WELCOMEWELCOMETOTO

WELCOMEWELCOMETOTO

HYDROPUREHYDROPURE

THE COMPLETE WATER SOLUTION FOR PHARMACEUTICALS APPLICATION

THE COMPLETE WATER SOLUTION FOR PHARMACEUTICALS APPLICATION

WATER FOR PHARMACEUTICAL PURPOSEWATER FOR PHARMACEUTICAL PURPOSE

WATER SOURCE

SURFACE WATER UNDERGROUND WATER MUNICIPAL WATER

BOREWELL WATER

PONDSRIVERS/LAKES

IMPURITIES PRESENT IN WATERIMPURITIES PRESENT IN WATER

IMPURITIES

SUSPENDED SOLIDS DISSOLVED SOLIDS DISSOLVED

GASES

MICRO-

ORGANISMS

Turbidity Silt Colloids Organics

Inorganic Organics Silica

CO2,o2,H2S,

NH3

Bacteria, virus

Algae, Fungi

PURIFIED WATER (PW)PURIFIED WATER (PW)PARAMETERSPARAMETERS SPECIFICATIONSSPECIFICATIONS

Temperature- ºCTemperature- ºC AmbientAmbient

Conductivity - µs/cm Conductivity - µs/cm < 1@ 25 ºC< 1@ 25 ºC

Total organic carbonTotal organic carbon < 500 ppb< 500 ppb

pHpH 5-75-7

Microbial CountMicrobial Count 100 CFU/ml100 CFU/ml

Endotoxin unit-EU/mlEndotoxin unit-EU/ml Not applicableNot applicable

APPLICATIONS OF PURIFIED WATER :

Sterile Bulk API

Bulk API

Parenteral Dosage

Non Parenteral Dosage

Formulations

WATER FOR INJECTION (WFI)WATER FOR INJECTION (WFI)PARAMETERSPARAMETERS SPECIFICATIONSSPECIFICATIONS

Temperature- ºCTemperature- ºC 85 - 9085 - 90

Conductivity - µs/cm Conductivity - µs/cm < 1@ 25 ºC< 1@ 25 ºC

Total organic carbonTotal organic carbon < 500 ppb< 500 ppb

pHpH 5 -75 -7

Microbial CountMicrobial Count 10CFU/ 100ml10CFU/ 100ml

Endotoxin unit-EU/mlEndotoxin unit-EU/ml 0.250.25

APPLICATIONS OF WFI :

Sterile Bulk API

Parenteral

Biotechnology

Semiconductor Industries

WATER TREATMENT

IT IS DONE WITH A COMBINATION OF THE FOLLOWING TECHNOLOGIES :

Prefiltration

Softening

Demineralization

Microfiltration

Ultra Violet Sterilizer

Reverse Osmosis

Electrodeionization

Ultrafiltration

Distillation

WATER TECHNOLOGY DEVELOPMENT CHART

FOR PRODUCING PW GRADE WATEREARLIER (I GENERATION, 1970 - 1990

Pretreatment

Cation/Anion

Mixed Bed

ION Exchanger/UV

END

USE

LATER (II GENERATION, 1990-2000)

Pretreatment

Reverse Osmosis

Mixed Bed

ION Exchanger/UV

END

USEAND NOW (NEW GENERATION, 2000 AND AHEAD)

Pretreatment MF/UF*

RO Pass 1

RO Pass 2

Polishing UF*

END

USE

Pretreatment MF/UF*

RO Pass 1

Hot Water Sanitizable RO

EDIEND

USE

EDI-Electro deionization

*UF-Ultra filtration System

MF-Flow Micro filtration System

Hot Water sanitizable RO-RO capable to be sanitized by hot water at 85 ºC

PRETREATMENT METHODS

GOALS OF PRETREATEMENT :

• To Provide water quality that minimizes operating and maintenance

problem in final treatment Equipment. It consists of –

(A) DOSING SYSTEM

(B) FILTRATION TECHNOLOGIES

(C) SOFTENERS

(A) DOSING SYSTEM :

CHEMICAL DOSING

• Applications include:

• Inorganic coagulants such as alum and ferric chlorine

• Organic flocculants of various grades

• Antiscalants Dosing

• SMBS Dosing

• pH Correction

(A) FILTRATION TECHNOLOGIES :

For removal of particulate suspended matters. PREFILTRATION

Multigrade Filter Activated Carbon Filter

DESIGN FEATURES- SAND SELECTION PRESSURE, FLOW SIZING OF FILTER

DESIGN FEATURES- PARTICLE SIZE ABSORPTION CAPACITY CARBON GRADE

Removes

• Solid contamination

• Particulate matter like silt, dust, pollen, silica, undissolved minerals

• Turbidity

Removes• Proteinous Material• Low modecular weight Carbon compound• Organic Chlorine Compound• odour and Turbidity

(C ) SOFTENERS :

Removes hardness causing salts of Ca and MG.All Sodium (Na) salts are soluble in water and hence water is softened.

