Pharmaceutical Manufacturing interviewed Bob Livingston, principal of Arion Water, Inc. (Hyannis, Mass.) and a keynote speaker at the recent Water Summit and Utility Validation Conference in Philadelphia, to explore his views on USP's new standards for pharmaceutical-grade water. P.M. — What impact will changes in USP requirements have on pharmaceutical manufacturing operations’ overall water use and, specifically, their use of WFI?B.L. — At first, there will be little impact, although USP 27 was an important step in the right direction, removing wording which designates how WFI should be made. The pharmaceutical industry must be conservative because FDA is conservative. But now that the door has been officially opened, discussions will include technical alternatives to standard approaches. Some purified water system designs are and will continue to reliably exceed WFI water quality at ambient temperatures--some using heat, others ozone, and some without routine sanitization. This will demonstrate various approaches and provide a track record for future modifications to WFI designs. The biotech industry will embrace the alternative approaches, and pioneer their implementation before the pharmaceutical industry eventually comes around. PM — Why is this so?B.L. — Because leadership in the bioprocessing field comes from academia. They’re often better able to evaluate issues from a technical standpoint than their peers at drug companies. PM — What opportunities and risks do the new regulations present drug manufacturers?B.L. — It is a fact that many purified water systems employ approaches that are technically counterproductive, but are employed to appease regulators, such as use of 316 Stainless Steel, hot water sanitizations, continuous operation of RO/CEDI units, no processing of water in distribution, sanitary design, etc. The semiconductor industry uses none of these approaches, for sound technical and economic reasons, yet produces water with far higher microbial and endotoxin specifications. Until the pharmaceutical industry learns these lessons, the mistakes will be repeated with endless variety and predictable results. PM — Are drug manufacturers overly reliant on WFI today?B.L. — Yes, both overly reliant and hamstrung by inordinate costs, production bottlenecks and less-than-ideal water quality. WFI has its place, to be sure. WFI has never had a proven microbiological failure, and this is a fact not to be ignored. That said, however, WFI is used for too many applications where high quality purified water would easily suffice. PM -- Why?B.L. — The industry is regulated, and sound engineering has too often taken a back seat to regulatory perception administered by validation and QA/QC bureaucracies at the behest of FDA. PM -- What are the problems with “over-specifying” use of WFI, from both a cost and a quality perspective?B.L. — Costs are excessive by at least a factor of three, and up to 10. And the quality, with the important exception of microbial quality, is not there. WFI water is not high-purity water. WFI water quality is sufficient for most pharmaceutical manufacturing, but appears to be unacceptable for some biotech methods and products. PM — Is there anything that manufacturers can do to reduce the cost of WFI in their operations?B.L. — There is no substitute for WFI water, at least not if you hope your product may ever be sold in the European Union. But WFI water is over-used in manufacturing, and reliable sources of “high quality” purified water offer considerable opportunities to reduce manufacturing costs without risk. PM — What guidelines should pharmaceutical manufacturers in the U..S use to determine water quality levels most appropriate for various operations within their facilities? What “best practices” should companies use to map out their requirements?B.L. — The important step to safely implement wider use of high quality purified water is to have water that exceeds the existing specs for purified water and WFI water. Providing purified water with less than 1 cfu/100 ml, and no detectable endotoxins, is not any more expensive than providing standard purified water systems. The secret, though, is that very high quality water does, in fact, inhibit microbial growth. This has been demonstrated by the semiconductor industry for over 30 years, where all systems are operated at ambient temperatures, and no sanitizations are performed. PM — How does the “highly purified water” (HPW) category, as defined by the European Medicine Agency (EMEA) differ from WFI? Where should HPW be used? Where is WFI required?B.L. — EMEA changed the name but not the specifications. EMEA’s High Purity Water still permits 500 ppb TOC (food) and is only approximately 1 µs conductive. They missed the opportunity to realize the connection between high quality water and low-to-no bacteria. PM —Please comment on the various technologies used to generate HPW and their relative strengths and weaknesses.B.L. — Essentially, no new technologies have been introduced in years. Hot Water RO and CDI units are new, but the touchstone for any system’s efficacy is to see whether the semiconductor industry uses something new. In this case, they do not. It is not needed. So the tools remain the same. It is the all-important order in which they are applied, or the orchestration of technologies, that is key.
