[
Pharmaceutical Water System Fundamentals.
William V. Collentro, Coordinator
Ion Removal by
Reverse Osmosis
William V. Collentro
“Pharmaceutical Water System Fundamentals”
discusses technical justification, design considerations, operation, maintenance, compliance,
and validation for pharmaceutical water systems.
It is the intention of this column to be a useful
resource for daily work applications. The primary objective of this column is to provide a basic
summary of the function, selection, design consideration, proper operation, preventative maintenance, and regulatory expectations associated
with the individual unit operations employed in
pharmaceutical water systems.
Reader comments, questions, and suggestions
are needed to help us fulfill our objective for this
column. Please send your comments and suggestions to column coordinator William V. Collentro at
[email protected] or to journal coordinating editor
Susan Haigney at [email protected].
Editor’s Note: This paper continues subject matter previously discussed in “Pharmaceutical Water
System Fundamentals.” “Impurities in Raw Water”
was published in Volume 16, Number 1, of the Journal
of Validation Technology (JVT) (Winter 2010), and
“Pretreatment Unit Operations” was published in
JVT, Volume 16, Number 2 (Spring 2010).
KEY POINTS
The following key points are discussed in this article:
•The principle of reverse osmosis (RO) involves
the flow of water containing ions through a semipermeable membrane using pressure as a driving
force to significantly reduce the ion concentration
as well as other undesirable materials.
For more Author
information,
go to
gxpandjvt.com/bios
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•The system array, membrane configuration, and membrane composition and operation are described.
•Materials removed from the incoming water
stream are described.
•All RO membranes will exhibit microbial fouling,
organic and colloidal fouling, and scaling.
•RO membrane cleaning should be performed
periodically to remove bacteria, membrane foulants, membrane scalants, and bacterial endotoxins. Chemical sanitization destroys bacteria
and removes biofilm.
•Design considerations including instrumentation
for RO systems are discussed.
•Operating and maintenance considerations for
an RO system are discussed.
INTRODUCTION
Impurities in raw water and pretreatment unit operations have been discussed in previous papers in this
series. Ion removal is required for United States Pharmacopeia (USP) purified water systems to remove
dissolved and ionized impurities. Physical tests Section <645> of the United States Pharmacopeia-National
Formulary presents the conductivity criteria for both
USP purified water and water for injection (WFI).
In addition, feed water to multiple effect distillation
units and pure steam generators require ion removal.
It is suggested that the long-term successful operation
of a vapor compression distillation unit is enhanced by
ion removal. Finally, ion removal may be appropriate
for certain pharmaceutical processing applications
that do not technically require compendial water.
As an example, the initial rinse in multiple steps for
[
ABOUT THE AUTHOR
William V. Collentro is a senior consultant and founder of Water Consulting Specialists, Inc.,
Doylestown, PA (www.waterconsultingspecialists.com), and has more than 40 years experience in water
purification. He may be reached by e-mail at [email protected].
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iv thome.com
William V. Collentro, Coordinator.
Figure 1: Principals of reverse osmosis.
clean-in-place (CIP) applications using deionized
water may decrease the volume of compendial water
required for final rinse applications.
This paper discusses the use of reverse osmosis for
ion removal. General information, design considerations, and operation and maintenance considerations
are described. Additional ion removal unit operations
such as ion exchange employing cation and anion
resins and membrane processes using ion exchange
resin membranes and electronic field (continuous
electrodeionization) that are used for ion removal
in pharmaceutical water systems will be discussed
in the next issue of this series.
REVERSE OSMOSIS–
GENERAL DISCUSSION
The principle of reverse osmosis (RO) is associated
with the flow of water containing ions through a semipermeable membrane using pressure as a driving force.
This is illustrated in Figure 1. The left section of the
figure indicates water in two chambers, separated by
a semi-permeable membrane. Initially, water in the
left chamber does not contain ions, while water in
the right chamber contains ions. Note the level of
water in each chamber. The middle section of the
figure indicates the results of “osmosis.” The “ion free”
water flows through the semi-permeable membrane
resulting in a change in water level and an attempt to
equalize the concentration of ions in both chambers.
To “reverse” the “osmosis” process, the right section of
the figure indicates the result of pressure applied to the
right chamber. Water and a very small level of ions
flow back through the semi-permeable membrane,
under pressure, resulting in chamber levels and ionic
concentration similar to those in the left section of the
figure. The process depicted in the right section of the
figure represents the principle of reverse osmosis.
