Design and Construction

of USP Purified Water

Systems

Feed Water Analysis

USP Purified Water System

Feed Water Analysis

Official Monograph
United States EPA NPDWR
Equivalent European Regulations
Equivalent Japanese Regulations
World Health Organization
Reference

USP Purified Water System

Feed Water Analysis

United States EPA National
Primary Drinking Water
Regulations (NPDWR)
Regulated Items
Total Viable Bacteria
Private Water Supplies

USP Purified Water System

Feed Water Analysis

Regulated Items Microorganisms
Cryptosporidium
Giardia lamblia
Legionella
Total Coliform
Turbidity
Viruses

USP Purified Water System

Feed Water Analysis

Regulated Items Disinfection
Byproducts

Bromate
Chlorite
Haloacetic Acids (HAA5)
Total Trihalomethanes
(TTHMs)

USP Purified Water System

Feed Water Analysis

Regulated Items Disinfectants

Chlorine
Chloramines
Chlorine Dioxide

USP Purified Water System

Feed Water Analysis

Regulated Items Inorganic
Chemicals

Antimony
Arsenic
Asbestos
Barium
Beryllium
Cadmium
Total Chromium
Copper

USP Purified Water System

Feed Water Analysis

Regulated Items Inorganic
Chemicals

Cyanide
Fluoride
Lead
Mercury
Nitrate
Nitrite
Selenium
Thallium

USP Purified Water System

Feed Water Analysis

Regulated Items Organic
Chemicals (53 Total)

Sewage/Wastewater Treatment
Herbicides
Landfill Leachates
Chemical/Industrial Facility Waste
Fumigants
Petroleum /Refinery Waste
Insecticides

USP Purified Water

System
Feed Water Analysis
Regulated Item Radionuclides
Alpha Particles
Beta Particles and Photon Emitters
Radium 226
Uranium

USP Purified Water

System
Feed Water Analysis
Total Viable Bacteria
No limit in NPDWR
Total Coliform (Confirmed as Fecal Coliform
or E. coli, used as indicator)
Action Limit of 500 cfu/ml in non
enforceable General Information Section of
USP
TVB may only indicate a fraction of viable
organisms present

USP Purified Water

System
Feed Water Analysis
Regulated Items - Testing
Municipality?
Pharmaceutical Facility?
Compliance?
Obligation?
Consequences?

Periodic Monitoring

USP Purified Water System

Periodic Monitoring
General Monitoring Storage and
Distribution System
Point-of-Use TVB
Online Conductivity
Online TOC

USP Purified Water System

Periodic Monitoring
General Monitoring Water
Purification System
Final TVB
Inline RO Feed Water and Product Water
Conductivity plus % Rejection of Ions
Inline Post RO Polishing Conductivity

USP Purified Water System

Periodic Monitoring
Frequent Monitoring Water
Purification System
Silt Density Index (Test Kit)
Total Hardness (Test Kit)
Chlorine (Test Kit)

USP Purified Water System

Periodic Monitoring
Less Frequent Monitoring Water
Purification System
Inline ORP for Reducing Agent Injection
Monitoring
Inline Total Hardness Monitor
Inline Chlorine Monitor

USP Purified Water System

Pretreatment Periodic
Monitoring
Raw
Water

Post
Multimedi
a

Post
Activated
Carbon

Post UV

Post Lead
Water
Softener

Post
Polish
Water
Softener

Post
Cartridge
Filter

NPDWR
Tests

TVB

BET

Chlorine

TOC

TSS

Total
Hardness

Total Iron

Turbidity

SDI

USP Purified Water System

RO/Polishing Periodic
Monitoring
Post RO
Break
Tank

Post RO

Post CEDI

Post UV

Post Final
Filter

TVB

BET

pH

TOC

Carbon
Dioxide

USP Purified Water System

Periodic Monitoring
Summary
Monitoring of Pretreatment and Ion
Removal steps identifies a problem
before it effects point-of-use values.
Frequency of the monitoring program
established for each application
Regulatory concerns

