10/31/2017 Selection Criteria for WFI Production Equipment

Selection Criteria for WFI Production

Equipment
Thu, 09/01/2005 - 12:00am by Marita A. King

THERE ARE SEVERAL METHODS for producing water-for-injection (WFI). Multiple-

effect distillation (Figure 1) and vapor compression (Figure 2) are the two primary
methods recognized by the FDA. Each are established methods, offering different
advantages depending on the proposed application. This article provides an overview
of the key features of each technology and important issues for consideration.

Key design features drive the selection of multiple-effect versus vapor compression
technologies. Multiple-effect stills are noted for their multiple column design which re-
uses steam energy through the process. They have minimal moving parts, but require
cooling water for final distillation of product. Vapor compression units are driven by a
more mechanical process involving a compressor and other moving parts to compress
steam, thus reducing evaporation temperature (Boyles Law). This greater energy
efficient design also requires minimal feedwater treatment. Both systems are powered
by either steam or electric heating for operational flexibility in all capacity ranges.

In making a determination between the two technologies, the previous conventional

wisdom was to base a decision on WFI capacity requirements. A break-even point of
~600 gallons/hour (gph) balanced the higher capital cost of vapor compression

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against the lower utility consumption costs, (such as cooling water), for multiple-
effect stills. Therefore, the cost of producing WFI above 600 gph favored vapor
compression technology. Vapor compression is estimated to cost $10-12 per 1000
gallons of WFI, while multiple-effect is $18-25 for the same 1000 gallons. On the
other hand, the higher capital costs of vapor compression usually did not provide a
desirable return on investment for capacity requirements below 600 gph.
However,greater analysis of facility needs and costs compared with strengths and
advantages of each technology has resulted in cross-over of this break-even point in
both directions. Making an informed selection requires a better understanding ofthe
main design features of each.

Figure 1. Multiple-effect Water Still

Figure 1. Multiple-effect Water Still

(Photo courtesy of COR srl and COR-USA)

Multiple-Effect Design

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Multiple-effect still design is easily recognized by its multiple columns (i.e. effects)
which re-use heat energy through the additional effects. The first column is heated by
an external source such as plant steam (electric heating is available from some
suppliers in smaller models) with remaining columns heated by the pure steam
produced from the initial evaporation process. This pure steam is utilized as both a
heating source for additional columns as well as a preheating source for incoming
feedwater. In turn, the feedwater helps condense the pure steam so that the
remaining pure steam produced during the process requires minimal cooling water in
the final condenser. Key equipment features include the following:

Column Design
There are two main types of internal column design which drive the method of
evaporation: falling film and natural circulation. A column designed on the falling film
principle brings feedwater in from the top where it is flash evaporated as it falls over
the heated interior tubes. Natural circulation fills the column from the mid-point of a
column approximately one third;overflow is directed to the next column.

Another consideration is the type of separation, once the water is evaporated in the
column. Falling film relies on an initial 180 degree turn of the steam to remove
heavier droplets and impurities followed by centrifugal flow. Natural circulation relies
on centrifugal flow from the outset; pure steam is then directed through a secondary
separation system. The secondary separation is a select design by a particular
manufacturer and will take the steam through a series of turns to remove any final
impurities that may have been carried upward during the centrifugal separation. This
component is usually a baffle, although demister pads, a tight collection of stainless
steel wire mesh, may also be used. It should be noted that the use of demister pads is
not an accepted practice in the U.S., although the ISPE Baseline Guide for Water &
Steam Systems does not discourage it [1].

At this point, pure steam, meeting criteria for sterile WFI, is available to continue to
the next column to provide heating for incoming feedwater or for uses, such as
sterilization of process lines and tanks. The level of functionality will depend on the
manufacturer and should be evaluated if steam use will be desired from the still. The
outlet pressure may be limited to production pressure or be designed for additional

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capability such as controlled steam pressure, or even operation as a pure steam

generator.

Preheaters and Evaporators

Preheaters will make the multiple-effect still operate more efficiently with regards to
steam and water consumption, but are not always a standard feature. A preheater can
be installed prior to the first column for additional benefit,or prior to all columns for
maximum benefit.

Evaporators will be located internally or externally to the column. The evaporators

bear the brunt of varying pressures and temperatures. If there is any severe failure to
the still, it will most likely be with the evaporator. For this reason, the first evaporator
should have a double-tube sheet design; it should be decided in the specification
process if all evaporators should be of double tube-sheet design since this is not a
standard with all manufacturers. Another key consideration with evaporators is
location since this will impact accessibility. The falling film method of evaporation
places the evaporator inside the column, while with natural circulation, it is located
externally. The reason it should even be a consideration is the rare possibility of stress
corrosion which would dictate evaporator replacement. Likewise, evaporators internal
to the column are more susceptible to such stress, and are harder to replace than
external evaporators.

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Figure 2. Vapor Compression Still

Figure 2. Vapor Compression Still

(Photo Courtesy of COR srl and COR-USA)

Condenser
The design of the condenser will partially determine the amount of cooling water
required. Some are designed with smaller, more tightly compacted tubes providing a
greater surface area for cooling final steam and distillate. Other considerations are:
whether it is fully drainableboth shell and tube sides; whether the cooling water flow
is continuous or on/off, will also have an effect on overall use of utilities. Likewise, if

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distillate temperature needs to be lowered from 97C, an aftercooler may be required.

