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Transcript of GMP Inspections En
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7/21/2019 GMP Inspections En
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| Slide 1 of 57 October 2007
Dr A J van Zyl
Technical Officer
HTP/PSM/QSM
World Health Organization (WHO!eneva" S#itzerland
vanzyla$#ho%int
Training Workshop on PharmaceuticalDevelopment with a focus on Paediatric
Formulations
15 October 2!
Tallinn" #stonia
1
!ood Man&fact&ring Practice' (!MP and n')ection'
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!ood Man&fact&ring Practice' (!MP and n')ection'
Outline and Ob$ectives of presentation
ntrod&ce WHO !MP te*t'
+ Main )rinci)le'
+ S&))le,ent'
+ Other'
n the conte*t of Pre-&alification
.&rrent and f&t&re a))roache'
n')ection' in )re-&alification
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!ood Man&fact&ring Practice' (!MP and n')ection'
WHO !MP te*t Main )rinci)le'WHO Technical 0e)ort Serie'" 1o% 234" 5336
+ Anne* 7
0eg&larly revie#ed and &)dated
Divided into 8cha)ter'8 or 8-&ality 'y'te,'8
Q&ality a''&rance"
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!ood Man&fact&ring Practice' (!MP and n')ection'
9% Q&ality a''&rance
5% !ood ,an&fact&ring )ractice' for )har,ace&tical )rod&ct'(!MP
6% Sanitation and hygiene
7% Q&alification and validation
:% .o,)laint'
;% Prod&ct recall'
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!ood Man&fact&ring Practice' (!MP and n')ection'
2% Per'onnel
93% Training
99% Per'onal hygiene
95% Pre,i'e'
96% >-&i),ent
97% Material'
9:% Doc&,entation
9;% !ood )ractice' in )rod&ction
9
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!ood Man&fact&ring Practice' (!MP and n')ection'
Other te*t'Sterile )rod&ct'
Her?al ,edicine'
0adio)har,ace&tical'
H@A.
Water 'y'te,'
Sa,)ling etc
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!ood Man&fact&ring Practice' (!MP and n')ection'
Al'o to con'ider #hen nece''ary
P./S g&ideline'
SO g&ideline'+ Sa,)ling
+ 0i' ,anage,ent+ .lean roo,'
.H g&ideline'+ .H Q2
BSA CDA
+ !&ideline' and g&idance
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!ood Man&fact&ring Practice' (!MP and n')ection'
.onte*t in Pre-&alificationProd&ct ')ecific (do'age for, in')ection'
SOP' follo#ed
+ Planning" )re)aration" cond&ct" re)ort+ n')ection tea,
A))ro)riate g&ideline' &'ed
0e)ort #ith reference' to te*t" and rating+ .ritical" ,aor" ,inor
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!ood Man&fact&ring Practice' (!MP and n')ection'
A critical deficiency#a' defined a' a deficiency #hich had)rod&ced" or led to a 'ignificant ri'of )rod&cing" either a)rod&ct #hich #a' har,f<o the h&,an )atient or a )rod&ct#hich co&ld re'< in a har,f&l re'id&e in a food )rod&cingani,al%
A ,aor deficiency#a' defined a' a non=critical deficiency"#hich had )rod&ced or ,ight )rod&ce a )rod&ct #hich did notco,)ly #ith it' ,areting a&thori'ation%
A ,inor deficiency #a' defined a' a deficiency #here ano?'ervation ,ade co&ld i,)rove the -&ality 'y'te, and -&ality
a''&rance a))roach of the ,an&fact&rer" ?&t #hich did not havea ,aor i,)act on the -&ality of the )rod&ct%
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!ood Man&fact&ring Practice' (!MP and n')ection'
n')ection a))roach
1or,ally a 8ro&tine ty)e8 of !MP in')ection
O)ening ,eeting" follo# the flo#" clo'ing ,eeting
On 'ite in')ection ()rod&ction and -&ality control and
doc&,entation revie#
Q&ality 'y'te,' a))roach
Modern challenge' incl&ding ri' a''e'',ent
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!ood Man&fact&ring Practice' (!MP and n')ection'
!&iding )rinci)le'
0i' ?a'ed orientation
Science ?a'ed )olicie' and 'tandard'
ntegrated -&ality 'y'te,'
nternational 'tandard'
P&?lic intere't
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!ood Man&fact&ring Practice' (!MP and n')ection'
Prod&ct -&ality and )erfor,ance en'&red thro&gh+ de'ign (,an&fact&ring )roce''e'
Prod&ct and )roce'' ')ecification'
+ Bnder'tanding of affect of for,&lation and )roce'' factor'
on )rod&ct -&ality and )erfor,ance
Q&ality ?y de'ign (?&ild -&ality into the )rod&ct
nteraction ?et#een revie#" co,)liance and in')ection
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!ood Man&fact&ring Practice' (!MP and n')ection'
Where to 'tartE
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12%1
Premises
Principle
,)ortant a')ect' to ?e e)t in ,ind to en'&re the '&ita?ility of
the o)eration' to ?e carried o&t for different do'age for,' and
)rod&ct range
Focation
De'ign
.on'tr&ction
Ada)tation
Maintenance
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12%&
Premises
Principle
Pre,i'e' ,&'t ?elocated to ,ini,izeri'' of cro''=conta,ination" e%g%notlocated ne*t to a,alting factory #ithhigh air?orne level' ofyea't
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12%2
Premises
'eneral
The layo&t and de'ign 'ho&ld ai, to
Mini,ize ri'' of error'
Per,it effective cleaning
Per,it effective ,aintenance
Avoid cro''=conta,ination" ?&ild=&) of dirt and d&'t
Avoid any adver'e effect on the -&ality of )rod&ct'
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Premises
Design Principles
Gee) in ,ind
Material flo#
Peo)le flo#
Proce'' flo#
#nsure logical flow
12%1
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Q C Ofces
Gowning
Canteen
Incoming
goods
Corridor
CorridorShipping
Corridor
Packaging
Weighing Processing
Filling
Raw
Materials
&
Packaging
Storage
Washing MachineShop
Finished
ProdctsStorage
Corridor
!tilities and Ser"ices
Waste #reatment
