William V. Collentro

ULTRAPURE WATER Pharma 2010

New Brunswick, New Jersey

May 20-21, 2010

Compendial Water System – Feed Water Analysis

Official MonographUnited States EPA National Primary Drinking Water

Regulations (NPDWR)Equivalent European RegulationsEquivalent Japanese RegulationsWorld Health Organization Reference

Compendial Water System – Raw Water Analysis

United States EPA – NPDWRRegulated ItemsTotal Viable Bacteria“Private” Water Supplies

MicroorganismsCryptosporidiumGiardia lambliaHeterotrophic Plate CountLegionellaTotal Coliform (including fecal coliform and E. coli)TurbidityViruses (enteric)

Compendial Water System – Raw Water – Regulated Items

Raw Water Microorganisms – Health Effects

Parameter Health Effects

Cryptosporidium Gastrointestinal Illness

Giardia lamblia Gastrointestinal Illness

Heterotrophic Plate Count No direct health effects but employed to indicate the general bacteria contamination level of water

Legionella Legionnaire’s Disease

Total Coliform Indicator of the presence of pathogens

Turbidity Associated with disease causing organisms

Viruses Gastrointestinal Illness

Raw Water Microorganisms – Health Effects

Parameter Source

Cryptosporidium Human and Animal Fecal Waste

Giardia lamblia Human and Animal Fecal Waste

Heterotrophic Plate Count Environmental Bacteria

Legionella Environment – Cooling/Heating Systems

Total Coliform Natural, Human Fecal Waste, Animal Fecal Waste

Turbidity Soil Runoff, Construction

Viruses Human and Animal Fecal Waste

Raw Water Microorganisms – Health Effects

Parameter Maximum Contaminant Level/Treatment Technique

Cryptosporidium SWTR – Monitored and Controlled

Giardia lamblia 99.9% Removal/Inactivation

Heterotrophic Plate Count

≤500 cfu/ml

Legionella No Limit but Requires Control of Giardia and Viruses

Total Coliform NMT 5% positive/month (≥40 samples/month), NMT 2 consecutive confirmation for E.coli or Fecal Coliform

Turbidity ≤1 NTU (≤0.3 NTU at least 95% of tests)

Viruses 99.99% Removal/Deactivation

Disinfection Byproducts

BromateChloriteHaloacetic Acids (HAA5) Total Trihalomethanes (TTHMs)

Compendial Water System – Raw Water – Regulated Items

Disinfection Byproduct – Bromate

MCL = 0.010 mg/lOzone Primary Disinfecting AgentIncreased Risk of Cancer

Disinfection Byproduct – ChloriteMCL = 1.0 mg/lChlorine Dioxide Primary Disinfecting AgentAnemia, Nervous System

Compendial Water System – Raw Water – Regulated Items

Haloacetic Acids (HAA5) – (0.060 mg/l)

Dichloroacetic AcidTrichloroacidic Acid Monochloroacidic Acid Bromoacetic AcidDibromoacetic AcidIncreased Risk of Cancer

Compendial Water System – Raw Water – Regulated Items

Total Trihalomethanes (0.80 mg/l)

ChloroformDibromochloromethaneBromodichloromethaneBromoformIncreased Risk of Cancer, Liver, Kidney, or

Central Nervous System

Compendial Water System – Raw Water – Regulated Items

Regulated Item – Disinfectants (Distribution)

ChlorineChloraminesChlorine Dioxide

Compendial Water System – Raw Water

Compendial Water System – Raw Water

Regulated Items – Inorganic ChemicalsAntimonyArsenicAsbestosBariumBerylliumCadmiumTotal ChromiumCopper

Compendial Water System – Raw Water

Regulated Items – Inorganic ChemicalsCyanideFluorideLeadMercuryNitrateNitriteSeleniumThallium

Compendial Water System – Raw Water

Regulated Items – Organic Chemicals (53 Total)

Sewage/Wastewater TreatmentHerbicidesLandfill LeachatesChemical/Industrial Facility WasteFumigantsPetroleum /Refinery WasteInsecticides

Compendial Water System – Raw Water

Regulated Item – RadionuclidesAlpha ParticlesBeta Particles and Photon EmittersRadium 226Uranium

Compendial Water System – Feed Water Analysis

Total Viable BacteriaNo “enforceable” 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 USPTVB only indicates a fraction of viable organisms

present

Compendial Water System – Feed Water Analysis

Regulated Items - TestingMunicipality? Pharmaceutical Facility?Compliance?Obligation?Consequences?

