This article was originally published in the July – August 2017 issue of Pharmaceutical Engineering® magazine.

Despite the advantages of ozone technology as a powerful commercially available oxidant and disinfectant, this technology has not been adopted broadly by the pharmaceutical industry. This article contains the rationale for applying ozone technology in a packaged system, which offers greater reliability and efficacy, using best practices that eliminate variables common in on-site integrated ozone systems. This approach is novel and innovative; it provides known results with new tools that quantify and estimate mass transfer efficiency, decrease the risk of misapplication, and increase success.

Virtually all users of pharmaceutical water systems pursue lower maintenance and operational costs, increased reliability, and improved life cycle management. Biopharmaceutical companies are looking for innovative methods and newer technology to increase throughput, quality, and uptime.

Ozone technology delivers the most powerful commercially available oxidant and disinfectant with few detrimental or detracting issues. Ozone sanitization and disinfection has been used for decades, and its adoption in pharmaceutical water systems has been increasing for several years, although it has not yet been adopted broadly in the industry.

When used in lieu of hot water or chemical sanitization for ambient temperature purified-water systems, ozone prevents the accumulation of microbials and organics and requires less maintenance over the life cycle of the water system. In addition, at 24/7 administration ozone is:

  • 85% less expensive than hot water sanitization five times a week
  • 20% less expensive than once-weekly hot water sanitization
  • Tens of thousands of dollars less than twice yearly chemical sanitization 1-2

This paper emphasizes the need to understand this technology, its efficacy, and adoption into pharmaceutical water systems to address problems and limitations of legacy processes. This article also explores the efficacy of applying ozone technology in a “packaged” system using best practices. This approach eliminates variables common in on-site integrated ozone systems, and allows easier implementation at lower cost, with better and more predictable results.


Ozone (O3) is triatomic oxygen, which oxidizes carbon compounds in water to carbon dioxide (CO2) when sufficient ozone and time are provided. (Many complex organics oxidize to smaller complex compounds before oxidation to CO2.) Since microbials, bacteria, pathogens, and endotoxins all contain carbon, ozone is an excellent biocide that destroys these organisms by oxidation.

There are three ways to produce ozone:

Electrolysis produces small amounts of ozone in situ from the water system. This method cannot adjust readily to dynamic conditions when loading requirements can change quickly.

UV production is a viable ozone-generating method but has limitations of cost, efficiency, and concentration; it is also energy inefficient when compared to other methods.

Corona discharge is the most efficient commercialized method for ozone production. It uses a reaction chamber with a dielectric barrier in which high voltage is applied to an oxygen feed gas to generate ozone. Modern corona discharge units are adjustable to throttle ozone production up or down under dynamic conditions when load and demands change. Most advanced corona discharge ozone generators use enriched oxygen from oxygen concentrators (usually +90% by weight) as the feed gas due to more efficient ozone production and lower overall operating costs.

Ozone EfficiencyTable A

Ozone has a short half-life (the time required for the ozone concentration to dissipate to 50%). In 25°C water, 50% of the ozone decays in approximately 15 minutes (Table A). Different temperatures and water chemistries influence this rate. Ozone reverts to oxygen more rapidly at higher temperatures, for example.

Ozone’s short half-life allows disinfection regimes to be calculated easily, according to the concentration required to achieve the desired effect: maintaining pristine systems devoid of microbials and organics. The sidebar below shows a simplified example of these calculations and how to assess the ozone needed for a given concentration.

By: Nissan Cohen and Brian L. Johnson

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About the Authors
Nissan Cohen is a worldwide expert in total organic carbon, high purity, ultrapure, reclaim-and-recycle water systems, with profound expertise in instrumentation, automation, and organic contamination oxidation systems using ozone, UV, ion exchange, and catalysts. He has written over 35 published technical articles, and is a recipient of the Pharmaceutical Engineering Article of the Year award. An ISPE member since 1995, Cohen is a contributing author and chapter leader of ISPE Baseline® Guide Water and Steam Systems and Good Practice Guide (GPG) Ozone Sanitization of Pharmaceutical Water Systems, Co-Chair and coordinating author of the GPG Approaches to Commissioning and Qualification of Pharmaceutical Water and Steam Systems, a member of the Pharmaceutical Engineering® Committee, Chair of ISPE’s Water and Steam Forum, and Founder and Chair of ISPE’s Discussion Forums. He earned a BS in agriculture and genetics at the University of Wisconsin and Ruppin Institute, and an MS in agricultural water systems from Hebrew University.

Brian Johnson is the Director and CEO of Pacific Ozone, which he and his wife Karen Johnson acquired in 1997. Between 2005 and 2014 he served the International Ozone Association on the Board of Directors and the executive committee for the association’s Pan American Group. Johnson has also contributed to numerous articles and publications on commercial ozone applications. From 1994 to 1997 he served as a director of A Sport, Inc., a holding company that acquired Snowboards, Inc., as well as additional major sports product brands including Straightline. From 1986 to 1994, he was chief executive officer and shareholder of Snowboards, Inc., a sports products manufacturer that owned Avalanche Snowboards and Universal Bindings. Johnson has remained an active investor in various enterprises including power sports, technology and real estate development.

1. Cohen, Nissan. “Comparison of Ozone and Hot Water Sanitization in Pharmaceutical Water Systems.” ISPE Water Conference, June 2010, Arlington, Virginia, US.
2. ———. “The Efficacy of Ozone and Chemical Sanitization for Microbial Control.” Ultrapure Water Pharmaceutical Conference. June 2013, Lombard, Illinois, US.