Productivity & GMP

8/10/2019 Productivity & GMP

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PREFORMULATION AND PRODUCTION MANAGEMENT

PRODUCTIVITY AND GMP CONSIDERATIONS

Seminar on,

PRODUCTIVITY

&

GMP CONSI DERATIONS

PRODUCITVITY

Definition

Reasons to Increase Productivity

o! to Increase Productivity

Econo"ic Gro!t# and Productivity

Main Processes of A Co"$any %ro" ic# Productivity Is

Created and Distri'uted

Measurin( An Inter$retin( Partia) Productivity

Ot#er As$ects of Productivity

PRODUCTIVITY

DEFINITION:

Nagaraja y s D ept.of Pharmaceutics


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Productivity "ay 'e defined as t#e ratio of out$ut to in$ut*

Out$ut + "eans t#e a"ount or t#e no* of units $roduced*

In$ut + are various resources )i,e -and and 'ui)din(. e/ui$"ent

and "ac#inery. "ateria). )a'our etc*

In a'road sense. $roductivity is considered for t#e entire $rocess.

!#i)e efficiency is referred to individua) o$eration and "ac#ines*

REASONS TO INCREASE THE PRODUCTIVITY 0

It is a)!ays necessary to increase $roductivity continuous)y for various

reasons*

For management:-

To se)) "ore and earn (ood $rofits*

To c)ear t#e de'ts or )oans ac/uired fro" different sources

To esta')is# 'etter $osition in t#e "ar,et*

For worker !

To (et #i(#er !a(es and standards of )ivin(*

To !or, in 'etter !or,in( conditions*

To attain 1o' security and satisfaction*

For "# tomer !

To o'tain artic)es at reduced $rice*



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HO$ TO INCREASE THE PRODUCTIVITY:

T#e resources s#ou)d 'e uti)i2ed 1udicious)y for increasin(

$roductivity 'y3

Ma,in( $ro$er use of ra! "ateria)s and reducin( t#e "anufacturin(

defects* T#is can 'e ac#ieved 'y usin( t#e ri(#t $rocess. ri(#t desi(n

and ri(#t stora(e faci)ities*

I"$rovin( !or, study tec#ni/ue and trainin(. so t#at )a'our can rise

to t#e occasion and (ive #i(#er $roductivity*

Maintainin( t#e e/ui$"ent in (ood !or,in( condition and reducin(

setu$ costs*

Ada$tin( $ro$er construction and )ayout*

S#ortenin( t#e !or, for 4 or 5 day6!ee, and )en(t#enin( t#e s#ifts

to 78 to 74 #rs6day*

9ee$in( !a(es "ore c)ose)y to out$ut and $rovidin( "erit a!ards*

Deve)o$in( and uti)i2in( Standard ti"e in service industries*

I"$rovin( co""unication to encoura(e everyone to !or, to!ards

t#e sa"e desired o'1ectives*

Redesi(nin( t#e ne! tec#no)o(ies a)so increases t#e $roductivity*

Cyc)e ti"e reduction*



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Productivity can 'e considered as increased. if "ore $roducts are

$roduced fro" t#e sa"e a"ount of resources*

ECONO%IC &RO$TH AND PRODUCTIVITY:

Econo"ic activity can 'e identified !it# $roduction and

consu"$tion* Production is a $rocess of co"'inin( various

i""ateria) and "ateria) in$uts of $roduction so as to $roduce too)s

for consu"$tion*

:y t#e #e)$ of $roduction function. it is $ossi')e to descri'e si"$)y

t#e "ec#anis"s of econo"ic (ro!t#*

Econo"ic (ro!t# is created 'y t!o co"$onents*

a; Increase in $roduction in$ut* '; Increase in $roductivity*



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T'e (ig#re re)re ent an e"onomi" growt' )ro"e

Revie!in( t#e $rocess in t#e su'se/uent years one and t!o.

$roduction #as increased fro" va)ue T 7 to T


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a* T#e (ro!t# caused 'y an increase in $roduction in$ut*

+* T#e (ro!t# caused 'y an increase in $roductivity*

C#aracteristic of t#e (ro!t# effected 'y an in$ut

increase is t#at t#e re)ation 'et!een out$ut and in$ut re"ains

unc#an(ed*

An increase in $roductivity is c#aracteri2ed 'y a

s#ift of t#e $roduction function and a conse/uent c#an(e to t#e

out$ut and in$ut re)ation*

T#e for"u)a of tota) $roductivity is nor"a))y !ritten

as fo))o!s*

Tota) Productivity > Out$ut /ua)ity and /uantity In$ut /ua)ity and /uantity

Accordin( to t#is for"u)a. c#an(es in in$ut and

out$ut #ave to 'e "easured inc)usive of 'ot# /uantitative and

/ua)itative c#an(es*

%AIN PROCESSES OF A CO%PANY FRO% $HICH

PRODUCTIVITY IS CREATED AND DISTRI UTED:

A co"$any can 'e divided into su' $rocesses in different !ays* Yet.

t#e fo))o!in( are identified as t#e "ain $rocess*

a; Rea) Process*

'; Inco"e Distri'ution $rocess*



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c; Production Process*

d; Monetary Process*

e; Mar,et Va)ue Process*

Productivity is created in t#e rea) $rocess. $roductivity (ains are

distri'uted in t#e inco"e distri'ution $rocess and t#ese t!o $rocesses

to(et#er constitute t#e $roduction $rocess*

a* REA PROCESS:

Rea) $rocess (enerates t#e $roduction out$ut and it can 'e

descri'ed 'y "eans of t#e $roduction function*

It refers to a series of events in !#ic# $roduction in$uts of

different /ua)ity and /uantity are co"'ined into $roducts of

different /ua)ity and /uantity*

Products can 'e a $#ysica) (oods. i""ateria) services and "ost

often co"'inations of 'ot#*

'; INCO%E DISTRI UTION PROCESS:

