Water Purification System for a

Laboratory Facility

Millipore Corporation
Bioscience Division
Christopher Yarima
Mike Kelly

Outline

Contaminants in Water

Pure Water Applications and Quality Standards

Water Purification Technologies

Key Water Purification System Design Steps

Systems

Questions

Water Chemistry Contaminants

Ground & Surface Water

Surface Water
- Lower in dissolved ions
- Higher in organic materials
- Higher in particulates
- Higher in biological material

Ground Water
- Higher in dissolved ions
- Lower in organic
materials
- Lower in particulates
- Lower in biological
Material

Contaminants in Potable Water

Inorganic Ions

Organics

HH
H-C-C-OH
HH

Cations

Anions

Na+

Cl-

Ca+2

HCO-3

Natural

Man Made

Tannic Acid

Pesticides

Humic Acid

Herbicides

Particles

Non Dissolved Solid Matter

(Colloids)

(Small deformable solids with a net negative

charge)

Microorganisms

Bacteria , Algae , Microfungi

(Endotoxin)

(Lipopolysaccharide fragment of Gram

negative bacterial cell wall)

Measurement of Contaminant level

Contaminant Measurement Unit
Inorganic Ions

Conductivity
(Resistivity)

s/cm
M.cm

Organics

Total Oxidizable
Carbon (T.O.C.)

ppb (g/L)

Particles (Colloids)

Silt Density Index /

Fouling Index

Rate of pluggage of
0.45 m
membrane.

Bacteria

Colony count on 0.45 cfu/ml

m membrane.

Endotoxin

-Rabbit

Inoculation

test
-LAL Test

Endotoxin units/ml

Measurement Units

Thickness of a Human hair = 90 microns

Smallest visible particle = 40 microns

1 Micron = 10-6 Meters

Smallest bacteria = 0.22 micron

ppm : Parts per Million = mg/Liter

ppb : Parts per Billion = microgram/Liter

ppt : Parts per Trillion = nanogram/Liter

1 ppb = 1 Second in 32 Years. !!!

Water Standards

Standards and Common Terms

Ultrapure/Reagent Grade
Critical Applications

Ultrapure
Type 1

Water for HPLC,GC, HPLC ,AA , ICP-MS, for

buffers and culture media for mammalian cell
culture & IVF, reagents for molecular biology...

Pure/Analytical Grade
Standard Applications

Pure

Type II

Buffers, pH solutions,culture media

preparation ,clinical analysers and
weatherometers feed.

Pure/Laboratory Grade
General Applications

Type III

Glassware rinsing, heating baths,

humidifiers and autoclaves filling

Laboratory Water Purity Specifications

Consolidated Guidelines
Contaminant Parameter (units)
Ions
Resistivity (M-cm)
Organics
Particles
Bacteria

Silica (ppb)
TOC (ppb)
particles > 0.2 um (#/ml)
Bacteria (cfu/ml)
Endotoxin (EU/ml)

Type 1 Type 2 Type 3

> 18.0

> 1.0

> 0.05

< 10
< 20
<1

< 100
< 50
NA

< 1000
< 200
NA

<1
< 0.001

< 100
NA

< 1000
NA

Regulatory Agencies with Published Standards:

ASTM: American Society for Testing and Materials
CLSI: Clinical and Laboratory Standards Institute
(previously NCCLS: National Committee for Clinical Laboratory Standards)

CAP: College of American Pathologists

ISO: International Organization for Standardization
USP: United States Pharmacopoeia
EU: European Pharmacopoeia

ASTM Standards for Laboratory Reagent Water

ASTM: American Society for Testing and Materials

CLSI*, water quality specifications

CLSI guidelines should be read to understand scope and detail for each requirement

CLRW; Clinical Laboratory Reagent Water

SRW; Special Reagent Water

CLRW water quality with additional quality parameters and levels defined by
the laboratory to meet the requirements of a specific application
For example: CLRW quality with low silica and CO 2 levels

