water to employ distillation as the final step in the purification of WFI.  Secondly, the user should incorporate at least one membrane process in the production of pure water to include at a minimum a porous membrane as the final filtration process.  The user should make sure that a quality temperature compensated inline conductivity measurement is included in the system at the production and at the delivery points. 

Figure IX-1.  USP Standards for Purified Water & Water for Injection