There were many predictions on how the pharmaceutical water market may be altered when the recent European Pharmacopeia (EP) Water for Injection (#WFI) Monograph change was adopted. Previously this monograph had limited the method of manufacture for WFI exclusively to distillation. Decades in the making, the EP WFI monograph was officially modified in the spring of 2017 allowing for alternate, and most logically membrane based, WFI production methods for water used in the manufacture of parenteral products sold into the European Union. Although there were many concerns surrounding this change, eventually the European Medicines Agency was confronted with enough scientific and operating data from the industry, coupled with an international push to harmonize standards, to recommend that alternate methods to distillation for generation of WFI be included in the EP WFI monograph. In the #pharmaceuticalwater industry where not much has changed over the last couple decades and with minimal new technologies introduced to the marketplace during that period, this was a big deal.
Distillation has long been synonymous with the production of WFI, driven primarily by the EP monograph mandate, but also in that it is a very forgiving process. Although the feed water to distillation units should be carefully monitored for impurities that may cause scale or oxidation, short term operation will successfully produce WFI when fed potable water in most cases. In addition, once commissioned and validated, the operation of these systems require few modifications or tuning adjustments and have limited maintenance requirements. Pharmaceutical distillation units, however, are constructed of high grade stainless steels and require significant plant utilities, (e.g. plant steam, chilled water, and electricity) to operate. Compared to membrane based systems such as #reverseosmosis (RO), distillation based systems generally will have higher operating costs and require a larger capital investment. Stills are expensive.
Impact on WFI Market
There was no shortage of prognostications on the effect of the EP WFI monograph change may have on the pharmaceutical water industry. Certain companies such as large volume parenteral manufacturers and RO system fabricators had long lobbied for the change, and some hopefully predicted that distillation would be readily phased out as a commercially viable treatment technology. Other companies that either successfully operated or manufactured distillation units forecast minimal changes to the WFI market moving forward and that distillation would continue its dominance of the industry. What has occurred in the first year was not a universal acceptance of alternate WFI production methods but more of a moderate impact on the marketplace.
While there has not been any sort of mass de-commissioning of existing distillation units for WFI manufacturing, membrane based systems for new WFI generation systems has certainly gained a foothold. There have been several WFI generation systems, mostly featuring RO, Electrodeionization (EDI), and terminal ultrafiltration (UF) that have been designed, installed, and successfully validated in the U.S. over the last year. Many of these employ #ozone for sanitization of the WFI storage and distribution systems eliminating the need for plant steam entirely. Yet, over that same time period there have been many distillation units validated for WFI generation as well.
The Look Ahead
There has undoubtedly been modest interest in membrane based WFI generation since the EP WFI monograph change was promulgated. Our experience is that most forward thinking companies that are willing to challenge traditional pharmaceutical industry standards have been the most receptive, in addition to those on a tight budget. We predict this interest will only increase as more non-traditional WFI systems successfully undergo regulatory scrutiny and inspections. The ultimate impact on the industry remains uncertain. There will inevitably be some highly publicized, ill-designed and operated systems that will cause some to be reluctant to consider alternatives to distillation. Other case studies will flaunt the capital and operating cost savings for membrane based WFI systems as paragons for future projects. For the foreseeable future, the WFI industry will continue to adopt change cautiously as the regulatory expectations, especially among EU inspectors) are revealed. Nevertheless, in the stagnant pharmaceutical water industry any type of change is welcome.