Premises
#(ample of )aterials and People Flow
Arrival of good' >ntrance for vi'itor' >ntrance for Worer' Shi),ent of good'
Material Clo#
Peo)le Clo# Zone .lean
Zone Pacaging
Zone .ontrolled
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12%*" 12%+2
Premises
,onstructionS&ita?le ,aterial'
>lectrical '&))ly
S&ita?le lighting (e')ecially for vi'&al on=line chec'
Te,)erat&re and relative h&,idity control
A))ro)riate and effective ventilation
The'e ,ay affect )rod&ct' d&ring ,an&fact&re or 'torage a' #ella' f&nctioning of e-&i),ent
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Premises
The te,)erat&re and relative
h&,idity 'ho&ld ?e
controlled" ,onitored in
accordance #ith an SOP" andthe re'<' recorded% The
li,it' 'ho&ld ?e a))ro)riate
according to the ,aterial'
'tored and )rod&ct
)roce''ed
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Premises
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12%11 - 12%+.
Premises
/pecific areas
0evie# 'o,e reco,,endation' for ')ecific area' in the follo#ing
'lide' (Part 5
Ancillary area'
Storage area'
Weighing area'
Prod&ction area'
Q&ality control area'
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Premises
T O ( F > T S
A (0
F O . G
. A 1 T > > 1
C A . T O 0 . H A 1 ! >
0 O O M
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Premises
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Premises
Se)arate receiving and
di')atch ?ay'
Materials and
products protectedfrom weather
Area to clean inco,ing
,aterial' )rovided
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Premises
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Premises
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Premises
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12%1." 12%1!
Premises
/torage areas 0 2
A))ro)riate te,)erat&re and relative h&,idity condition' #ithin
defined li,it'
Provided, controlled, monitored and recorded
!ood 'torage condition' clean" dry and a))ro)riate light'
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12%21
Premises
/torage areas - &
Printed )acaging ,aterial'
.ritical to en'&re co,)liance #ith correct la?elling of )rod&ct'
S)ecial attention to 'a,)ling
S)ecial attention to 'afe and 'ec&re 'torage
>n'&re co,)liance #ith ')ecification'" )revent ,i*=&)'
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12%2+
Premises
Weighing areas
Weighing o)eration' + in 'e)arated area'
A))ro)riate de'ign ('ee al'o training ,aterial on H@A.
Provi'ion for d&'t control
S,ooth" i,)ervio&'" d&ra?le" ea'y=to=clean fini'he'
.leaning )roced&re' and record'
Doc&,entation" e%g% SOP'" log' and record'
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Premises
De'ign of area' for #eighing of
,aterial'
Pro)er air '&))ly
D&'t control ,ea'&re'
(incl&ding e*traction of d&'t
and air >a'ily cleana?le '&rface'
1o area' for d&'t
acc&,&lation
Protection of ,aterial"
)rod&ct and o)erator
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Premises
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12%2&
Premises
Production areas 0 1
Mini,ize ri' of cro''=conta,ination
Dedicated and 'elf=contained facilitie' for 'o,e )rod&ct' '&cha' highly 'en'itizing ,aterial' (e%g% )enicillin' or ?iological
)re)aration' (e%g% live ,icroorgani','
Se)arate facilitie' for other )rod&ct' '&ch a' 'o,e anti?iotic'"hor,one'" cytoto*ic '&?'tance'
1on=)har,ace&tical' nor,ally not in the 'a,e facility" e%g%)e'ticide'" her?icide'
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Equipment
All a')ect' incl&ding
De'ign" in'tallation"
o)eration" )erfor,ance"
')ecification'" log'",aintenance" &'e"
cleaning" -&alification"
cali?ration etcI
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Equipment
.ontent' and direction of flo#
indicated
e%g% #ater line'" e-&i),ent
co,)onent'" air=handling
'y'te,'
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1&%! - 1&%1
Materials
/tarting )aterials -
P&rcha'ing + i,)ortant o)eration
Cro, a))roved '&))lier' + if )o''i?le" direct fro, the,an&fact&rer
S)ecification' for ,aterial'
.on'ign,ent chec' Integrity of packageSeal intactCorresponds with the purchase orderDelivery noteSuppliers labels
.leaned and la?elled #ith infor,ation
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Materials
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Documentation
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alidation
/copeWHO g&ideline foc&'e' ,ainly on the overall conce)t of
validation
t 'erve' a' general g&idance only
Princi)le' ,ay ?e &'ef&l
+ in production and control of active pharmaceutical
ingredients !PIs" and finished pharmaceutical products
@alidation of ')ecific )roce''e' and )rod&ct' (e%g% 'terile
)rod&ct ,an&fact&re re-&ire' ,&ch ,ore con'ideration and a
detailed a))roach ?eyond the 'co)e of the g&ideline 2%1
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alidation
/copeMany factor' affecting the different ty)e' of validation
Man&fact&rer' 'ho&ld )lan validation to en'&re
+ regulatory compliance and
+product #uality, safety and consistency
The general te*t in the g&ideline ()art 9 of )re'entation ,ay ?ea))lied to validation and -&alification of
+premises, e#uipment, utilities and systems
+processes and procedures
More ')ecific )rinci)le' addre''ed in the a))endice' ()art' 5 to
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Qualification and Validation
!ood Man&fact&ring Practice' (!MP and n')ection'
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!ood Man&fact&ring Practice' (!MP and n')ection'
Btilitie'
H@A.
