`
`This article
`reviews the
`physical
`chemistry of the
`safe production
`of hydrogen
`peroxide vapor
`and how to
`maintain a
`constant
`concentration of
`the vapor in a
`chamber. This
`article also
`reviews the
`calculations and
`procedures used
`to obtain the
`maximum
`concentration of
`vapor without
`allowing
`condensation of
`liquid to occur.
`
`Figure 1. Hydrogen
`peroxide vaporization
`processes .
`
`The Physical Chemistry of
`Decontamination with Gaseous
`Hydrogen Peroxide
`
`by Carl Hultman , Aaron Hill, and Gerald McDonnell
`
`Introduction
`
`The decontamination of surfaces con(cid:173)
`
`taminated with microorganisms within
`critical, enclosed areas is an important
`consideration to pharmaceutical, re(cid:173)
`search, and other facilities. A safe and reliable
`way to decontaminate hard surfaces (including
`those in isolators, laminar flow cabinets, and
`cleanrooms) involves exposing the surfaces to
`3 Gas phase
`gas-phase hydrogen peroxide. 1
`•
`hydrogen peroxide is a known rapid, broad(cid:173)
`spectrum antimicrobial which, as part of a
`controlled process, can allow for reproducible
`area decontamination. Hydrogen peroxide also
`has a rather safe profile, both from a user and
`environmental perspective, in comparison to
`traditional fumigation methods that have used
`
`2
`•
`
`formaldehyde, ethylene oxide, or propylene
`oxide gas. An understanding of the physical
`chemistry behind the generation and control of
`gaseous hydrogen peroxide is important to op(cid:173)
`timize the safety, efficacy, and reproducibility
`of a given decontamination process. This ar(cid:173)
`ticle discusses the physical chemistry behind a
`typical process and the procedures needed to
`achieve optimal decontamination using gas(cid:173)
`eous hydrogen peroxide.
`
`Liquid and Gaseous
`Hydrogen Peroxide
`Hydrogen peroxide (H 2O2) is widely used as an
`antiseptic, disinfectant, and sterilant. 4 It is a
`desirable biocide because it demonstrates broad
`spectrum antimicrobial activity, has low toxic-
`
`W eight P ercent of H ydrogen Peroxide
`
`GAS
`
`~
`~
`::::, ro w a..
`
`E
`~
`
`25
`
`GAS + LIQUID
`
`I
`
`Line B
`
`LIQUID
`
`??
`
`PUIIDft~llrJ' IITll'III i:n11:lft11:: i:Dlftlt:
`
`ldAIIIMlY/J:J:AAII AAY ? nn 7
`
`2
`
`35
`
`77.8
`
`100
`
`Continued on page 24.
`
`Novartis Exhibit 2028.001
`Regeneron v. Novartis, IPR2021-00816
`
`
`
`Decontamination Methods
`
`Hydrogen Peroxide Weight
`
`(%w/vl
`
`t = 25 C
`
`Vapor
`1.87
`8.0
`24.1
`35
`56.4
`
`Liquid
`32.1
`55.7
`73.9
`77.8
`88.3
`
`Table A. Equilibrium concentrations of hydrogen peroxide vapor
`that wi ll fo rm (evaporate) over liquid hydrogen peroxide (see
`Figure 1, Evaporation) .
`
`ity, and breaks down into water and oxygen in the environ(cid:173)
`ment. For example, liquid hydrogen peroxide solution is used
`directly on the skin at up to 6% w/v and at higher concentra(cid:173)
`tions as a general surface disinfectant. Pure hydrogen perox(cid:173)
`ide exists as a liquid at room temperature (25°C) and atmo(cid:173)
`spheric pressure (101.35kPa). For antimicrobial applica(cid:173)
`tions, greater efficacy is observed as the concentration is
`increased, which is particularly important to achieve spori(cid:173)
`cidal activity; however, at high concentrations, liquid hydro(cid:173)
`gen peroxide is unstable/reactive and may be explosive or
`undergo spontaneous combustion depending on how it is
`6 Therefore, liquid preparations are used at lower
`handled.5
`•
`concentrations diluted in water (generally 3 to 59% by weight)
`and often in synergistic formulations with other biocides
`(including peracetic acid). The antimicrobial activity of hy(cid:173)
`drogen peroxide is dramatically increased when in a gaseous
`phase. For example, the efficacy ofhydrogen peroxide against
`bacterial spores has been shown to be similar at a gaseous
`concentration oflmg/L in comparison to ~400mg/L in liquid.5
`To generate the gas, it is necessary to heat liquid hydrogen
`peroxide, generally by flash vaporization on a hot surface that
`will be discussed in more detail. Under these gaseous condi(cid:173)
`tions, even lower concentrations (~0.lmg/L) of peroxide are
`rapidly antimicrobial and may be used to achieve sporicidal
`activity.