It refers to a series of events in !#ic# t#e unit $rices of constant

/ua)ity $roducts and in$uts a)ter causin( a c#an(e in inco"e

distri'ution a"on( t#ose $artici$atin( in t#e e?c#an(e*



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T#e "a(nitude of t#e c#an(e in inco"e distri'ution is direct)y

$ro$ortiona) to t#e c#an(e in $rices of t#e out$ut and in$uts and

to t#eir /uantities*

Productivity (ains are distri'uted. for e*(* to costu"ers as )o!er

$roduct $rices or to staff as #i(#er $ay*

"* THE PRODUCTION PROCESS:

T#e $roduction $rocess of consist of t#e rea) $rocess and t#e

inco"e distri'ution $rocess* A resu)t and criterion of success of

t#e $roduction $rocess is $rofita'i)ity*

%actors descri'in( t#e $roduction $rocess are t#e co"$onents

of $rofita'i)ity i*e* returns and costs*

T#ey differ fro" t#e factors of t#e rea) $rocess in t#at t#e

co"$onents of $rofita')y are (iven at no"ina) $rices !#ere as in

t#e rea) $rocess t#e factors are at fi?ed $rices*

.* %ONETARY PROCESS:

It refers to events re)ated to financin( t#e 'usiness*

e* %AR/ET VA UE PROCESS:

It refers to a series of events in !#ic# investors deter"ine t#e

"ar,et va)ue of t#e co"$any in t#e invest"ent "ar,ets*



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%EASURIN& AND INTERPRITIN& PARTIA PRODUCTIVITY 0

T#e ter" of $artia) $roductivity i))ustrates !e)) t#e fact t#at tota)

$roductivity is on)y "easured $artia))y or a$$ro?i"ate)y*

Measure"ent of $artia) $roductivity refers to t#e "easure"ent

so)utions !#ic# do not "eet t#e re/uire"ents of tota)

$roductivity "easure"ent*

T#e so)utions are.

i* Sin()e %actor Productivity0 + it refers to t#e "easure"ent

of $roductivity t#at is ratio of out$ut and one in$ut factor*

ii* Va)ue Added Productivity0+so"eti"es it is $ractica')e to

e"$)oy t#e va)ue added as out$ut and Productivity

"easured in t#is !ay is ca))ed as va)ue added $roductivity*

iii* Unit Cost Productivity0+ Productivity can 'e e?a"ined in

cost accountin( usin( unit costs*

iv* Efficiency Ratios0+ !#ic# te)) so"et#in(

a'out t#e ratio 'et!een t#e va)ue $roduced and sacrifices

"ade for it. are avai)a')e in )ar(e no*

v* Mana(eria) Contro) Ratio Syste"0+ t#ese syste"s are

co"$osed of sin()e "easures !#ic# are inter$reted in

$ara))e) !it# ot#er "easures re)ated to t#e su'1ects*

T'e mea #re o( )artia0 )ro.#"ti1it2 are,



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7; P#ysica) Measures*


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-a'our $roductivity0 Avera(e $roducts of )a'our Bavera(e

out$ut $er !or,er or $er !or,er #our. and out$ut !#ic#

cou)d 'e "easured in $#ysica) ter"s and in $rice ter"s;*

CONTENTS

&OOD %ANUFACTURIN& PRACTICES

Introduction

Definition

O'1ectives

Various As$ects of GMP

Pre"ises

E/ui$"ent and Utensi)s

Personne)

Sanitation

Anci))ary Area

Medica) Devices 6 Services

Ra! Materia)s

Manufacturers

Re$rocessin( and Recovery

Pac,a(in( and -a'e)in(

Stora(e

Steri)e Products

Considerations for %inis#ed Products



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GMP re(u)ations !ere introduced in t#e for" of a"ended sc#edu)e+

" in 7 *

T#e Sc#edu)e+M #as a(ain 'een a"ended in+


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T#e re/uire"ent is 'road)y stated t#at it casts a tre"endous

'urden of $roof on t#e %DA. es$ecia))y in cases !#ere t#ere

ar(ua')e varia')es in "et#odo)o(y. $rocedure or e/ui$"ent*

It a)so cost a #eavy 'urden on t#e industria) $#ar"acist. #o!ever.

'ecause it re/uires #i" to $roduce dru( $roducts 'y usin(

"anufacturin( $ractices t#at are 'ot# (ood and current*

In ot#er !ords. #e "ust ,ee$ u$ !it# advances and ado$t t#ose

t#at !i)) increase assurance of dru( inte(rity accordin( to t#e

re/uire"ents of t#e Act*

A)) $roduction $ersonne) s#ou)d understand GMP at )east as it

a$$)ies to t#eir $articu)ar area of res$onsi'i)ity and a)so to ,no!

!#at an %DA ins$ector )oo,s for*

O:JECTIVES0

T#e $roduction $rocess are c)ear)y defined. syste"ica))y revie!ed

and va)idated*

A)) t#e necessary faci)ities are $rovided*

Critica) $rocessin( ste$s. ,ey e/ui$"ents and services are

va)idated*

O$erators are trained to carry out $rocedure correct)y*



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Records of $roduction. in+$rocces. fina) contro) and distri'ution

are "aintained*

Syste" is avai)a')e to reca)) $roducts*

Co"$)aints are "ade to ta,e in to consideration*K

T E VARIOUS ASPECTS O% GMP0

To ac#ieve t#e o'1ectives )isted a'ove eac# )icensee s#a)) evo)ve

"et#odo)o(y and $rocedure !#ic# s#ou)d 'e docu"ented and

,e$t for reference and ins$ection*

GMPLS are "andatory = t#e co"$)iance !it# t#e" is a

$rere/uisite for t#e (rant or rene!a) of a "anufacturin( )icense*

%o))o!in( are t#e as$ects !#ic# are considered in GMP*

3! PRE%ISES:

A*-OCATION AND SOURROUNDING0

T#e factory 'ui)din( for "anufacture of dru(s s#a)) 'e situated =

s#a)) #ave suc# "easures to avoid ris, of conta"ination fro". o$en

se!a(e. drain. $u')ic )avoratory. and any ot#er factory !#ic#

$roduce disa(reea')e or o'no?ious odour. fu"es. e?cessive soot.

dust. s"o,e. c#e"ica) or 'io)o(ica) e"issions*

:*:UI-DING0



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T#e $re"ises used for "anufacturin(. $rocessin(. $ac,in(. )a'e)in( and

testin( $ur$ose s#a)) 'e.