CaCI2 + 2Na+ 2Ca+ + 2NaCI

SOFTENER LOCATION

AFTER REMOVAL OF MICROBIAL CONTROL AGENT

BEFORE REMOVAL OF MICROBIAL CONTROL AGENT

Protect Softener From Microbial growth

Gives better Resin life & Capacity

♣CONTROL OF MICROBIAL GROWTH IN PRETREATMENT

• By addition of Microbial control agent such as chlorine

• Periodic Heat or Chemical Sanitization.

• Use of Ultraviolet Light.

• Avoiding Dead leg and stagnation.

♣MATERIAL OF CONSTRUCTION FOR PRETERATEMENT EQUIPMENTS

• PVC, CPVC OR Polypropylene.

• FRP, MSRL OR SS for Vessels.

• SS OR PVDF for high temperature application

FINAL TREATMENT FOR PW GENERATION

As per USP 30 water can be produced by numbers of unit processes in various combinations. Some of them are as given below:

• Demineralization

• Micro filtration

• Ultra Violet Sterilizer

• Reverse Osmosis

• Electro Deionization

• Ultra filtration

DEMINERALIZATION OR DE-IONIZATION

These are used to remove dissolved solids from feed water. It is an Effective method of improving the chemical quality attributes of water by removing cations &anions. They use cation resin beds to remove negatively charged particles & Anion resin beds to remove positively charged particles. Mixed bed units cantaining both. Cation & Anion exchange resins are commonly used to give final polishing treatment.

DEMINERALIZATION OR DE-DEMINERALIZATION OR DE-IONIZATIONIONIZATION

♣ ♣ ADVANTAGES:ADVANTAGES:

Simple design & maintenanceSimple design & maintenance Flexible in water flow Flexible in water flow

Productions.Productions. Low capital cost.Low capital cost. Remove ionizable substances Remove ionizable substances

like ammonia, carbon dioxide & like ammonia, carbon dioxide & some organics. some organics.

♣♣ DISDIS--ADVANTAGES:ADVANTAGES:

Operation cost is high for TDS Operation cost is high for TDS in feed water.in feed water.

Requires Pretreatment to Requires Pretreatment to remove undissolved solids to remove undissolved solids to avoid resin fouling.avoid resin fouling.

Chlorinated water result in resin Chlorinated water result in resin degradation by oxidation hence degradation by oxidation hence dechlorination is required.dechlorination is required.

Required chemicals handling & Required chemicals handling & disposal.disposal.

Vessels are Excellent places for Vessels are Excellent places for microbial growth to occur microbial growth to occur between regeneration.between regeneration.

FUNDAMENTALS OF FILTRATION

0.0001µ 0.001 µ 0.01 µ 0.1 µ 1 µ

200D 20000D 200000D

IONS

Sugars Proteins

Synthetic dyes Carbon black

Emulsions

Viruses Bacteria

Reverse Osmosis

Nanofiltration

Ultrafiltration

Microfiltration

Pore Size

(microns)

Type of

Particles

Membrane Filtration

Process

ULTRA VIOLET LIGHT TREATMENT

Ultraviolet light rays strike microorganisms like bacteria, virus, yeast, mold or algae & break through their outer membrane to modify their DNA. The modified DNA code brings about the destruction of the organism. The ultraviolet radiation is a point of use application with no residual radiation characteristics. Proper prefiltration should be implemented to keep particulate from shielding organisms from shielding organisms from UV light.

♣ ADVANTAGES:

• Simple design & Maintenance.

• No waste stream.

• 254 mm design for microbial reduction.

•185 mm design for TOC reduction.

♣ DISADVANTAGES:

• Less shelf life of UV treated water.

• Requires close monitoring of UV intensity.

• No ion or endotoxin removal.

• Particulate can shield organisms from light.

REVERSE OSMOSIS UNIT

RO units employ a semi-permeable membrane & Substantial Pressure differential to drive water through the membrane to achieve chemical microbial & endotoxin quality improvement. Process stream consists of supply water (feed), product water (permeate) & Water (reject). A Semi-permeable membrane is permeable to water, while being impermeable to other substances such as salts, acids, bases, colloids, bacteria’s & Endotoxin.