`A further consideration in the comparison of liquid and
`gaseous peroxide is material compatibility; attention should
`be focused on two factors when considering surface contact:
`
`1. the effect of the material on the decomposition rate of the
`peroxide (therefore loss of activity)
`2. the effect of hydrogen peroxide on the material itself.
`
`With liquid hydrogen peroxide (of about 45% by weight or
`more), the possibility of forming detonatable mixtures on
`reaction with organic substances may exist. Commonly used
`materials have been categorized into four different classes
`according to the suitability of exposing these materials to
`liquid concentrations equal to or higher than 90% by weight
`of peroxide in water.7 Of note, Class 4 materials may cause
`decomposition of hydrogen peroxide, and particularly with
`concentrated liquid peroxide, cause damage to the surface or
`form explosive mixtures. Some of these Class 4 materials
`include wood products and polymers such as neoprene, buna
`rubber, silicone rubber, and tygon. These materials may
`undergo degradation and/or cause spontaneous combustion.
`Other Class 4 metals, including copper, lead, magnesium
`
`?4
`
`PHARMACEUTICAL ENGINEERING
`
`JANUARY/FEBRUARY 2007
`
`alloys, and stellite #6, act as catalysts that accelerate the
`decomposition of peroxide and also may encourage combus(cid:173)
`tion when in contact with other materials. Lubricants such as
`silicones, paraffin, and aroclors also are Class 4 materials.
`Highly concentrated solutions of peroxide also may degrade
`certain electrical components or other materials; an example
`is that liquid hydrogen peroxide can attack the plasticizers in
`PolyVinyl Chloride (PVC), thus making the surface brittle
`after extended exposure. Additionally, certain grades of stain(cid:173)
`less steel, such as 304 grade, can show slight corrosion or
`discoloration for liquid peroxide solutions ranging from 10 to
`100% by weight.
`
`Hydrogen Peroxide
`Evaporation and Condensation
`Hydrogen peroxide vapor can be conveniently produced from
`hydrogen peroxide/water solutions by two distinct processes,
`evaporation and flash vaporization - Figure 1. It is important
`to note that both processes will produce different concentra(cid:173)
`tions of hydrogen peroxide vapor in a given volume. When
`liquid hydrogen peroxide is allowed to evaporate into a dry,
`enclosed space, the concentration of hydrogen peroxide in the
`vapor state is much lower than the concentration in liquid
`state - Figure 2. This occurs because the water leaves the
`mixture at a higher rate than the peroxide due to the higher
`vapor pressure of water. For instance, if a 35% (by mass)
`hydrogen peroxide/65% water mixture evaporates into a dry
`enclosed space at 25°C, the resulting gas will consist of 2.15%
`(by mass) hydrogen peroxide and 97.85% water at saturation.
`Saturation refers to the point at which the air can not hold
`further peroxide/water and at which point condensation (or
`precipitation) or water/peroxide will occur. The concentra(cid:173)
`tion at which this occurs (referred to as the 'dew' point) can be
`predicted based on the peroxide/water concentrations, and
`the temperature of the gas -Figure 2. A detailed discussion of
`this phenomenon is discussed in the literature. 5
`The evaporation rate can be increased by applying an
`energy source, for example heat can be applied to boil the
`peroxide/water solution. Since water has a lower boiling
`point than hydrogen peroxide, the water will vaporize at a
`higher rate, giving a higher concentration of water in the
`gaseous state and an increased concentration of hydrogen
`peroxide in liquid state. With time, the higher peroxide liquid
`concentration may become unsuitable for materials in con(cid:173)
`tact with the liquid and can pose a safety risk.
