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CHAPTER 3 PREMISES AND EQUIPMENT

Principle
Pr emi ses and equi pment must be l ocated, desi gned, constr ucted, adapted and mai ntai ned
to sui t the operati ons to be carri ed out. Thei r l ayout and desi gn must ai m to mi ni mi se the
r i sk of er r or s and per mi t effecti ve cl eani ng and mai ntenance i n or der to avoi d cr oss-
contami nati on, bui l d up of dust or di rt and, i n general , any adverse effect on the qual i ty of
products.
Premises
General
3.1 Pr emi ses shoul d be si tuated i n an envi r onment whi ch, when consi der ed together wi th
measur es to pr otect the manufactur e, pr esents mi ni mal r i sk of causi ng contami nati on of
materi al s or products.
3.2 Premi ses shoul d be careful l y mai ntai ned, ensuri ng that repai r and mai ntenance operati ons
do not pr esent any hazar d to the qual i ty of pr oducts. They shoul d be cl eaned and, wher e
appl i cabl e, di si nfected accordi ng to detai l ed wri tten procedures.
3.3 Li ghti ng, temperature, humi di ty and venti l ati on shoul d be appropri ate and such that they
do not adver sel y affect, di r ectl y or i ndi r ectl y, ei ther the medi ci nal pr oducts dur i ng thei r
manufacture and storage, or the accurate functi oni ng of equi pment.
3.4 Premi ses shoul d be desi gned and equi pped so as to afford maxi mum protecti on agai nst the
entry of i nsects or other ani mal s.
3.5 Steps shoul d be taken i n or der to pr event the entr y of unauthor i sed peopl e. Pr oducti on,
storage and qual i ty control areas shoul d not be used as a ri ght of way by personnel who do
not work i n them.
Producti on Area
3.6 I n or der to mi ni mi se the r i sk of a ser i ous medi cal hazar d due to cr oss-contami nati on,
dedi cated and sel f contai ned faci l i ti es must be avai l abl e for the pr oducti on of par ti cul ar
medi ci nal pr oducts, such as hi ghl y sensi ti si ng mater i al s (e.g. peni ci l l i ns) or bi ol ogi cal
pr epar ati ons (e.g. fr om l i ve mi cr o-or gani sms). The pr oducti on of cer tai n addi ti onal
pr oducts, such as cer tai n anti bi oti cs, cer tai n hor mones, cer tai n cytotoxi cs, cer tai n hi ghl y
acti ve drugs and non-medi ci nal products shoul d not be conducted i n the same faci l i ti es. For
those pr oducts, i n excepti onal cases, the pr i nci pl e of campai gn wor ki ng i n the same
faci l i ti es can be accepted pr ovi ded that speci fi c pr ecauti ons ar e taken and the necessar y
val i dati ons ar e made. The manufactur e of techni cal poi sons, such as pesti ci des and
her bi ci des, shoul d not be al l owed i n pr emi ses used for the manufactur e of medi ci nal
products.
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3.7 Pr emi ses shoul d pr efer abl y be l ai d out i n such a way as to al l ow the pr oducti on to take
pl ace i n areas connected i n a l ogi cal order correspondi ng to the sequence of the operati ons
and to the requi si te cl eanl i ness l evel s.
3.8 The adequacy of the wor ki ng and i n-pr ocess stor age space shoul d per mi t the or der l y and
l ogi cal posi ti oni ng of equi pment and mater i al s so as to mi ni mi se the r i sk of confusi on
between di ffer ent medi ci nal pr oducts or thei r components, to avoi d cr oss-contami nati on
and to mi ni mi se the r i sk of omi ssi on or wr ong appl i cati on of any of the manufactur i ng or
control steps.
3.9 Wher e star ti ng and pr i mar y packagi ng mater i al s, i nter medi ate or bul k pr oducts ar e
exposed to the envi ronment, i nteri or surfaces (wal l s, fl oors and cei l i ngs) shoul d be smooth,
free from cracks and open joi nts, and shoul d not shed parti cul ate matter and shoul d permi t
easy and effecti ve cl eani ng and, i f necessary, di si nfecti on.