Finally, one should consider the degassing capabilities of the still. If removal of carbon
dioxide is not adequately addressed through the pretreatment system, non-
condensable gases could accumulate during production and a condenser may not be
able to vent these gases adequately. The more effective stills will add a degasser to
alleviate collection and release of gases with the final product.

Vapor Compression Design

Over the years, vapor compression stills have been a dominant method of WFI
production for large volume parenterals (LVPs) due to the cost efficiencies provided
with the higher capacity WFI production. However, recent improvements with vapor
compression technology as well as a rethinking of WFI usage, makes it a compelling
choice for select smaller-scale operations, allowing them to break under the 600 gph
barrier. The units operate at lower temperatures with larger tubing, allowing them to
bypass the more exacting pretreatment requirements of a multiple-effect still. Thus,
the vapor compression unit can possibly be the more cost-effective choice when
evaluated as a full system. Likewise, without a need for cooling water, utility
consumption is further enhanced. Several key features for equipment design follow.
Compressor

Compressors that operate both at high and low speeds are now available, with the
lower speeds creating better operating efficiency. Compressors have evolved from
high speed centrifugal designs (10,000 rpm) which are belt-driven to lower speed
(3,600-5,000 rpm) direct drive systems [2] which use less energy. A further
enhancement has been the multistage blower compressor which runs under 4000
rpm, significantly reducing both operating noise level (below 65-70 dB) and
maintenance. A standardized approach to mechanical seal design can also reduce the
maintenance time typically associated with their changeover as well as prevent or
minimize leakage over a longer operating period. The issue of non-condensable gas
removal is as standard addressed by vapor compression designs by preceding the
compressor with a deaerator.

Evaporation
As with multiple-effect designs, there are different approaches to evaporation.

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Evaporators are either mounted vertically or horizontally. A vertically-mounted

compressor will evaporate water on either a falling-film or thin-rising film principle for
drier steam. Spray film units direct water over the horizontal surface area of the
evaporation tubes for a more wetted surface. Typically, evaporator tubing has not
been electropolished as standard due to the lower susceptibility of scale, but is now
either a standard or at least a standard option as a preventative measure. Since the
separation of impurities from the steam is done by more of a mechanical process (vs.
multi-effects centrifugal action), a secondary separation system is in place.
Commonly, a demister pad is used, but a newer approach utilizes a baffle similar to
those found in multiple-effect stills producing a design which is consideredmore sterile
as it is fully drainable.

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Table 1. Design Comparison Overview

Table 1. Design Comparison Overview

Design Comparison
In summary, there are several factors that will influence the suitability of a particular
distillation method to a desired application. An overview of design features is provided
in Table 1 [3] and should be taken into account when considering the following issues:

Consider the required volumes of clean utilities needed in the facility. Will primary water use be
WFI or USP? If there is only a small need for USP, it may be more effective to couple a vapor
compression unit with minimal pretreatment and use the WFI for both applications. Is there a
small pure steam requirement? The capability of a multi-effect still to be tapped for pure steam

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could be more advantageous than the additional investment of a dedicated pure steam
generator.
What utilities are already available? If steam is not readily available, electric-driven models are
available with both technologies, but only smaller volumes (75 gph) typically for multi-effect
design. Desire to minimize use of cooling water could also drive selection favoring a vapor
compression still. A USP system already on site could feed a multiple-effect still, thus taking
advantage of the lower acquisition cost as compared to vapor compression.
What maintenance resources are available? The multiple-effect still requires little maintenance
due to the minimal moving parts, but as part of a good preventive maintenance schedule, may
undergo descaling on a yearly basis. The vapor compression still will possibly require a more
frequent preventive maintenance schedule due to the moving parts, but the newer compressor
advances may help minimize the time required.
Are there any space constraints? Generally, multiple-effect stills take up less floor space than a
vapor compression still. However, gravity feed to a WFI holding tank may require additional
headroom than is available. Of the two multi-effect technologies, falling film type systems tend
to be more compact, but taller; while the natural circulation method requires more floor space
due to the external evaporators. In some models, a raised condenser may alleviate full height
demands.

As a final note: a simplified equipment evaluation is based on capital costs. A more

comprehensive approach would include the pretreatment for a complete WFI system
evaluation with the above-mentioned considerations applied. From this perspective,
one could also add operating costs to get an accurate overall view from which to guide
the selection process. The process is further enhanced by considering the key features
of each technology to help gauge which system may be most compatible with site
operation philosophies and capabilities of staff, and then fine-tune the process by
comparing the desired features with what is available from a particular manufacturer.

References
1 ISPE Baseline Pharmaceutical Engineering Guide: Water and Steam Systems,
(January, 2001).

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2 S. Green. Vapor Compression Based Water for Injection Systems for the
Pharmaceutical and Biotech Industry, ISPE Boston Area Chapter program,
(September 14, 2004).

3 C. Opl. Society of BioProcess Engineers (SBP) Conference, Ireland, (June, 2005).

[Revisions by M. King.]

Marita King is a Principal with COR-USA USA, 67 Highland Avenue, Hull,

Massachusetts 02045. She focuses on sales and marketing of COR vapor compression
and multiple-effect stills and generators, pure water systems, and pure steam
generators. She isalso Principal of MARITeK, a manufacturers

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