`The equilibrium concentration of peroxide in the vapor
`over a liquid is always lower than the concentration in the
`liquid. Table 1 shows the concentration of peroxide in the
`vapor over liquid solutions at different peroxide concentra(cid:173)
`tions at 25°C. The equilibrium concentration of peroxide in
`th e vapor is always lower because the water escapes the
`liquid at a higher rate than the peroxide. The reverse is true
`when peroxide/water vapor condenses to the liquid state. As
`shown in Table A, the equilibrium concentration of the liquid
`formed when a vapor of35% by weight peroxide conden e i
`about 77 .8% by weight peroxide. This is because the peroxide
`in the vapor has a greater desire to enter the liquid state than
`
`Continued on page 26.
`
`Novartis Exhibit 2028.002
`Regeneron v. Novartis, IPR2021-00816
`
`
`
`Decontamination Methods
`
`Weight Percent of Hydrogen Peroxide
`
`GAS
`
`LIQUID
`
`2
`
`35
`
`77.8
`
`100
`
`Figure 2 . A representation of the Hyd rogen Peroxide/Wat er Ph ase
`Diag ram. The upper solid li ne indicates the point at w hich the gas
`mixture is fo rmed (note higher concentrations at higher
`temperatures) and the lower solid line when liquid is present . Line
`A shows the conversion of 35 % liquid peroxide /water mixture (at
`25°C) to vapor at -2% peroxide. Line B shows the condensation
`of 35 % gaseous peroxide/ wat er mixtu re to liquid at -78%.
`
`the water in the vapor. Therefore, the peroxide condenses at
`a higher rate than the water, causing the higher concentra(cid:173)
`tion of peroxide in the resulting liquid.
`Flash vaporization is a distinct process which can be
`achieved by applying energy, e.g., by direct application of a
`peroxide/water mixture to a hot surface - Figure 1. Flash
`vaporization forces the water and hydrogen peroxide in the
`liquid solution to evaporate simultaneously, thereby produc(cid:173)
`ing gaseous concentrations of water and peroxide at approxi(cid:173)
`mately the same concentration as the starting liquid mix(cid:173)
`ture. The gas concentration will stay constant as long as
`condensation does not occur. Table B shows the concentra(cid:173)
`tions of hydrogen peroxide that will saturate the vapor and
`cause condensation. If the gas concentration is increased
`above saturation or if cooled to below the dew point, conden(cid:173)
`sation will occur. For example, when condensation occurs
`with a gas at -35% by weight peroxide it will condense as a
`liquid at -77.8% by weight peroxide - Figure 2.
`
`Physical Chemistry
`The vapor pressures of gases over multi-component liquid
`solutions may be calculated using the following equations: 5•8•9
`
`y w{liquid)= exp[{(1-Xw)2/RT}(Bo + B1 (1- 4X,J
`+ B/ 1 - 22C) (1 - 6Xw)J
`
`( 1 )
`
`(2)
`
`(3)
`
`Yp(liqui,o= exp[{X_//RT}(B0 + B1(3 - 4Xw)
`+ Bi l - 2Xw) (5 - 6X,.)]
`
`(4)
`
`where:
`- Pp(ga,, is the vapor pressure of the peroxide in the vapor in
`atmospheres
`- Pw!ga,1is the vapor pressure of water in the vapor in atmo(cid:173)
`spheres
`XP and Xw are the mole fractions of peroxide and water
`respectively in the liquid
`YP and Yw are the activity coefficients for peroxide and
`water respectively in liquid solution
`
`P 0
`P and Pa,, are the equilibrium vapor pressures in atmo(cid:173)
`spheres of pure peroxide and water respectively at the tem(cid:173)
`perature of interest. B0, B1, and B2 are empirically deter(cid:173)
`mined constants for hydrogen peroxide with the values shown
`below.
`
`B0 = -752 + 0.97t
`B1 = 85
`B2= 13
`
`tin degrees centigrade
`
`Vapor pressure data may be converted into gas phase concen(cid:173)
`tration units ofmg gas per liter using the ideal gas equation
`as shown below.
`
`mg/liter= P(Mol Wt)(l000 mg/g)/RT
`
`(5)
`
`The concentration in mg/liter calculated from equation five is
`the concentration at a given temperature that will cause
`condensation, where, P is pressure in atmospheres, Mol Wt
`is the molecular weight of the gas of interest in grams/mole,
`R is the ideal gas constant 0.082 latm/deg mole, and T is
`temperature (°K ).
