: : Pharmaceutical Factory Establishment Standards : 200504_ : 200504_ Pharmaceutical Factory Establishment Standards ----------------------------------------------------------------------------Standards for the Establiishment of Pharmaceutical

al Factories Part 1 General Princi les !rticle 1" #his set of Standards is formulated in accordance $ith re%ulations of Para%ra h 5& !rticle 5' of the Pharmaceutical !ffairs !ct (hereafter referred to as the !ct)" !rticle 2" Facilities and sanitary conditions of harmaceutical factories or sites shall com ly $ith the re%ulations of this set of Standards* matters not ro+ided for herein shall be %o+erned by other rele+ant la$s and re%ulations" !rticle ," -hen harmaceutical manufacturers of domestic medicines establish ne$ factories& relocate& e. and& reo en for business& or add ra$ medicinal materials& dosa%e forms& items of rocessin% or roducts& and are in com liance $ith /ha ter 2 of this set of Standards and also re%eulations of the Factory 0ana%ement Guidance !ct& the com etent industry suthorities of munici alities or counties (cities) shall issue them actin% on their a lication factory re%istration certificates& or a ro+e their alterations of re%istration* the com etent health aurhorities of munici alities or counties (cities) shall issue them actin% on their a lication ermit licenses for harmaceuticals in manufacturin%& or a ro+e their alterations of re%istration" Pharmaceutical manufacturers of domestic medicines holdin% by re%ulations of the recedin% Para%ra h factory re%istration certificates and ermit licenses for harmaceuticals in manufacturin%& $hen are found throu%h ins ections to be in com liance $ith re%ulations of Part ,
1

or Part 4& said manufacturers shall be issued certificates of harmaceutical G0P com liance or medical de+ice G0P com liance for the items 1ualified by ins ections by the central com etent health authority" -here forei%n harmaceutical manufacturers are found by ins ections to be in com liance $ith re%ulations of this set of Standards& said manufacturers shall be issued certificates of harmaceutical G0P com liance or medical de+ice G0P com liance for the items 1ualified by ins ections by the central com etent health authority" Part 2 2asic 3e1uirements for the Establishment of Factories !rticle 4" Pharmaceutical factories shall re1uirements and common facilities: ossess the follo$in% basic

(1) Factory sites shall be situated in sanitary locations $ith fresh air* factory roduction& rocessin% and ac4a%in% areas shall be constructed in accordance $ith rele+ant buildin% codes& and located at a sufficient distance from factory boundaries to re+ent ollution and fires* safety measures a%ainst atho%ens im lemented at factories and facilities that manufacture bio harmaceuticals or biotechnolo%y roducts may not interfere $ith ublic health or safety* factory se$ers shall be co+ered to re+ent the entry and e.it of animals to s read atho%ens" (2) Factory buildin%s shall be solid and safe& and desi%ned to re+ent rodents& insects and dust* interior ceilin%s& $alls and floors shall be smooth and free of crac4s and cre+ices& easy to clean& and nonconduci+e to the collection of dust* $here necessary& materials that are easily cleaned and disinfected may be used* all o eration areas shall be $ell illuminated and +entilated* $here necessary& e1ui ment for the re%ulation of tem erature& humidity and air urity may be installed" (,) 5 eration areas shall be clearly delineated (e"%" o$der manufacturin% room& li1uid manufacturin% room)* in factories that en+ironmental sanitation medicines are also manufactured& the o eration areas shall be se arated by an a ro riate distance from manufacturin% factories
2

of other medicines* $hen necessary& se aration $alls may be installed" (4) -arehouses for the stora%e of ra$ materials& su roducts and end roducts shall be established" lies& semi-finished

(5) #here shall be facilities for the treatment of dust and o$der& $aste$ater& ha6ardous $astes& to.ic containers& ha6ardous %ases& biolo%ical com onents and other ha6ardous com onents or materials" (7) #here shall be $ei%hin% facilities that com ly $ith re%ulations& and they shall be rectified re%ularly" (') #here shall be container $ashin% facilities" -here container $ashin% facilities are used in factories manufacturin% eye dro s& in8ectables and bio harmaceuticals or biotechnolo%y roducts& s ecial care shall be ta4en to re+ent contamination& and said facilities shall be installed se arately" (9) #here shall be hand-$ashin% facilities for em loyers& and facilities for the $ashin% or sterili6ation of $or4 clothes& ca s& face mas4s& %lo+es and shoes" Em loyee loun%es and sho$er rooms shall be established& as needed& outside of the o eration areas* a ro riate la+atory facilities shall be established in manufacturin% and rocessin% areas& se arated from o eration areas" (:) #here shall be testin% de artments (laboratory and instrument room)& and a ro riate testin% e1ui ment" ;o$e+er& if tests are conducted on a contract basis by an or%ani6ation a ro+ed by the com etent authority& in accordance $ith the /ontract <ru% 0anufacturin% and #estin% 5 eratin% Princi les& and clear document is ro+ided& establishment of said facilities may be $ai+ed" (10)For o eration areas in+ol+in% flammable or ha6ardous ra$ materials& sol+ents& semi-finished or intermediate roducts and finished roducts& a ro riate rotecti+e& first-aid and se%re%ation facilities shall be installed" 2oilers& $ater um s& +acuum um s& com ressors& %eneral use $ater rocessin% systems& urified $ater rocessin% systems (ion e.chan%e resin& etc")& $ater distillation systems& dust remo+al=e.haust systems& or air rocessin% systems shall be installed as needed at harmaceutical factories"
,

#he +arious ty es of facilities mentioned in Sub ara%ra h 7 throu%h Sub ara%ra h 10 of Para%ra h 1 may be installed at medical de+ice factories in accordance $ith actual needs" !rticle 5" Facilities used to manufacture harmaceuticals for internal use and intense to.ic dru%s for e.ternal use shall be 4e t strictly se arate& and may not be used interchan%eably" Sites and facilities for the manufacturin% of harmaceuticals for human and animal use shall be 4e t se arate* they may not be o erated in the same buildin% $ithout se aration" ;o$e+er& harmaceuticals for animal use that com ly $ith the standards %o+ernin% dru%s for human use are not sub8ect to this restriction" !rticle 7" Factories that manufacture harmaceutical o$ders shall& as needed& install the follo$in% facilities: (1) Pul+eri6in% facilities* (2) Screenin% facilities* (,) 0i.in% facilities* (4) <ryin% facilities* (5) <ust collection facilities* (7) 5ther rele+ant facilities" !rticle '" Factories that manufacture hard=soft ca sule harmaceuticals shall& as needed& install the follo$in% facilities: (1) Pul+eri6in% facilities* (2) Screenin% facilities* (,) 0i.in% facilities* (4) <ryin% facilities* (5) Gelatin blendin% facilities*
4

(7) Soft %elatin rocessin% facilities* (') Soft ca sule fillin% and ressin% facilities* (9) !utomatic or semi-automatic ca sule fillin% facilities* (:) <ust collection facilities" Facilities mentioned in Sub ara%ra h 5 throu%h Sub ara%ra h 9 of the recedin% Para%ra h are commonly used in factories that roduce soft ca sules* areas $here the facilities mentioned in Sub ara%ra h 5 and Sub ara%ra h 7 are installed shall be se arate from other areas* areas $here the facilities mentioned in Sub ara%ra h 7 and Sub ara%ra h ' are installed must ha+e e1ui ment for the re%ulation of air tem erature and humidity" !rticle 9" Factories that manufacture harmaceutical %ranules& tablets (includin% tablets for eye use)& coated tablets& or ills shall& as needed& install the follo$in% facilities: (1) Pul+eri6in% facilities* (2) Screenin% facilities* (,) 0i.in% or annealin% facilities* (4) <ryin% facilities* (5) Granulatin% facilities* (7) 0illin% facilities* (') #ablet ressin% or ill ma4in% facilities* (9) Gelatin or coatin% syru blendin%& atomi6in%& coatin%& +entilation& dryin%& olishin% facilities* (:) 0oldin% machines& buffin% machines* (10)<ust collection facilities" !reas $here the facilities mentioned in Sub ara%ra h 9 of the recedin% Para%ra h shall be installed se arately from other areas"

For factories manufacturin% tablets for eye use& there shall be additionally as need be& sterili6ation& air urification& ase tic fillin% ( ac4a%in%) and sterility test facilities" !rticle :" Factories that manufacture harmaceutical emulsions shall& as needed& install the follo$in% facilities: (1) Emulsion stirrin% facilities* (2) Emulsion blendin% facilities* (,) Emulsion fillin% ( ac4a%in%) facilities" !rticle 10" Factories that manufacture harmaceutical sus ensions& tinctures& e.tracts& fluid e.tracts or li1uid re arations (includin% eye dro s& hemodialysis solutions and la+a%e solutions) shall& as needed& install the follo$in% facilities: (1) Facilities for the manufacturin% of distilled $ater distillation or urified $ater* (2) >i1uid blendin% containers& settlin% tan4s or ceramic +ats* (,) Percolation facilities* (4) Soa4in% facilities* (5) Filtration facilities* (7) Stirrin% facilities* (') ?uantitati+e fillin% ( ac4a%in%) and container sealin% facilities* (9) ;eat com ression ( ressure-reduction) facilities* (:) Sterili6ation facilities" For factories manufacturin% li1uid re arations for eye use& there shall be additionally as need be& sterili6ation& air urification& ase tic fillin% ( ac4a%in%) and sterility test facilities" !rticle 11" Factories that manufacture harmaceutical aerosols shall& as needed& install the follo$in% facilities:
7

(1) Stirrin% facilities* (2) Fillin% facilities" !rticle 12" Factories that manufacture harmaceutical ointments (includin% eye ointments) or su ositories shall& as needed& install the follo$in% facilities: (1) Po$der %rindin% facilities* (2) Screenin% facilities* (,) ;eatin% +at* (4) 2lendin% facilities* (5) Fillin% ( ac4a%in%) facilities* (7) 5intment tube sealin% facilities* (') Su ository moldin% facilities* (9) Sterili6ation& air urification& ase tic fillin% ( ac4a%in%) and sterility test facilities* (:) <ust collection facilities" For factories that do not ma4e use of ointment tubes& the installation of facilities mentioned in Sub ara%ra h 5 and Sub ara%ra h 7 of the recedin% Para%ra h may be $ai+ed" !rticle 1," Factories that manufacture harmaceutical stic4s shall& as needed& install the follo$in% facilities: (1) 0i.in% facilities* (2) Fillin% facilities" !rticle 14" Factories that manufacture harmaceutical atches shall& as needed& install the follo$in% facilities: (1) ;eatin% facilities* (2) Stirrin% and 4neadin% facilities*
'

(,) /oatin% facilities* (4) /uttin% facilities" !rticle 15" Factories that manufacture harmaceutical im lants shall& as needed& install the follo$in% facilities: (1) Pressin% or moldin% facilities* (2) Sterili6ation facilities" !rticle 17" Factories that manufacture in8ectables (includin% dialysates) shall& as needed& install the follo$in% facilities: (1) Facilities for the roduction of $ater for in8ectables* (2) !m oule cuttin% facilities* (,) /ontainer dryin%& sterili6ation& coolin% and stora%e facilities* must effecti+ely sterili6e containers and re+ent contamination* (4) @n8ectable solution filterin% facilities* must include coolin% element and atho%en filter* for in8ectables in o$der form& this re1uirement may be $ai+ed* (5) Fillin% facilities $ith recise measurin% ca abilities* (7) @n8ectables container sealin% facilities* (') Sterili6ation facilities* (9) @n8ectables container seal and lea4 testin% facilities* (:) @n8ectables forei%n matter testin% facilities* (10)<istillation room (for em loyeesA $ashin% and distillation)* (11)/han%in% room (for em loyees to chan%ed into sterili6ed $or4 clothes& ca s& face mas4s& %lo+es and shoes)* (12)<ru% solution re aration room* (1,)<ru% solution fillin% and container sealin% room* (14)!nimal e. eriment area& facilities and e1ui ment& e1ui necessary animals and breedin% and obser+ation areas* ed $ith