Water
.o,)re''ed air
Stea, % % %
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Prefilter3ir flow patterns
34
)ain filter
Bni=directional T&r?&lentT&r?&lent
1 2 +
43,
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+
Prod&ction 0oo,
#(haust air treatment
,entral air handling unit
Terminal air treatment
at production room level
Fresh air treatment
6make0up air7
43, )ain subs8stems
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9ualification - e(amples of aspects to consider in:ualification 6O9" P97
Test
Differential )re''&re on filter'
Turbulent ; mi(ed
airflowDescription
ni0directional
airflow ;
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raw water in
S trap to sewer
Water i' e)t
circ&lating
To #ater
'oftener K
D )lant
Pretreatment -
schematicdrawing
cartride
filter
5 !icro!eters
acti"ated
carbon
filter
spra# ball
brea$ tan$
air brea$ to drain centrif%al p%!p
air filter
float
operated
"al"esand filter
e&cess water rec#cled
fro! deioniser
Water for Pharmaceutical se
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/eparate guideline in addition to basic ')PPart 9 Manage,ent and organization
Part 5 Material'" e-&i),ent" in'tr&,ent' and device'
Part 6 Woring )roced&re' and doc&,ent'" and
'afety in the la?oratory
Part 7 n')ecting the la?oratory
9ualit8 ,ontrol
!ood Man&fact&ring Practice' (!MP and n')ection'
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!ood Man&fact&ring Practice' (!MP and n')ection'
Q&ality control (al'o ,icro" #ater" environ,entI
Sa,)ling and te'ting
0eference Standard'
S)ecification'
Sta?ility te'ting
So&rce/ra# data
Q&alification and validation
!ood Man&fact&ring Practice' (!MP and n')ection'
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!ood Man&fact&ring Practice' (!MP and n')ection'
Other a')ect' to loo at incl&de
@alidation ()roce''" cleaning etc
.APA" fail&re inve'tigation
.hange control
Deviation'
.o,)laint'
Prod&ct -&ality revie#
!ood Man&fact&ring Practice' (!MP and n')ection'
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!ood Man&fact&ring Practice' (!MP and n')ection'
Bnli,ited re'o&rce' E
n')ector' E
Day' E
!&ideline' E
Q&ality 0i' Manage,ent Proce''
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!ood Man&fact&ring Practice' (!MP and n')ection'
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!ood Man&fact&ring Practice' (!MP and n')ection'
Planning and cond&ct of in')ection
Ty)e of )rod&ct('
Ty)e of ,aterial('
Pre,i'e'
.hange' (deviation'" additional )rod&ct'" cleaning
)roced&re" ca,)aign' etc
Btilitie' and a))lication'
!ood Man&fact&ring Practice' (!MP and n')ection'
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!ood Man&fact&ring Practice' (!MP and n')ection'
S&,,ary
!MP re,ain' i,)ortant co,)onent of en'&ring QA and-&ality
1e# a))roache' in -&ality (incl&ding ri' ,anage,ent"
.APA" PAT
,)act on total a))roach incl&ding+ Prod&ct de'ign" )rod&ct develo),ent" )ilot ?atche'"
)rod&ction ?atche'
Q&ality 'y'te,' and -&ality a''&rance
!ood Man&fact&ring Practice' (!MP and n')ection'
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!ood Man&fact&ring Practice' (!MP and n')ection'
Acno#ledge,ent'
WHO Training ,od&le'
+ La'ic and '&))le,entary
.H Q2
S !al'on and F &
!ood Man&fact&ring Practice' (!MP and n')ection'
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!ood Man&fact&ring Practice' (!MP and n')ection'
Than yo&