Instrument Feed Water

Confirm use of CLRW quality with manufacturer
Water quality must meet instrument manufacturers specifications

Also defined:
Commercially bottled purified water, autoclave and wash water and water
supplied by a method manufacturer (use as diluent or reagent)

*CLSI: Clinical and Laboratory Standards Institute

(previously NCCLS)

US and European Pharmacopoeia Pure Water

Purified and Highly Purified Water*
Conductivity:

USP Purified

EU Purified

EU Highly Purified

<1.3 uS/cm at 25oC

<4.3 uS/cm at 20oC

<1.1 uS/cm at 20oC

TOC:

< 500 ppb

< 500 ppb

<500 ppb

Bacteria:

<100 cfu/ml

<100 cfu/ml

<10 cfu/100 ml

N/A

N/A

<0.25 EU/ml

Endotoxin:

* Overview of USP28 and EP 4th edition, (refer to detailed specifications for exact norms).

Purification Technologies
Overview of Key Technologies
Advantages/Disadvantages
Summary

Purification Technologies

Filtration Depth and Screen Filters

Activated Carbon and chlorine removal

Mineral scale control Softening and Sequestering

Distillation

Reverse Osmosis

Deionization

Electrodeionization

Ultraviolet light

Purification Technologies

Filtration Summary

Depth Filters

Random Structure
Nominal retention rating
Works by entrapment within depths of filter
media
High dirt holding capacity

Screen/Membrane Filters

Uniform Structure
Absolute retention rating
Works largely by surface sieving
Low dirt holding capacity

Activated Carbon

Granules or beads of carbon

activated to create a highly porous
structure with very high surface area

Activation can be heat or chemical

Pore sizes typically <100 to 2000

Surface area typically 500 to >2000

m2/gram

Removal of organics by adsorption

Removal of chlorine by adsorptionreduction

Mineral Scale Control

Calcium and carbonate ions are common in tap water supplies

Scale forms when concentration exceeds solubility limits and CaCO3

precipitates as a solid

Higher concentrations increase risk of scale formation

Higher pH and higher temperature increase risk of scale formation

Important in domestic water systems and purification technologies

Ca++ + CO3=

CaCO3 (S)

Calcium carbonate scale

CO3=

CO3=
Ca++
CO3=

CO3=

Scale Control Ion-exchange Softening

"Hard water"

Cation
Exchange Resin

Ca++ + 2 ClMg++ + 2 ClR

Na Na

Na Na

Ca

Mg

4 Na+ + 4 Cl"Soft water"

Scale Control
Ion-exchange Softener Regeneration
Regenerated resin

Mg++ + 2 CLCa++ + 2 ClEXCESS Na+ Cl-

Na Na

Na Na

Ca

Mg

Na+

Cl-

conc. NaCl

Exhausted resin

Softeners are regenerated using a concentrated brine flush

Scale Control Chemical Sequestering

Chemical sequestering weakly binds calcium ion preventing calcium and carbonate ions from forming
scale

Liquid and solid chemical options available

Solid polyphosphate shown as example illustration

Ca++ + CO3=

CaCO3 (S)
CO3=

CO3=
Ca++
CO3=

CO3=
Polyphosphate chain

Double Distillation Principal

Benefits
Recondense
by cooling vapor

Cooling water
jacket

Removes wide class of

contaminants

Bacteria / pyrogen-free

Low capital cost

Limitations

Heat to
vapor

High maintenance

High operating cost

Low resistivity

Organic carryover

Low product flow

High waste water flow

Water storage

Natural Osmosis
Pure water will pass though the membrane trying to dilute the contaminants

Osmotic
Pressure
Water
Plus
Contaminants

~100 ppm NaCl

= 1 psi of osmotic pressure

Pure
Water

Semi-Permeable
Reverse Osmosis
Membrane

Reverse Osmosis
Pressure applied in the reverse direction exceeding the osmotic pressure
will force pure water through the membrane
A reject line is added to rinse contaminants to drain

Pressur
e

Water
Plus
Contaminants

Reject

Pure
Water

Semi-Permeable
Reverse Osmosis
Membrane

Reverse Osmosis Summary

Limitations

Benefits

All types of contaminants removed:

ions, organics - pyrogens, viruses,
bacteria, particulates & colloids.