`
`Achieving Optimal Concentration of
`Peroxide in Vapor Form
`As more vapor at a composition of 35% by weight peroxide is
`introduced into an enclosed chamber, the pressure and con(cid:173)
`centrations of the peroxide/water vapor in the chamber will
`increase. Eventually, a high enough concentration (expressed
`in mg/liter) will be reached at the operating temperature to
`cause the undesirable condensation ofliquid in the chamber.
`The maximum allowable concentration of peroxide in the
`vapor that will not cause condensation may be calculated
`using Equations one through five. One of the complications
`associated with condensation is that undesirable high con(cid:173)
`centrations of peroxide liquid solutions will be formed on
`surfaces. Also, as liquid condenses, it may not uniformly
`cover all solid surfaces which may lead to non-uniform disin(cid:173)
`fection/sterilization of surfaces. Other complications associ(cid:173)
`ated with condensation will be elaborated on in a later
`section. The gaseous state for hydrogen peroxide when used
`for decontamination is advantageous because:
`
`? "
`
`PUADl\i1ArtllTll"AI Cftlr.11u cco11ur.
`
`11\ 1\IIIA O V ICC ODI I I\ D V -, nn,
`
`Continued on page 28.
`
`Novartis Exhibit 2028.003
`Regeneron v. Novartis, IPR2021-00816
`
`
`
`Decontamination Methods
`
`Figure 3 . Dropwise condensation on contaminated metal surface.
`
`1. Gas will have uniform contact with all exposed surfaces,
`thus assuring that all surfaces are uniformly decontami(cid:173)
`nated.
`
`2. Gas will have uniform contact with surfaces with complex
`topographies. Examples include horizontal or vertical
`surfaces, cracks, and complex curvatures.
`
`3. Gas may be safely maintained in the chamber.
`
`4. Gas may be efficiently and quickly removed from the
`chamber at the end of a given decontamination time thus
`decreasing cycle time.
`
`As the antimicrobial efficacy increases with increased perox(cid:173)
`ide concentration, it is desirable to get the peroxide concen(cid:173)
`tration in the gas as high as possible in the chamber without
`having condensation occur. It is possible to calculate the
`maximum pressure (and/or concentration) of peroxide (or mg/
`L of peroxide in the chamber) that will initiate condensation
`using Equations one through five by knowing:
`
`1. the concentration of the flash vaporized gas being used to
`fill the chamber
`
`2. the total pressure in the chamber
`
`3. the humidity in the carrier gas (e.g. , air used to circulate
`gas into and out of the chamber showing the design of the
`decontamination system - Figure 4) and the decontamina(cid:173)
`tion chamber
`
`4. the chamber temperature5•8•9
`
`?R
`
`PUARMAr.rnr,r.41 FNr.lNFFRINr.
`
`.IANIIARY/FFRRIIARY 7007
`
`As these equations can often be time consuming to do by
`hand, computer programs have been developed to calculate
`the optimum decontamination conditions for any given en(cid:173)
`closed volume. 10 Table B shows examples of the maximum
`peroxide concentration allowed in the chamber to prevent
`condensation ofliquid at various temperatures at two differ(cid:173)
`ent humidity levels for the carrier gas. Calculations assumed
`flash vaporization of 35% by weight peroxide. Note that
`increasing the relative humidity in the carrier gas decreases
`the maximum concentration of peroxide that may be achieved
`in the decontamination chamber.
`
`Why Condensation Should be Avoided
`As described above, high concentration of peroxide in the
`liquid state (as occurs with condensation) can be antimicro(cid:173)
`bial, but also poses some further disadvantages. The first is
`material compatibility. As shown in Figure 1 and Table A, the
`concentration of a liquid formed when 35% by weight gas
`condenses will be about 78% by weight peroxide. This is
`higher than the recommended maximum concentration of
`45% by weight peroxide to assure suitable interactions with
`other materials. As discussed above, this peroxide concentra(cid:173)
`tion or higher may not only cause spontaneous combustion
`and also may accelerate decomposition of peroxide or cause
`degradation of materials. Incompatible materials can in(cid:173)
`clude painted surfaces and electronics. Peroxide condensa(cid:173)
`tion also can decrease the useful life of chamber materials in
`particular, those used in flexible-walled isolators. Once the
`condensate is formed it will eventually have to be evaporated
`from the chamber as peroxide is removed at the end of a
`decontamination phase. The slow evaporation will cause the
`peroxide concentration in the liquid to reach even higher
`unsuitable concentrations regarding safety and degradation
`of materials.