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RO System Array
A reverse osmosis system consists of three primary flow
streams. A pretreated feed water stream to the reverse
osmosis unit is pressurized by a high-pressure pump,
generally of multi-stage centrifugal-type. The pressurized feed water flows to reverse osmosis membranes
contained in pressure vessels configured in a custom
arranged “array.” As the pretreated water passes through
the reverse osmosis membranes array, a portion of water
passes radially through the membrane removing nearly
all ionic material. The wastewater (i.e., water that did
not pass through the “first” RO membrane) becomes
feed water for the next membrane in series. Water from
the final reverse osmosis membrane is the waste stream
from the reverse osmosis system. Product water from
each reverse osmosis membrane array is collected in a
common permeate water manifold.
Figure 2 demonstrates a reverse osmosis system
with two individual membranes per vessel and vessels
arranged in a 3:2:1 array. The diagonal line in the rectangular symbol used for a reverse osmosis membranes
indicates the membrane. Subsequently, water that flows
through the diagonal line indicates water passing from
the feed water-waste stream to the permeate collection
manifold. Water removed from the membrane that
has not passed through the membrane, as indicated,
becomes the feed water to the next membrane (or membranes in a pressure vessel) in the next array. While the
feed water-waste flow through the membranes in the
individual pressure vessels occurs in series, as noted in
Figure 2, pressure vessels with membranes are arranged
in parallel within an “array” determined by a computerized projection to maximize system operation.
Within the indicated 3:2:1 array, pressurized feed
water from the discharge of the RO feed water pump
flows to three vessels arranged in parallel. As water
passes through the first membrane in each array, a
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Pharmaceutical Water System Fundamentals.
Figure 2: 3:2:1 reverse osmosis array.
Waste
Pretreated
feed water
Product
portion of water (determined by the capacity of the
RO membrane) is removed as product with > 95% of
the ions removed. A larger portion of the water, with
increased ionic concentration, is the waste from each
of the first (lead) membranes in the first array pressure
vessels. This waste flows as feed water to each of the
three other membranes in the pressure vessel. The
combined waste from the first three individual pressure
vessels is fed to tubing that directs the feed-waste flow
to the second array, containing two pressure vessels.
It is important to note that the membrane array is
3:2:1. As feed water passes through each membrane,
product water is removed. Subsequently, as indicated,
the ionic concentration of the feed-waste water increases
and the flow rate decreases. An RO membrane array
provides a method of maintaining the velocity of water
through the membranes by reducing the number of
pressure vessels arranged in parallel as water passes from
the “lead” membranes to the final or “tail” membrane(s)
minimizing the potential for precipitation of concentrated “salts” of certain ions. For the indicated example,
there are three pressure vessels and six membranes in
the first array, two pressure vessels and four membranes
in the second array, and a single pressure vessel and two
membranes in the final array. Feed-waste water from
the second array is directed to the final array. Waste
from the second membrane in the final array is directed,
through instrumentation and valves, to drain.
Two calculations may be used to characterize system operation. These include system recovery and
system performance.
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RO System Recovery. The flow rate of feed water
recovered as product water is expressed as “percent
recovery,” calculated by the following equation:
% Recovery = (Product Water Flow Rate/Feed Water
Flow Rate) x 100
Generally, RO units with membranes configured in an array will exhibit about 75% recovery
of feed water.
RO System Performance. RO unit performance
is determined by inline measurement of feed water and
product water conductivity. Feed water and product
water conductivity values are generally displayed on
either a direct reading meter or screen. The “percent
rejection” is used to determine ionic removal and is
calculated by the following equation where C indicates the conductivity value of indicated feed water
and product water:
% Ion Rejection = [(Cfeed - Cproduct) / Cfeed] x 100
In theory, reverse osmosis membranes will remove
97–99+ % of the ionic material in water. However,
membranes do not remove gases, reactive or non reactive. Carbon dioxide, as an example, will pass through
a reverse osmosis membrane. The carbon dioxide will
react with the product water from the RO unit, increasing conductivity per the following equation:
CO2 + 2 H2O↔ H3O+ + HCO3iv thome.com
William V. Collentro, Coordinator.