Low operating costs due to low energy

needs.

Minimum maintenance (no strong acid

or bases cleaning)

Good control of operating parameters.

Ideal protection for ion-exchange resin

polisher: a large ionic part already
removed ( resin lifetime), particulates,
organics, colloids also eliminated (no
fouling).

Not enough contaminants removed for

Type II water.

RO membrane sensitivity to plugging

(particulates), fouling (organic,colloids),
piercing (particle, chemical attack) and
scaling (CaCO3) in the long run if not
properly protected.

Need of right pressure (5 bars) & right pH

for proper ion rejection.

Flow fluctuation with pressure and

temperature.

Membrane sensitivity to back pressure

Preservative rinsing needed

Need optimized reject

Ion Exchange
Cation Exchange Resin

R - SO-3 H+ + Na+

IX resin (+)

R - SO-3 Na+ + H+

Ion (-)
Particulate

H2O

Colloid (-)
Organics

R - NH4OH- + Cl-

R - NH4 Cl- + OH-

Fines (-)

Anion Exchange Resin

Limitations

Benefits

Effective at removing ions

Resistivity 1-10 M.cm with a single pass

through the resin bed.
Resistivity 18 M.cm with proper pretreatment

Easy to use: Simply open the tap and get water

Low capital cost

Limited or no removal of particles, colloids, organics or

microorganisms
Capacity related to flow rate and water ionic content

Regeneration needed using strong acid and base

Prone to organic fouling

Multiple regenerations can result in resin breakdown and water
contamination
Risk of organic contamination from previous uses

Electrodeionization (EDI, CDI, ELIX, CIX)

RO Feed Water
Ion Exchange Resin

Na+

ClNa+

H+ Cl-

Waste

Na+ Cl-

(commercialize by Millipore in mid 80s)

Conductive
Carbon
Beads

Performance enhancements:

Cl-- Na++
H+ Cl-

OH-

Continuous deionization technique

where mixed bed ion-exchange
resins, ion-exchange membranes and
a small DC electric current
continuously remove ions from water

OHNa+
Product

Ion-exchange added to waste

channels improve ion transfer and
removal.
Conductive beads aded to cathode
electrode channel reduces risk of
scale and use of a softener

Cations driven toward negative electrode by DC current

Anions driven toward positive electrode by DC current
Alternating anion permeable and cation permeable membranes effectively separate
ions from water
RO feed water: Avoids plugging, fouling and scaling of the EDI module

Electrodeionization
Benefit

Very efficient removal of ions

and small MW charged organic
(Resitivity > 5 M-cm)

Low energy consumption

Limitations

Typical <100 watt light bulb

High water recovery

No chemical regeneration

Low operating cost

Low maintenance

No particulates or organic
contamination (smooth,
continuous regeneration by
weak electric current)

Good feed water quality required

to prevent plugging and fouling of
ion-exchange and scaling at
cathode electrode

RO feed water ideal

New enhancements minimize

risk of scale.