(15)!rea& facilities and e1ui ment necessary for conductin% late count&
9

sterility tests and other tests* (17)Free6e-dryin% facilities" #he rooms mentioned in Sub ara%ra h 12 and Sub ara%ra h 1, of the recedin% Para%ra h shall be strictly se arated from other o eration areas* they shall be e1ui ed $ith double doors that seal ti%htly& air urification and sterili6ation facilities& and facilities for the re%ulation of tem erature and humidity" !rticle 1'" Factories that manufacture antibiotics shall& as needed& install the follo$in% facilities: 1" For in8ectable antibiotics (1) For li1uid form antibiotics& the facilities mentioned in !rticle 17 shall be installed* for o$er form antibiotics& rele+ant facilities in !rticle 17 shall be installed in accordance $ith actual needs& and ase tic fillin% ( ac4a%in%) facilities $ith a ro riate tem erature and humidity control ca abilities& and automatic or semiautomatic recision scales shall also be installed additionally" (2) <oors=$indo$s that o en to the e.terior shall be double doors=$indo$s that seal ti%htly" (,) #here shall be otency and safety testin% facilities for antibiotic ra$ materials and roducts" (4) Pre aration rooms (for dryin%& sterili6ation and stora%e of ac4a%in% materials and containers& and other re aratory tas4s related to ac4a%in%) and ac4a%in% rooms ($ith a ro riate tem erature and humidity control ca abilities& and automatic or semi-automatic recision scales) shall be installed in rocessin% and ac4a%in% areas" 2" For non-in8ectable antibiotics (includin% ca sules& tablets& li1uids& ointments& etc"): #he +arious ty es of facilities described in the rules %o+ernin% each dosa%e form shall be installed* in rocessin% and ac4a%in% areas& air urification and sterili6ation e1ui ment& and e1ui ment for the re%ulation of tem erature and humidity& shall be installed in accordance $ith actual needs* furthermore& the facilities
:

mentioned in @tem 2 and @tem , of the recedin% Sub ara%ra h shall also be installed" ," 0anufacturin%& rocessin%& re- ac4a%in%& ac4a%in% and other o eration areas used in the manufacturin% of enicillin roducts shall be located in a com letely se arate buildin%* the air rocessin% system for this buildin% shall be inde endent from the systems of other dru% roduction areas" !rticle 19" Factories that manufacture bio harmaceuticals or biotechnolo%y roducts shall ha+e o eration areas $ith interior ceilin%s& $alls& doors& floors and other structural com onents that are easily cleaned and disinfected* and shall also& as needed& install the follo$in% facilities: (1) Facilities for the breedin% and se%re%ation of animals used in manufacturin% and testin%& and animals that ha+e been inoculated $ith microor%anisms* (2) !reas& facilities and e1ui ment for safety testin% and bioassayin%* (,) Factories that collect animal blood or use other animal roducts in the manufacturin% of +accines shall ossess $ater sources and facilities sufficient for re1uired rinsin%" (4) -aste $ater remo+al and disinfection facilities shall be installed in the o eration areas" (5) 0icroor%anism culturin% facilities* (7) 0icroor%anism filterin% facilities* (') 0icroor%anism inoculation and collection facilities* (9) Free6e-dryin% facilities* (:) <ilution facilities* (10)Fillin% ( ac4a%in%) and container sealin% facilities* (11)0icroor%anism stora%e facilities* (12)@ntermediate and end roduct stora%e facilities* said facilities should be 4e t at tem eratures a ro riate to each ty e of roduct stored" (1,)2lendin% solution and culture medium roduction facilities*
10

(14)Pre-use and ost-use sterili6ation and disinfection facilities for containers& solutions and culture mediums used in manufacturin% and testin%* (15)#hermostats& sterili6ation facilities& refri%eration and free6in% facilities& automatic re%ulators& thermometers and necessary recordin% instruments* (17)Facilities for the incineration or destruction of animal remains and other $aste materials* (1')Em loyeesA chan%in% and bathin% facilities* (19)!nimal dissection and or%an %rindin% facilities* (1:)5ther rele+ant facilities" !reas $here s ores& bacteria or +iruses are handled shall be com letely se arated from other areas" !reas $ith the facilities mentioned in Sub ara%ra h ' throu%h Sub ara%ra h 10 of Para%ra h 1 shall be ase tic facilities& and shall be e1ui ed $ith necessary ase tic air conditioners" !reas $ith the facilities mentioned in Sub ara%ra h 10 of Para%ra h 1 shall be ase tic air conditioners $ith dehumidifyin% ca abilities" !rticle 1:" Factories that %rind /hinese herbal medicines shall& as needed& install the follo$in% facilities: (1) Pul+eri6in% facilities* (2) Screenin% facilities* (,) <ryin% facilities* (4) <ust collection facilities* (5) 3e- ac4a%in% and ac4a%in% facilities" !rticle 20" Factories that concoct sliced /hinese herbal medicines shall& as needed& install the follo$in% facilities:

11

(1) Sortin% and rocessin% facilities* (2) Slice rocessin% facilities* (,) Slicin% facilities* (4) <ryin% facilities* (5) /oncoctin% facilities* (7) 3e- ac4a%in% and ac4a%in% facilities* (') 5ther rele+ant facilities" !rticle 21" Factories that manufacture /hinese herbal lasters= oultices and adhesi+e ads shall& as needed& install the follo$in% facilities: (1) Pul+eri6in% facilities* (2) 0i.in% facilities* (,) Paste boilin% +at and stirrin% facilities* (4) Plaster coatin% facilities* (5) /uttin% facilities" !rticle 22" Factories that manufacture fla4ed /hinese herbal medicines shall& as needed& install the follo$in% facilities: (1) Slicin% (mincin%) facilities* (2) Screenin% facilities* (,) 0i.in% facilities* (4) <ryin% facilities" !rticle 2," Factories that manufacture /hinese herbal li1uids& essences& li1uors& syru s& or 8ellies shall& as needed& install the follo$in% facilities: (1) /uttin% (mincin%) facilities* (2) Soa4in% facilities* (,) Filterin% facilities* (4) 2oilin% or concentration facilities*
12

(5) <istillation facilities* (7) Stirrin% facilities* (') >i1uid fillin% ( ac4a%in%) facilities* (9) BBBB !rticle 24" Factories that manufacture /hinese herbal concentrates shall& as needed& install the follo$in% facilities: (1) /uttin% (mincin%) facilities* (2) E.tractin% facilities* (,) Filterin% facilities* (4) Pressure-reducin% and concentration facilities* (5) #hermostatic or +acuum dryin% facilities" !rticle 25" Factories that manufacture hard %elatin ca sule shells shall& as needed& install the follo$in% facilities: (1) Gelatin dissol+in% facilities* (2) 0oldin% facilities* (,) <ryin% facilities* (4) /a sule cuttin% and 8oinin% facilities* (5) Sterili6ation and distillation facilities* (7) 0icroor%anism testin% facilities* (') 5 eration areas shall be installed $ith air urification facilities& and facilities for the re%ulation of tem erature and humidity" !rticle 27" Factories that manufacture medicinal %ases shall& as needed& install the follo$in% facilities: (1) Stora%e facilities* (2) Ca ori6in% facilities* (,) !ir com ression facilities*

1,

(4) Purifyin% facilities* (5) Fillin% facilities" !rticle 2'" @n factories that manufacture medical materials& o eration areas shall be se arated based on the ty e of material roduced* they shall also& as needed& install the follo$in% facilities: (1) /otton fluffin%& s readin% or cardin% machines* $here these rocedures are contracted out to other factories& installation of said facilities may be $ai+ed" (2) Pressure de%reasin% facilities* (,) 3insin% facilities* (4) <ehydration facilities* (5) <ryin% facilities (dryin% room)* (7) S innin% machines& $ea+in% machines and other te.tile facilities* $here these rocedures are contracted out to te.tile factories& installation of said facilities may be $ai+ed" (') Gau6e cuttin% facilities* (9) 2anda%e cuttin% facilities* (:) ! ro riate facilities to banda%es after dryin%* re+ent recontamination of %au6e and

(10)#a e adhesi+e or medical material annealin% facilities* (11)Soa4in% and blendin% facilities* to be installed at factories usin% the sol+ent method* (12)/oatin% facilities* (1,)<ryin% and sterili6in% facilities* (14)Ground fabric rocessin% facilities* (15)Fabric cuttin% and rollin% facilities* (17)Soa4in% and dryin% facilities for medicinal %au6e* (1')!se tic testin% facilities for semi-finished and end roducts shall be installed as needed"

14

#he facilities mentioned in Sub ara%ra h 1 throu%h Sub ara%ra h 5 of the recedin% Para%ra h are commonly used in the manufacturin% of de%reased cotton* the facilities mentioned in Sub ara%ra h 2 throu%h Sub ara%ra h 9 are commonly used in the manufacturin% of medicinal %au6e and banda%es* the facilities mentioned in Sub ara%ra h 10 throu%h Sub ara%ra h 15 are commonly used in the manufacturin% of adhesi+e ta e* the facilities mentioned in Sub ara%ra h 15 and Sub ara%ra h 17 are commonly used in the manufacturin% of first aid adhesi+e ta e and medicinal %au6e" !rticle 29" Factories that manufacture syrin%es shall& as needed& install the follo$in% facilities: (1) Gas rocessin% facilities* (2) Grindin% rocessin% facilities* (,) Graduation mar4 facilities* (4) Syrin%e 8oint ins ection facilities* (5) Glass al4alinity testin% facilities* (7) /rac4 detectin% facilities* (') ;eat im act testin% facilities* (9) Standard +olume testin% facilities* (:) !irti%ht testin% facilities" !rticle 2:" Factories that manufacture electric instruments for medical use shall& as needed& install the follo$in% facilities: (1) >athes* (2) <rillin% machines* (,) Dac4s* (4) Grindin% machines or %rindin% $heels* (5) Electric facilities of 1=4 horse o$er or %reater* (7) Punchin% machines* (') Po$er distribution anel for use in testin%*
15

(9) Colta%e detectors* (:) 5hmmeters" !rticle ,0" Factories that manufacture blood collection and blood transfusion de+ices (that incor orate lastic tubes) shall& as needed& install the follo$in% facilities: (1) ;i%h-s eed stirrin% facilities* (2) Stir coolin% facilities* (,) Plastic ellet facilities* (4) ;i%h- ressure steam sterili6ation facilities* (5) ;i%h-fre1uency $eldin% facilities* (7) -ater sterili6ation facilities* (') !se tic o eration rooms" !rticle ,1" Factories that manufacture hy odermic needles shall& as needed& install the follo$in% facilities: (1) Strai%ht line facilities* (2) Grindin% facilities* (,) Eeedle +al+e seat facilities* (4) #i%htenin% facilities* (5) 2end testin% facilities* (7) Fle.ibility testin% de+ices* (') Pull-out testin% de+ices* (9) Pinch meters* (:) 0icrocali ers* (10)0icrometers" !rticle ,2" 3e- ac4a%in%& ac4a%in% and labelin% areas shall& as needed& install the follo$in% facilities:

17

(1) -ei%hin% instruments and other necessary re- ac4a%in% facilities (countin% de+ices& automated re- ac4a%in% facilities& etc") (2) <am - roof ac4a%in% facilities* (,) 2ottle sealin%=sto in% machines* (4) Semi-automatic or automatic am oule labelin% facilities* (5) 2atch number rintin% facilities* (7) 3e+ol+in% or re%ular o eration tables" !rticle ,," Facilities at medical de+ice factories shall be installed based on actual manufacturin% needs* facilities used in the ins ection and testin% of roducts to ensure roduct com liance shall be a ro riately monitored& mana%ed& rectified and maintained" Part , Good 0anufacturin% Practices for Pharmaceuticals /ha ter 1 General Princi les !rticle ,4" #he manufacturin%& rocessin%& re- ac4a%in% and ac4a%in% of harmaceutical roducts shall be %o+erned by the ro+isions of Part ," ;o$e+er& for acti+e harmaceutical in%redients& medicinal %ases and harmaceutical adhesi+e ads& the cate%ories to be im lemented& as $ell as the im lementation methods and schedule& shall be determined se arately by the central com etent health authority" !rticle ,5" #erms used in Part , are defined as follo$s: (1) Pharmaceuticals: refer to harmaceuticals mentioned in !rticle 7 of the !ct (2) 3a$ materials: any materials used in the manufacture of harmaceuticals& includin% those that do not remain in the end roduct" (,) Semi-finished or intermediate roducts: any roducts that are obtained durin% the manufacturin% rocess& and that& $ith further rocessin%&
1'

can become finished roducts" (4) Products: acti+e harmaceutical in%redients& or re arations that contain acti+e harmaceutical in%redients and may contain other nonacti+e in%redients& for $hich all manufacturin% rocesses ha+e been com leted" (5) >abelin%: refers to all te.t and %ra hics that a ear on labels& instruction sheets or ac4a%es& or that come $ith roducts" (7) Pac4a%in% materials: include roduct containers& ca s& and any materials used in the outer ac4a%es of roducts" (') End roducts: refer to harmaceutical roducts that ha+e been ac4a%ed& and $hose outer ac4a%in% clearly indicates the contents therein" (9) 2atch: refers to a s ecific amount of harmaceutical or other substance roduced under a sin%le set of manufacturin% instructions& and that is consistent in character and 1uality" ;o$e+er& under conditions of continuous roduction& a batch refers to a s ecific amount of harmaceutical or other substance roduced $ithin a s ecific time eriod& or that& $ithin s ecific arameters& is consistent in character and 1uality" (:) 2atch number: refers to any definite combination of letters& numbers or other symbols that can be used to loo4 u com rehensi+e information on a batch of roducts or other substances" (10)/ontent: refers one of the follo$in%: 1" #he unit 1uantity of the com onents of a harmaceutical* 2" #he otency or efficacy of a harmaceutical* that is& the treatment efficacy as determined throu%h testin% or sufficient clinical data" (11)Fiber: a substance $hose len%th is at least three times its $idth" (12)Eon-fiber releasin% filter: a filter $hich after any a ro riate retreatment& such as $ashin% or flushin%& $ill not release fibers into the filtrate of the roduct that is bein% filtered" (1,)Calidation: $ritten documentation attestin% that any rocedure& manufacturin% rocess& mechanical de+ice& ra$ material& action or system is ca able of achie+in% its antici ated effect"

19

(14)!cti+e harmaceutical in%redient: an acti+e substance or in%redient that is roduced throu%h hysical& chemical or biotechnolo%ical rocesses for use in the manufacture of a harmaceutical& bio harmaceutical or biotechnolo%ical roduct" (15)#am er- roof ac4a%in%: ac4a%in% $ith an identifyin% mar4 or barrier that enables consumers to clearly identify the contained roduct" (17)2iotechnolo%y roduct: any roduct that has been roduced by means of %ene recombination or cell fusion& or microor%anisms obtained throu%h cell culturin%& fermentation& tissue e.traction& roliferation of embryos or acti+e animal or lant substances& or any other biotechnolo%y method" (1')2io harmaceuticals: substances such as blood serum& antito.ins& +accines& or to.oids that are manufactured usin% microbiolo%ical and immunolo%ical methods" (19)/linical trial dru%: a harmaceutical or lacebo that is under%oin% clinical trials& and has not yet obtained a ro+al" !rticle ,7" Pharmaceutical manufacturers shall im lement +alidation rocedures* the cate%ories to be im lemented& as $ell as the im lementation methods and schedule& shall be determined by the central com etent health authority" /ha ter 2 En+ironmental Sanitation !rticle ,'" Pharmaceutical factory sites shall be situated in sanitary locations $ith fresh air* factory roduction& rocessin% and ac4a%in% areas shall be constructed in accordance $ith rele+ant buildin% codes& and located at a sufficient distance from factory boundaries to re+ent ollution and fires" #he safety measures a%ainst atho%ens im lemented at factories or facilities that manufacture bio harmaceuticals or biotechnolo%y roducts may not interfere $ith ublic health or safety* factory se$ers shall be
1:

co+ered to re+ent the entry and e.ist of animals to s read atho%ens" !rticle ,9" @n treatin% ha6ardous $aste materials& to.ic containers& ha6ardous %ases& dust& $aste$ater& biolo%ical com onents and other ha6ardous com onents or materials& harmaceutical factories shall act not only in accordance $ith rele+ant la$s& but also $ith the follo$in% rinci les: (1) For ha6ardous $aste materials and to.ic containers& stora%e facilities shall be established& and these materials and containers shall be decom osed in accordance $ith their ro erties& and then a ro riately incinerated or buried" @f to.ic containers are to be reused& they shall be $ashed and ri%orously controlled& and may not be used to hold food roducts" (2) For ha6ardous %ases and dust& airti%ht facilities& local e.haust +entilation systems and ne%ati+e ressure rocedures shall be established* these substances shall& in accordance $ith their ro erties& be scrubbed& collected& o.idi6ed& reduced& combusted& or other$ise a ro riately treated" @f e.haust %as contains dust& it shall first be sub8ected to centrifu%in%& filterin%& scrubbin%& or some other form of dust-remo+al rocessin%* the emission of such %ases must com ly $ith air ollutant emission standards" (,) For the rocessin% of $aste$ater& im ermeable stora%e ools shall be established& and acidification& al4ali6ation& neutrali6ation& acti+e carbon adsor tion& or other effecti+e methods shall be used to brea4 do$n or remo+e $aste$ater to.ins* the release of $aste$ater must com ly $ith $ater release standards" /ha ter , Factory 2uildin%s and Facilities !rticle ,:" Factory buildin%s shall be $ell constructed and safe* manufacturin%& rocessin% and ac4a%in% areas shall be com letely se arated from offices& rece tion rooms& laboratories& restaurants and their associated la+atories* the use of asbestos shall be a+oided"

20

#he buildin%s described in the recedin% Para%ra h shall be desi%ned to re+ent the entry of rodents& insects and dust* interior ceilin%s& $alls and floors shall be smooth and free of crac4s and cre+ices& easy to clean& and non-conduci+e to the collection of dust* $here necessary& materials that are easily cleaned and disinfected& such as e o.y resins shall be used" @nterior ducts shall be constructed of materials that do not easily collect dust& and shall be hidden $here ossible* draina%e facilities and draina%e e.its shall be e1ui ed to re+ent $aste$ater bac4flo$" !rticle 40" !reas at harmaceutical factories used for the stora%e of ra$ materials& roduct containers& ca s& and labelin% and ac4a%in% materials& and for the manufacture& rocessin%& re- ac4a%in%& ac4a%in% and stora%e of roducts& shall be a ro riately si6ed and located" #hese areas shall be suitably arran%ed& $ith o eration areas clearly delineated by roduction ty e" 0oreo+er& a ro riate $or4 s ace and le+els of insulation and cleanliness shall be established as needed" >e+els of cleanliness& as mentioned in the recedin% Para%ra h& shall be established in accordance $ith the ty e of roduct bein% manufactured" 5 eration areas re1uirin% the same le+el of cleanliness shall be %rou ed to%ether* buffer 6ones or entry rooms shall be established bet$een areas $ith different le+els of cleanliness& and different colors or ty es of $or4 clothes may be used to indicate the cleanliness le+els of the +arious o eration areas" Eo o eration area may be used as a assa%e$ay by ersonnel from other o eration areas* assa%e$ays for eo le and for the trans ort of %oods shall be se arate& and shall not cross" Facilities for the stora%e of ra$ materials& roduct containers& ca s& labelin% and ac4a%in% materials& semi-finished or intermediate roducts& and roducts shall be %i+en F re-ins ection&G Fa ro+ed for useG and Fnot a ro+ed for useG desi%nations* if items are resent that need to be 4e t fro6en or are to.ic& a ro riate stora%e facilities shall be established"

21

Semi-finished or intermediate roducts shall be stored se arately* if they are not stored se arately& s ecial care shall be ta4en to re+ent contamination and de%radation of 1uality" -here bio harmaceutical and harmaceutical factories use biotechnolo%ical methods to manufacture harmacolo%ically acti+e substances or acti+e harmaceutical in%redients& they shall establish inde endent or se arate factory buildin%s for this ur ose* the air rocessin% system for these buildin%s shall be inde endent from the systems of other dru% roduction areas" ;o$e+er& $here said factories manufacture non-contaminatin% biotechnolo%y roducts& inde endent factory buildin%s and air rocessin% systems shall not be necessary" -here harmaceutical factories manufacture en+ironmental sanitation a%ents& en+ironmental sanitation a%ent manufacturin%& rocessin% and reac4a%in% areas& as $ell as ra$ material stora%e facilities& shall be se arated from harmaceutical manufacturin%& rocessin% and reac4a%in% areas by a distance of no less than ei%ht meters" -here harmaceutical factories manufacture harmaceutical feed additi+es& the harmaceutical feed additi+e o eration area shall be inde endent from other o eration areas" -here harmaceutical factories use their harmaceutical roduction facilities to manufacture food roducts& cosmetics or %eneral %oods& care shall be ta4en to re+ent cross-contamination& and +alidation rocedures shall be carried out" !rticle 41" !ll o eration areas in harmaceutical factories shall be e1ui ed $ith a ro riate illumination and +entilation facilities* $here necessary& said areas shall also be e1ui ed $ith a ro riate facilities for the re%ulation of tem erature and humidity" Each roduction and rocessin% area shall& in accordance $ith its air
22

urity re1uirements& be e1ui ed $ith a ro riate air filtration systems& includin% re-filters and articulate filters" @n areas for the stora%e of ra$ materials& roducts& semi-finished or intermediate roducts& and areas $here roducts are manufactured& rocessed& re- ac4a%ed or ac4a%ed& conditions conduci+e to the re+ention of 1uality de%radation shall be maintained" !rticle 42" Factories shall locate manufacturin%& rocessin%& reac4a%in%& ac4a%in% and other areas used in the roduction of enicillin roducts& as $ell as related facilities& in a com letely se arate buildin%* the air rocessin% system for this buildin% shall be inde endent from the systems of other dru% roduction areas" Factories shall establish inde endent o eration areas for hi%hly sensiti6in% substances such as antibiotics (ce halos orins& etc")& hormone dru%s& cytoto.ic dru%s (includin% anticancer dru%s)& and dru% and nondru% roducts that are hi%hly hysiolo%ically acti+e" @f a s ecial need arises to use said roduction areas and facilities for the manufacture of other roducts& s ecial measures shall be established to re+ent crosscontamination& and +alidation rocedures shall be carried out" #he im lementation date for the re1uirements mentioned in the recedin% Para%ra h shall be determined by the central com etent health authority" !rticle 4," For harmaceutical factory roduction areas in+ol+in% ha6ardous or flammable ra$ materials& sol+ents& semi-finished or intermediate roducts& or roducts& a ro riate rotecti+e& first-aid and se%re%ation facilities shall be established" Facilities used in the manufacturin%& rocessin% and re- ac4a%in% rocess shall be airti%ht from start to finish* $here facilities are not airti%ht and dust or ha6ardous %ases are roduced& local e.haust +entilation systems and ne%ati+e ressure rocedures shall be established"
2,