Co"$ati')e !it# ot#er "anufacturin( o$erations t#at "ay 'e carried

out in t#e sa"e or ad1acent area or section*

Ade/uate !or,in( s$ace s#ou)d 'e $rovided to a))o! order)y =

)o(ica) $)ace"ent of e/ui$"ent. "ateria)s = "ove"ent of $ersonne)

so as to avoid t#e ris, of "i? u$. conta"ination = cross

conta"ination*

Desi(ned. constructed. and "aintained to $revent entry of insects.

$ests. 'irds. ver"inLs = rodents*

S#a)) 'e !e)) )i(#ted. effective)y venti)ated. !it# air contro))ed

faci)ities = "ay #ave $ro$er air #and)in( units to "aintain

conditions inc)udin( te"$erature = #u"idity as defined for t#e

re)evant $roduct = t#ese areas s#a)) 'e re(u)ar)y "onitored for

co"$)iance !it# re/uired s$ecifications*

Provided !it# draina(e syste". as s$ecified for t#e various

cate(ories of $roducts. !#ic# s#a)) 'e of ade/uate si2e = so

desi(ned as to $revent 'ac, f)o! and6or $revent insects = rodents

enterin( t#e $re"ises*



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T#e !a))s and f)oor s#a)) 'e free fro" crac, and o$en 1oints =

$er"it easy c)eanin(. $aintin( = disinfection*

C*&ATER SYSTEM0

T#e !ater used s#ou)d 'e $ure and of drin,a')e /ua)ity*

T#ere s#a)) 'e va)idated syste" for treat"ent of !ater dra!n fro"

o!n or any ot#er source to render it $ota')e as t#e case "ay 'e. so

as to $roduce $urified !ater confir"in( to $#ar"aco$oeia)

s$ecifications*

D*DISPOSA- O% &ASTE0

T#e dis$osa) of !aste fro" t#e "anufactory s#a)) 'e in confor"ity

!it# t#e re/uire"ents of Environ"ent Po))ution Contro) :oardH*

Dis$osa) "et#ods vary considera')y accordin( to situation so"e are.

7; Return to donor or "anufacturer*


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T#e e/ui$"ent used in t#e "anufacturin( $rocess "ust 'e of

a$$ro$riate desi(n. ade/uate si2e and suita')y )ocated for its

intended use. c)eanin(. saniti2ation and "aintenance*

T#e surface of t#e $roduction e/ui$"ent t#at co"es in contact !it#

t#e ra! "ateria). inter"ediate or AIS s#ou)d not 'e reactive.

additive or adsor$tive to an e?tent t#at !ou)d affect t#e /ua)ity of

t#e $roduct* Any su'stances associated !it# o$eration of e/ui$"ent suc# as

coo)ants. )u'ricants. #eatin( f)uids etc* s#ou)d not a)ter /ua)ity*

C)osed e/ui$"ent s#ou)d 'e used !#enever a$$ro$riate* en o$en

e/ui$"ent is used. a$$ro$riate $recautions "ust 'e ta,en to

"ini"i2e t#e ris, of conta"ination*

A set of current dra!in(s "ust 'e "aintained for e/ui$"ent and

critica) insta))ations*

:*MAINTENANCE AND C-EANING0

Sc#edu)e and $rocedures "ust 'e esta')is#ed for t#e $reventive

"aintenance of e/ui$"ent*

&ritten $rocedures "ust 'e esta')is#ed for t#e c)eanin( and its

su'se/uent re)ease for use in "anufacturin(*



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Trainin( s#ou)d 'e re(u)ar)y conducted 'y /ua)ified individua)s and

s#ou)d cover. at a "ini"u". t#e $articu)ar o$erations t#at t#e

e"$)oyee $erfor"s and GMP as it re)ates to t#e e"$)oyees

functions*

:*PERSONNE- YGIENE0

Personne) s#ou)d !ear c)ot#in( suita')e for "anufacturin( activity

!it# !#ic# t#ey are invo)ved* Additiona) $rotective a$$are). suc# as

#ead. face. #and. and ar" coverin(s* S#ou)d 'e !orn !#en

necessary. to $revent conta"ination*

Personne) "ust avoid direct contact !it# inter"ediates or active

in(redients*

S"o,in(. eatin(. drin,in(. c#e!in(. and stora(e of food "ust 'e

restricted to certain desi(nated areas se$arate fro" "anufacturin(

area*

A)) $ersonne) $rior to e"$)oy"ent and t#ereafter s#ou)d 'e

Su'1ected to $eriodic "edica) c#ec, u$ and $ersonne) sufferin(

fro" any infectious diseases or #avin( o$en )esions on t#e e?$osed

surface of 'ody s#ou)d not en(a(e in t#e activities t#at cou)d resu)t

in t#e co"$ro"isin( t#e /ua)ity of $roduct*



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T#e $ersonne) #and)in( 'eta+)actu" anti'iotic s#a)) 'e tested for

$enici))in sensitivity 'efore e"$)oy"ent and t#ose #and)in( se?