RO membrane are commercially produced in spiral wound configuration.

Membrane are made in two basic materials,

(1) Cellulose Acetate (CAP)

(2) Thin film composite TFC/CPA Polyamide.

REVERSE OSMOSIS UNITREVERSE OSMOSIS UNIT

♣ ♣ ADVANTAGES:ADVANTAGES: RO units eliminate or RO units eliminate or

significantly reduce significantly reduce chemical handling & chemical handling & disposal.disposal.

RO has more effective RO has more effective microbial control than microbial control than deionization systemdeionization system

Removes ionized salts & Removes ionized salts & non-ionic materials like non-ionic materials like colloids, bacteria, endotoxin colloids, bacteria, endotoxin & some dissolved organics.& some dissolved organics.

RO element typically RO element typically reduces the level of raw reduces the level of raw water salts, colloids, water salts, colloids, organics, bacteria & organics, bacteria & endotoxin by 90% to 99%.endotoxin by 90% to 99%.

♣♣DISADVANTAGES:DISADVANTAGES: Water consumption can be Water consumption can be

significantly higher unless significantly higher unless waste water is reused.waste water is reused.

Energy consumption is Energy consumption is higher.higher.

No removal of dissolved No removal of dissolved gases like CO2 & ammonia.gases like CO2 & ammonia.

RO membrane must be RO membrane must be protected from scale protected from scale formation, membrane fouling formation, membrane fouling & degradation, Hence & degradation, Hence remedial action is must in remedial action is must in pretreatment.pretreatment.

CONTINUOUS ELECRO DEIONIZATION (EDI)

The name EDI indicates combinations of two difference technologies viz. Electro dialysis & ion exchange resin deionization. It removes ionized species from water using electrically active media & an electrical potential to effect ion transport. It forces ions out of the feed stream into an adjacent stream via an electric potential. An EDI device typically comprises of semi-permeable ion exchange membrane, permanently changed media & a Power supply that can create a DC electrical field.

The Process uses a combination of ion selective membrane & ion exchange resins sandwiched between two electrodes anode & cathode under a voltage potential to remove ions from the RO pretreated water.

CONTINUOUS ELECTRO CONTINUOUS ELECTRO DEIONIZATION(EDI)DEIONIZATION(EDI)

♣ ♣ ADVANTAGES:ADVANTAGES:

Eliminates needs of Eliminates needs of regeneration chemicals.regeneration chemicals.

Produces consistent water Produces consistent water quality.quality.

Electrical field in Electrical field in membrane/resin module membrane/resin module provides some bacterial provides some bacterial control.control.

Removes ionizable Removes ionizable substances such as carbon substances such as carbon dioxide, ammonia & some dioxide, ammonia & some organics.organics.

♣ ♣ DISADVANTAGES:DISADVANTAGES:

Does not remove non-ionic Does not remove non-ionic contaminants.contaminants.

Requires pretreatment for Requires pretreatment for microbial reduction.microbial reduction.

ULTRAFILTRATION SYSTEMULTRAFILTRATION SYSTEM

♣ ♣ ADVANTAGES:ADVANTAGES:

UF removes some UF removes some contaminants such as contaminants such as endotoxin & organics, better endotoxin & organics, better than micro filtration.than micro filtration.

Can tolerate more rigorous Can tolerate more rigorous sanitization procedures using sanitization procedures using hot water, ozonated water.hot water, ozonated water.

Reject rate is less than that of Reject rate is less than that of RO units.RO units.

♣♣ DISADVANTAGES:DISADVANTAGES: UF cannot remove ionic UF cannot remove ionic

contaminants, where as RO contaminants, where as RO can.can.

UF membrane are some times UF membrane are some times more difficult to integrity test.more difficult to integrity test.

UF requires a drain water UF requires a drain water stream, which can be a stream, which can be a significant cost factor.significant cost factor.

Ultrafiltration is a cross flow Process. A pressurized feed stream flows parallel to a porous membrane filtration surface. Application of pressure difference causes the membrane to act like a sieve. Substances smaller than the pore size of the membrane are passed while large solutes or particles are rejected as concentrate & goes to drain as reject bleed.

DISTILLATION

TYPES OF DISTILLATION

SINGLE STAGE/COLUMN

DISTILLATION

MULTICOLUMN

DISTILLATION

1) Water distilled only once

2) High operating cost

1) Water distilled depending on number of columns

2) Lower operating cost

PURE STEAM

GENERATION

Clean steam generator.