As discussed previously, the hydronium ion exhibits
a very high equivalent conductance when compared
with other ions. While RO membrane manufacturer’s
data may indicate a stated reject in excess of 99%, the
actual rejection is lower due to the presence of reactive
gasses in product, such as carbon dioxide or ammonia.
The actual percent ion rejection for a specific application will be a function of the analytical profile of the
feed water supply to the system, feed water pressure,
and feed water temperature.
Figure 3: Spiral wound reverse osmosis membrane.
RO Membrane Configuration
The vast majority of RO membranes employed for
pharmaceutical water systems have a spiral wound
configuration. A spiral wound membrane is shown
in Figure 3.
Figure 3 illustrates the feed water and product
water flow as well as the waste flow. Water passes
“down” the membrane, parallel to the membrane
surfaces. As indicated, a portion of the water flows
in a perpendicular direction to the feed water flow
through the membrane. The permeate collector is a
tube down the center of the membrane containing
holes for collection of permeate throughout the length
of the membrane. The membrane surface is shown.
While difficult to demonstrate, Figure 4 depicts a
single membrane “envelope.”
The membrane is actual flat sheets. The sheets are
precision cut to produce the same dimensions. The
sheets are placed together with the membrane surfaces
facing outward and a permeate carrier positioned
between each membrane. The indicated “envelope” is
created by sealing three sides of the membrane-permeate-carrier-membrane arrangement. The open side of
the envelope is attached to the “permeate collector”
shown in Figure 3. The attached membrane is wrapped
around the permeate carrier in a configuration similar
to a “jelly roll” producing the spiral wound configuration. The spiral wound membrane contains an outer
retaining “wrapping” material. Three types of wrapping are described as follows.
Tape-wrapped Membranes. Tape-wrapped membranes, as indicated, use a tape material wrapped
around the spiral wound membrane. The use of tape
wrapped membranes is generally limited to domestic,
commercial, and light industrial application. They
should not be used for pharmaceutical applications.
Brackish-water Membranes. Brackish-water
membranes use a hard fiberglass reinforced outer shell
to secure the spiral wound membrane. The rigid nature
of the exterior of a brackish-water membrane provides
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Figure 4: Membrane to permeate collector.
Permeate collector tube
End of membrane envelope
Water flow
RO membrane surface
an annular space between the exterior of the encased
membrane and the inside diameter of the pressure vessel. A mechanism must be provided to avoid “bypass” of
feed water around the membrane, through this annual
space. A “brine seal” is added to the lead end of the
membrane consisting of a flexible annual section of
non-organic leaching elastomers. Unfortunately, the
brine seal produces a stagnant area down the length
of the membrane in the annular space between the
pressure vessel and the outer shell. This stagnant area
provides a location for bacteria to accumulate and replicate. There are numerous pharmaceutical RO systems
employing brackish-water membranes. It is strongly suggested that brackish-water membranes are not appropriate for applications where microbial control is a concern,
including all pharmaceutical applications.
Full-fit (loose-wrapped) Membranes. These
membranes use a mesh-type material to secure the
spiral wound configuration. The membranes exhibit
a “snug” fit when installed in pressure vessels. When
pressurized during normal operation, the exterior of
the mesh expands slightly to form a tight seal to the
interior walls of the pressure vessels. Bypass of feed
water and the undesirable dead leg associated with a
brine seal are both eliminated. Any RO membranes
used for pharmaceutical applications should be of
full-fit (loose-wrapped) type.
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Pharmaceutical Water System Fundamentals.
RO Membrane Composition And Operation
Virtually all RO membranes used for pharmaceutical
applications are thin film-composite polyamide-type.
Polyamide exhibits outstanding rejection of ions.
Unfortunately, the material is relatively fragile. By
supporting polyamide in a “sandwich” with polysulfone, a more rugged polymer, it is possible to provide
membrane material with good physical strength and
excellent ion rejection. It should be noted that polyamide, unlike polysulfone, is not chlorine tolerant.
Subsequently, residual disinfecting agent must be
removed from feed water to the RO system with polyamide thin film-composite membranes.
An RO system can be designed, fabricated, and
operated with hot water sanitization provisions. Fullfit membranes capable of withstanding hot water
sanitization temperatures (80°C) are available. RO
system design should include 316L Stainless Steel
tubing, membrane pressure vessels with elastomers
(end adapters), and appropriate support accessories
for the hot water sanitization operation. Hot water
sanitization may be performed every two to four
weeks based on product water total viable bacteria
levels. However, it is necessary to conduct chemical
sanitization, discussed later in this article, about once
every six months to remove biofilm.
