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1 Stilmas Presentation

2. PHARMA WATER QUALITY SPEC. &DESIGN CRITERIA

…Stilmas is a 100% pharma – o r i e n t e dcompany…

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USP

SOURCE: USP 27 page 2630 - Fig. 2. Water for pharmaceutical purposes.

DRINKING WATER MEETSQUALITY ATTRIBUTES OF

EPA NATIONALPRIMARY DRINKING

WATER REGULATIONS

Typical Treatment Steps:

- Softening - Reverse Osmosis - Dechlorization - Ultrafiltration - Deionization - Distillation

WATER FOR SPECIALPHARMACEUTICAL

PURPOSES(e.g. bulk pharmaceuticalchemicals, process water)

PURIFIEDWATER

Distillationor ReverseOsmosis

WATER FOR INJECTION

(WFI)

INGREDIENTWATER

NONPARENTERALDOSAGEFORMS

STERILEPURIFIED

WATER

Packaging andSterilization

Packaging andSterilization

PACKAGED WATERSTERILE WATER FOR INJECTION

STERILE WATER FOR IRRIGATIONSTERILE BACTERIOSTATIC WATER

FOR INJECTIONSTERILE WATER FOR INHALATION

FOROTHERUSES

WATER QUALITYDECISION TREE

To beharmonizedwith USP27WFI mono-

graph

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PHARMA WATERS QUALITY SPECS &NEW TREND

COMPENDIALWATER

PURIFIED WATER( in bulk )

WATER FOR INJECTION( in bulk )

WATERHIGHLY

PURIFIED( in bulk )

PHARMACOPOEIA

PARAMETERS E.P. 5th Ed.

USP xx

E.P. 5th Ed. (Only

By Distillation )

USP xx(By Distillation

or equivalent /superior )

E.P. 5th Ed.(Double-pass

Reverse Osmosiscoupled with other

suitabletechniques asultrafiltration anddeionisation )

Conductivity 4.3 S/cm (20

C)

It meets therequirements 645

(1)

1.1 S/cm (20

C)

It meets the

requirementsof all the testsunder Purified

Water

It meets the

requirements ofall the tests

under Water forinjection

TOC 0.5 mg/l 0.5 mg/l 643

It meets therequirements of all

the tests under Purified Water

Oxidizablesubstances

Pass the test (2) Deleted

Nitrates Pass the test Not considered

Heavy metals 0.1 ppm Deleted

Aluminium Pass the test

(3) Not considered

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COMPENDIALWATER

PURIFIED WATER( in bulk )

WATER FOR INJECTION( in bulk )

WATERHIGHLY

PURIFIED( in bulk )

PHARMACOPOEIA

PARAMETERS E.P. 5th Ed. USP xx

E.P. 5th Ed.

(Only By Distillation )

USP xx(By Distillation or

equivalent /superior )

E.P. 5th Ed.(Double-pass

Reverse Osmosiscoupled with othersuitable techniquesas ultrafiltrationand deionisation )

Microbialcontamination(action limit)

100 CFU/ml 100 CFU/ml 10 CFU/100 ml 10 CFU/100 ml 10 CFU/100 ml

Bacterial

endotoxins

0.25 IU/ml

(3) N.A. 0.25 IU/ml 0.25 EU/ml 0.25 IU/ml

NOTES

(1)Stage 1 :Table Temperature Versus Conductivity (e.g. 1.1 S/cm (20

C))Stage 2 : 2.1 S/cm (25

C)Stage 3 : 2.1 C 4.7 S/cm (25

C) as function of pH(2)Alternatively to TOC test

(3)Only if water is intended for use in the manufacture of dialysis solutions

PHARMA WATERS QUALITY SPECS &NEW TREND

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P.W./WFI DESIGN CRITERIA

PW WFI

•Production Cold (20°

C) Hot (85°

C - 95°

C)

• Storage Cold (T 20°

C) Hot ( 70 T 85°

C)

• Distribution Cold (T 20°

) Hot/cold (At User Points) To be studied case by case

• Type of User Points Manual Manual/Automatic

• Sanitiz/Steriliz Heating at 85°

C Superheated WFI at 125°

C

Ozone Pure Steam(Specific Cases)

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EQUIPMENT DESIGN AND MATERIAL S

-RESISTANT TO HIGH PURITY WATER

-RESISTANT TO SANITIZATION (HEAT OR CHEMICALS)

-ADEQUATE SURFACE FINISHES

-DRAINABLE

-PREVENTION OF CONTAMINATION BY OTHER FLUIDS (HEAT EXCHANGERS)

-PREVENTION OF CONTAMINATION BY MATERIAL (SEAL PUMPS, GASKETS)

-EXPOSED TOTALLY TO SANITIZING AGENTS-VALVES / INSTRUMENTS

-NO DEAD AREAS / NO “DEAD LEGS”

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Stilmas Presentation


CRITICAL PROCESS PARA METERS CONTROL AND RECORD

-TEMPERATURE

-CONDUCTIVITY

-FLOW-RATE

-PRESSURE

-TOC

DESIGN FOR PROPER MO NITORING

-INSTRUMENTS

-SAMPLING POINTS

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DISTRIBUTION LOO PS

POINTS TO CONSIDER

-CONTINUOUS RECIRCULATION SYSTEMS: “LOOP”

-CONTROL OF TEMPERATURE (PRODUCTION/SANITIZATION)

-CONTROL OF RETURN LOOP MINIMUM VELOCITY (or better Reynolds Number)

-CONTROL OF RETURN LOOP CONDUCTIVITY

-VENTING FILTRATION OF STORAGE TANK

-HEATING OF FILTER (only WFI)

-STERILIZATION OF FILTER (only WFI)

-TESTING FOR INTEGRITY OF FILTER (only WFI)

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POINTS TO CONSIDER

-POSSIBILITY TO SANITIZE STORAGE TANK + LOOP

-DRAINABILITY

-SPRAY-BALLS INSIDE THE STORAGE TANK

- ABSENCE OF “DEAD -LEGS”

-TURBOLENT FLOW IN DISTRIBUTION SYSTEM

-NO “POINT OF USE” FILTERS

-RESPECT OF “CONTEMPORARY USAGE FACTOR” -SAMPLING POINTS

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DESI GN

1 CONTINUOU S RECIRCULATION SYSTEM S: “ LOOP” 2 RESPECT OF “CONTEMPORARY USAGE FACTOR” 3. TURBO LENT FLOW IN DISTRIBUTION SYSTEM4 ABSENCE OF “DEAD -LEGS” 5. SAMPLING POINTS6. DRA INABILITY7. AUTOM ATIC SANITIZATION OF STORAGE TAN K + LOOP8. SPRAY -BALLS INSIDE THE STORAGE TANK

M ONI TORI NG & CONTROL

1. CONTRO L OF TEMPERA TURE PRODUCTION/SANITIZATION)

2. CONTROL OF RETURN LOOP M INIMUM FLOW VELOCITY

3. CONTRO L OF RETURN LOOP COND UCTIVITY

DISTRIBUTION SYSTEM: LOOPS

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PW storage anddistributionsystem.

For HPWsystems UV-

Lamps can beinstalled tocontrol thebacterialgrowth.

3. THE PROD UCTSDISTRIBUTION SYSTEM: LOOPS

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Storage tank and deliverypumps.

The heat exchanger on the returnallows the temperature keeping andthe sterilization by overheatedwater.


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The heat exchangeron the loop returnallows thetemperature keepingand the sterilizationby overheated water.

Sub-loops with localcoolers can feedcold points of use.


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