Two sides of a different coin find commonalities

Over the years, high purity water specialists have drawn comparisons between the pharmaceutical and semiconductor industries. They are, after all, both users of very high purity water but, in spite of the obvious similarities in the water treatment processes, there has never been very much common ground between them. One of the reasons is that the two industries have widely differing definitions of 'pure'. Against the odds, the human body is much less susceptible to trace contaminants in water than are silicon chips, and the purity levels specified for semiconductor rinse water are generally more than – an order of magnitude greater than those for compendial pharmaceutical water grades. Comparisons between pharmaceutical and semiconductor water qualities have always been difficult to make because, for most of the last century, pharmaceutical water quality was specified in terms of wet chemistry tests, which were difficult to interpret in terms of operational parameters like conductivity and Total Organic Carbon (TOC). The 1996 23rd Edition of the United States Pharmacopoeia (USP23) was the first to define water quality in easily measurable terms, and these have not changed in subsequent editions. Although it has been done many times, it is still interesting to compare the USP standards with those specified in ASTM D 5127-99 for Type E-1.2 rinse water for semiconductor devices with 0.25µm line widths.

Importance of conductivity The most important measure of ionic impurities is conductivity (and its reciprocal resistivity). USP requires a conductivity of <1.3µS/cm (that is 0.8M?.cm in terms of resistivity) at point-of-use at 25°C. The semiconductor equivalent specification calls for 0.055µS/cm (18.2M?.cm) – more than 20 times more pure. The words "at point-of-use" are critical. Contamination of water after treatment can reduce conductivity and to ensure that the specification is met at point-of-use, the pharmaceutical industry has set an informal standard of 0.1µS/cm at point of production. Producing water at precisely 1.3µS/cm is not particularly easy as single-pass reverse osmosis or simple two-bed deionisation will not achieve it consistently. However, mixed-bed ion exchange or continuous electro-deionisation (CEDI) achieves a much higher purity of 0.1µS/cm, but at an increased cost. TOC is a critical parameter in semiconductor rinse water. It was a seminal study by General Electric in the mid-1980s that identified a correlation between TOC and gate oxide defect density and set the trend for improvements in both TOC monitoring and TOC removal technologies. The current standard for TOC in Type E-1.2 water is 1µg/l. By comparison the USP standard is 500µg/l. Pyrogens are essentially bacterial endotoxins, which cause a fever when injected into the body. It was the pharmaceutical industry's concern over these macro-molecules that led to the development of the LAL test and to the current USP endotoxin standard in Water for Injection of 0.25EU/ml. The LAL test has been enthusiastically taken up by the semiconductor industry as an indicator of bacterial contamination, but purity standards are, again, set at an order of magnitude higher than those in the USP at 0.03EU/ml. Viable bacteria are, quite clearly, of major concern in parenteral solutions and the like, so it is surprising that the USP does not set a limit for bacteria, even in Water for Injection. There is a recommended limit of 100cfu/ml for purified water and 10cfu/100ml in Water for Injection, and this is generally supported by the Food and Drugs Administration inspectorate, whose main inspection aim is to ensure that the bacteria levels in a water system are under control. Even this guideline is two orders of magnitude worse than the 0.1cfu/100 ml set for Type E-1.2 water. One area where the semiconductor and pharmaceuticals industries do have common problems is in maintaining treated water quality, once it has been produced, in storage and distribution. While distribution systems in both industries consist essentially of a storage tank and recirculating ring main, there are major differences in approach. The main concerns in pharmaceutical water are airborne contaminants like carbon dioxide, which can increase the conductivity above the 1.3µS/cm maximum, and bacteria that can proliferate in distribution pipework. These contaminants are equally unwelcome in semiconductor rinse systems but so are species like metal ions and trace organics. This effectively rules out stainless steel, the industry standard in pharmaceuticals, as a material of construction. Stainless steel is the material of choice for pharmaceutical systems as it allows routine sanitisation by hot water to control bacterial growth.