USP Purified Water System – “Classical” Periodic

Monitoring

General Monitoring –

Storage and Distribution SystemPoint-of-Use TVBOnline ConductivityOnline TOC

USP Purified Water System – “Classical” Periodic

Monitoring

General Monitoring –

Water Purification SystemFinal TVBInline RO Feed Water and Product Water Conductivity – RO Unit % Rejection of IonsInline Post RO Polishing Conductivity

USP Purified Water System – “Classical” Periodic

Monitoring

Frequent Monitoring –

Water Purification SystemSilt Density Index (Test Kit)Total Hardness (Test Kit)Chlorine (Test Kit)

USP Purified Water System – “Classical” Periodic

Monitoring

Less Frequent Monitoring –

Water Purification SystemInline ORP for Reducing Agent Injection Inline Total Hardness MonitorInline Chlorine Monitor

USP Purified Water System – Suggested Periodic

Monitoring Raw Water Post

MultimediaPost Activated Carbon

Post UV Post Lead Water Softener

Post Polish Water Softener

Post Cartridge Filter

NPDWR Tests X - - - - - -

TVB X X X X X X X

BET X - X - - - X

Chlorine X X X - - - -

TOC X X X - - - -

TSS X X X - X X -

Total Hardness

X - X - X X -

Total Iron X X X - X X -

Turbidity X X - - - - -

SDI - - - - - - X

USP Purified Water System – Suggested Periodic

Monitoring Post RO Break Tank

Post RO Post CEDI Post UV Post Final Filter

TVB X X X X X

BET X X - - -

pH X X - - -

TOC X X X X X

Carbon Dioxide

X X - - -

Compendial Water System – Periodic Monitoring

• 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

Raw Water Impurities – Current Issues

Trihalomethanes (Chloroform)Removal Process?VolatilePresence in USP/EP Water for Injection?Ozonated USP Purified Water SystemsChloride Pitting Corrosion of Austenitic Stainless

Raw Water Impurities – Current Issues

MononchloramineDisinfection Properties in Raw Feed WaterpH of Feed WaterType of Activated Carbon“EBCT” Critical!!!DetectionTOC Interference During RemovalEffect on Microbial ResultsCareful Selection of Polishing Components

Raw Water Impurities – Current Issues

Catalytic Activated Carbon Volume Required =

(EBCT) x Flow Rate/7.48

Where, EBCT is the “Empty Bed Contact Time” expressed in minutes, Flow Rate is expressed in gallons per minute and the Catalytic Activated Carbon volume is expressed in cubic feet. AT pH = 8.0, Monochloramine = 3.0 mg/l, and TOC < 3.0 mg/l, EBCT = 8.0.

Raw Water Impurities – Current Issues

Use of 185 Nanometer UV Downstream of ROTOC Reduction to Meet 0.50 mg/l?TOC Reduction to Control Bacteria?Generation of Hydroxyl RadicalVery Strong OxidantViolation of USP General Notices SectionFragmentation of Organic MaterialChloride and Nitrate Ions - GenerationDegradation in Conductivity

Raw Water Impurities – Current Issues

Use of 185 Nanometer UV Downstream of RONon Representative TVB Data“Delivered” Water – With Hydroxyl Radical“Delivered” Water – Without Hydroxyl RadicalEffect on Other Product IngredientsEffect on Research“Duplication” of Data Based on Use

Conclusions

There is an increasing regulatory focus on the quality of water (chemical and microbial) throughout a

compendial water system. Knowledge of impurities in raw water and their removal by water purification

unit operations is critical. There is no “magic” bullet. A technical sound pretreatment system remains a

critical part of any compendial water system.

Questions?