WFI by Microwave Continuous Process

By William Greco page 1 of 5

July 2009
Warrington, Pa.
w2gre@verizon.net

Executive Summary

The most widely used raw material in the Pharmaceutical Industry is water.
Water used for the manufacture of cell culture medium and cleaning of equipment is
termed USP (United States Pharmacopedia) WFI (water for injection).
The grade of water most difficult and most expensive to produce is WFI.
WFI is commonly produced by distillation or reverse osmosis. Many WFI systems
utilize carbon filtration and deionization for pre-treatment before distillation.
The water must then be recycled in a hot, closed loop system and stored in tanks
at a high temperature to prevent microbial growth.
Microwave WFI systems are being developed to provide energy efficient means of
providing medical grade water that can be used in a continuous process.

Advantages of Microwave WFI Systems

The substantial aspect of a microwave WFI system is the ability to thermally
deactivate endotoxins in a continuous process, which eliminates expensive system
elements such as ultra-filtration membranes, stainless steel piping loops and storage
tanks, at the same time saving energy. On demand WFI by continuous process has the
advantage of being more pure than WFI stored over a period of time in tanks.
These characteristics have the following applications :
Laboratories

In standalone systems

In a range of large systems that meet various requirements

To select and protect by sterilization vulnerable connections to WFI water production

To save energy in the production of WFI

Lightweight and portable Microwave Powered Continuous Flow WFI equipment can be
rapidly deployed during emergencies (when the main system is off-line).
 WFI by Microwave Continuous Process

By William Greco page 2 of 5

July 2009
Warrington, Pa.
w2gre@verizon.net

Endotoxins
Endotoxins are prevalent in potable water and are the structural component in bacteria
which are released when bacteria cellular membranes break or are lysed. The term
gram-negative bacteria is associated with endotoxin cells that have a thinner structure
with distinct layers. There is an outer layer which is more like a cytoplasmic membrane
in composition with the typical trilaminar structure. The Gram-negative cell wall is
associated with endotoxic activity, with which are associated the pyrogenic effects of
Gram-negative infections. Endotoxins originating from the lipopolysaccharide cell walls
of gram-negative bacteria, with significant biological toxicity, must be removed.

WFI Production By A Microwave Device

The production of WFI is being achieved by the use of applying a microwave antenna
in conjunction with pressurization to directly couple the microwave source with turbulent
water. Microwave heating of water is known as volumetric heating due to direct
coupling of microwaves with the rotation and vibration transitions of water. High water
pressure is required to prevent the water from boiling. At present very small experimental
microwave devices have been able to produce a WFI flow rate of 13 milliliters per
minute utilizing a pressure of 0.69 MPa with 150 watts of microwave power and exit
temperatures between 155o C. and 158o C.

Note:
MPa = mega pascal 1 PSI = 0.0068947 MPa and 1 MPa = 145 PSI
0.69 MPa = 100 PSI
0.01585
1 mL_second = 0.01585 GPM  = 0.00343 gpm
conversion
60 
13
1 mL_Min = 0.000264 gpm  13 mL_Min 0.000264  = 0.00343 gpm

13 mL/Min = 0.00343 gpm 158oC = 316oF.

 WFI by Microwave Continuous Process

By William Greco page 3 of 5

July 2009
Warrington, Pa.
w2gre@verizon.net

Applying Scaling Laws

1
c  e 3
= 
c0  e0 
where:
e = power required to produce desired capacity c
e0 = power required to produce reference capacity c0
Solving for e0 :
c3 0.0253
e0 = to scale the process up to 0.025 gpm  150 watts  = 58 KW
c0 3 scaling up the process
0.003433

The development and extension of the method of moments technique for analyzing
electromagnetic scattering by arbitrary shaped three-dimensional homogeneous lossy
dielectric objects has allowed combined field integral equations to define the
requirements for coupling rotation and vibration of water molecules with microwaves.
The surfaces of the homogeneous three-dimensional arbitrary geometrical shapes are
modeled using surface triangular patches, similar to the case of arbitrary shaped
conducting objects. The development and extensions required to treat three dimensional
lossy dielectric objects can be calculated. Numerical results and their comparisons are
also possible. The 58 KW required to produce 1.5 gallons per hour of WFI may be
reduced by correlating the rotational and vibrational responses of the water molecule to
the microwave frequency and complex permittivity. Fine tuning elements to match
impedance between the microwave source frequency, transmission components,
and movement of the water molecules may in the future improve the absorbance of
electromagnetic energy.
Microwave frequencies of 915 MHz and 2.45 GHz are now being used in the
experimental process. Waveguides capable of providing up to 5.9 MW to microwave
antennas are available.
Coaxial adapters can be used to transition from a waveguide element to a shielded
coaxial cable with a higher dielectric constant. In waveguide systems, loads are
frequently used to absorb excess energy. The wavelength of radiation inside the
waveguide is determined by the properties of the material inside the waveguide and the
frequency of the radiation.
 WFI by Microwave Continuous Process

By William Greco page 4 of 5

July 2009
Warrington, Pa.
w2gre@verizon.net

A simplified diagram of a WFI Microwave Continuous production system is shown in

Figure-1 above.

Direct placement of microwaves into flowing water using an antenna has the advantage
of adaptable chamber design. One or more antennas can be employed in the design.
Decreased size of the entire apparatus can be achieved due to an increase in volumetric
efficiency.

Experimental Results Obtained

These units have been tested with 550 CFU/ml (CFU= Colony Forming Units) of
B. stearothermophilus and the outlet samples were sterile.
 WFI by Microwave Continuous Process

By William Greco page 5 of 5

July 2009
Warrington, Pa.
w2gre@verizon.net

Experimental Results Obtained (continued)

Next mixed cultures of 4.5 x 107 CFU/ml Ps. Aeruginosa plus E. coli and 3.2 x 105
CFU/ml B. stearothermophilus the B. stearothermophilus spore counts were
1.16 x 105. All outlet microbial counts indicated sterility, which shows the effectual use
of the microwave WFI systems used for destroying microorganisms. The influent, which
was boiled prior to the test for 5 minutes to release endotoxins from gram negative
bacteria, contained 2100 EU/mL. The outlet effluent contained less than 0.21 EU/mL,
which meets USP WFI requirements of a maximum of 0.25 EU/ml (EU = Endotoxin
Units).

Conclusion
The system described in this essay is being developed and is presently in experimental
operation.

William Greco
2404 Greensward N.
Warrington, Pa. 18976

Lossy Material = A material that dissipates energy of electromagnetic or acoustic energy

passing through. (The lossy dielectric material in this essay is simply flowing water.)

Permittivity = Permittivity of a material under given conditions is a measure of the

extent to which it concentrates electrostatic lines of flux. It is the ratio of the amount of
stored electrical energy when a potential is applied, relative to the permittivity of a
vacuum. The relative static permittivity is the same as the relative permittivity evaluated
for a frequency of zero.