Sanitization Provisions

USP Purified Water System

Sanitization Provisions
Frequency
Determined by microbial monitoring
Must include storage, distribution, ion
removal, and pretreatment
Employs chemical and thermal methods
Ineffectiveness of Steam
Biofilm requires chemical sanitizing agent

USP Purified Water System

Sanitization Provisions
Fundamentals
TVB destruction a function of concentration
and time for chemical sanitization
TVB destruction a function of temperature
and time for hot water with 65C lowest
temperature
Dead Leg for thermal sanitization
Dead leg for chemical sanitization

USP Purified Water System

Sanitization Provisions
Fundamentals
Removal of Biofilm
Activated Carbon Issues
RO Waste Recirculation Issues
Pretreatment and Ion removal Recirculation
Issues
Hot water sanitizable ion removal systems
Pretreatment must be included

USP Purified Water System

Sanitization Provisions
Execution - Pretreatment
Hot Water Sanitizable Activated Carbon
Chemical Sanitization with 1% solution of
Hydrogen Peroxide and Peracidic Acid
(except activated carbon unit)
Replace activated carbon media every 6-12
months
Dynamic-Stagnant-Dynamic Procedure

USP Purified Water System

Sanitization Provisions
Execution Ion Removal
Continuous operation (make-up and
recirculation)
Hot Water Sanitization Provisions (entire system)
RO membrane rotation every 6 months
Chemical Sanitization with 1% solution of
Hydrogen Peroxide and Peracidic Acid annually
Dynamic-Stagnant-Dynamic Procedure

USP Purified Water System

Sanitization Provisions
Execution Storage & Distribution
Ozonation
Periodic Hot Water
Membrane Filtration discouraged
Chemical Sanitization with 1% solution of
Hydrogen Peroxide and Peracidic Acid
annually
Dynamic-Stagnant-Dynamic Procedure

Validation Criteria

Validation Criteria
Commissioning Documentation
Reference in IQ and OQ
Credit for inspection and testing
Factory Acceptance Test (FAT)
Documentation
Turnover Packages (TOP)
Coordination
Interface

Validation Criteria
IQ Format
Unit operation based with all support
documentation for components and
accessories verified. Support documents in
document or as an appendix/attachment.
Provides understanding of component by
individuals preparing, reviewing, and
executing IQ
Component based program for items such as
valves, gauges, pumps, etc. Poor tool for
individuals to understand the system.

Validation Criteria
IQ Information
Limits on material? The more information
available, the better. If a accessory breaks,
it must be replaced. The model number,
serial number, and/or manufacturer may
change or no longer exists. Cut sheets of
accessories provide an excellent vehicle for
identifying a like-for-like replacement
which significantly reduces the Change
Control effort.

Validation Criteria
IQ Information
All support information should reference
the original manufacturers part number.
Project specifications should clearly state
that the name of the manufacturer as well
as the part number be provided. The vast
majority of this information is coded to
the water purification equipment
manufacturers model number, useless for
replacement on a like-for-like basis.

Validation Criteria
OQ Information
Prepared and executed in an integrated
basis. Individual Unit Operation will
impact the operation of other components.
Execution must provide exact operating
condition. As an example, if media is not
installed in a pretreatment component
during execution of a FAT, execution
(partial) may be required after installation
and start-up.

Validation Criteria
OQ Information Considerations
Fixed alarm and operating set points
versus adjustable set points
Processor access levels
Alarm set points and time delays
Control set points and time delays
View screen navigation
ALERM banner display
OPERATOR OVERRIDE banner display

Validation Criteria
PQ Criteria
Post start-up and commissioning
30 day sample period
Sampling plan to duplicate water use
Working days
Attempt to duplicate water demand
Attempt to duplicate actual conditions at
individual points-of-use

Validation Criteria
PQ Criteria
Every point-of-use every day if practical
TOC grab samples from each points-of-use
Conductivity grab samples from points-ofuse
Suggest transition for about 30-60 days
after successful execution
Continues for one year period
Monitoring never stops