Removal of Impurities. Unlike deionization
systems using cation and anion resin, which only
remove anions (with the exception of macroporous
or acrylic anion organic scavengers), reverse osmosis
will remove other pretreated feed water contaminants
such as the following:
•Colloids. Colloids should be completely removed.
•Colloids in a complex with naturally occurring
organic material (NOM). Colloids of silica, aluminum, and iron may exist in a complex with NOM.
The complex should be removed by RO.
•NOM and all organic material with a molecular
weight > 150–250 daltons
•Anticipated RO product water total organic carbon (TOC) levels should be more than 0.100
mg/l below the USP “Physical Test” Section
<643> implied limit of 0.500 mg/l.
•It is important to indicate that the ability of
reverse osmosis to remove residual disinfecting agent compounds such as trihalomethanes
(THMs), particularly chloroform, is poor. The
Table contains a summary of measured THM
levels through a classical USP purified water
system using RO and continuous electrodeionization (CEDI) (Collentro, unpublished data).
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•RO units operating in a continuous mode, discussed later in this article, exhibit product water
TOC levels < 0.025 mg/l.
•Bacterial endotoxins. RO product water bacterial
endotoxin levels are generally < 0.001 IU/ml.
Again, continuously operating RO units will
provide greater reduction when compared with
“cycled” RO units.
•Particulate matter. Particulate matter is removed
by the RO membranes to non-detectable levels.
•Bacteria
•From a conservative perspective, RO membranes
are capable of removing any material < 0.001
microns in size. Gram-negative bacteria in a
water system (non nutrient-starved environment)
are rod shaped, approximately 0.6 micron long
and approximately 0.2 microns in diameter.
While complete bacteria removal should be
achieved, many RO systems exhibit the presence
of product water total viable bacteria.
•Numerous factors impact RO product water total
viable bacteria levels. These factors are summarized later in this article.
•It is suggested that a properly designed, operated, and maintained RO system should exhibit
product water total viable bacteria levels < 10100 cfu/100 ml, membrane filtration of a 100
ml sample, R2A or PCA culture media, 30-35°C
incubation temperature, and 72- to 120-hour
incubation time period.
•Continuous RO system operation (versus cyclic
operation) significantly reduces RO product
water total viable bacteria levels.
RO SYSTEM PROBLEMS–FOULING
AND SCALING
As RO membranes concentrate impurities in the
feed water stream during normal operation, scaling
and fouling of the membranes will occur. Scalants
may include sulfate, carbonate, and bicarbonate
precipitates formed with trace concentration of
cationic impurities such as calcium, magnesium,
iron, aluminum, barium, etc. Scale formation can
be minimized by proper operation of the pretreatment section water softening unit discussed in the
second part of this series of articles. Important
water softener parameters include adequate salt
dosing during regeneration, “short-cycling” of the
operating cycle to avoid multivalent ion “breakthrough,” and operation of two units in series. The
concentrating nature of RO system operation makes
iv thome.com
William V. Collentro, Coordinator.
Table: Measured trihalomethane compounds in a USP purified water
“generation” system.
Location
Trihalomethane Compounds
Concentration (μg/l)
Municipal feed water
Chloroform
40
Dibromochloromethane
9.0
Bromodichloromethane
20
Bromoform
0.66
Chloroform
32
Dibromochloromethane
6.6
Bromodichloromethane
17
Bromoform
0.60
Chloroform
11.9
Dibromochloromethane
1.7
Bromodichloromethane
4.6
Bromoform
<0.50
Chloroform
12.1
Dibromochloromethane
1.7
Bromodichloromethane
4.8
Bromoform
<0.50
Chloroform
9.7
Dibromochloromethane
0.60
Bromodichloromethane
3.1
Bromoform
<0.50
Post activated carbon
Post re-circulating RO system
Post CEDI system
USP purified water distribution loop
the final or “tail” membranes in an array most susceptible to scaling.