>i%htin%& s$itches& soc4ets& motors and other electric de+ices for o eration areas that roduce dust& $here or%anic sol+ents are used& or $here ha6ardous substances are resent& shall& as needed& be e. losionroof& airti%ht& or isolated from o eration area" 2oilers& ressure +essels& cranes and other ty es of dan%erous e1ui ment and facilities shall be ins ected and a ro+ed in accordance $ith rele+ant re%ulations before use" !rticle 44" Pharmaceutical factories shall& as needed& establish em loyee loun%es and sho$er rooms outside of $or4 areas" 0anufacturin% and rocessin% areas shall be installed $ith a ro riate la+atory facilities& and $aste$ater& %arba%e and other $aste materials roduced in said areas shall be treated in a safe and sanitary manner" >a+atory facilities shall be se arated from $or4 areas" !rticle 45" Pharmaceutical factories shall& as needed& install facilities for the rocessin% of %eneral use and $aste$ater& and facilities for the roduction of boiler $ater or distilled $ater" -ater su ly facilities shall be 4e t from contaminatin% roducts" !rticle 47" /ontainer $ashin% facilities shall be installed* $here container $ashin% facilities are used to $ash containers for eye dro s& in8ectables& or bio harmaceutical or biotechnolo%y roducts& s ecial care shall be ta4en to re+ent contamination& and said facilities shall be installed a$ay from other container $ashin% facilities" !rticle 4'" Pharmaceutical factories shall carry out the manufacturin%& rocessin% and re- ac4a%in% of sterile roducts in ase tic room areas" #he ase tic room areas mentioned in the recedin% Para%ra h shall& as
24

needed& be installed $ith the follo$in% facilities: (1) Floors& $alls and ceilin%s that are easily cleaned and disinfected* (2) #em erature and humidity control systems* (,) ;i%h erformance air filtration systems ca able of maintainin% ositi+e ressure* (4) -or4 area sur+eillance systems* (5) /leanin%& disinfection& and other systems for maintainin% sterile conditions" 5 eration areas for sterile roducts that cannot be sterili6ed durin% the final sta%e of roduction must not only com ly $ith the recedin% Para%ra h& but must also be installed $ith hi%h erformance air filters and laminar flo$ facilities for the circulation of sterile air" Furthermore& e.cessi+e traffic ( ersonnel and ob8ects) into and out of said areas shall be a+oided" /ha ter 4 Facilities !rticle 49" Facilities at harmaceutical factories used for the manufacture& rocessin%& re- ac4a%in%& ac4a%in% and stora%e of roducts shall be a ro riately desi%ned& si6ed and located for ease of use& cleanin% and maintenance" Facilities needed for the roduction of different dosa%e forms shall be ositioned accordin% to manufacturin% rocess se1uence" !rticle 4:" #he surfaces of facilities at harmaceutical factories that come into direct contact $ith ra$ materials& semi-finished roducts& intermediate roducts or roducts shall be made of non-reacti+e& nonreleasin% and non-adsor ti+e materials* $here any rocess re1uires the use of lubricants& coolants or other similar substance& said substances may not come into contact $ith ra$ materials& roduct containers& ca s& semifinished roducts& intermediate roducts or roducts"
25

!rticle 50" Facilities and a liances at harmaceutical factories used for the manufacture& rocessin%& re- ac4a%in%& ac4a%in% and stora%e of roducts shall be re%ularly cleaned and maintained& and o erational rocedures shall be established in $ritin%" Facilities and a liances in ase tic room areas shall be made of materials that are easily cleaned& dried and disinfected& and shall be re%ularly cleaned& disinfected and maintained" !rticle 51" #he roduction ca acities of mechanical facilities used at harmaceutical factories to roduce a sin%le roduct shall be carefully coordinated to ensure consistency of roduct 1uality" !utomated machinery and electronic facilities used in the manufacturin% rocess& as $ell as soft$are and e1ui ment related to com uters or to the manufacture& rocessin%& re- ac4a%in%& ac4a%in% or stora%e of harmaceuticals& shall be re%ularly recalibrated& ins ected& e.amined and maintained" /om uter systems used to control roduction and roduction mana%ement records shall be ro erly maintained& and alterations may not be made to said systems $ithout ermission from the ersonnel in char%e* all data that is in ut or rinted shall be chec4ed for accuracy& and its eriod of +alidity shall be determined based on the com le.ity and reliability of the com uter system" !ir used by dryin% facilities durin% the manufacturin% rocess shall first be treated $ith a urification filter" Facilities used to manufacture harmaceuticals for internal and e.ternal use shall be 4e t strictly se arate& and may not be used interchan%eably"

27

Pharmaceutical factories shall install $ei%hin% facilities that com ly $ith re%ulations& and shall recalibrate said facilities re%ularly" !rticle 52" -here a harmaceutical factory manufactures& rocesses or ac4s in8ectables& and has not installed filtration facilities ca able of filterin% out fibers& said factory may not use li1uid filtration facilities that can ossibly release fibers" !rticle 5," Pharmaceutical factories shall 4ee facilities and e1ui ment for the roduction of harmaceuticals for human and animal use se arate& and these t$o ty es of roduction may not be carried out in the same structure unless the t$o areas are com letely se arated" ;o$e+er& harmaceuticals for animal use that com ly $ith the standards %o+ernin% dru%s for human use are not sub8ect to this restriction" !rticle 54" Pharmaceutical factories shall& in accordance $ith the re1uirements of the roducts bein% manufactured& install necessary manufacturin%& rocessin%& re- ac4a%in% and ac4a%in% facilities" !rticle 55" Pharmaceutical factories shall& in accordance $ith their s ecification testin% re1uirements for ra$ materials& semi-finished roducts& intermediate roducts and roducts& establish testin% de artments and a ro riate testin% facilities" ;o$e+er& if tests are conducted on a contract basis by an or%ani6ation a ro+ed by the com etent authority& in accordance $ith the /ontract <ru% 0anufacturin% and #estin% 5 eratin% Princi les& and clear documentation is ro+ided& establishment of said facilities may be $ai+ed" #estin% de artments shall include testin% and instrument laboratories" @nstrument laboratories shall be se arate from testin% laboratories& and shall be 4e t at an a ro riate tem erature and le+el of humidity and air urity* testin% laboratories shall be installed $ith sufficient and easy to use test benches& test stands& dru% cabinets& fume hoods& $ater su ly and $ashin% facilities& as $ell as electric heatin%& thermostatic and dryin%
2'

facilities& and shall also be stoc4ed $ith utensils and containers& chemical rea%ents and solutions& standard solutions and other necessary items" -here eye re arations& in8ectable dru%s& bio harmaceutical or biotechnolo%y roducts are roduced& areas& facilities and e1ui ment necessary for conductin% late count& sterility tests and other tests shall be installed as needed* said areas and facilities shall be e1ui ed $ith necessary culture mediums and control strains" -here in8ectable dru%s and bio harmaceutical or biotechnolo%y roducts are roduced& areas& facilities and e1ui ment necessary for conductin% yro%en tests shall be installed as needed* said areas and facilities shall be e1ui ed $ith necessary rabbits and breedin% areas" -here antibiotics and bio harmaceutical or biotechnolo%y roducts are roduced& areas& facilities and e1ui ment necessary for conductin% safety tests shall be installed as needed* said areas and facilities shall be e1ui ed $ith necessary animals and breedin% and obser+ation areas" -here antibiotics& hormones and bio harmaceutical or biotechnolo%y roducts are roduced& areas& facilities and e1ui ment necessary for conductin% bioassays shall be installed as needed" #he s ecifications of ase tic rooms and dissection laboratories shall be determined in accordance $ith the re1uirements of the tas4s to be erformed* microor%anism strains& culture mediums and animals necessary for conductin% bioassays shall be ade1uately stoc4ed and maintained" /ha ter 5 5r%ani6ation and Personnel !rticle 57" ?uality control de artments and manufacturin% de artments at harmaceutical factories shall be established se arately"
29

!rticle 5'" ! erson shall be laced in char%e of each harmaceutical factory de artment& and sufficient ersonnel shall be assi%ned to carry out and su er+ise the manufacture& rocessin%& re- ac4a%in%& ac4a%in% or stora%e of each roduct" !rticle 59" #he erson in char%e& su er+isors and em loyees of each harmaceutical factory de artment shall all ossess suitable educational bac4%rounds& and shall all under%o ractical trainin% in im lementin% the rules rescribed in Part , of this set of Standards* em loyees $ho $or4 in ase tic room areas shall under%o s eciali6ed trainin% in ase tic room o erations" !rticle 5:" Pharmaceutical factories shall establish in $ritin% sanitary standards for em loyees* said standards shall include the follo$in% items: (1) 3e%ular health e.aminations in accordance $ith the nature of the em loyeeAs 8ob* (2) 0easures to re+ent em loyees $ith illnesses or o en $ounds from ha+in% a ne%ati+e im act on harmaceutical safety or 1uality* (,) 3ules re1uirin% em loyees to $ash or disinfect their hands $hen enterin% $or4 areas& refrain from $earin% 8e$elry& eatin%& drin4in%& smo4in%& or en%a%in% in any other beha+ior that may im act sanitation in manufacturin% areas* (4) Standards for the ty es of $or4 clothes& hoods& face mas4s& %lo+es& arm co+ers& and shoe co+ers for each 8ob" /ha ter 7 0ana%ement of 3a$ 0aterials and Product /ontainers and /a s !rticle 70" Pharmaceutical factories shall establish detailed 1uality s ecifications for ra$ materials and roduct containers and ca s& as $ell as o erational rocedures for the acce tance& labelin%& stora%e& handlin%& sam lin%& testin% and ins ection of these items"
2:

/ontainers that hold ra$ materials& roduct containers or ca s shall be clearly labeled $ith batch numbers and status& endin%-ins ection& a ro+ed for use& not a ro+ed for use& or to be isolated* this information shall be entered into the dis osition record of each batch" /ontainer ca s shall& as needed& be fitted $ith children safety de+ices to re+ent accidental consum tion" !rticle 71" -hen harmaceutical factories recei+e shi ments of ra$ materials& roduct containers or ca s& they shall collect re resentati+e sam les from each batch for testin%* a note of this action shall be made on the ori%inal container" /ontainers holdin% the sam les described in the recedin% Para%ra h shall be a ro riately labeled to facilitate trac4in% of sam le names& batch numbers& sam lin% basis& ori%inal container and name of sam ler" !rticle 72" #he sam les referred to in the recedin% !rticle shall be tested in accordance $ith the follo$in% rinci les: (1) E+ery ra$ material shall be tested to determine $hether it is in com liance $ith documented s ecifications" ;o$e+er& aside from identification tests& other tests may be $ai+ed if the test re orts ro+ided by the su lier are e+aluated and found to be reliable" (2) Products containers and ca s shall be tested to determine $hether they are in com liance $ith established s ecifications" (,) -here ra$ materials& roduct containers or ca s are susce tible to contamination by filth& insects& forei%n ob8ects or microor%anisms& thus affectin% their intended uses& rele+ant test items and methods shall be included in the 1uality s ecifications for said items& and each batch shall be ins ected for contamination" !rticle 7," -here ra$ materials& roduct containers or ca s are tested
,0

and found to be in com liance $ith documented s ecifications& harmaceutical factories may a ro+e them for use* $here said items are not in com liance& they shall not be a ro+ed for use" 3a$ materials& roduct containers or ca s that are a ro+ed for use shall be used in the order of a ro+al" ;o$e+er& $here said items ha+e been stored for lon% eriods& e. osed to the air or hi%h tem eratures& or sub8ected to other detrimental conditions& retestin% shall be carried out" 3a$ materials& roduct containers or ca s that are not a ro+ed for use shall be labeled to this effect& and 4e t isolated rior to their ro er dis osal" /ha ter ' 0anufacturin% Process /ontrol !rticle 74" #o insure that each roduct batch is of consistent 1uality& harmaceutical factories shall ha+e desi%nated ersonnel establish rocess control standards for e+ery roduct& and ha+e said standards inde endently re+ie$ed by other ersonnel" #he rocess control standards mentioned in the recedin% Para%ra h shall include the follo$in% items: (1) Product name& content and dosa%e form* (2) Eame and $ei%ht or +olume of each acti+e in%redient er roduct by unit $ei%ht& +olume or dosa%e form& and total $ei%ht or +olume of unit dosa%e form* (,) Eames and s ecifications of all ra$ materials* if a code name or number is used to re resent a ra$ material& said code shall be sufficient to determine the nature of the material* (4) ?uantity of each roduct batch* (5) -ei%ht or +olume re1uired by each ra$ material for each roduct batch" ;o$e+er& the 1uantities of ra$ materials used to roduce a %i+en dosa%e form may be increased or +aried $ithin a reasonable
,1

ran%e* said ran%e shall be e. lained in the manufacturin% rocess control standards* (7) ! ro riate theoretical $ei%hts or +olumes for each sta%e of the manufacturin% rocess* (') #heoretical roduction 1uantity& includin% u 1uantity limits e. ressed as ercenta%e* er and lo$er roduction

