Water for Pharmaceutical Use-new

8/12/2019 Water for Pharmaceutical Use-new

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WATER FOR PHARMACEUTICAL PURPOSE

TOPICS

Types of water and their qa!ity

Use of water in phar"a#eti#a! "anfa#trin$

Prifi#ation of water and steps

%eneration of hi$h!y prified water

%eneration of water for in&e#tion

'istri(tion of hi$h!y prified water syste"

Testin$ instr"ents ) "ethods *a!idation of water syste"

T+PES OF WATER

Raw water ,Non pharmacopoeia untreated water Pota(!e water,Non pharmacopoeial. Should meet the requirement of

USEPA and the federal register, part 141( 41 !"#4$4,%ul&',1')*+ested for dissoled solid, micro-ial count,

pathogens and ions. e can use /ndian standard Pro#ess water,Non pharmacopoeial . Prepared from pota-le water as

per the process Prified water,Purified water 0oered pharmacopoeia, P USP, /P

etc. +o -e tested for P2, conductiit&, toc,3 micro-ial count. Hi$h!y prified water, 0oered -& pharmacopoeia, EP "$$". +o -e

tested for P2, conductiit&, toc 3 particulate count, endotoin 3micro-ial count

Water for in&e#tion, 0oered -& pharmacopoeia , USP, P, etc. +o -e

tested for P2, conductiit&, toc , particulate count endotoin 3micro-ial count

Test para"eter PW HPW WFI

P2 56 56 56S7cm 1.8 1.8 1.8+90 pp- 5$$ 5$$ 5$$0U71$$ml 1$,$$$ 1$ 1$EU NA $."5 $."5

:P0;1$,"5 NA 1$$,1$ 1$$,1$

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Use of water in pharmaceutical manufacturing Used as raw material Used for primar& cleaning Used for final rinsing

Pota(!e water,

Not to -e used in drug product S&nthesis of intermediates and AP/ not intended for sterile use in

further steps of manufacturing /nitial rinse of equipment for intermediate for non sterile AP/, non

sterile AP/ non sterile drug product inal rinse of equipment for intermediate for non sterile AP/, non sterile

AP/

Prified water,


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C!arifi#ation

0larification is generall& a multi6step process to reduce tur-idit& andsuspended matter.

Steps include the addition of chemical coagulants that react to form floc.+he floc settles -& grait& in settling tan=s or is remoed as the waterpercolates through a grait& filter.

+he clarification process effectiel& remoes particles larger than "5microns. +he clarification process is not 1$$> efficient? therefore, water treated

through clarification ma& still contain some suspended materials.Li"e Treat"ent

+he addition of lime (0a* and soda ash (Na"098* reduces the leel ofcalcium and magnesium and is referred to as @ lime softening. +hepurpose of lime softening is to precipitate calcium and magnesiumh&droides ( hardness* and then clarif& the water. +he process is

inepensie -ut onl& marginall& effectie, usuall& producing water of 5$to 1"$ ppm ( 8 to gpg* hardness. Bisinfection Bisinfection is one of the most important steps to municipal

water treatment. Usuall&, chlorine gas is fed into the suppl& after the waterhas -een clarified and 7 or softened. +he chlorine =ills -acteria. /n order tomaintain the @ =ill potential, an ecess of chlorine is fed into the suppl& tomaintain a residual. +he chlorine leel must -e constantl& monitored toassure that no harmful leels of chloramines or chlorinated h&drocar-onsdeelop.

Ph adCustment


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WATER FOR PHARMACEUTICAL PURPOSEmicron filter al=ali dosing U dou-le pass mied -ed resin7 ediU cold storage 3 distri-ution

Besign "

!aw water chlorine dosing ("65ppm* alum dosing (optional* storagein precipitation tan= multigrade filter car-on -ed filter ion echangers

1$ micron filter uf cold storage tan= 3 distri-ution loop%eneration of hi$h!y prified water

!aw water chlorine dosing ("65ppm* alum dosing (optional* storagein precipitation tan= multigrade filter car-on -ed filter softener 1$micron filter al=ali dosing U dou-le pass mied -ed resin7(nonregenara-le* Uf hot storage 3 distri-ution loop

%eneration of water for in&e#tion

Besign 1!aw water chlorine dosing ("65ppm* alum dosing (optional* storage inprecipitation tan= multigrade filter car-on -ed filterSoftener 1$ micron filter al=ali dosing U dou-le pass ro0old distri-ution multicolumn distillation plant

Besign "!aw water chlorine dosing ("65ppm* alum dosing (optional* storagein precipitation tan= multigrade filter car-on -ed filter 1$ micron filter

ion echangers 1$ micron filter hot storage 3 distri-utionmulticolumn distillation plant hot storage 3 distri-ution line

STORA%E - 'ISTRI.UTIO/ S+STEM

S+9!AFE +ANG Storage tan= should -e made of SS81): and should -e eletropolished and

passiated -efore use. Storage tan= should hae more than 1 ;1$$ slope for complete drainage Storage tan= should -e designed to withstand the pressure of minimum 11."