From first effect of multi effect WFI still.

CHARACTERISTICS

No super heat generation

Free from microbes & pathogens

No additives.

APPLICATION

Parenteral & Non-Parenteral dosage

In Manufacture of API.

Sterilization of USP water system

& fermentation vessels.

PURIFIED WATER STORAGE PURIFIED WATER STORAGE AND AND DISTRIBUTION SYSTEM DISTRIBUTION SYSTEM

• FUNDAMENTAL & CONCEPTS• INSTUMENTATION• ORBITAL WELDING• ELECTROPOLISHING• PASSIVATION• SANITIZATION• COMMISSIONING & VALIDATION

STORAGE & DISTRIBUTION SYSTEM

DESIGN PARAMETERS

Velocity : 2.5mtr/sec in supply line 1mtr/sec minimum in return line

Pressure : Positive pressure is require to avoid vacuum during high usage and microbial growth

Temperature : To be maintain as per system and users requirement.

Peak Consumption : Flow rate to be maintain according to diversity factor.

Deadleg : <6D To avoid microbial contamination

Drainability : 100% with line slope of 1:100 max.

STORAGE TANK Location : As close as the generation

plant

Type : Vertical / Horizontal

MOC : Contact Parts SS316L..

Nozzle Connection : Tri-Cover End

Surface Finish : Inside 250 Grit Electropolished, Spray ball to keep interior surface wet for microbial control

JACKET in case of Hot system

Turn Over : 1-5 time per hour

Change Over : 0.5-1times per hour

Durability : 100%

Instrumentation is for on line Control and Monitoring the operation of high purity water distribution

systems

Following parameters to be monitor by PLC

PRESSURE CONDUCTIVITY TEMPERATURE FLOW

TOC OZONE LEVEL

CONTROLLER

INSTRUMENTATION

ORBITAL WELDING Orbital welding is an automatic pulse TIG (Tungsten Inert Gas) welding for round pipes/equipments.

Fusion technology is being used for thin wall section up to 2.5 mm maximum where filter wire is not required i.e. no addition of different material reduces the contamination.

During orbital welding argon gas is being used as a inert gas as well as for purging.

Joint Geometry is square butt type fusion welding to get full penetration.

Latest Orbital welding transformer (Inverter based control unit) is fully Automatic / Computerized where print out for welding parameters.

(Documentation), program saving and fine control can be done.

Close head Orbital welding is recommended to get good quality of joints and to avoid foreign contamination.

BOROSCOPY

Boroscope is an instrument which is used for the inspection of piping

internal surface & weld joints. It is the current pharmaceutical industry

practice to use a boroscope for documentation of orbital welding joint.

With the use of boroscope video recording of the weld joints (Internal

Surface) can be done & maintained as a documentation for audit.

Normal practice is to do 10% boroscopy of the total welding joints and

100 % in critical application (product line).

ELECTROPOLISHING

Electropolishing is the process where the metal is removed from object’s surface through an electro chemical process similar to electroplating but the reverse of it.

Object is dipped in an electrolyte and subjected to a direct electrical current. The object is maintained anodic with the catholic connection of a nearly metal conductor.

During the process a film of varying thickness covers the surface, thick over micro depression and thin over micro projection.

In summary, electropolishing removes the metal and smoothens the surface which is primary and most advantageous effect of electropolishing.

PASSIVATION

Procedure : 1) Detergent wash

2) water Rinse

3) Acid Wash ( Passivation Step)

4) Final Process Water Rinse

Chemicals : HNO3 nitric acid is commonly used for stainless steel, concentration 10-15%

Advantages : Removes iron, metallic contaminants, organic/inorganic soil and foreign particles.

SANITIZATION

Periodic sanitization of storage and distribution system is generally required based on monitoring the microbial quality of the system; required frequency of sanitization should be formally established.

♣TYPES OF SANITIZATION

1) CHEMICAL

2) OZONE

3) HEAT

Systems that will be steam sterilized must be fully drainable to assure complete condensate removal. It’s a good engineering practice to allow for the draining of the equipment and associated piping. A good engineering practice is also to minimize or eliminate dead legs common practice is to limit dead legs to less than 6 times pipe diameters or less. Industry experts have suggestion using a guideline of 3D or less.

SYSTEM DRAINABILITY

COMMISSIONING

INSTALLATION RECHECK

PRESSURE TESTING

CLEANING AND PASSIVATION

LABELINC AND TAGGING

AS BUILT DRAWING

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