UTILITY REQUIREMENTS FOR STERILE PRODUCT MANUFACTURING
Any utility in direct product contact is subject to formal qualification through the confirmation of the quality of the delivered material at each use point. Water-for-injection (WFI) systems are considered the most critical of all, and the qualification period for WFI is the longest and may be as long as 3 months. The remaining product contact utilities can be qualified more rapidly. Nonproduct utility requirements can be satisfied by commissioning.
Water for Injection
The most important utility in sterile manufacturing is WFI. Not only is it a major component in many formulations, it is also utilized as a final rinse of process equipment, product contact parts, utensils, and components. In some facilities, it may be the only grade of water available and is used for the initial cleaning of items as well.
The WFI may be produced by either distillation (multiple effects or vapor compression) or reverse osmosis (generally in conjunction with deionization) and is ordinarily stored and recirculated at an elevated temperature greater than 70 ° C to prevent microbial growth. Where cold water is required, it may be supplied by using
point heat exchangers or using a separate cold loop (usually without a storage capability). Point-of-use cool water drops and reduced temperature circulation loops are generally sterilized or high-temperature sanitized at defined and validated intervals. The design details of the WFI system vary with the incoming water quality, local utility costs, and operational demands. Very small operations may not have a WFI system and will utilize larger (5 L or larger) packages of WFI for formulation and cleaning.
Other grades of water may be present in parenteral facilities for use as initial rinses and detergent cleaning. The water utilized for these purposes is generally of relatively low bioburden and is often deionized, softened, ultra-filtered, or in some instances prepared by distillation or reverse osmosis, resulting in chemical purity similar to, if not identical to, WFI. Systems for the preparation of this water are subject to qualification, validation, and routine analysis to assure consistent quality.
Clean (Pure) Steam
Sterilizers and SIP systems in the facility are supplied with steam which upon condensation meets WFI quality requirements (testing steam condensate for microbial content is not fruitful). The steam can be produced directly from the water of sufficient purity to meet the input requirements of the steam generator. Steam generators are phase transition technologies that operate like a still, so it is no more necessary to provide these devices with WFI feed water than it would be to double distill WFI. (Production from WFI is certainly possible, but that is both expensive and an unnecessary precaution.) Modest quantities of steam can be produced from the first effect of a multiple-effect WFI still, however, with a resultant loss of WFI output.
Air or nitrogen used in product contact is often supplied in stainless steel piping and ordinarily equipped with point-of-use filters; quite often an additional filter is placed within the distribution loop or at the entry point into a room resulting in a form of redundant filtration. Compressed air is typically provided by oil-free compressors to minimize potential contaminants and is often treated with a drier to obviate the possibility of condensation within the lines which could be a source of contamination. Nitrogen is supplied as a bulk cryogenic liquid. Argon and carbon
dioxide has also been utilized as inerting gases, while propane or natural gas may be needed for the sealing of ampoules.
The operation of a parenteral facility often entails other utilities for the operation of the equipment. These include plant steam, jacket cooling water, and instrument air.
Production and Processes -PHARMACEUTICAL MANUFACTURING HANDBOOK (SHAYNE COX GAD, PH.D., D.A.B.T.)