Weakly charged ions more

difficult to remove

Dissolve CO2 and silica

Moderate capital investment

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Contaminant Removal Efficiency

Distillation
Reverse Osmosis
Ultrapure Ion Exchange
Electrodeionization
Ultraviolet light
Carbon
Ultrafiltration
Microporous Filtration

2311BD10

Water Purification System Design

Multi-Step Purification Process
RO systems
RO + EDI systems
Progard Pack
Pretreatment
pack
RO cartridge
protection

Tap water

Reverse
Osmosis
Remove up to
99% of feed
water
contaminants

Both
Elix Technology

UV Lamp

Electrodeionization
Consistent
production
of high resistivity
and low TOC water

Production of
water with low
levels of
Bacteria

Type III

Type II

Low Bacteria

Product
Water

Water Purification System

Overview of Design Considerations

Major phases in a project

Definition of the needs

Design of a total solution

Budget estimation

Tender (Bid) process

Delivery of the units, accessories and consumables

Installation

Users training/Commissioning

Additional phases

Preventive maintenance
Full support for validation

Major phases in a project

Definition of the needs

Design of a total solution

Budget estimation

Tender (Bid) process

Delivery of the units, accessories and consumables

Installation

Users training/Commissioning

Additional phases

Preventive maintenance
Full support for validation

Design Process
Key Steps
Dishwasher
Direct Feed

Define the pure water requirements and

specifications

Ultrapure
Polishing
for HPLC

Design the distribution loop

Design the makeup system and storage tank

Review and Finalize specifications and design

General
Glassware
Rinsing

monitoring
UV
pump

sterile
filtration

Tap
Water

Pure
Water
Storage

Design Process: Step 1

Defining the pure water requirements and

specifications

Dishwasher
Direct Feed

What purity level?

How much water?

When is it needed?

Where is it needed?

Ultrapure
Polishing
for HPLC

General
Glassware
Rinsing

Defining the pure water requirements and specifications

What purity level?

What labs and locations need purified water?

What kind of work will be carried out in each lab, at each location?

General rinsing/washing to sensitive trace analysis,?

Are there instruments that will need pure water?

Glassware washers, steam sterilizers, autoclaves..?

Are there any maximum purity level requirements?

What water quality is needed for each location?

Ionic, Organic, and Microbiological Quality?

Are there alert and action levels?

Are there standard specifications to follow?

How much water? When? Where?

Dishwasher
Direct Feed

Ultrapure
Polishing
for HPLC

General
Glassware
Rinsing

Definition of the needs

Questions to select the right configuration and design

What purity level?

How much water? When? Where?

How much water is needed each day?

In each lab, at each location,..?

By the individual users, instruments, ultrapure polishing systems?

How is the demand distributed during the day?

Steady demand over the course of a day?

Peak demands at certain times of the day?

How many floors need water?

Dishwasher
Direct Feed

Where is each location?

Are there remote locations that need water?

What are the distances between each location?

Ultrapure
Polishing
for HPLC

General
Glassware
Rinsing

Defining the pure water requirements and specifications

What purity level?

How much water? When? Where?

Additional questions:

Does the equipment need to be validated?

At all locations?

Who will do the maintenance?

Is a service/maintenance contact required?

Are the water quality requirements similar between locations?

How many researchers/scientists will work in each lab?

Where can the equipment be located (space)?

Where can piping be run?

Are there plans for future expansion?

Ultrapure
Polishing
for HPLC

Dishwasher
Direct Feed

General
Glassware
Rinsing

Step 2: Designing the Distribution Loop

Define the distribution piping

Design Layout
Materials, welding method, valve type, pipe diameter
Design Considerations

Define Loop Purification and Monitoring Equipment

Determine distribution pump performance

Flow rate and pressure

Distribution Loop Layout Options:

Gravity Feed

Distribution Loop Layout Options:

Single Loop and make-up system Central Location

Distribution Loop Layout Options:

Single Loop and Duplex-central make-up system

Distribution Loop Layout Options:

Multiple Loop and make-up systems

Distribution Loop Layout Options:

Multiple Loop and make-up systems and POU systems

Satellite Units

Design Considerations; Avoid Dead legs

6D rule CFR212 regulations of 1976

Good Engineering practice requires

minimizing the length of dead legs and
there are many good instrument and valve
designs available to do so.
6D rule
0.59
Maximum dead leg = 6 times the pipe diameter
0.59 X 6 = 3.5
Maximum dead length of 3.5 inches