Fouling of RO membranes is also a concern. Organic
material, colloidal material, or organic material complexed with colloidal material may contribute to membrane fouling. Periodic RO feed water measurement to
determine the “silt density index” should be performed
to determine the nature and extent of foulants present
in feed water. This test technique uses the flow rate
decrease through a 0.45-micron filter disc, at constant
pressure, to determine foulants in RO feed water.
All RO membranes will exhibit microbial fouling,
organic/colloidal fouling, and scaling. Subsequently,
periodic membrane cleaning is required. However,
prior to discussing membrane cleaning, it is appropriate
to address the manner in which impurities form “layers”
on the RO membrane surface. Figure 5 demonstrates
the manner in which RO feed water impurities accumulate (or replicate) on the membrane surface.
The layer furthest from the membrane surface
contains scalants. Again, the thickness/amount of
scalants would be greatest on “tail” membranes in
an array compared to “lead” membranes. Proceeding
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radially inward to the RO membrane surface, the next
layer contains nutrient–rich colloidal and organic
foulants. The thickness of this layer and amount
of foulants is greatest for the “lead” membranes in
the RO membrane array. Finally, the layer of the
membrane surface contains bacteria and bacterial
endotoxins in a “biofilm.” It is important to note
that this layer is adjacent to the nutrient-rich foulant
layer. It is also important to note that RO product
water total viable bacteria levels increase proportionally with the amount of bacteria on the surface of the
membranes, a function of bacteria levels in the feed
water, temperature, and cleaning frequency.
REVERSE OSMOSIS SYSTEM CLEANING
RO membrane cleaning should be performed periodically. While the primary objective of cleaning for
RO systems used in pharmaceutical water systems is
to remove bacteria, removal of membrane foulants
and bacterial endotoxins must also be considered. A
review of Figure 5 provides information for effective
membrane cleaning. Because scalants are on the outer
portion of the membrane “layer,” the initial cleaning
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Pharmaceutical Water System Fundamentals.
Figure 5: Layering of material on RO membrane surface.
Feed water flow
To next membrane
or waste
Scalants
Bacteria in biofilm
Foulants
RO membrane
Surface
Permeate flow
step employs a low pH cleaning agent. Low pH dissolves many precipitates. This cleaning operation is performed in a dynamic mode such that dissolved material
is constantly removed and replaced with “fresh” low pH
cleaning agent. Subsequent to completion of the low
pH cleaning operation, the RO membranes are rinsed
prior to proceeding with the next cleaning step.
Again, referring to Figure 5, once scalants are
removed, the exterior “layer” contains foulants. As
indicated, this material primarily consists of organic
compounds. Most organic compounds are removed
with an alkaline (high pH) cleaning solution. A circulating flow of high pH cleaning solution removes the
foulant “layer.” Quite often, the initial color of the water
from the membranes during this operation will be light
yellow to dark brown. Cleaning should proceed until
no color is noted. Subsequent to completion of the high
pH cleaning operation, the RO membranes are rinsed
prior to proceeding with the next cleaning step.
Sanitization, Bacteria, And Biofilms
The final cleaning step is membrane sanitization to
destroy bacteria and remove biofilm. Sanitization
must consider direct contact with all bacteria to provide
destruction as well as contact to remove the established
biofilm. The suggested sanitizing agent is a 1% mixture
of peracetic acid and hydrogen peroxide. The sanitizing
agent should be introduced at a pressure of about 30-40
psig, adequate to establish flow to waste and product.
Any “dead legs,” such as valves or capped sections of
tubing, should be opened or loosened to allow sanitizing agent to come in contact with all surfaces. The
1% concentration of sanitizing agent should be verified using test strips. Based on extensive experience,
a dynamic-stagnant-dynamic sanitization is required
for bacteria destruction and biofilm removal. Once
the concentration of sanitizing agent is verified, the
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flow of sanitization solution should be stopped. The
sanitizing solution should be allowed to sit in a stagnant condition in the RO system for a time period of
at least one hour. During this period, with no flow,
diffusion of sanitizing agent will occur to all walls and
surfaces using concentration difference as the driving
force. This is particularly important for break-up of the
biofilm. The one hour time period may be extended,
based on validation of the sanitization cycle, to ensure
that biofilm is removed to the point where post sanitization RO product water bacteria levels are < 100
cfu/100 ml for a reasonable time period (1-3 months).