#or"ones. cytoto?ic su'stances and ot#er $otent dru(s s#a)) 'e

$eriodica))y e?a"ined for adverse effects* T#ese $ersonne) s#ou)d

'e "oved out of t#ese sections Be?ce$t in dedicated faci)ities;. 'y

rotation. as a #ea)t# safe(uard*

A)) $ersonne) $rior to and durin( e"$)oy"ent s#a)) 'e trained in

$ractices !#ic# ensure $ersonne) #y(iene* Instructions to t#is effect

s#a)) 'e dis$)ayed in c#an(e roo"s and ot#er strate(ic )ocations*

A)) $ersonne) s#a)) 'e instructed to re$ort a'out t#eir i))ness or

a'nor"a) #ea)t# condition to t#eir i""ediate su$ervisor so t#at

a$$ro$riate action can 'e ta,en*

7! SANITATION:

T#e "anufacturin( area s#a)) not 'e used for any ot#er $ur$ose*

Manufacturin( $re"ises s#a)) 'e Maintained c)ean and in an order)y

"anner. free fro" accu"u)ated !aste. dust. de'ris etc3



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A routine sanitation Pro(ra""e s#a)) 'e dra!n u$ and o'served

!#ic# s#a)) 'e $ro$er)y recorded and !#ic# s#a)) indicate.

+S$ecific areas to 'e c)eaned and c)eanin( interva)s

+C)eanin( $rocedures to 'e fo))o!ed. inc)udin(

e/ui$"ent to 'e used for c)eanin(3 and

+Personne) assi(ned to and res$onsi')e for c)eanin(

o$eration* Records of co"$)iance in res$ect of saniti2ation s#a)) 'e

"aintained for ins$ection*

8! ANCI ARY AREAS:

Rest and refres#"ent roo"s s#a)) 'e se$arate fro" ot#er areas*

T#ese areas s#a)) not )ead direct)y to t#e "anufacturin( and stora(e

areas*

%aci)ities for c#an(in(. storin( c)ot#es. !as#in( and toi)et $ur$ose

s#a)) 'e easi)y accessi')e and ade/uate for t#e no of users* Toi)ets.

se$arate for "a)es and fe"a)es. s#a)) not 'e direct)y connected !it#

$roduction or stora(e areas* T#ere s#a)) 'e !ritten instructions for

c)eanin( and disinfection of suc# areas*

Maintenance !or,s#o$s s#a)) 'e se$arate and a!ay fro" $roduction

areas* enever s$ares. c#an(ed $arts and too)s are stored in t#e



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$roduction area. t#ese s#a)) 'e ,e$t in dedicated roo"s or )oc,ers*

Too)s and s$are $arts for use in steri)e areas s#a)) 'e disinfected

'efore t#ese are carried inside t#e $roduction area*

Areas #ousin( ani"a)s s#a)) 'e iso)ated fro" ot#er areas*

9! %EDICA DEVICES SERVICES:

T#e "anufacturer s#a)) $rovide.

Ade/uate faci)ities for first aid*

Medica) e?a"ination of !or,ers at t#e ti"e of e"$)oy"ent and

$eriodica) c#ec, u$ t#ereafter once in a year. !it# $articu)ar

attention 'ein( devoted to freedo" fro" infectious conditions*

Records t#ereof s#a)) 'e "aintained3 and

%aci)ities for vaccination or ot#er e?i(encies* T#e )icensee s#a))

$rovide services of a /ua)ified $#ysician for assessin( t#e #ea)t#

status of a)) e"$)oyees*

;! RA$ %ATERIA :

Res$onsi')e $erson "ust ,ee$ an inventory of a)) ra! "ateria)s to

'e used and "aintain records as $er sc#edu)e U*

A)) inco"in( "ateria)s s#a)) 'e $urc#ased fro" a$$roved sources

under va)id $urc#ase vouc#ers*



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Identified and containers e?a"ined for inte(rity of $ac,a(e and

assi(ned contro) no*

If a sin()e de)ivery of "ateria) is "ade u$ of different 'atc#es. eac#

'atc# s#a)) 'e considered a se$arate 'atc# for sa"$)in(. testin( and

re)ease*

Syste"ica))y sa"$)ed 'y *C* $ersonne)*

T#ere s#a)) 'e ade/uate se$arate area for "ateria)s under test.

a$$roved and re1ected*

Stoc, rotation is on t#e 'asis of first in first out $rinci$)e*

Cons$icuous)y )a'e)ed indicatin( t#e na"e of t#e "ateria)s. contro)

no. na"e of t#e "anufacturer and 'e s$ecifica))y )a'e)ed under test

or a$$roved or re1ected*

A*PRODUCTION AREA0

T#e $roduction area s#a)) 'e desi(ned to "a,e $roduction uni+ f)o!

and !it# )o(ica) se/uence of o$erations*

In order to avoid ris, of cross+conta"ination. Se$arate dedicated

and se)f contained faci)ities s#a)) 'e "ade avai)a')e for t#e

$roduction of sensitive $roducts )i,e $enici))in or 'io)o(ica)

$re$arations !it# )ive "icro+or(anis"s*se$erate dedicated faci)ities



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s#a)) 'e $rovided for t#e "anufacture of conta"ination causin( and

$otent dru(s suc# as :eta )actu". se? #or"ones and cytoto?ic

su'stances*

&or,in( s$ace s#ou)d 'e ade/uate to $er"it order)y and )o(ica)

$)ace"ent of e/ui$"ent and "ateria)s and "ove"ent of $ersonne)

to avoid cross+conta"ination and to "ini"i2e ris, of o"ission or

!ron( a$$)ication of any "anufacturin( and contro) "easures* Pi$e !or,. e)ectrica) fittin(s. venti)ation o$enin(s. and si"i)ar

service )ines s#a)) 'e desi(ned. fi?ed and constructed to avoid t#e

for"ation of recesses*

:*MANU%ACTURING PROCEDURES0

Manufacture s#a)) 'e carried out in accordance !it# "aster for"u)a*

Critica) ste$s in t#e $rocess re)atin( to se)ection. !ei(#in(. and

"easurin( of ra! "ateria) addition durin( various sta(es s#a)) 'e

va)idated*

Manufacture s#a)) 'e su$ervised and $erfor"ed 'y co"$etent

$ersons*

Durin( "anufacture. E/ui$"ent. vesse)s and containers s#a)) 'e

identified t#rou(# $ro$er )a'e)in(. t#at inc)udes t#e na"e of t#e

$roduct. 'atc# no. 'atc# si2e and sta(e of "anufacture* -a'e)s s#a))



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'e attac#ed to a)) "ec#anica) "anufacturin( e/ui$"ent durin( t#eir

o$eration !it# cons$icuous )a'e)s 'earin( t#e na"e of t#e $roduct

and 'atc# no*

Dai)y activities s#a)) 'e are recorded*

Products not $re$ared under ase$tic conditions are re/uired to 'e

free fro" $at#o(ens )i,e sa)"one))a. E* co)i. Pyocyanea. etc*

Sa"$)in( and testin( in $rocess "ateria)s and dru( $roducts s#a)) 'e

carried out to "onitor t#e $roduct /ua)ity*

C*PRECAUTIONS AGAINST CONTAMINATIONS AND MI@ UP0

T#e )icensee s#a)) $revent cross+conta"ination of dru(s !it# se?