Maximum length 6X pipe diameter

(our example max is 3.5 inches)

Design Considerations; Flow Velocity

Design system for 3 to 5 f/s (~1 to 1.5 m/s) to:

Maintain turbulent flow
Minimize biofilm on internal walls
Balance between velocity and pressure drop
Higher velocity results in too high a pressure drop
Requiring a larger pump and risk of increased water temperature

Define Loop Purification and Monitoring

Equipment

Loop purification equipment to maintain water quality

UV lamp
Bacteria control
TOC Reduction
Filtration
Membranes for Bacteria and particle control
Ultra-filtration for Pyrogen removal
Deionization Ion removal

Loop Water Purity Monitoring

Resistivity
TOC
Bacteria
Temperature
Sanitant Monitors (Ozone)

Loop Monitoring

Sanitary Sampling Valve

TOC

Resistivity

Loop Bacteria Sampling

Sanitary Sampling Valve

Designed for sanitary

Designed for sanitary
sampling (bacteria and
sampling (bacteria and
endotoxin)
endotoxin)
Mid-stream sampling
Mid-stream sampling
Zero-Dead leg when closed
Zero-Dead leg when closed
Sanitize easily in place
Sanitize easily in place
Direct attachment to samplers
Direct attachment to samplers

Determine the Distribution Pump

Requirements

Pump selection is based on flow rate and pressure requirements

Flow rate required defined in step 1

Pressure requirement
Total Pressure requirement can be estimated by adding:
piping pressure loss
+
loop equipment pressure loss
+
pressure due to elevation changes
+
pressure required at furthest point of use (25 psi typical)

Select a pump that delivers the required flow rate and pressure
Reduce pressure loss by increasing pipe diameter, (keeping balance
with flow required and target velocity)
For added reliability a duplex pumping system can be used

Distribution Systems
Water Flow Dynamics; Pressure drop

Determining pressure drop through fittings:

Fittings; (elbows, tees, unions, etc..)

Flow through fittings creates turbulence and adds to
pressure drop
Equivalent pipe length method most common
Express each fitting as a length of pipe

1 foot

Example:
2 ft + 1 ft + (1) 90o elbow
90o elbow = 2 equivalent feet of pipe
2 + 1 + 2 eq-ft = 5 feet total length
2 feet

90o
elbow

Distribution Systems
Water Flow Dynamics; Pressure drop

Determining pressure drop through additional loop equipment

Refer to manufacturers specifications

UV lamps: Typically 2 to 3 psi
Filters and housings:

Pressure loss data

20 inch Code-0 Durapore

Determine the Distribution Pump Requirements

Case Study Pressure drop and Pump Requirement Calculations

Velocity and Pressure drop Table Piping Loop

Type in the yellow cells.
External diameter (in)

1 1/4

Internal diameter (in)

Flowrate in the loop (gal/min)
(see Flowrate Table)
Total length of the loop (ft)
Fittings (eq. length in m of PVC tube)
Qty
Elbows 90
90
Long Elbows 90
0
Elbows 45
0
Tees (straight)
30
Tees (90)
0
Ball valves in line
5
Union fittings
15
Total eq. length (in ft of pipe)
Total length of the pipe (pipe + fittings) (ft)

1.28

Total Pressure Drop

Velocity
Required Velocity : 4 1 f/s

nominal
pipe

15

1/2
1/2
3/4
1
1 1/4

0.59
0.79
0.098
0.59
0.79
0.098
0.79
0.106
0.98
0.95
1.26
0.118
1.28
1.57
0.146
Flowrate Table
Instant. Q POU Qty Total Instant. Q
15
gpm
1
15 gpm
gpm
0 gpm
gpm
0 gpm
gpm
0 pgm
gpm
0 gpm
Sum of Total instant. Q
15 gpm
47.5 psi
48
Simult. use factor
100%
3.8 f/s
3.8
Total flowrate in the loop 15 gpm
Velocity OK
2000
Eq.
315
0
0
75
0
2
60
452
2452