3.10 Pi pework, l i ght fi tti ngs, venti l ati on poi nts and other servi ces shoul d be desi gned and si ted
to avoi d the cr eati on of r ecesses whi ch ar e di ffi cul t to cl ean. As far as possi bl e, for
mai ntenance purposes, they shoul d be accessi bl e from outsi de the manufacturi ng areas.
3.11 Dr ai ns shoul d be of adequate si ze, and have tr apped gul l i es. Open channel s shoul d be
avoi ded where possi bl e, but i f necessary, they shoul d be shal l ow to faci l i tate cl eani ng and
di si nfecti on.
3.12 Pr oducti on ar eas shoul d be effecti vel y venti l ated, wi th ai r contr ol faci l i ti es (i ncl udi ng
temper atur e and, wher e necessar y, humi di ty and fi l tr ati on) appr opr i ate both to the
pr oducts handl ed, to the oper ati ons under taken wi thi n them and to the exter nal
envi ronment.
3.13 Wei ghi ng of starti ng materi al s usual l y shoul d be carri ed out i n a separate wei ghi ng room
desi gned for that use.
3.14 I n cases wher e dust i s gener ated (e.g. dur i ng sampl i ng, wei ghi ng, mi xi ng and pr ocessi ng
oper ati ons, packagi ng of dr y pr oducts), speci fi c pr ovi si ons shoul d be taken to avoi d cr oss-
contami nati on and faci l i tate cl eani ng.
3.15 Premi ses for the packagi ng of medi ci nal products shoul d be speci fi cal l y desi gned and l ai d
out so as to avoi d mi x-ups or cross-contami nati on.
3.16 Pr oducti on ar eas shoul d be wel l l i t, par ti cul ar l y wher e vi sual on-l i ne contr ol s ar e car r i ed
out.
3.17 I n-pr ocess contr ol s may be car r i ed out wi thi n the pr oducti on ar ea pr ovi ded they do not
carry any ri sk for the producti on.
Storage Areas
3.18 Stor age ar eas shoul d be of suffi ci ent capaci ty to al l ow or der l y stor age of the var i ous
categori es of materi al s and products: starti ng and packagi ng materi al s, i ntermedi ate, bul k
and fi ni shed products, products i n quaranti ne, rel eased, rejected, returned or recal l ed.
3.19 Stor age ar eas shoul d be desi gned or adapted to ensur e good stor age condi ti ons. I n
par ti cul ar , they shoul d be cl ean and dr y and mai ntai ned wi thi n acceptabl e temper atur e
l i mi ts. Wher e speci al stor age condi ti ons ar e r equi r ed (e.g. temper atur e, humi di ty) these
shoul d be provi ded, checked and moni tored.
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3.20 Recei vi ng and di spatch bays shoul d pr otect mater i al s and pr oducts fr om the weather .
Recepti on areas shoul d be desi gned and equi pped to al l ow contai ners of i ncomi ng materi al s
to be cl eaned where necessary before storage.
3.21 Wher e quar anti ne status i s ensur ed by stor age i n separ ate ar eas, these ar eas must be
cl ear l y mar ked and thei r access r estr i cted to author i sed per sonnel . Any system r epl aci ng
the physi cal quaranti ne shoul d gi ve equi val ent securi ty.
3.22 Ther e shoul d nor mal l y be a separ ate sampl i ng ar ea for star ti ng mater i al s. I f sampl i ng i s
per for med i n the stor age ar ea, i t shoul d be conducted i n such a way as to pr event
contami nati on or cross-contami nati on.
3.23 Segr egated ar eas shoul d be pr ovi ded for the stor age of r ejected, r ecal l ed or r etur ned
materi al s or products.
3.24 Hi ghl y acti ve materi al s or products shoul d be stored i n safe and secure areas.
3.25 Pr i nted packagi ng mater i al s ar e consi der ed cr i ti cal to the confor mi ty of the medi ci nal
pr oduct and speci al attenti on shoul d be pai d to the safe and secur e stor age of these
materi al s.