(9) Product container& ca and ac4a%in% material s ecifications (alon% $ith label si%ned and dated by ins ector and sam les or co ies of all other labelin%)* (:) /om lete manufacturin% and control manuals& sam lin% and test rocedures& s ecifications and %uidelines" !rticle 75" Pharmaceutical factories shall establish in $ritin% rocess control rocedures* said rocedures shall be a ro+ed by the 1uality control de artment" -here actual o erations de+iate from documented rocedures& said de+iation shall be recorded& a determination of ho$ best to handle the de+iation shall be made& and an e. lanation shall be %i+en" !rticle 77" #o insure the each roduct batch is of consistent 1uality and inte%rity& harmaceutical factories shall ta4e ste s to e+aluate and +alidate the consistency of rocess control o erations& includin% related e1ui ment and facilities& for each roduct* documented rocedures for the +alidation of each manufacturin% rocess shall also be established& and shall be com lied $ith and +alidated on a re%ular basis" !ll ori%inal +erification records and statistical analysis data related to e+aluation and +alidation rocedures shall be com iled and filed for future reference" !rticle 7'" Pharmaceutical factories shall clearly mar4 the contents and roduct batch manufacturin% sta%e dates and times of mi.in% and stora%e containers& roduction lines and main manufacturin% facilities used in the roduction and manufacture of each roduct batch& and enter said information into the batch manufacturin% record"
,2

!rticle 79" @n re%ard to the 1uantities of ra$ materials used by harmaceutical factories in the manufacture of roducts& the amounts of acti+e in%redients in each roduct batch may not fall belo$ the nominal 1uantity" -ei%hin%& di+idin% and other rocedures carried out on ra$ materials shall be erformed in desi%nated se%re%ation areas& and shall be a ro riately su er+ised and controlled" <ocumented o erational rocedures shall include detailed test and control rocedures for re resentati+e sam les from each batch of semi-finished or intermediate roducts" <urin% the manufacturin% and roduction rocess& the 1uality control de artments of harmaceutical factories shall carry out tests on semifinished or intermediate roducts in accordance $ith established test rocedures& thereby determinin% $hether to a ro+e said roducts for use* semi-finished or intermediate roducts that are not a ro+ed for use shall be labeled to this effect and 4e t isolated" !rticle 7:" -here harmaceutical factories $ei%h& mi.& ul+eri6e& form tablets from& fill& re- ac4a%e or carry out other related rocedures on antibiotic o$der& and said rocedures are carried out in areas also used for the roduction of %eneral harmaceutical roducts& ste s shall be ta4en to re+ent cross-contamination& and +alidation rocedures shall be carried out" Pharmaceutical factories shall include a ro riate measures to re+ent contamination by harmful microor%anisms in the documented o erational rocedures for roducts that do not re1uire sterili6ation* ste s or other a ro riate measures to ensure sterili6ation results shall be established for roducts that re1uire sterili6ation"

,,

/ha ter 9 0ana%ement of Pac4a%in% and >abelin% !rticle '0" Pharmaceutical factories shall establish in $ritin% mana%ement rocedures for the acce tance& labelin%& stora%e& handlin%& sam lin% and testin% of ac4a%in% and labelin% materials" -here o+er-the-counter dru% roducts for human use are roduced& ac4a%in% for said roducts shall be tam er- roof& and shall be 4e t intact durin% the manufacturin%& shi in% and retail dis lay rocess* moreo+er& said ac4a%in% shall be desi%ned in such a manner that tam erin% is easily detectable by consumers" Prior to the acce tance or use of labelin% and ac4a%in% materials& re resentati+e sam les shall be ta4en from each batch for testin%* testin% results shall be recorded and sam les reser+ed" -here test results com ly $ith established s ecifications& said materials may be a ro+ed for use* $here said materials are not in com liance& they shall not be a ro+ed for use" !rticle '1" Pharmaceutical factories shall& in accordance $ith roduct ty e& content and dosa%e form& se arately store and a ro riately mar4 labels and other labelin% materials* stora%e areas for said materials may not be entered $ithout the consent of the ersonnel in char%e" Pac4a%in% or labelin% materials that ha+e e. ired or are not a ro+ed for use shall be returned or destroyed" #he amounts of labelin% materials recei+ed& used and returned shall be 4e t trac4 of& and no discre ancies shall be allo$ed" Hnused ortions of labelin% materials rinted $ith batch numbers shall be destroyed* unused labelin% materials that are not rinted $ith batch numbers shall be a ro riately identified and stored"

,4

!rticle '2" Prior to ac4a%in% and labelin% roducts& harmaceutical factories shall first ins ect ac4a%in% and labelin% materials to ensure that they are correct and suitable for use* said ins ection results shall be entered into the batch manufacturin% record" Pac4a%in% and labelin% facilities shall be ins ected rior to use to ensure that all harmaceuticals from the re+ious run and ac4a%in% and labelin% materials not suited to the resent run ha+e been com letely remo+ed* said ins ection results shall be entered into the batch manufacturin% record" <urin% the final sta%e of roduction& roducts that ha+e already been ac4a%ed and labeled shall be ins ected to ensure that e+ery container or ac4a%e is correctly labeled" !rticle '," #o ensure that the in%redients& contents& 1uality and urity of roducts ready for use are in com liance $ith established s ecifications& harmaceutical factories shall& unless other re%ulations a ly& label said roducts $ith a usa%e eriod or e. iration date as determined throu%h stability testin%* roducts that must be re ared before use shall be clearly labeled $ith the method of re aration and usa%e eriod follo$in% re aration" /ha ter : Stora%e& Shi in% and Sales

!rticle '4" Pharmaceutical factories shall establish in $ritin% roduct stora%e rocedures* said rocedures shall include the follo$in% items: (1) Se%re%ation measures for roducts a$aitin% a ro+al for use* (2) ! ro riate tem erature& humidity and li%ht e. osure standards to ensure that roduct in%redients& contents& 1uality and urity are not ad+ersely affected by stora%e" !rticle '5" Pharmaceutical factories shall establish in $ritin% shi
,5

in%

and sales rocedures* said rocedures shall include the follo$in% items: (1) 0easures to ensure that roducts are sold in the order of manufacture* (2) Shi in% and sales methods that ensure roduct in%redients& contents& 1uality and urity are not ad+ersely affected by en+ironmental factors* (,) Systems to ensure rom t recyclin%" /ha ter 10 ?uality /ontrol !rticle '7" Pharmaceutical factories shall establish in $ritin% 1uality de artment duties and o erational rocedures* said duties and rocedures shall include the follo$in% items: (1) E.amination of a ro+al& non-a ro+al and manufacturin% records for all ra$ materials& roduct containers& ca s& semi-finished or intermediate roducts& ac4a%in% materials& labelin% materials and roducts* (2) E.amination of o erational rocedures s ecifications that affect roduct in%redients& contents& 1uality and urity* (,) @ns ection of facilities used in the testin% of ra$ materials& roduct containers& ca s& semi-finished or intermediate roducts& ac4a%in% materials& labelin% materials and roducts* (4) Establishment in $ritin% of o erational rocedures %o+ernin% the calibration of instruments& de+ices& meters and recordin% a aratuses* said rocedures shall clearly rescribe calibration methods& schedules& accuracy limits& as $ell as usa%e restrictions and remedial measures for items that do not com ly $ith accuracy limits* (5) Establishment in $ritin% of o erational rocedures %o+ernin% sam le 1uantities& test inter+als and test methods for roduct stability testin%" !rticle ''" S ecifications& standards& sam lin% lans& test rocedures& and test control measures established for the +arious de artments of a harmaceutical factory& and any alterations related to said items& shall be e.amined and a ro+ed by the 1uality control de artment of said factory rior to im lementation"
,7

Pharmaceutical factories shall faithfully follo$ the o erational %uidelines that they ha+e established and 4ee records of the im lementation rocess* $here a de+iation from said %uidelines occurs& said de+iation shall be recorded& a determination of ho$ best to handle the de+iation shall be made& and an e. lanation shall be %i+en" Pharmaceutical factories shall select senior s ecialist ersonnel from each de artment to establish a 1uality assurance system to re%ularly assess the status of factory o erations* this rocess shall include establishment of self-assessment rocedures for the im lementation of re%ulations of Part , of this set of Standards& as $ell as the roduction of records and re orts for future reference" !rticle '9" Pharmaceutical factories shall test e+ery batch of roducts to ensure that they are in com liance $ith established s ecifications* each batch of roducts that must not contain harmful microor%anisms shall& $here necessary& be sub8ected to a ro riate tests" 3e resentati+e sam les shall be remo+ed from each batch of roducts or end roducts& and ta4en from the ra$ materials containin% acti+e in%redients used in ma4in% said roducts& and laced in reser+e* said reser+e sam les shall be stored under indicated conditions& and shall be of at least t$ice the 1uantity needed for all re1uired tests" ;o$e+er& the 1uantity of reser+e sam les for sterility and yro%en tests shall be determined in accordance $ith re1uirements" 3eser+e sam les shall be retained until one year after the e. iration date of the roduct from $hich it $as ta4en* reser+e sam les of roducts that do not re1uire e. iration dates shall be 4e t for at least three years after the date of dis atch of the last batch of said roduct" !rticle ':" Pharmaceutical factories shall use a ro riate methods to breed& maintain and dis ose of animals re1uired for the testin% of ra$
,'

materials& semi-finished or intermediate roducts& and roducts" >aboratory animals shall be mar4ed* records sufficient to trace their usa%e history shall be 4e t" !rticle 90" Pharmaceutical factories shall& $here necessary& test nonenicillin antibiotics to ensure that they ha+e not been contaminated by enicillin& hormone or ce halos orin roducts" /ha ter 11 3ecords and 3e orts !rticle 91" #he manufacturin%& control& shi in% and sales records rescribed in Part , of this Part shall all be stored in suitable locations& made a+ailable for ins ection& and used at least once a year in the assessment of roduct 1uality standards* said records shall be 4e t until one year after the e. iration date of the batch of roducts or end roducts in 1uestion" ;o$e+er& records for roducts that do not re1uire e. iration dates shall be 4e t for three years after the date of dis atch of the batch of roducts or end roducts in 1uestion" -hen rele+ant com etent authorities ma4e ins ections& they may hotoco y& or co y by other means& the records described in Para%ra h 1 or co ies of said records" !rticle 92" Pharmaceutical factories shall 4ee batch manufacturin% records for each batch of roducts roduced* said records shall contain com rehensi+e manufacturin% and 1uality control information on the roduct batch in 1uestion" Pharmaceutical factories shall roduce accurate co ies of manufacturin% mana%ement standards& +erify the accuracy of said co ies& and si%n and date them"

,9

Pharmaceutical factories shall ma4e detailed records of the im ortant ste s in the manufacture& rocessin%& re- ac4a%in%& ac4a%in% and stora%e of each batch of roducts* said records shall include the follo$in% items: (1) <ate and roduct batch number* (2) @dentification mar4s for each batch of ra$ materials and semi-finished or intermediate roducts* (,) @dentity of ma8or facilities and roduction lines* (4) ?uantity and +olume of ra$ materials used in roduct rocessin%* (5) 0anufacturin% rocess& testin% and control results* (7) Pre- and ost-use ins ection of labelin% and ac4a%in% areas* (') 3atio of actual roduction out ut to theoretical out ut at a sta%es of manufacturin% rocess* ro riate