Construction differences By contrast, semiconductor rinse systems are usually constructed from exotic plastics like PVDF, which although nominally suitable for elevated temperatures, lose much of their structural integrity when heated. This means that sanitisation is generally a chemical process, which is rather more involved than hot water and is, therefore, carried out less frequently. For this reason the exclusion of bacteria from the distribution system is critical, and semiconductor water storage tanks are generally nitrogen blanketed to preclude both bacteria and carbon dioxide. This technique is fairly unusual in pharmaceutical systems, where engineers rely on hydrophobic bacterial air filters. Further, semiconductor systems incorporate polishing plant – ultraviolet irradiation, mixed-bed ion exchange, reverse osmosis and/or ultrafiltration – in the ring main to remove trace contaminants which may have entered the storage tank. In pharmaceutical systems ultraviolet disinfection units are common but other polishing equipment is seen as a potential source of bacterial contamination and is excluded. This makes maintaining point-of-use quality rather more difficult in pharmaceutical systems. System validation is common to both industries. In the semiconductor industry the main concern is the verification of water quality while the pharmaceutical industry places as much, if not more, emphasis on the verification of system installation. This is because pharmaceutical manufacturers working to USP standards are subject to inspection by the US Food and Drugs Administration, which requires compliance with system integrity to the extent that even simple pipework modifications can often take weeks to implement. This means that a clear audit trail is necessary, covering qualification of design, installation and operation, with water quality forming part of ongoing performance qualification procedures. In the semiconductor industry there is no such requirement for system validation, although ASTM D 5127-99 provides some general advice on the installation and rinsing of plastic pipes. The result of these two differing approaches is that the installation of pharmaceutical systems is a very protracted procedure but, once installed and qualified, water quality is usually achieved very quickly. Semiconductor ring mains are usually installed quite quickly but rinse down to achieve water quality at point of use can take a long time.

Learning from each other High Wycombe-based water treatment plant contractor ELGA Process Water has installed many pharmaceutical and semiconductor water treatment and distribution systems, and believes that both industries could learn from the other. Its experience led it to develop ORION, a standardised pharmaceutical water treatment system which is factory assembled and fully validated prior to delivery to reduce the lengthy on-site Installation Qualification procedures. For the semiconductor market, ELGA Process Water ensures that process plant and pipework used in the distribution and polishing loop is fabricated, assembled and rinsed with ultrapure water in clean, virtually sterile conditions. The assembled components are then sealed in airtight bags before being taken to the installation area. While this increases costs, the additional investment is a worthwhile one. If equipment is assembled in cleanroom conditions the rinse down time, particularly for particles, is dramatically reduced. Steps like these, which are intended to reduce the time the commissioning team spends on site and to provide an operating system much more quickly, are effective only if the system design is right. Water treatment plant, such as reverse osmosis, ion exchange and distillation, performs predictably, and design qualification is a procedure that any ISO 9000 certified engineering company will employ routinely. The design of distribution systems, on the other hand, is much more difficult. The hydraulic design must ensure that there are no dead legs or areas of low velocity, which could encourage bacterial growth, while ensuring adequate flows are available at each point of use. This is not a job for an inexperienced engineer. All too often pipework has to be modified during installation to accommodate 'clashes' with the pipework of other services, resulting in a system that may differ quite a bit from that which was designed.

Better by design Pharmaceutical manufacturing is generally a batch process with intermittent water draw-off, and this means that distribution systems, consisting of a continuous loop feeding each point of use in turn, are relatively easy to design. The zero draw-off condition, with high ring main velocities, means that low velocity conditions can be tolerated for short periods. Semiconductor systems are generally continuous and the layout of semiconductor factories means that rinse water distribution systems are usually designed like central heating systems with flow and return headers. These systems are inherently more susceptible to dead legs and low flows, especially as manufacturing demands vary and new machines are installed or old ones removed. To summarise, the differing water quality requirements of the pharmaceutical and semiconductor industries has led to cultural differences in the way that water treatment systems are designed and installed. However, some of the problems, particularly those associated with distribution system validation, are common to both. The storage and distribution system is often seen as less glamorous than the 'high tech' water treatment plant that supplies it, but it is critical to maintaining the quality of water at point of use. The message is simple: make sure that the water treatment system supplier knows as much about distribution system design as he does about water purification.