`Decontamination reproducibility is a further concern. When
`condensation occurs, the surfaces in the chamber may not get
`uniformly exposed, depending on how condensation occurs.
`Condensation can occur either in a drop wise or film form ,
`depending on the nature of the contact surface. The determin(cid:173)
`ing property is the surface tension of the solid surface. In
`general, film condensation occurs if the surface tension of the
`solid is at least 10 dynes/cm higher than the surface tension
`of the liquid condensing. The surface tension ofliquid perox(cid:173)
`ide/water solutions range from 73 dynes/cm (pure water) to
`
`Temperature('C) Maximum Hydrogen Peroxide Concentration
`(mg/L)
`(no condensation)
`
`0% Relative Humidity
`Carrier Gas
`
`10% Relative Humidity
`Carrier Gas
`
`0
`10
`20
`30
`40
`50
`60
`
`0.35
`0.77
`1.56
`3.01
`5.49
`9.60
`16.13
`
`0.28
`0.63
`1.28
`2.50
`4.60
`8.11
`13.68
`
`Table B. Maximum peroxide vapor concentration at various
`temperatures.
`
`Continued on page 30.
`
`Novartis Exhibit 2028.004
`Regeneron v. Novartis, IPR2021-00816
`
`
`
`Decontamination Methods
`
`about 80 dynes/cm (pure peroxide). The surface tension for
`78% by weight peroxide liquid is about 78 dynes/cm. There(cid:173)
`fore, drop-wise condensation will occur on solid surfaces with
`surface tensions less than about 88 dynes/cm when gas at
`35% by weight peroxide vapor is condensing. Recall that 35%
`by we-igh peroxide vapor condenses as 78% peroxide in the
`liquid. Polymer materials surface tensions typically range
`from 20 to 45 dynes/cm or lower. Therefore, drop wise conden(cid:173)
`sation should occur on most polymer materials. Clean metal
`and glass surfaces typically have surface tensions that are
`higher than 200 dynes/cm. Contamination on a metal or glass
`surface may dramatically drop the surface tension allowing
`for drop wise condensation. Figure 3 shows how a contami(cid:173)
`nant on a metal surface causes drop wise condensation. This
`will not allow the entire surface to be exposed to liquid
`resulting in a non-uniform surface exposure to peroxide.
`Even if film wise condensation occurs, there is a possibility of
`non-uniform liquid exposure on the surface due to developing
`liquid flow patterns on vertically sloped surfaces.
`A further complication associated with condensation of
`liquid is the additional time required to remove peroxide from
`the chamber at the end of an exposure phase. Gas can quickly
`be removed from the chamber by purging with an inert gas
`(such as air). Additional time is necessary to remove peroxide
`in the liquid form due to the time required to evaporate the
`liquid from all surfaces. If a material is permeable to liquid
`water or peroxide, additional time will be needed to remove
`any liquid that absorbed into the solid surface. Examples
`include porous materials and certain polymers, which are
`permeable to liquid water and/or peroxide.
`Finally, condensed peroxide at high concentration may
`have un-suitable (even violent) reactions with certain mate(cid:173)
`rials in the decontamination chamber. Special safety precau(cid:173)
`tions should be in place to handle any standing liquid hydro(cid:173)
`gen peroxide condensate that can be violently reactive and
`will cause severe burns.
`
`Decomposition of Hydrogen Peroxide
`Hydrogen peroxide, especially in gaseous form or impure
`liquid solutions, is not a very stable compound. In particular,
`it spontaneously decomposes to form oxygen and water as
`shown below:
`
`decomposed to water and oxygen in a destroyer and the water
`removed in a dryer. Drying the carrier gas stream is impor(cid:173)
`tant as the water content in the carrier gas will affect the
`point at which condensation will occur as shown in Table B.