Gg and full acuum required for steam steriliHation

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WATER FOR PHARMACEUTICAL PURPOSE or heating of water heat echanger used should not contaminate the highpurit& water. Bou-le tu-e t&pe or limpet t&pe heat echanger s&stem is preferred,

otherwise tu-e and shell pressure differential should -e monitored. Storage tan= should -e proided with temperature indicator to control andmonitor the temperature ( incase of hot loop * Storage tan= ent shall -e proided with h&dropho-ic steriliHing grade filterhoused in SS81): steam Cac=eted housing *for hot distri-ution loop* Spra& -all in return line shall -e placed inside storage tan= to ensure that tan=surface a-oe water leel is continuousl& flushed. :eel indicator should -e sanitar& t&pe /nlet outlet Coints should -e sanitar& t&pe

'istri(tion p"p

Bistri-ution pump should -e made of SS81): with dou-le mechanical sealand proided with tangential casing drain ale

Pump should -e designed to maintain minimum 1 water change per hour (i.ecomplete water of storage tan= should recirculated minimum once in a hour* Pump should -e designed to maintain 16" Gg7 cm "pressure of water indistri-ution loop

'istri(tion pipe!ine

Bistri-ution pipeline should -e made of SS81): pipeline, electroplated andpassiated -efore use. (Passiation procedure should -e proided -& tu-emanufacturer*

Bistri-ution loop should -e designed to withstand the steam pressure ofminimum 1." Gg and full acuum required for steam steriliHation Bistri-ution loop should -e continuos with minimum dead leg of not more

than ) times of tu-e diameter and slope of more than 1;1$$ towards point of use forcomplete drainage All Coints shall -e of sanitar& t&pe I +ricloer for alues and instruments andor-ital welding qualification criteria for or-ital welding is gien -elow. +o hae -etter control on endotoin self sanitiHed, hot distri-ution loop ( morethan #$J0 * is required. Suppl& elocit& in distri-ution pipeline shall -e -etween 56' fps and returnelocit& shall -e -etween 86'fps. All point of uses (P9U* ales shall -e Hero dead leg diaphragm ales withP+E facing Fas=et in the line should -e made of P+E or silicone (No as-estos gas=etshould -e used*

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I/STRUME/TATIO/

!eturn distri-ution line shall -e equipped with on line conductiit& meter,-ac=pressure alue and rotameter. +90 anal&Her ma& -e installed on line -ut suita-ilit& of the apparatus should-e tested periodicall& as per USP "5. 0onductiit& meter should -e cali-rated as per USP"5 :ocation of on line +90 anal&Her and conductiit& meter should -e selectedas its worst case.

0ali-rated !+B shall -e placed in the line to control and monitor thetemperature of the distri-ution s&stem. No of !+Bs should -e selected -ased on thelength and configuration of pipeline.

CO/TROLS

Bistri-ution and generation s&stem shall -e proided with dumping ale fordumping of water in case of nonconformance with respect to conductiit& , +90 andtemperature. 9perational specification of conductiit& and +90 should -e well -elowthe compendial requirement so that action time is aaila-le -efore crossing the

0ompendial specification. Point of use ale shall -e automaticall& controlled to preent the use of water

in case of nonconformance. +here shall hae alarm s&stem to warn the operator on crossing the alert limitof conductiit&,+90 and temperature. S&stem shall -e controlled -& P:0 for operation and SanitiHation to minimiHethe human interention and to incorporate automatic control and safet& features. P:0 should hae interface with other s&stem li=e P0 for ma=ing trends andother controls.

P:0 should hae


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WATER FOR PHARMACEUTICAL PURPOSEthan #$J0 temperature with continuous recirculation is self6sanitiHed. /n this caseSanitiHation is carried out initiall& and after an& shutdown.

TESTI/% I/STRUME/TS)METHO'S

09NBU0+//+K

/NS+U


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WATER FOR PHARMACEUTICAL PURPOSEeld criteria for distri-ution pipe Coints elding shall -e carried out in clean room (class 1$$,$$$ area* and shall -e

carried out -& qualified welder. elding shall -e done -& using automatic or-ital welding machine in argon(''.''>* atmosphere. All weld must -e full& penetrated around the entire weld perimeter with nocreices or entrapment sites. All welds shall -e smooth, uniform and complete and flat, no concae on theoutside. +he weld shall hae a uniform, complete weld -ead width on the inside withno coneit&.

+he inner weld -ead shall contain no concait&. +here shall -e no isi-le sign of oidation 7 discoloration of the inner weld. +he Coint shall -e square facing and properl& aligned. +u-ing surfaces shouldnot -e offset in an& plane or direction -& more than M76 $.$$8 inches. +he weld width shall -e nominal 17# inch M76 178" inch wide All defectie welds shall -e reCected. /nitial 8 samples welds and line welds of theO n M 1 num-er shall -e Dra& tested for weld qualification.

P0

ater s&stem is alidated in three phases.

P2ASE / A:/BA+/9N S+UBK;

9nce the water generating s&stem and distri-ution piping has -een erified, hainginstalled as per /L protocol and operating as specified in 9L protocol, the initialphase of water s&stem alidation shall -e underta=en. /n this phase water samplingshall -e done from all sampling points for a period of two wee=s. /f there is an&

failure with respect to an& qualit& attri-utes in -etween two wee=s of the Phase /stud&, inestigation shall -e carried out to find out the cause of failure and properaction shall -e ta=en for rectif&ing the pro-lem. /n this case, Phase / stud& has to re6initiated.

Phase // alidation Stud&;+his stud& is to demonstrate that the s&stem consistentl& produces the desiredqualit& of purified water when operated in conformance with the S9Ps. +hesampling shall -e done from all the sampling points for a period of two wee=s.

Phase /// alidation Stud&;+he third phase of alidation is designed to demonstrate that when the water s&stemis operated in accordance with the S9Ps oer a long period of time (one &ear* , itshould consistentl& produce water of desired qualit& attri-utes. Buring this period

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WATER FOR PHARMACEUTICAL PURPOSEsampling shall -e done as per the routine sampling plan which includes a minimumof one point of use dail&, with all points of use tested in rotation.

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Water for Pharmaceutical Use-new

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