#or"ones. 'eta )actu" anti'iotics. and antineo$)astic dru(s 'y

a$$ro$riate "et#ods. !#ic# "ay inc)ude+

Carryin( out Production in se(re(ated areas fo))o!ed 'y a$$ro$riate

c)eanin(*

Usin( a$$ro$riate $ressure differentia) in t#e $rocessin( area3

Provide a$$ro$riate air )oc,s and e?#austs

Desi(nin( steri)e air syste"s for steri)e $roducts3

Usin( UV )a"$s*

Pac,a(in( )ine s#a)) 'e inde$endent and ade/uate)y se(re(ated* It

s#a)) 'e ensured t#at a)) )eft overs of t#e $revious $ac,a(in(



27/47



o$erations. inc)udin( )a'e)s. cartons and ca$s are c)eared 'efore t#e

c)osin( #ours*

-ine c)earance s#a)) 'e $erfor"ed 'y a$$ro$riate c#ec,)ist and

record*

Any necessary in $rocess contro)s and environ"enta) contro)s

s#ou)d 'e carried out and recorded*

Individua) containers of )i/uid ora)s. $arentera)s and o$#t#a)"ic

so)utions s#a)) 'e e?a"ined a(ainst ')ac,+!#ite 'ac,(round fittin(

!it# diffused )i(#t after fi))in( to ensure freedo" fro"

conta"ination !it# forei(n sus$ended "atter*

=! REPROCESSIN& AND RECOVERY:

If a $roduct 'atc# #as to 'e re$rocessed. return $rocedures s#a)) 'e

esta')is#ed. aut#ori2ed and recorded suc# re$rocessin( s#a)) 'e

va)idated*

Recovery of t#e $roduct residue "ay 'e carried out 'y incor$oratin(

in su'se/uent 'atc#es of t#e $roduct. if $er"itted in t#e "aster

far"u)a*Recovered "ateria) t#at !i)) a)ter t#e /ua)ity of $roduct

s#ou)d not 'e used



28/47



-i"its. a$$roved 'y t#e /ua)ity contro). s#ou)d 'e esta')is#ed for

t#e a"ount of recovered "ateria) !#ic# "ay 'e added to a

su'se/uent 'atc#es*

:atc#es incor$oratin( residues s#ou)d not 'e re)eased unti) t#e

'atc#es fro" !#ic# t#e residues ori(inated #ave 'een tested and

found suita')e for use*

An investi(ation s#a)) 'e carried out in to t#e causes necessitatin(

re$rocessin( and corrective "easures s#a)) 'e ta,en*

3>! PAC/A&IN& AND A E IN&?

A)) containers and c)osures s#a)) co"$)y !it# $#ar"aco$oeia)

re/uire"ents* Suita')e s$ecifications. test "et#ods. c)eanin( $rocedure and

steri)i2ation $rocedure. !#en indicated. s#a)) 'e used to assure t#at

containers. c)osures and ot#er co"$onent $arts of dru(s $ac,a(es. are

suita')e and t#ey are not reactive. additive. adsor$tive or )eac# to an e?tent

t#at si(nificant)y !i)) affect t#e /ua)ity or $urity of dru(*

Measure $#ysica) and c#e"ica) c#an(es of a)) containers and

c)osures under e?tre"e #eat. "oisture and )i(#t conditions*

Measure $#ysica) $rotection $rovided 'y containers*



29/47



To?icity. co"$ati'i)ity and sta'i)ity studies s#a)) 'e carried out for

containers and c)osures*

-ea,a(e test for a"$ou)es. co))a$si')e tu'es. stri$ $ac,s. $in #o)es

in stri$s s#ou)d 'e conducted

&ritten $rocedures s#a)) 'e esta')is#ed for $ac,a(in( and )a'e)in(*

:efore enterin( in to $ac,a(in( area. $ac,a(in( )ine c)earance s#a))

'e c#ec,ed*

Prior to issue. a)) )a'e)s for containers. cartons and 'o?es and a))

circu)ars. inserts and )eaf)ets s#a)) 'e e?a"ined and re)eased 'y

/ua)ity contro) $ersonne)*

Prior to $ac,a(in( and )a'e)in( of a (iven 'atc# of dru( it "ust 'e

ensured t#at t#e 'atc# #as 'een du)y tested. a$$roved and re)eased

'y t#e /ua)ity contro) $ersonne)*

To $revent $ac,a(in( and )a'e)in( errors. a ,no!n no of )a'e)in(

and $ac,a(in( units are issued and if re/uired coded*

U$on co"$)etion of $ac,a(in( and )a'e)in( o$eration. co"$arison

s#a)) 'e "ade 'et!een nu"'er of )a'e)in( and $ac,a(in( units and

no of units )a'e)ed and $ac,a(ed*

Unused coded and s$oi)ed )a'e)s and $ac,a(in( "ateria)s are

destroyed*



30/47


31/47



uarantine status if ensured 'y !are#ousin( se$arate area s#a)) 'e

$rovided and access to suc# areas s#a)) 'e restricted to aut#ori2ed

$ersons*

T#ere s#a)) 'e a Se$arate sa"$)in( area for active ra! "ateria)s and

e?ci$ients* If sa"$)in( is $erfor"ed in any ot#er area. it s#a)) 'e

conducted in suc# a!ay as to $revent conta"ination. cross

conta"ination and "i? u$* Se(re(ation s#a)) 'e $rovided for t#e stora(e of re1ected. reca))ed or