Qual i ty Control Areas
3.26 Normal l y, Qual i ty Control l aboratori es shoul d be separated from producti on areas. Thi s i s
par ti cul ar l y i mpor tant for l abor ator i es for the contr ol of bi ol ogi cal s, mi cr obi ol ogi cal s and
radi oi sotopes, whi ch shoul d al so be separated from each other.
3.27 Contr ol l abor ator i es shoul d be desi gned to sui t the oper ati ons to be car r i ed out i n them.
Suffi ci ent space shoul d be gi ven to avoi d mi x-ups and cross-contami nati on. There shoul d be
adequate sui tabl e storage space for sampl es and records.
3.28 Separate rooms may be necessary to protect sensi ti ve i nstruments from vi brati on, el ectri cal
i nterference, humi di ty, etc.
3.29 Speci al r equi r ements ar e needed i n l abor ator i es handl i ng par ti cul ar substances, such as
bi ol ogi cal or radi oacti ve sampl es.
Anci l l ary Areas
3.30 Rest and refreshment rooms shoul d be separate from other areas.
3.31 Faci l i ti es for changi ng cl othes, and for washi ng and toi l et pur poses shoul d be easi l y
accessi bl e and appropri ate for the number of users. Toi l ets shoul d not di rectl y communi cate
wi th producti on or storage areas.
3.32 Mai ntenance wor kshops shoul d as far as possi bl e be separ ated fr om pr oducti on ar eas.
Whenever parts and tool s are stored i n the producti on area, they shoul d be kept i n rooms or
l ockers reserved for that use.
3.33 Ani mal houses shoul d be wel l i sol ated fr om other ar eas, wi th separ ate entr ance (ani mal
access) and ai r handl i ng faci l i ti es.
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I Chapter 3 Premises and equipment _______________________________________
Equipment
3.34 Manufacturi ng equi pment shoul d be desi gned, l ocated and mai ntai ned to sui t i ts i ntended
purpose.
3.35 Repai r and mai ntenance oper ati ons shoul d not pr esent any hazar d to the qual i ty of the
products.
3.36 Manufactur i ng equi pment shoul d be desi gned so that i t can be easi l y and thor oughl y
cl eaned. I t shoul d be cl eaned accordi ng to detai l ed and wri tten procedures and stored onl y
i n a cl ean and dry condi ti on.
3.37 Washi ng and cl eani ng equi pment shoul d be chosen and used i n order not to be a source of
contami nati on.
3.38 Equi pment shoul d be i nstal l ed i n such a way as to pr event any r i sk of er r or or of
contami nati on.
3.39 Pr oducti on equi pment shoul d not pr esent any hazar d to the pr oducts. The par ts of the
pr oducti on equi pment that come i nto contact wi th the pr oduct must not be r eacti ve,
addi ti ve or absor pti ve to such an extent that i t wi l l affect the qual i ty of the pr oduct and
thus present any hazard.
3.40 Bal ances and measur i ng equi pment of an appr opr i ate r ange and pr eci si on shoul d be
avai l abl e for producti on and control operati ons.
3.41 Measuri ng, wei ghi ng, recordi ng and control equi pment shoul d be cal i brated and checked at
defi ned i nter val s by appr opr i ate methods. Adequate r ecor ds of such tests shoul d be
mai ntai ned.
3.42 Fi xed pi pewor k shoul d be cl ear l y l abel l ed to i ndi cate the contents and, wher e appl i cabl e,
the di recti on of fl ow.
3.43 Di sti l l ed, dei oni zed and, where appropri ate, other water pi pes shoul d be sani ti sed accordi ng
to wri tten procedures that detai l the acti on l i mi ts for mi crobi ol ogi cal contami nati on and the
measures to be taken.
3.44 Defecti ve equi pment shoul d, i f possi bl e, be r emoved fr om pr oducti on and qual i ty contr ol
areas, or at l east be cl earl y l abel l ed as defecti ve.