Subsequent to the stagnant flow condition, the flow of
sanitizing agent is re-established for a time period of
approximately 15-30 minutes. This provides hydraulic
force to remove the “loose” biofilm, allowing entry to
the flowing stream and direct discharge to drain. A
rinse is conducted to remove all sanitizing agent from
all points in the RO system.
It is suggested that RO membrane chemical cleaning
and sanitization be performed off site. Each RO membrane has a unique serial number. The serial number
and location of the membrane within an array should
be recorded as membranes are removed for off-site
cleaning. The membranes are placed in double plastic
bags, sealed, and shipped to the RO membrane cleaning company using a “chain-of-custody” form (original and two copies). Upon receipt at the membrane
cleaning company, the membrane’s serial numbers are
verified. The membranes are individually tested for
integrity, scaling, fouling, percent ion rejection, and
flow rate. Assuming that the membrane parameters are
within pre-established guidelines, membrane cleaning
is performed. The cleaning should be performed in a
manner that allows parallel flow of cleaning agents,
unlike the parallel/series arrangement in the installed
membrane array. Upon completion of the cleaning
iv thome.com
William V. Collentro, Coordinator.
Figure 6: RO continuous operation.
process, measurement of integrity, scaling, fouling,
percent ion rejection, and flow rate are repeated. The
membranes are returned using chain of custody with
a formal report documenting all data including serial
numbers. Obviously, two sets of RO membranes are
required for this process because a set of membranes
must be installed when a set is removed. Generally, this
operation should be performed every 3-6 months as part
of a preventative maintenance program. Each time a new
(or cleaned) set of membranes is installed, the RO system
must be sanitized (chemically or hot water).
REVERSE OSMOSIS–DESIGN
CONSIDERATIONS
There are several factors that should be considered when
specifying an RO System. The factors include, but are
not limited to, the following:
•RO systems should be operated in a continuous
mode. Figure 6 provides a flow diagram of a reverse
osmosis unit operating in a continuous mode.
Required support components are included. Pretreated feed water flows to an upstream RO break
tank. The water is re-pressurized and flows to the
RO unit. Product water from the RO unit flows
to a continuous electrodeionization unit (CEDI).
Product water from the CEDI unit flows through an
inline ultraviolet sanitization unit and 0.1 micron
final filtration system. The final “loop” product
water flows to the top of a USP purified water storage tank or distillation unit/pure steam generator
feed water tank. The tank is equipped with valve
provisions to deliver water to the tank, deliver water
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to a drain with air break, or return water to the RO
break tank depending upon the water level in the
tank. The divert-to-drain valve may be used for
rinsing operations such as removal of sanitizing
solution. This system provides continuous flow
through the RO unit, minimizing microbial proliferation on membrane surfaces and eliminating RO
membrane pressure cycling associated with start/
stop operation for tank filling and periodic product
water rinse-to-drain operation for flushing.
•The RO break tank in the continuous flow system
may be used as a location for introduction of sanitization chemicals, allowing bacteria and biofilm
control throughout the loop. The tank may also
be provided with an external heating jacket for
RO/CEDI units with hot water sanitization design.
The re-pressurization pump downstream of the RO
break tank but upstream of the RO unit may be
used with variable frequency drive (VFD) motor for
lower RO feed water pressure required for periodic
hot water or chemical sanitization.
•It is important to note that termination of product
water flow from an operating RO unit will result
in near instantaneous membrane failure. The
“three-valve” arrangement of automatic valves
at the top of the USP purified water, distillation
unit, or pure steam generator feed water tank,
operates such that a valve is always open when the
RO unit is operational. When a valve position is
changed (e.g., make-up to recirculation), one of
the three valves will automatically open before
another valve automatically closes.
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Pharmaceutical Water System Fundamentals.
•When the RO/CEDI loop is in a re-circulating
mode, valves positioned in parallel in the RO
waste-to-drain stream automatically change the
waste flow from the previously indicated normal 25% value to 5-10%. This minimizes the
amount of water delivered to waste while continuing a waste flow for removal of contaminants
including bacteria.
•The RO unit is provided with a cartridge pre-filter. The preferred micron rating for the cartridge
filters is one micron or less. The micron rating is
a function of pretreatment system design, operation, and maintenance. Well maintained systems
may employ sub micron filters. The suggested
material of construction for the filter housing
is 304L or 316L Stainless Steel. Cartridge filterto-housing seal mechanism should be double
O-ring, not flat gasket or “knife-edge.”