retained $roducts* Suc# areas. "ateria)s and $roducts s#a)) 'e

suita')y "ar,ed and secured*

i(#)y #a2ardous. $oisonous and e?$)osive "ateria)s suc# as

narcotic. $syc#otro$ic dru(s and su'stances $resentin( $otentia)

ris,s of a'use. fire or e?$)osion s#a)) 'e stored in safe and secure

areas and ade/uate fire $rotection "easures s#a)) 'e $rovided in

suc# areas*

Se$arate dis$ensin( area for +)actu". se? #or"ones and cytoto?ic

su'stances or any suc# s$ecia) cate(ories of $roducts s#a)) 'e

$rovided !it# $ro$er su$$)y of fi)tered air and suita')e "easures for

dust contro) to avoid conta"ination* Suc# areas s#a)) 'e under

differentia) $ressure*



32/47



Sa"$)in( and dis$ensin( of steri)e "ateria)s s#a)) 'e conducted in a

s$ecific condition BGrade A;*

Rodent treat"ent s#ou)d 'e done re(u)ar)y and at )east once in a

year and record "aintained*

Storage S)e"i(i"ation Tem)erat#re Con.itionCold Not to exceed 8 0C

Freezer -100

to -200

C Cool 8 0to 15 0C Room temperature 15 0 to 30 0C

Warm 30 0 to 40 0C Excessive eat !"ove 40 0C

34! STERI E PRODUCTS:

C)eanu$ area is constructed to !it#stand "oisture. stea" and

deter(ents and is usua))y c)ass 7. 88.888 c)ean area*

T#e cei)in( &a))s and f)oors s#ou)d 'e constructed of

i"$ervious "ateria) so t#at "oisture !i)) run off and not 'e #e)d*

T#ese areas s#ou)d 'e e?#austed ade/uate)y. so t#at t#e #eat and

#u"idity !i)) 'e re"oved for t#e co"fort of $ersonne)*

Precautions "ust 'e ta,en to $revent accu"u)ation of dirt and t#e

(ro!t# of "icroor(anis"s 'ecause of t#e #i(# #u"idity and #eat*

Ade/uate sin, and counter s$ace "ust 'e $rovided*



33/47



Ca'inets and counters s#ou)d $refera')y 'e constructed of

stain)ess stee) and #un( fro" !a)). so t#at t#ere are no )e(s to

accu"u)ate dirt !#ere t#ey rest on t#e f)oor*

A)) )i(#t fi?tures. uti)ity service )ines and venti)ation fi?tures

s#ou)d 'e recessed in !a))s to e)i"inate 1oints and ot#er )ocations

for t#e accu"u)ation of dirt*

Personne) enterin( t#e ase$tic area s#ou)d enter on)y t#rou(# an

air )oc,*

T#ey s#ou)d 'e attired in steri)e covera))s !it# steri)e c)ot#s.

steri)e #ats. "as,s. (o(()es and foot covers etc* in and out

"ove"ent ri(id)y 'e restricted durin( a fi))in( o$eration*

To re"ove fine de'ris do!n to t#e su'"icron ran(e. inc)udin(

"icro or(anis"s. a EPA fi)ter. defined as at )east * F

efficient in re"ovin( $artia)s of 8*4 "icro "eter si2e and )ar(er

and co"$osed of ()ass fi'ers and fi))ers or e)ectrostatic

$reci$itators "ay 'e e"$)oyed*

AIR ORNE PARTICU ATE C ASSIFICATION FOR

%ANUFACTURE OF STERU E PRODUCTS

GradeMa?i"u" No* of Per"itted Partic)es Per Cu'ic

Meter

Ma?i"u" No* Via')e

Microor(anis"s

Per"itted Per Cu'ic

Meter



34/47



8* + " "

A3>> at re t 68>> B4


35/47



USUA--Y NO! AT RIS9

7.88.888

B GRADE DH;%ORM. %I-- = SEA-

ENVIRON%ENTA %ONITORIN& SCHEDU E

A; Particu)ate Monitorin( In Air M"#$%l B "ont#)y;

:; EPA fi)ter inte(rity testin( # ' " * $*'$i#+ $ - "#$%l ."/ LAF

'*1 ."/ '* $i4 " */ $i"# BYear)y;*

C; Air c#an(e rates "ont#)y

D; Air $ressure differentia)s dai)y

E; Te"$erature and #u"idity dai)y

%; Micro'io)o(ica) "onitorin( 'y sett)e $)ates and6or s!a's in ase$tic

areas dai)y. and at decreased fre/uency in ot#er areas*

36! CONSIDERATION FOR FINISHED PRODUCTS:

STORAGE

DISTRI:UTION

Records s#a)) 'e "aintained on t#e distri'ution of eac# 'atc#

of a $roduct in order to faci)itate t#e reca)) of t#e 'atc# if

necessary*



36/47



T#e aut#orities s#a)) 'e $ro"$t)y infor"ed !#en one or "ore

'atc#es are to 'e !it#dra!n for" sa)e or use 'ecause t#ey

are defective*

COMP-AINTS AND PRODUCT DE%ECTS

A)) co"$)aints t#reof concernin( $roduct /ua)ity s#a)) 'e

carefu))y received and recorded accordin( to !ritten

$rocedures*

Eac# co"$)aint s#a)) 'e Investi(ated and records of

investi(ation and su'se/uent action ta,en t#ereof s#a)) 'e

"aintained*

Re$orts of any #a2ardous reactions resu)tin( fro" t#e use of a

dru( a)on( !it# co""ents and docu"ents s#a)) 'e re$orted

to t#e concerned aut#orities*

Manufacturer s#a)) "aintain !ritten instructions of dea)in(

suc# co"$)aints concernin( t#e /ua)ity of $roduct*

37! 5UA ITY CONTRO SYSTE%S:

Every "anufacturin( esta')is#"ent s#a)) #ave a /ua)ity contro)

de$art"ent* T#is s#a)) contro) a)) ra! "ateria)s. "onitor a)) in $rocess

/ua)ity c#ec,s and contro) t#e /ua)ity and sta'i)ity of finis#ed $roduct*



37/47



Ade/uate faci)ities. trained $ersonne) and a$$roved $rocedures

s#ou)d 'e "ade avai)a')e for ins$ectin( and testin( of startin( and

$ac,a(in( "ateria)s. inter"ediates. 'u), and finis#ed $roducts and

a)so "onitorin( environ"enta) conditions for GMP $ur$ose*

Sa"$)es of a)) "ateria)s ta,en 'y /ua)ified $ersonne) 'y "et#ods

a$$roved 'y /ua)ity contro)*

Test "et#ods are va)idated*

Ade/uate standards and rea(ents are "aintained*

So$s s#a)) 'e avai)a')e sa"$)in(. ins$ectin( and testin( of a))

"ateria)s*

No 'atc# of Product is re)eased for su$$)y $rior to certification 'y a

/ua)ified $#ar"acist t#at it is in accordance !it# a)) )e(a)

re/uire"ents*

Se$arate areas s#a)) 'e $rovided eac# for $#ysicoc#e"ica).

'io)o(ica). "icro'io)o(ica) or radio+isoto$e ana)ysis* Se$arate air

#and)in( units and ot#er re/uire"ents s#a)) 'e $rovided for

'io)o(ica). "icro'io)o(ica) and radio+isoto$e testin( areas*

P#ar"aco$oeia. reference standards. s$ectra s#a)) 'e avai)a')e

Records "aintained

38! 5UA ITY ASSURANCE:



38/47



T#is is !ide ran(in( conce$t concernin( a)) "atters t#at individua))y or

co))ective)y inf)uence t#e /ua)ity of $roduct* It is t#e tota)ity of t#e

arran(e"ents "ade !it# t#e o'1ect of ensurin( t#at t#e $roducts are of

t#e /ua)ity re/uired for t#ere intended use*

T#e syste" of /ua)ity assurance a$$ro$riate to t#e

"anufacture of $#ar"aceutica) $roducts s#a)) ensure t#at0+

T#e $#ar"aceutica) $roducts are desi(ned and deve)o$ed in a

!ay t#at ta,es account of t#e re/uire"ent of GMP. G-P and GCP*

Ade/uate arran(e"ents are "ade for "anufacture su$$)y and use

of t#e correct startin( and $ac,a(in( "ateria)s*

Ade/uate contro)s on startin( "ateria)s. inter"ediate $roducts.

'u), $roducts and ot#er in $rocess contro)s. ca)i'rations and

va)idations are carried out*

T#e finis#ed $roduct is correct)y $rocessed and c#ec,ed in

accordance !it# esta')is#ed $rocedures*

P#ar"aceutica) $roducts are not re)eased for sa)e or su$$)y 'efore

aut#ori2ed $erson #ave certified t#at $roduct co"$)y !it#

re/uire"ents of )a'e) c)ai"*

39! DOCU%ENTATION:



39/47



Docu"entation is an essentia) $art of /ua)ity assurance syste" and. as

suc#. s#a)) 'e re)ated to a)) as$ects of GMP* Its ai" is to define t#e

s$ecifications for a)) "ateria)s. "et#od of "anufacture and contro)3

t#erefore it is defined as a "et#od of $re$arin( !ritten "ateria) t#at (ives

t#e co"$)ete descri$tion of $rocess in ter"s of s$ecifications. instructions.

contro)s etc*

Docu"ents s#a)) 'e desi(ned. $re$ared. revie!ed. and contro))ed

!#erever a$$)ica')e*

Docu"ents s#a)) 'e a$$roved. si(ned and dated 'y aut#ori2ed

$ersons*

S#a)) s$ecify t#e tit)e. nature and $ur$ose* Any a)teration "ade in

t#e entry of a docu"ent s#a)) 'e si(ned and dated*

T#e Records s#a)) 'e "ade or co"$)eted at t#e ti"e of eac#

o$eration in suc# a !ay t#at a)) si(nificant activities concernin(

t#e "anufacture of $#ar"aceutica) $roducts are tracea')e*

Records and associated SOPLS s#a)) 'e retained at )east one

year after t#e e?$iry date of finis#ed $roduct*

A* MASTER %ORMU-A RECORDS0

Master for"u)a records are defined as a !ritten $rocedures t#at (ive

a co"$)ete descri$tion of a)) as$ects of its "anufacture. $ac,in( and



40/47



contro) !it# an intension to ensure t#e identity. stren(t#. /ua)ity and $urity

of eac# dosa(e unit t#rou(# out its entire se)f )ife*

It s#a)) (ive.

Patent or $ro$rietary na"e. (eneric na"e. stren(t# and dosa(e

for"*

Descri$tion or identification of fina) container. $ac,a(in(

"ateria). )a'e)s and c)osures to 'e used* T#e identify /ua)ity and /uantity of eac# ra! "ateria) to 'e used

irres$ective of !#et#er or not it a$$ears in t#e finis#ed $roduct*

T#e $er"issi')e overa(e t#at "ay 'e inc)uded in a for"u)ated

'atc# s#ou)d 'e indicated*

A descri$tion of a)) vesse)s and e/ui$"ent and t#e si2es used in

t#e $rocess*

Manufacturin( and contro) instructions a)on( !it# $ara"eters

for critica) ste$s suc# as "i?in(. dry ')endin(. sievin(.