Validation Criteria
PQ Microbial Monitoring
Duplicate sampling schedule over length
of intense monitoring program and less
frequently thereafter
Different agar (PCA versus R2A)
Different incubation temperatures (22C
and 30-35C)
Extended incubation time period (3, 5,
8, and 10 days)

Validation Criteria
PQ Microbial Monitoring
EP Monograph Reference
Verify enumeration parameters
Bacteria identification
MIS
Riboprinter

Gram Stain
Objectionable organisms
Summary Report

Operating Procedures

Standard Operating
Procedures
General Considerations
Prepared, reviewed, and accepted
before OQ execution
Verbatim compliance
Keep as concise as possible
Do not include maintenance procedures
Control of copies important
Formal training

Standard Operating
Procedures
General Considerations
Video tape training sessions
Training Manuals
System P&IDs mounted in water system
area
Documentation of individual attending
training sessions
Periodic retraining
Personnel incident/excursion retraining

Preventative Maintenance
Program

Preventative Maintenance
Program
Objective
- Proactive not reactive
- Shutdown Considerations frequency
- Cost of lost production time
- Cost of quarantine of product
- Cost of lost product
- Micro delay

Preventative Maintenance
Program
Pretreatment Component Example
Activated Carbon Unit
Item

Suggested
Frequency

Consequences

Media
Replacement

Six Months

TOC and/or Chloramine

Breakthrough

Sanitize Column
Internals

Six Months

Microbial Excursion

Replace Gaskets

Two Years

Leak/Shutdown

Access Gaskets

Six Months

Leak/Shutdown

Clean/Replace
Distributors

One Year

Failure Media in Product Water

Instrument
Calibration

One Year

Improper System Operation

Replace Valve
Diaphragms

Two Years

Bypass/Cross Contamination

Preventative Maintenance
Program
Ion Removal Component Example
Reverse Osmosis Unit
Item

Suggested
Frequency

Consequences

Rotate RO
Membranes

Six Months

Loss in Product Water Flow Rate

and Quality (Chemical and TVB)

Contract Clean
Rotated
Membranes

Six Months

Loss in Product Water Flow Rate

and Quality (Chemical and TVB)

Chemical
Sanitization

Six Months

TVB Excursions

Interconnector ORings

Six Months

Waste-to-Product Leak

End Fitting O-Rings

Six Months

Waste-to-Product Leak

Instrument
Calibration

One Year

Loss of System Control

Preventative Maintenance
Program
Ion Removal Component Example
Reverse Osmosis Unit
Item

Suggested
Frequency

Consequences

Replace Feed
Water Pump Seals

Two Years

Pump Leak Introduction of

Air/Water TVB Increase

Vale
Seals/Diaphragms

Two Years

Bypass

Sanitize Pressure
Vessels

Six Months

TVB Excursions

Change Prefilters

One Week

Foulant Increase Resulting in TVB

Increase

Hot Water Sanitize

(if equipped)

Two Weeks

TVB Excursions

Replace Rotated
Membranes

Three Years

Loss in Product Water Flow Rate

and Quality (Chemical and TVB)

Preventative Maintenance
Program
Storage & Distribution Loop Example
USP Purified Water Storage Tank
(No
Ozone)Suggested
Item
Consequences
Frequency

Instrument
Calibration

One Year

Loss of Level Control

Inspect Rupture
Disc

Six Months

TVB Excursion

Replace Rupture
Disc

One Year

TVB Excursions

Replace
Hydrophobic Vent
Filter Cartridge

Six Months

TVB Excursion

Inspect Tank
Interior

Six Months

Rouging/Biofilm

Replace Manway

One Year

TVB Excursion/Leak

Preventative Maintenance
Program
Ion Removal Component Example
Reverse Osmosis Unit
Item

Suggested
Frequency

Consequences

Repassivate

One -Two Years

Rouging Biofilm TVB Increase

Derouge &
Repassivate

Two -Three Years

Rouging Biofilm TVB Increase

Hot Water
Sanitization

One Week One

Month

TVB Excursions

Chemical
Sanitization

Six Months

Biofilm TVB Excursion

Thank you!
Questions?