(9) /om rehensi+e labelin% control records& includin% sam les or co ies of all labelin%* (:) Product container and ca identification mar4s and usa%e 1uantity* (10)Sam lin% record* (11)<ates and times of each ma8or ste in the roduction rocess& as $ell as si%natures and dates for o eration ersonnel& direct su er+isors or ins ectors in+ol+ed in each ste " !rticle 9," #he test records roduced by harmaceutical factories shall include all test data used in determinin% com liance $ith established s ecifications and standards* said data shall include the follo$in% items: (1) Sam lin% location& 1uantity& batch number or other clear identifyin% code& sam lin% date& and date of test com letion* (2) 2asis of all test methods* (,) -ei%ht or +olume of all sam les tested* (4) /om rehensi+e records of all data %enerated durin% testin% rocess& includin% charts& %ra hs and s ectra roduced by test instruments& and clearly listin% all the ra$ materials& roduct containers& ca s& semifinished roducts& intermediate roducts or roducts tested& alon% $ith
,:

the batch numbers of said items* (5) 3ecord of all test-related calculations* (7) 3ecords of test results and com arison of said results $ith established s ecifications* (') Eames and dates for all ersonnel in+ol+ed in conductin% tests* (9) Si%natures of ins ectors testifyin% that the ori%inal records ins ected are accurate& truthful and in com liance $ith established s ecifications" !rticle 94" #he manufacturin% and 1uality control records (includin% ac4a%in% and labelin% control records) for all roducts manufactured by harmaceutical factories shall be e.amined by the 1uality control de artments of said factories to ensure that all roducts are in com liance $ith all established documented o erational rocedures rior to release& shi ment or sale" -here the theoretical roduction 1uantity e.ceeds the u er or lo$er roduction 1uantity limits rescribed by manufacturin% control standards& or if any other similar discre ancy occurs& or if any batch or ra$ material does not conform to s ecifications& a thorou%h in+esti%ation shall be conducted e+en if said batch of roducts has already been shi ed or sold* such in+esti%ations shall be e.tended to other batches of the roduct in $hich said discre ancy occurred& and to any other roducts that may be affected by said discre ancy" -ritten records shall be 4e t of the in+esti%ations described in the recedin% Para%ra h* said records shall include in+esti%ation conclusions and methods" !rticle 95" Pharmaceutical factoryAs shi in% and sales records shall include roducts names& contents& dosa%e forms& reci ient names and addresses& and shi in% dates and 1uantities"

40

!rticle 97" Pharmaceutical factories shall ma4e $ritten records of roduct com laints& and 4ee said records in roduct com laint files* said files shall be stored in a suitable location& or in a facility $here they can be easily accessed for ins ection" #he $ritten records referred to in the recedin% Para%ra h shall be 4e t until the e. iration date of the roduct in 1uestion& or for one year after the com laint $as recei+ed& $hiche+er eriod is lon%er" ;o$e+er& for roducts that do not re1uire e. iration dates& said records shall be 4e t for at least three years after the date of dis atch of the roduct in 1uestion" !rticle 9'" 3ecords of returned roducts 4e t by harmaceutical factories shall include roduct names& contents& batch numbers& reasons for return& 1uantities& dis osition dates& final dis osition methods* said records shall be 4e t in accordance $ith the re%ulations rescribed in !rticle 91" /ha ter 12 ;andlin% of /om laints and 3eturned Products !rticle 99" Pharmaceutical factories shall establish in $ritin% rocedures for the handlin% of oral and $ritten com laints from consumers* all oral and $ritten com laints shall be in+esti%ated and assessed by the 1uality control de artments of said factories" -here harmaceutical factories disco+er serious and unantici ated roduct defects& they shall re ort said defects to the rele+ant com etent authorities& and handle said defects in accordance $ith the sti ulations of the !ct" -ritten records shall be 4e t of the handlin% of all com laints* said records shall be ro erly collated and filed"

41

!rticle 9:" Pharmaceutical factories shall ro erly identify and se arately store returned roducts" @f there are any doubts re%ardin% a roductAs safety& in%redients& contents& 1uality or urity due to stora%e or shi in% conditions& the condition of the roduct& container& ac4a%in% or labelin%& or any other rele+ant circumstances either before or after the roduct is returned& unless the roductAs safety& in%redients& contents& 1uality and urity are confirmed to be in com liance $ith established s ecifications throu%h testin% or in+esti%ation& said roduct shall be destroyed" ;o$e+er& $here said roduct can be brou%ht into com liance $ith established s ecifications throu%h remanufacturin%& remanufacturin% may be carried out" /ha ter ,0 Pharmaceuticals for Hse in /linical #rials !rticle :0" #he roduction and manufacturin% of harmaceuticals for use in clinical trials by harmaceutical factories shall& unless other$ise re%ulated by re%ulations of this /ha ter& be %o+erned by other rele+ant re%ulations rescribed in this Part" !rticle :1" -here harmaceutical factories ha+e not yet established +alidated manufacturin% rocesses for harmaceuticals for use in clinical trials& or ha+e not yet established com rehensi+e manufacturin% control standards& said factories shall establish in $ritin% o erational rocedures and 4ee detailed and accurate records for each batch of roducts manufactured and each batch of ra$ material used" 2atch manufacturin% records shall be 4e t until clinical trials are com leted& or until at least t$o years after the roduct is com leted& $hiche+er eriod is lon%er" !rticle :2" -here harmaceutical factories roduce bio harmaceuticals or biotechnolo%y roducts for use in clinical trials& im urities caused by +irus inacti+ation=remo+al or other or%anisms may not e.ceed the limits im osed on other similar roducts on the mar4et" -here o erational rocedures for said roducts ha+e not yet been +alidated& 1uality control tests shall be erformed"

42

!rticle :," -here harmaceutical factories roduce harmaceuticals for use in clinical trials& said harmaceuticals& in addition to com lyin% $ith re%ulations %o+ernin% labelin% in the !ct& must also be labeled Ffor use in clinical trials only&G and mar4ed $ith the name of the arty that commissioned the clinical trial and a trial code sufficient to identify the trial location and research ersonnel in+ol+ed" ;o$e+er& $here harmaceuticals for use in clinical trials are tested in closed trials (double-blind trials)& dru% name& otency and efficacy may be re laced by roduct codes& serial numbers and ac4a%in% batch numbers" !rticle :4" Pharmaceutical factories shall determine suitable e. dates for harmaceuticals for use in clinical trials based on the ro erties& container characteristics and stora%e conditions* the e. dates mar4ed on said harmaceuticals may not e.ceed the e. dates mar4ed on the ori%inal roduct ac4a%in%" iration roduct iration iration

-here clinical trials do not ro+ide stability testin% information& the usa%e eriod of a re ac4a%ed roduct may not e.ceed 25I of the remainin% ortion of the usa%e eriod of the ori%inal bul4 roduct& or the si.-month eriod follo$in% re ac4a%in%& $hiche+er eriod is shorter" !rticle :5" -here a harmaceutical factory has a harmaceutical for use in clinical trials manufactured or tested on a contract basis& said contract shall clearly state that the roduct in 1uestion is for use in clinical trials only" !rticle :7" -here harmaceutical factories destroy harmaceuticals for use in clinical trials& destruction of said harmaceuticals may not ta4e lace until all clinical trials and the final re ort are com leted* detailed records shall be 4e t of the destruction rocess& and said records shall be reser+ed by the manufacturer" Part 4 Good 0anufacturin% Practices for 0edical <e+ices

4,

/ha ter 1 General Princi les !rticle :'" 0anufacturers of medical de+ices (hereafter referred to as the manufacturers) shall com ly $ith re%ulations of this Part" ;o$e+er& $here the 0edical <e+ice 0ana%ement 0easures or other rele+ant la$s or re%ulations a ly& com liance $ith this Part may be $ai+ed" !rticle :9" #erms used in this Part are defined as follo$s: (1) !cti+e medical de+ice: any medical de+ice relyin% for its functionin% on a source of electrical ener%y or any source of o$er other than that directly %enerated by the human body or %ra+ity* (2) !cti+e im lantable medical de+ice: any acti+e medical de+ice that is totally or artially introduced& sur%ically or medically& into the human body or by medical inter+ention into a natural orifice& and that is intended to remain after the rocedure* (,) @m lantable medical de+ice: any medical de+ice that is totally or artially introduced by sur%ical means into the human body or a natural orifice& or to re lace an e ithelial surface or the surface of the eye& that is intended to remain after the rocedure for at least ,0 days& and that can only be remo+ed by medical or sur%ical inter+ention* (4) @n-+itro dia%nostic de+ice: any medical de+ice that is a rea%ent& instrument& or system used for the collection& re aration and e.amination of s ecimens from the human body for use in the dia%nosis of disease or other conditions (includin% determination of the state of health)* (5) /ustomer com laint: any $ritten& electronic or oral communication that alle%es deficiencies related to the identity& 1uality& durability& reliability& safety or erformance of a medical de+ice that has been laced on the mar4et* (7) !d+isory notice: su lementary information or ad+ice issued by the manufacturer u on deli+ery of a medical de+ice& re%ardin% the use& modification& return or destruction of said de+ice& for the ur ose of ta4in% correcti+e or re+enti+e action or com lyin% $ith re%ulatory re1uirements*
44

(') 3is4 analysis: the in+esti%ation of a+ailable information to identify ha6ards and assess ris4s" !rticle ::" 0anufacturers of medical de+ices that fall under the /lass 1 cate%ory as defined in !ttachment 2 of the 0edical <e+ice 0ana%ement 0easures& unless said de+ices must be sterile& are not re1uired to com ly $ith re%ulations of this Part" -here medical de+ices that must be sterile& as described in the recedin% Para%ra h& are /lass 1 or /lass 2 medical de+ices that ha+e been %ranted a fi+e-year %race eriod by the central com etent health authority& the manufacturers of said roducts shall come into com liance $ith re%ulations of this Part by Dune 21& 2005" /ha ter 2 0ana%ement 3es onsibility !rticle 100" 0anufacturers shall clearly establish 1uality includin% ob8ecti+es for& and commitment to& 1uality" olicies&

#he 1uality olicies described in the recedin% Para%ra h shall be rele+ant to manufacturersA or%ani6ational %oals and the e. ectations and needs of their customers" 0anufacturers shall ensure that these 1uality olicies are understood& im lemented and maintained at all le+els of the or%ani6ation" !rticle 101" 0anufacturers shall clearly define and document the res onsibility& authority and interrelation of ersonnel $ho mana%e& erform and +erify $or4 affectin% 1uality& articularly ersonnel $ho need the or%ani6ational authori6ation to erform the follo$in% tas4s: (1) @nitiate action to re+ent the occurrence of any nonconformities relatin% to roducts& rocess or 1uality system* (2) @dentify and record any 1uality system* roblems relatin% to roducts& rocess or

(,) @nitiate& recommend or ro+ide solutions throu%h desi%nated channels*

45

(4) Cerify the im lementation of solutions* (5) /ontrol further rocessin%& deli+ery or installation of nonconformin% roduct until the deficiency or unsatisfactory condition has been corrected" !rticle 102" 0anufacturers shall identify resource re1uirements and ro+ide ade1uate resources& includin% the assi%nment of trained ersonnel for mana%ement& erformance of $or4 and +erification acti+ities includin% internal 1uality audits" !rticle 10," 0anufacturers shall a oint a member of their o$n mana%ement team $ho& irres ecti+e of other res onsibilities& shall define authority for the follo$in% tas4s: (1) Ensurin% that a 1uality system is established& im lemented and maintained in accordance $ith re%ulations of this Part* (2) 3e ortin% on the erformance of the 1uality system to the mana%ement for re+ie$ and as a basis for im ro+ement of the 1uality system* (,) Ensurin% the safety and effecti+eness of manufactured medical de+ices" !rticle 104" 0anufacturers shall re+ie$ their 1uality systems at defined inter+als sufficient to ensure its continuin% suitability and effecti+eness in satisfyin% the re1uirements of this Part and the manufacturerAs stated 1uality olicies and ob8ecti+es" 3ecords of said re+ie$s shall be 4e t and maintained" /ha ter , ?uality Systems !rticle 105" 0anufacturers shall establish& document and maintain 1uality systems as a means of ensurin% that roducts conform to s ecified re1uirements" 0anufacturers shall re are a 1uality manual co+erin% the re1uirements of this Part* said manual shall include or ma4e reference to the 1uality system rocedures and outline the structure of the documentation used" !rticle 107" 0anufacturers shall adhere to the follo$in% 1uality system rocedures:

47

(1) Pre are documented rocedures consistent $ith the 1uality olicy and the re1uirements of this Part* (2) Effecti+ely im lement the 1uality system and its documented rocedures" #he 1uality system rocedures described in the recedin% Para%ra h shall be de endent u on the com le.ity of the $or4& the methods used& and the trainin% re1uired by the ersonnel in+ol+ed" !rticle 10'" 0anufacturers shall establish in $ritin% a 1uality detailin% ho$ 1uality re1uirements are to be met" lan

#he 1uality lan described in the recedin% Para%ra h shall be consistent $ith the re1uirements of manufacturersA 1uality systems& and shall be documented in a format to suit the su lierAs o eration" 0anufacturers shall %i+e consideration to the follo$in% acti+ities& as a ro riate& in meetin% s ecified re1uirements for roducts& ro8ects or contracts: (1) Pre aration of 1uality lans* (2) #he identification and ac1uisition of any controls& rocesses& facilities& (includin% ins ection and test facilities)& fi.tures& resources and s4ills that may be needed to achie+e the re1uired 1uality* (,) Ensurin% the com atibility of the desi%n& the roduction rocesses& installation& ser+icin%& ins ection and test rocedures and the a licable documentation* (4) #he u datin%& as necessary& of 1uality control& ins ection and testin% techni1ues& includin% the de+elo ment of ne$ instruments* (5) #he identification of any measurement re1uirement in+ol+in% ca ability that e.ceeds the 4no$n state of the art& in sufficient time for the needed ca ability to be de+elo ed* (7) #he identification of suitable +erification at a reali6ation of roducts* ro riate sta%es in the

(') #he clarification of standards of acce tability for all features and re1uirements& includin% those that contain a sub8ecti+e element*
4'

(9) #he identification and re aration of 1uality records" 0anufacturers shall establish and maintain medical de+ice manufacturin% rocedure& installation and maintenance files& or a location $here rele+ant information can be accessed" Said files or information shall include roduct s ecifications and 1uality system re1uirements (includin% rocess and 1uality assurance) for each roduct ty e or model" /ha ter 4 /ontract 3e+ie$ !rticle 109" 0anufacturers shall establish in $ritin% and maintain rocedures for contract re+ie$ and for the coordination of re+ie$ acti+ities" !rticle 10:" 2efore submittin% a tender& or acce tin% a contract or order& manufacturers shall re+ie$ said tender& contract or order to ensure that the follo$in% conditions are met: (1) 3e1uirements are ade1uately defined and documented* $here an order is laced orally and there is no accom anyin% documentation& ste s shall be ta4en to ensure that re1uirements ha+e been met before said order is acce ted" (2) !ny discre ancies bet$een items in contact=order and tender ha+e been resol+ed" (,) /ontract=order re1uirements are ca able of bein% fulfilled" 0anufacturers shall identify contract amendments and accurately communicate said amendments to rele+ant de artments $ithin the or%ani6ation" 3ecords of the re+ie$ rocedures described in the Para%ra hs shall be 4e t and maintained" recedin% t$o

49

/ha ter 5 <esi%n /ontrol !rticle 110" 0anufacturers shall control and +erify roduct desi%n& and establish in $ritin% and maintain rocedures to ensure that s ecified re1uirements are met" ;o$e+er& roducts for $hich the central com etent health authority does not mandate the im lementation of desi%n control& are not re1uired to com ly $ith the ro+isions of this /ha ter" 0anufacturers shall& in the course of the desi%n rocess& assess the need for ris4 analysis and 4ee and maintain records of any ris4 analysis erformed" !rticle 111" 0anufacturers shall draft lans for each desi%n and de+elo ment acti+ity* said lans shall com ly $ith the follo$in% conditions: (1) Each lan shall document or refer related acti+ities" (2) @m lementation res onsibility shall be defined" (,) <esi%n and de+elo ment tas4s shall be assi%ned to 1ualified ersonnel e1ui ed $ith ade1uate resources" (4) Plans shall be u dated as desi%ns e+ol+e" 0anufacturers shall define or%ani6ational and technical interfaces bet$een the different %rou s in+ol+ed in the desi%n rocess* necessary information shall be documented& circulated and re+ie$ed on a re%ular basis" !rticle 112" 0anufacturers shall identify& document and ade1uately re+ie$ roduct desi%n in ut re1uirements (includin% a licable statutory and re%ulatory re1uirements)" -here said re1uirements are incom lete& ambi%uous or conflictin%& solutions shall be reached in consultation $ith those res onsible for im osin% said re1uirements"

4:

<esi%n in ut shall ta4e into consideration contract re+ie$ results" !rticle 11," 0anufacturers shall document desi%n out ut* said out ut shall com ly $ith the follo$in% conditions: (1) <esi%n out ut shall com ly $ith desi%n in ut re1uirements& and e. ressed in terms that can be +erified and +alidated a%ainst desi%n in ut re1uirements" (2) <esi%n out ut shall contain or ma4e reference to acce tance criteria" (,) <esi%n in ut shall identify the desi%n characteristics that are crucial to the safe and ro er functionin% of the roduct (e"%" o eration& stora%e& shi in%& maintenance and handlin% re1uirements)" (4) <esi%n out ut documentation shall be re+ie$ed before release" !rticle 114" 0anufacturers shall& in the course of the desi%n rocess& lan and conduct formal $ritten re+ie$s of desi%n results" Partici ants in said re+ie$s shall include re resentati+es of all de artments in+ol+ed in re+ie$ of the desi%n sta%e* $here necessary& other s ecialist ersonnel shall be as4ed to artici ate" 3ecords of said re+ie$s shall be 4e t and maintained" !rticle 115" 0anufacturers shall erform desi%n +erification at a ro riate sta%es in the desi%n rocess to ensure that desi%n sta%e out ut com lies $ith desi%n sta%e in ut re1uirements" 3ecords of the desi%n +erification measures referred to in the recedin% Para%ra h shall be 4e t and maintained" !rticle 117" 0anufacturers shall erform desi%n +alidation and clinical e+aluations to ensure that roducts com ly $ith established user needs and s ecified re1uirements* records of these acti+ities shall be 4e t and
50

maintained as art of the desi%n +alidation rocess" #he clinical e+aluations referred to in the recedin% Para%ra h shall include rele+ant scientific literature and established e+idence ro+in% that similar desi%ns and materials are clinically safe& or use clinical studies or e. eriments to ensure that said e1ui ment conforms to s ecified functions" !rticle 11'" !ll desi%n alterations and modifications made by manufacturers shall be identified& documented and re+ie$ed& as $ell as a ro+ed by authori6ed ersonnel& rior to im lementation" /ha ter 7 <ocument and <ata /ontrol !rticle 119" 0anufacturers shall establish in $ritin% and maintain rocedures for the control of all documents and data %o+erned by the ro+isions of this Part* $here feasible& said rocedures shall include ori%inal documents of e.ternal ori%in (such as standards and client dra$in%s) <ocument and data control by manufacturers shall com ly $ith the follo$in% conditions: (1) <ocuments and data shall be re+ie$ed and a authori6ed ersonnel rior to issue" ro+ed for ade1uacy by

(2) ! master list or e1ui+alent document control rocedure identifyin% the current re+ision status of documents shall be established and be readily a+ailable to re+ent the use of obsolete or in+alid documents" (,) Calid +ersions of a ro riate documents shall be made a+ailable at all locations $here o erations essential to the effecti+e functionin% of the 1uality system are erformed" (4) 5bsolete or in+alid documents shall be rom tly remo+ed from all oints of issue or use& or other ste s shall be ta4en to ensure that inad+ertent use does not occur"
51

(5) 5bsolete documents retained for le%al or information ur oses shall be a ro riately identified" (7) 0anufacturers shall retain at least one co y of obsolete control documents& and shall determine the eriod of retention" Said eriod shall be sufficient to ensure that the s ecifications to $hich medical de+ices ha+e been manufactured are a+ailable for at least the s ecified usa%e eriod of said roducts" !rticle 11:" !lterations to documents shall& unless other$ise desi%nated& be re+ie$ed and a ro+ed by the same functional units=or%ani6ations that erformed the ori%inal re+ie$ and a ro+al" @f other functional units=or%ani6ations are assi%ned to re+ie$ said alterations& said units=or%ani6ations shall ha+e access to bac4%round information used in the ori%inal re+ie$ u on $hich to base their re+ie$ and a ro+al" -here feasible& the nature of the alteration shall be indicated in the document or an a ro riate attachment" /ha ter ' Purchasin% !rticle 120" 0anufacturers shall establish in $ritin% and maintain urchasin% rocedures to ensure that all roducts urchased com ly $ith s ecified re1uirements" Purchasin% documents shall clearly describe the roducts bein% urchased* $here feasible& said documents shall include the follo$in% items: (1) Product ty e& class& %rade or other recise identifyin% information* (2) Product name or other ro er identification and a licable +ersions of s ecifications& %ra hics& rocess re1uirements& ins ection instructions and other rele+ant technical data& includin% items re1uired for roduct& rocedure& rocess e1ui ment and ersonnel a ro+al or +alidation* (,) Eame& serial number and +ersion of the 1uality system standard used"
52

-here it is necessary to +erify a urchased roduct on the subcontractorAs remises& +erification arran%ements and the method of roduct release shall be s ecified in the urchasin% documents" 0anufacturers shall re+ie$ and a ro+e urchasin% documents for ade1uacy of s ecified re1uirements rior to release" @n accordance $ith the ro+isions of /ha ter :& for medical de+ices $ith s ecified traceability re1uirements& manufacturers shall retain co ies of rele+ant urchasin% documents" !rticle 121" 0anufacturers shall ado t the follo$in% measures in re%ard to subcontractors: (1) E+aluate and select subcontractors based on their ability to meet subcontractin% re1uirements& includin% 1uality system and s ecific 1uality assurance re1uirements" (2) <efine the method and e.tent of control e.ercised o+er subcontractors based on roduct ty e and im act of subcontracted roduct on 1uality of end roduct* $here a licable& the subcontractorAs 1uality audit re orts or 1uality records demonstratin% the subcontractorAs ca abilities and erformance shall be consulted" (,) Establish and maintain subcontractor 1uality records" 0anufacturers shall not ta4e testimonials from clients re%ardin% subcontractors as e+idence for use in effecti+e subcontractor 1uality control" /ha ter 9 /ontrol of /ustomer-su lied Products

!rticle 122" 0anufacturers shall establish in $ritin% and maintain rocedures for control of the +erification& stora%e and maintenance of
5,

customer-su

lied roducts"

/ustomer-su lied roducts& as referred to in the recedin% Para%ra h& are su lies ro+ided by customers that are incor orated into roducts or used in related acti+ities" -here customer-su lied roducts are lost& dama%ed or other$ise unsuitable for use& the manufacturer shall record the roblem and re ort it to the customer" /ha ter : Product @dentification and #raceability !rticle 12," -here a ro riate& manufacturers shall establish in $ritin% and maintain rocedures detailin% suitable means for identifyin% their roducts at the +arious sta%es of recei+in%& roduction& deli+ery and installation" #he rocedures described in the recedin% Para%ra h shall include instructions ensurin% that $here returned medical de+ices are re rocessed due to s ecial re1uirements& said roducts are ro erly identified and differentiated at all times" !rticle 124" For roducts $here traceability is re1uired& manufacturers shall establish in $ritin% and maintain rocedures to ensure uni1ue identification of indi+idual roducts or roduct batches" 3ecords shall be 4e t of said identification" 0anufacturers shall establish and maintain traceability rocedures* said rocedures shall define the e.tent of traceability and facilitate correcti+e and re+enti+e measures" #he e.tent of traceability for acti+e im lantable medical de+ices and im lantable medical de+ices shall include records of all com onents& materials and en+ironmental conditions that could ossibly re+ent said de+ices from com lyin% $ith s ecified re1uirements"
54