steri)i2in( t#e $roduct etc* T#eoretica) yie)d to 'e e?$ected fro" t#e for"u)ation at

different sta(es of "anufacture and $er"issi')e yie)d )i"its*

T#e re/uire"ent of in $rocess /ua)ity contro) tests and ana)ysis

to 'e carried out*



41/47


42/47



Records and reference sa"$)es s#a)) 'e retained at )east for One

year after e?$iry or e?$ected "ar,et )ife of $roduct*

Reference Sa"$)es of startin( "ateria)s and finis#ed $roducts

s#a)) 'e of sufficient si2e to ena')e necessary ana)ysis to 'e

carried out durin( t#e retention $eriod and s#a)) stored under

reco""ended conditions*

3;! VA IDATION:

Va)idation is a esta')is#in( docu"ented evidence. !#ic# $rovides #i(#

de(ree of assurance t#at a s$ecific $rocess or e/ui$"ent !i)) consistent)y

$roduce a $roduct "eetin( its $redeter"ined s$ecifications and /ua)ity

c#aracteristics*

Va)idation studies s#a)) 'e an essentia) $art of GMP and s#a)) 'e

conducted as $er t#e $redefined $rotoco)s* T#ese s#a)) inc)ude

va)idation of $rocessin(. testin( and c)eanin( $rocedures*

Records of resu)ts and conc)usions s#a)) 'e $re$ared.

docu"ented and "aintained*



43/47



Processes and $rocedures s#a)) 'e esta')is#ed on t#e 'asis of

va)idation study and under(o $eriodic reva)idation to ensure t#at

t#ey re"ain ca$a')e of ac#ievin( t#e intended resu)ts*

en any ne! "aster for"u)a or "et#od of $re$aration is

ado$ted. ste$s s#a)) 'e ta,en to de"onstrate its suita'i)ity for

routine $rocessin(*

Si(nificant c#an(es in t#e "anufacturin( $rocess inc)udin( any

c#an(es in e/ui$"ent or "ateria)s t#at "ay affect $roduct /ua)ity

s#a)) 'e va)idated*

3

Goods !#ic# #ave 'een re1ected. reca))ed or returned s#a)) 'e

stored in ade/uate and se(re(ated areas*

A %inis#ed $roduct returned fro" "anufacturers o!n stores or

!are#ouse BE(. 'ecause of s$oi)ed or da"a(ed )a'e)s or outer

$ac,a(in(; "ay 'e re)a'e)ed or 'u),ed for inc)usion in to

su'se/uent 'atc#es. $rovided t#at t#ere is no ris, to t#e $roduct

/ua)ity and t#e o$eration is s$ecifica))y aut#ori2ed and

docu"ented*



44/47


45/47



T#e reca))ed $roducts s#a)) 'e stored se$arate)y in secured

se(re(ated areas*

T#e notification of reca)) s#ou)d inc)ude.

+ Trade na"es. stren(t#. $ac, si2e and c)ass*

+ :atc# nu"'er*

+ Nature of t#e defect or reason for reca))*

+ Date of reca)) or !it#dra!a)*

+ Action to 'e ta,en*

4>! TRAININ&:

A)) $roduction. /ua)ity assurance and store $ersonne) and a))

ot#er $ersonne) !#ose duties ta,e t#e" in to "anufacturin(

areas. s#ou)d 'e trained in t#e $rinci$)es of GMP and in t#e

$ractice of t#e tas,s assi(ned to t#e"*

Ne!)y recruited $ersonne) s#ou)d receive trainin( on t#e t#eory

and $ractice of GMP. and trainin( a$$ro$riate to t#e duties

assi(ned to t#e"* S$ecific trainin( s#a)) 'e $rovided for $ersonne) !or,in( in areas

of conta"ination. e(* C)ean area or area !#ere #i(#)y active.

to?ic. infectious or sensiti2in( "ateria)s are #and)ed*



46/47



T#e conce$t of /ua)ity assurance and a)) ot#er "easures ca$a')e

of i"$rovin( its understandin( and i"$)e"entation s#ou)d 'e

fu))y discussed durin( t#e trainin( sessions*

Continuin( trainin( s#ou)d a)so 'e (iven and its $ractica)

effectiveness s#ou)d 'e $eriodica))y assessed* &ritten trainin(

$ro(ra"s s#ou)d 'e avai)a')e. a$$roved 'y eit#er t#e #ead of

$roduction or t#e #ead of /ua)ity contro). as a$$ro$riate* T#e

trainin( records s#ou)d 'e ,e$t*

43! AUDIT PAI:

Audits on a)) syste"s. $rocedures and o$erations s#ou)d 'e

re(u)ar)y conducted in order to "onitor co"$)iance !it# and t#e

effectiveness of GMP and /ua)ity assurance $rinci$)es in t#e

various o$erations*

Audits "ay 'e in #ouse or carried out 'y )oca) re(u)atory

aut#orities or t#e re(u)atory aut#orities of countries to !#ic#

co"$anies !is# to e?$ort*

Audits s#ou)d fo))o! a $re arran(ed $ro(ra""e and inc)ude

ins$ection of t#e fo))o!in(

+ Or(ani2ationa) "atters and res$onsi'i)ities

+ ua)ification and trainin( $ro(ra""ers



47/47



+ Co"$)iance !it# #y(iene re/uire"ents and entry

restrictions*

+ C)eanin( and disinfection $ro(ra""e*

+ Medica) c#ec,s on $ersonne)

+ Production faci)ities. $re"ises. and e/ui$"ent

inc)udin( *C*

+ Production o$erations. docu"entations. stora(e.

#o)din(. distri'ution and "ateria) "ana(e"ent

+ ua)ity assurance as$ects suc# as co"$)aints.

returned (oods and va)idation

+ Su$$)iers of starin( and $ac,a(in( "ateria)s*

+ T#ird $arty contractors for "anufacturin(.

$ac,a(in(. ana)ysis and !#ere re/uired distri'ution

of "edicines*

Audit s#ou)d 'e detai)ed and conducted 'y co"$etent and

i"$artia) $ersons fro" t#e co"$any*

Audit re$orts s#ou)d 'e "ade*

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