Distribution Pump specs Table

( Pressure drop of loop and accessories )
Accessories
Pump feed pressure
Loop pressure drop
UV Lamp
5 m loop filter
DI tanks
Super-Q
0.22 loop filter
other (to be specified)
other (to be specified)
Adjusted pressure on BPR
Highest elevation difference (ft)
0
Total pressure drop in the Loop
Required pressure @ distribution pump outlet
Required flowrate @ distribution pump outlet

Diameter of PP pipe
(Ashai-America)
Nominal
Ext
PN
thick.
inch
inside

psi
0
47.5
3.0
0.0
0
0
10
0

from above

details
details

25.0
0.0
85.5
86 psi
15 gpm

198 feet
15 gpm

25
25
25
16
16

Example
Exampleworksheet
worksheettool
tool

Helps
Helpstrack
trackand
and
automatically calculate all
automatically calculate all
key parameters
key parameters
Sizing
Sizingand
andselection
selectionofof
correct
correctpump
pumpisisaakey
keystep
step
in the design process
in the design process

Determine the Distribution Pump Requirements

Pump
Pumpperformance
performancecurve
curve

15
15GPM
GPMand
and180
180feet
feetofof
head (~78 psi) shown as
head (~78 psi) shown as
an example
an example
Select
Selectthe
thepump
pumpthat
that
meets
the
minimum
meets the minimum
requirements
requirements

Step 3 - Design the Makeup Purification

System and Storage Tank

Select the make-up purification system to match the water

quality required

Size the makeup purification system to match the quantity

required per day

Size the storage tank to meet peak demands during the day

Determine the pretreatment needed

Makeup System Sizing and Quality

Match to the quality requirement (defined in step 1)

RO/EDI or RO/DI system for Type 2 pure water applications
RO system for Type 3 more general applications

Size the makeup system to match the quantity required per day
(defined in step 1)
Plans for future expansion?
Are Duplex systems needed?
Back-up for maintenance-down time.
Option to add for future expansion

Sizing Makeup System and Tank

Sizing the makeup system is done in
conjunction with the storage tank
Sizing Examples:

Company A needs water to clean vessels in the first two hours of

the day shift. They need a total of 1200 Gallons in two hours.

1500 Gallon Tank with 100 gph make-up rate

Company B needs pure water to feed automated Filling machine.

They need 200 gallons per hour for an 8 hour shift.

200 Gallon Tank with 200 gph make-up rate

Determine the pretreatment needed for

the makeup water system

Determine feed flow rate base on the make-up system water

recovery rate

Complete feed water analysis

Feed Flow Rate = RO Product / RO recovery rate

conductivity, chlorine, fouling index, pH, hardness, alkalinity..

Select pretreatment options based on feed water analysis and

manufacturers recommendations

Multimedia Sand Particulate contamination

Carbon Filters Chlorine and some organic removal
Softeners Hard water (Mg++ or Ca++ contamination)
Cartridge Filters Particulate and carbon options

Design Process Step 4

Step 4 - Finalize Design

Prepare Process Flow Diagram (PFD),

supporting documents and specifications

Design Controls and Monitoring

Review Validation requirements

Review who will maintain the equipment

Consider service/maintenance plans

Review requirements, specifications, design,

equipment and PFD with customer/client

Update and Finalize design as needed

Outline

Contaminants in Water

Pure Water Applications and Quality Standards

Water Purification Technologies

Key Water Purification System Design Steps

Systems

Questions

???

Water Purification System for a

Laboratory Facility

Thank You!!

Millipore Corporation
Bioscience Division
Christopher Yarima
Mike Kelly