`For example, at 25°C, the maximum allowed concentration of
`peroxide vapor drops from 2.184 mg/liter to 1.805 mg/liter as
`the moisture content in the carrier gas goes from 0% RH up
`to 10% RH. This is a 17.4% drop in the maximum allowed
`peroxide concentration that may be introduced into the de(cid:173)
`contamination chamber.
`
`Measuring and Controlling
`Peroxide Gas Concentration
`As shown above, Equations one through five may be used to
`calculate the maximum level of hydrogen peroxide that may
`be achieved in a chamber without causing condensation.
`Once the maximum peroxide vapor concentration is known,
`it is possible to develop an operating cycle that gives the
`maximum concentration of peroxide while preventing con(cid:173)
`densation. The controlled variables for the cycle will include
`air flow rate, rate of injecting liquid peroxide into the flash
`vaporizer, concentration of the liquid to be flash vaporized,
`and the chamber temperature, volume, and humidity level.
`The peroxide and water concentrations during a cycle can be
`monitored using either infrared spectroscopy or electrochemi(cid:173)
`cal methods. 10-11 It is desirable to run the peroxide concentra(cid:173)
`tion as high as possible, but at the same time reducing the
`risk of producing condensation (typically targeting less than
`90% of the saturation level). It should be noted that these
`detector systems can only be used to monitor gas concentra(cid:173)
`tions, where condensation of liquid will cause the sensor to
`fail. Overall, higher levels of peroxide vapor concentration
`will result in higher kill rates and therefore shorter cycle
`times, but it is recommended that this should be balanced by
`ensuring that condensation does not occur. Once the cycle is
`developed for a given volume and temperature, it may not be
`
`Therefore, the concentration of peroxide gas in the steriliza(cid:173)
`tion chamber will steadily decrease over time, depending on
`the chamber area, material of construction, contents, etc. A
`simple procedure to maintain a constant peroxide concentra(cid:173)
`tion involves continually circulating the gas in the steriliza(cid:173)
`tion chamber through a system that regenerates fresh perox(cid:173)
`ide vapor as shown in Figure 4. This design is successfully
`used in gaseous hydrogen peroxide decontamination sys(cid:173)
`tems. Fresh peroxide gas produced from a flash vaporizer is
`introduced into the chamber as gas in the chamber is re(cid:173)
`moved, thereby maintaining a consistent peroxide vapor
`concentration. Further, the removed peroxide gas can be
`
`30
`
`PHARMACEUTICAL ENGINEERING JANUARY/FEBRUARY 2007
`
`iT'u
`
`Decontamination
`Area
`
`Liquid
`Hydrogen
`Peroxide
`
`Figure 4. Typical Vaporized Hydrogen Peroxide (VHP)
`gecontamin@tion ~y~tem, Vapor io produGfJd by flcrnh vaporization
`of liquid hydrogen peroxide and blown into a volume to be
`decontaminated. The vapor concentration is held constant by a
`constant flow of gas through a destroyer (e.g. , x) , air blower .
`
`Concludes on page 32.
`
`Novartis Exhibit 2028.005
`Regeneron v. Novartis, IPR2021-00816
`
`
`
`Decontamination Methods
`
`necessary to monitor peroxide and water concentration as long
`as the carrier gas flow and liquid peroxide injection rate are
`held constant.
`In conclusion, hydrogen peroxide in the vapor phase offers
`an effective, controllable, fast, and safe means of decontami(cid:173)
`nating surfaces within a closed chamber of any size. Correct
`control of decontamination cycles is important to ensure that
`optimal and safe cycles are used for validated, repeatable
`applications.
`
`References
`1. Akers, J.E., Agalloco J.P., Kennedy C.M ., "Experience in
`the Design and Use of Isolator Systems for Sterility
`Testing," PDA J Phann Sci Technol ., 1995, 49(3):140-4.
`
`2. Klapes, N.A, and D. Vesley, ''Vapor-Phase Hydrogen
`Peroxide as a Surface Decontaminant and Sterilant,"
`Appl. Environ. Microbial ., 1990, 56: 503-506.
`
`3. Krause, J. , G. McDonnell , and H. Riedesel ,
`"Biodecontamination of Animal Rooms and Heat-Sensi(cid:173)
`tive Equipment with Vaporized Hydrogen Peroxide ,"
`Contemp. Topics Lab Anim Sci., 2001, 40: 18-21.