•The RO feed water pump should be of multi-stage
centrifugal type. Metallic components in contact
with water should be of stainless steel construction. Pump selection should be based on projected
RO determined by the membrane manufacturer’s computerized projection after three years of
operation. The pump should be provided with a
totally enclosed, fan-cooled (TEFC) motor powered
through a VFD. Control of the VFD should be
through a central controller. It is strongly suggested
that VFD control be based on two factors; product water flow rate and percent of full operating
rpm. This method of control will avoid excessive
transmembrane and product-to-waste pressures
when the membranes require cleaning by reducing
product water flow rate based on a maximum pump
flow/pressure (rotating speed/motor cycles).
•Many RO units employ waste recycle. This process diverts a portion of RO waste to the feed line,
upstream of the RO high pressure pump. This
practice is strongly discouraged for systems where
microbial control is desired. The re-circulated
waste may contain concentrated contaminants
from feed water including bacteria. Waste recirculation may be eliminated by employing the
re-circulating RO/CEDI loop described earlier or
increasing the waste flow rate.
•Sample valves should be provided for monitoring RO performance, determining feed water
quality, and establishing the need for membrane cleaning and/or sanitization. As a minimum, sample valves should be provided at the
following locations:
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•Feed water to the RO pre-filter
•Product water from the RO pre-filter
•RO high pressure pump discharge
•RO wastewater
•RO product water from each pressure vessel. To
ensure a representative sample, a sanitary-type
check valve should be positioned in the product
water tubing from each pressure vessel. A zero
dead leg diaphragm-type sample valve should be
positioned in the tubing between the check valve
and the pressure vessel.
•Instrumentation and controls are critical to the
long-term successful operation of an RO unit. The
following monitoring and control functions should
be considered:
•RO pre-filter pressure
•RO pre-filter product water pressure
•RO feed water conductivity–remote indication
with alarm
•RO feed water temperature—remote indication
with alarm
•Post RO high pressure pump pressure—remote
indication with alarm
•RO feed water flow rate—remote indication
with alarm
•RO array discharge pressures
•Product water conductivity remote indication
with alarm
•Product water pressure remote indication
with alarm
•Product water temperature remote indication
with alarm
•Waste flow rate remote indication with alarm
•Waste pressure remote indication with alarm
•Product water flow rate remote indication with
alarm (may be determined by “processor” calculation of the difference between feed water
and wastewater flow rate).
OPERATING AND MAINTENANCE
CONSIDERATIONS
Operating and maintenance considerations for an
RO system should include but not be limited to
the following:
•Periodic (daily to weekly) determination of
feed water silt density index
•Periodic replacement of RO pre-filter cartridges
(weekly to every other week)
•RO membrane rotation with new or cleaned
membranes followed by sanitization
(three to six months)
iv thome.com
William V. Collentro, Coordinator.
•Periodic hot water sanitization
(weekly to monthly)
•Periodic chemical sanitization
(three to six months)
•Replacement of membrane interconnector
O-rings, end adapter O-rings, and end adapter
gaskets (three to six months)
•Calibration of instrumentation
(six to 12 months)
•Feed water analysis (weekly)
•Total hardness as calcium carbonate
•Total alkalinity as calcium carbonate
•Total chlorine
•Free chlorine
•TOC
•pH
•Total viable bacteria
•Product water analysis (daily–weekly)
•TOC
•Total viable bacteria.
gxpandjv t.com
NEXT ARTICLE
The next article in this series will discuss application of additional ion removal unit operations such
as ion exchange employing cation and anion resins,
and membrane processes using ion exchange resin
membranes and electronic field CEDI (continuous
electrodeionization) used for ion removal in pharmaceutical water systems.
GENERAL REFERENCE
Collentro, William V., Pharmaceutical Water, System Design,
Operation, and Validation, Interpharm Press, Buffalo
Grove, IL, 1999. JVT
ARTICLE ACRONYM LISTING
CEDI Continuous Electrodeionization
CIPClean-in-Place
NOM Naturally Occurring Organic Material
RO
Reverse Osmosis
TEFC Totally Enclosed Fan Cooled
THMsTrihalomethanes
TOC
Total Organic Carbon
USP
United States Pharmacopeia
VFD
Variable Frequency Drive
Journal
of
Validation T echnology [Summer 2010]
75