`
`4. McDonnell, G., and Russell, AD. , "Antiseptics and Disin(cid:173)
`fectants: Activity, Action, and Resistance," Clin. Microbial.
`Rev. , 1999, 12: 147-179.
`
`5. Schumb, W.C., Hydrogen Peroxide, monograph series,
`American Chemical Society, Reinhold Pub. Corp. , 1955
`6. Block, S.S. , 1991. Peroxygen Compounds. p. 167-181. In
`S.S. Block (ed. ). Disinfection, Sterilization, and Preserva(cid:173)
`tion. 4th ed. Lea and Febiger, Philadelphia, PA
`
`7. Davis, Jr., N.S. andJ. Keefe, Jr.,J. Am. Rocket Society, p.
`63, March-April 1952 Buffalo.
`
`8. Scatchard, G. , G. Kavanagh, and L. Ticknor, J. , Am.
`Chem. Soc. , 74, 3715, 1952.
`
`9. Pitzer, K. and L. Brewer, Thermodynamics, McGraw Hill,
`1961, Chapter 16 - 20.
`
`10. Day, R. and A Underwood, Quantitative Analysis, McGraw
`Hill, 1961, chapter 14.
`
`11. Adams, D., G. Brown, C. Fritz, and T. Todd, "Calibration
`of a Near-Infrared (NIR) H 20 2 Vapor Monitor," Pharma(cid:173)
`ceutical Engineering, Vol. 18, No. 4, 1998, p. 66-82.
`
`12. Electrochemical Co. , "Engineering Materials for Use with
`90% Hydrogen Peroxide," Part 1, 1 December 1950.
`
`About the Authors
`Dr. Carl Hultman received his BS in chem(cid:173)
`istry from the University of Wisconsin and
`his PhD in physical chemistry from the Penn(cid:173)
`sylvania State University. He is currently a
`professor of chemistry at Gannon University
`in Erie, Pennsylvania . Dr. Hultman has pub(cid:173)
`lished papers and received a patent for work
`in surface chemistry. His research interests
`include sublimation of solids, molten salt electrochemistry,
`and synthesis of nano-particle metal oxides. He is a member
`of the American Chemical Society. He can be contacted by
`phone at 1+814-825-5144 or by e-mail at: hultman@
`gannon.edu.
`Gannon University, Department of Chemistry, University
`Square, Erie , Pennsylvania 16541.
`
`Aaron Hill received his BS and MS degrees
`in mechanical engineering from the Gannon
`University in Erie, Pennsylvania. He is cur(cid:173)
`rently an engineering manager at Steris Cor(cid:173)
`poration at their Erie, Pennsylvania facility.
`Hill has received four patents pertaining to
`vaporized hydrogen peroxide equipment. He
`was the project leader for several new vapor(cid:173)
`ized hydrogen peroxide decontamination systems developed
`at Steris Corporation. He is a member of the American
`Society of Mechanical Engineers. He can be contacted by
`phone at: +1-814-870-8109 x8113 or by e-mail at:
`aaron_hill@steris.com.
`Steris Corporation, 2424 W. 23rd St., Erie, Pennsylvania
`16506.
`
`Dr. Gerald McDonnell has a BSc (Hons. ) in
`medical laboratory sciences from the Univer(cid:173)
`sity of Ulster and a PhD in microbial genetics
`from Trinity College Dublin. He is currently
`a Senior Director, Technical Affairs for Steris
`Corporation, based at their European head(cid:173)
`quarters in Basingstoke, UK. Dr. McDonnell
`is widely published in the decontamination
`and sterilization area. His research interests include infec(cid:173)
`tion prevention, decontamination microbiology, emerging
`pathogens, and the mode of action/resistance to biocides. Dr.
`McDonnell is the current editor of the Central Sterilisation
`Club (UK), and a member of the American Society of Micro(cid:173)
`biology , Society for Applied Microbiology , Council of
`Healthcare Advisors, European Biological Safety Associa(cid:173)
`tion, and AAMI. He can be contacted by phone at: +44-1256-
`866560 or by e-mail at: gerry_mcdonnell@steris.com.
`STERIS Limited, STERIS House Jays Close, Viables,
`Basingstoke , Hampshire RG22 4AX, UK. ij
`
`Novartis Exhibit 2028.006
`Regeneron v. Novartis, IPR2021-00816
`
`