0anufacturers shall re1uire that their a%ents or distributors maintain and retain medical de+ice sales records for ins ection ur oses" /ha ter 10 Production Process /ontrol !rticle 125" 0anufacturers shall identify and lan the roduction& installation and ser+ice rocesses that directly affect 1uality& and shall ensure that these rocesses are im lemented under controlled conditions" #he controlled conditions referred to in the recedin% Para%ra h shall include the follo$in%: (1) -here the absence of certain roduction& installation or ser+ice rocedures $ould ad+ersely affect 1uality& said rocedures shall be established in $ritin%" (2) Suitable roduction& installation and ser+ice facilities shall be used in a suitable $or4 en+ironment" (,) 3ele+ant la$s& standards& and 1uality lans or documented rocedures shall be com lied $ith" (4) Suitable rocess arameters and monitored and controlled" roduct characteristics shall be ro+ed"

(5) -here necessary& rocesses and facilities shall be a

(7) -or4manshi criteria (e"%" documented standards& re resentati+e sam les or illustrations) shall be sti ulated in a clear and ractical manner" (') Facilities shall be suitably maintained to ensure continuin% rocess ca abilities" -here rocess results cannot be fully +erified throu%h subse1uent roduct ins ection and testin% (includin% manufacturin% deficiencies that only become a arent $ith roduct use)& said rocess shall be carried out by 1ualified o erators& or the arameters of said rocess shall be
55

continuously monitored and controlled& to ensure that s ecified re1uirements are met" /onditions re1uired for rocess o eration& includin% rele+ant facilities and ersonnel& shall be sti ulated" !rticle 127" -here contact bet$een ersonnel and roducts or the roduction en+ironment could ad+ersely affect roduct 1uality& manufacturers shall establish in $ritin% and maintain re%ulations %o+ernin% ersonnel health& cleanliness and attire" 0anufacturers shall ensure that all tem orary ersonnel re1uired to $or4 under s ecial conditions recei+e necessary trainin% or $or4 under the su er+ision of trained ersonnel" !rticle 12'" -here medical de+ices meet the follo$in% conditions& manufacturers shall establish in $ritin% re1uirements for the en+ironments to $hich said de+ices are e. osed: (1) Said de+ices are sterile at time of su ly" ly& but re1uire sterili6ation (2) Said de+ices are not sterile at time of su rior to use"

(,) 3emo+al of microor%anisms or dust& or other en+ironmental conditions are critical to the use of said de+ices" (4) En+ironmental conditions durin% the roduction rocess are critical to said de+ices" -here necessary& en+ironmental conditions shall be controlled or monitored" !rticle 129" -here roducts meet the follo$in% conditions& manufacturers shall establish in $ritin% roduct cleanliness re1uirements: (1) Said roducts are cleaned by the manufacturer rior to sterili6ation or
57

use" (2) Said roducts are not sterile at time of su rior to sterili6ation or use" ly& but re1uire cleanin%

(,) Said roducts need not be sterile at time of use& but their le+el of cleanliness is critical to usa%e results" (4) !%ents used in the manufacture of said roducts re1uire remo+al" -here necessary& roducts cleaned in accordance $ith re%ulations of Sub ara%ra h 1 and Sub ara%ra h 2 of the recedin% Para%ra h may be $ai+ed from the s ecial re1uirements re%ardin% control of ersonnel and roduction en+ironment rescribed in the recedin% t$o !rticles" !rticle 12:" 0anufacturers shall establish in $ritin% and maintain re1uirements for maintenance and re air acti+ities $here said acti+ities may affect roduct 1uality" 0aintenance and re air records shall be 4e t and maintained" !rticle 1,0" -here necessary& manufacturers shall establish o erational %uidance documents and acce tance criteria re%ardin% the installation and ins ection of medical de+ices" @nstallation and ins ection records made by manufacturers or their authori6ed re resentati+es shall be retained" -here contracts do not re1uire manufacturers or their authori6ed re resentati+es to ta4e res onsibility for roduct installation& those $ho urchase said roducts shall be ro+ided $ith documented installation and ins ection instructions" !rticle 1,1" -here com uter soft$are is a lied in rocess control& manufacturers shall establish in $ritin% and maintain rocedures for the +alidation of said soft$are a lication" 3ecords shall be 4e t of +alidation results"
5'

!rticle 1,2" -here medical de+ices re1uire sterili6ation& manufacturers shall sub8ect said de+ices to a +alidated sterili6ation rocess* records shall be 4e t of all control arameters in+ol+ed in said sterili6ation rocess" /ha ter 11 @ns ection and #estin% !rticle 1,," 0anufacturers shall establish in $ritin% and maintain rocedures for ins ection and testin% acti+ities in order to +erify that roducts meet s ecified re1uirements" #he ins ection and testin% referred to in the recedin% Para%ra h& as $ell as the records to be established of said acti+ities& shall be detailed in the 1uality lan or in documented rocedures" !rticle 1,4" 0anufacturers shall a incomin% roducts: ly the follo$in% control measures to

(1) 0anufacturers shall ensure that incomin% roducts are not used or rocessed until said roducts ha+e been ins ected or other$ise +erified as com lyin% $ith s ecified re1uirements" Cerification of com liance $ith s ecified re1uirements shall be carried out in accordance $ith the 1uality lan or documented rocedures" (2) @n determinin% the nature and amount of recei+in% ins ection& consideration shall be %i+en to the amount of control im lemented at the subcontractorAs remises and the records of conformance ro+ided" (,) -here incomin% roducts are released for ur%ent roduction ur oses rior to +erification& said roducts shall be clearly identified and a record 4e t in order to facilitate immediate recall and re lacement in the e+ent of noncom liance $ith s ecified re1uirements" !rticle 1,5" 0anufacturers shall im lement the follo$in% in- rocess ins ection and testin% measures:
59

(1) @ns ect and test roducts in accordance $ith 1uality documented rocedural re1uirements"

lan or

(2) ;old roducts until re1uired ins ection and tests ha+e been com leted or necessary re orts ha+e been recei+ed and +erified* ho$e+er& this re1uirement does not a ly to roducts that are released under ositi+e-recall rocedures" Products released under ositi+e-recall rocedures must still be ins ected and tested in accordance $ith Sub ara%ra h 1 of the recedin% Para%ra h" !rticle 1,7" 0anufacturers shall carry out final ins ection and testin%& and create a record of said acti+ities& in accordance $ith the 1uality lan or documented rocedures& to ensure that end roducts are in com liance $ith s ecified re1uirements" #he 1uality lan or documented rocedures for final ins ection and testin% shall re1uire that all s ecified ins ection and tests (includin% those s ecified either on recei t of roduct or in- rocess) ha+e been carried out and that results meet s ecified re1uirements" Eo roduct shall be dis atched until all the acti+ities s ecified in the 1uality lan or documented rocedures ha+e been satisfactorily com leted and the associated data and documentation is a+ailable and authori6ed" !rticle 1,'" 0anufacturers shall establish and maintain records that %i+e e+idence that roducts ha+e been ins ected and=or tested" #he records described in the follo$in% conditions: recedin% Para%ra h shall meet the

(1) Said records shall sho$ clearly $hether roducts ha+e assed or failed the ins ection or tests erformed accordin% to acce tance criteria*
5:

$here roducts fail to ass any ins ection or test& the rocedures for control of nonconformin% roducts shall a ly" (2) 3ecords shall identify the ins ection authority res onsible for the release of roducts" (,) 0anufacturers shall record the identity of ersonnel erformin% any ins ection or testin% of acti+e im lantable medical de+ices or im lantable medical de+ices" /ha ter 12 /ontrol of @ns ection& 0easurin% and #est Facilities !rticle 1,9" 0anufacturers shall establish in $ritin% and maintain rocedures to control& calibrate and maintain ins ection& measurin% and test facilities (includin% test soft$are) used by the manufacturer to demonstrate the conformance of roduct to the s ecified re1uirements" #he ins ection& measurin% and test facilities referred to in the recedin% Para%ra h shall be used in a manner that ensures that the measurement uncertainty is 4no$n and is consistent $ith the re1uired measurement ca ability" !rticle 1,:" -here test soft$are or com arati+e references (such as test hard$are) are used as suitable forms of ins ection& they shall be chec4ed to ro+e that they are ca able of +erifyin% the acce tability of roducts& rior to release for roduction& installation or ser+icin%& and shall be rechec4ed at rescribed inter+als" 0anufacturers shall establish the e.tent and fre1uency of such chec4s and shall maintain records as e+idence of control" -here the a+ailability of technical data ertainin% to the ins ection& measurin% and test facilities is a s ecified re1uirement& such data shall be made a+ailable& $hen re1uired by the customer or the customerAs re resentati+e& for +erification that the ins ection& measurin% and test
70

facilities is functionally ade1uate" !rticle 140" 0anufacturers shall a ly the follo$in% control rocedures to ins ection& measurin% and test facilities: (1) <etermine the measurements to be made and the accuracy re1uired& and select the a ro riate ins ection& measurin% and test facilities that are ca able of the necessary accuracy and recision" (2) @dentify all ins ection& measurin% and test facilities that can affect roduct 1uality& and calibrate and ad8ust them at rescribed inter+als or rior to use& a%ainst certified e1ui ment ha+in% a 4no$n +alid relationshi to internationally or nationally reco%ni6ed standards* $here no such standards e.ist& the basis used for calibration shall be documented" (,) <efine the rocess em loyed for the calibration of ins ection& measurin% and test facilities includin% details of facility ty e& uni1ue identification& location& fre1uency of chec4s& chec4 method& acce tance criteria and action ta4en $hen results are unsatisfactory" (4) @dentify ins ection& measurin% and test facilities $ith a suitable indicator or a ro+ed identification record to sho$ the calibration status" (5) Produce and maintain calibration records for ins ection& measurin% and test facilities" (7) !ssess and document the +alidity of re+ious ins ection and test results $hen ins ection& measurin% or test facilities are found to be out of calibration" (') Ensure that the en+ironmental conditions are suitable for the calibrations& ins ections& measurements and tests bein% carried out" (9) Ensure that the handlin%& reser+ation and stora%e of ins ection& measurin% and test facilities are such that the accuracy and fitness for use are maintained" (:) Safe%uard ins ection& measurin% and test facilities& includin% both test hard$are and test soft$are& from ad8ustments that $ould in+alidate the calibration settin%"

71

/ha ter 1, @dentification of @ns ection and #est Status !rticle 141" 0anufacturers shall identify the ins ection and test status of roducts by suitable means to indicate the conformance or nonconformance of roduct $ith re%ard to ins ection and tests erformed" #he identification of ins ection and test status shall be maintained& as defined in the 1uality lan or documented rocedures& throu%hout roduction& installation and ser+icin% of roducts to ensure that only roducts that ha+e assed the re1uired ins ection and tests& or released under an authori6ed concession& is dis atched& used or installed" /ha ter 14 /ontrol of Eonconformin% Products !rticle 142" 0anufacturers shall establish in $ritin% and maintain control rocedures to ensure that roducts that do not conform to s ecified re1uirements are re+ented from unintentional use or installation" #he control rocedures referred to in the recedin% Para%ra h shall ro+ide for identification& documentation& e+aluation& se%re%ation ($hen ractical) and dis osition of nonconformin% roducts& and for notification of rele+ant authorities" !rticle 14," 0anufacturers shall define the res onsibility for re+ie$ and authority for dis osition of nonconformin% roducts" Eonconformin% roducts shall be re+ie$ed in accordance $ith documented rocedures& and handled in one of the follo$in% manners: (1) 3e$or4ed to meet the s ecified re1uirements* (2) !cce ted $ith or $ithout re air by concession* (,) 3e-%raded for alternati+e a lications*

72

(4) 3e8ected or scra

ed"

-here re1uired by contract& the ro osed use or re air of roducts that do not conform to s ecified re1uirements shall be re orted for concession to the customer or customerAs re resentati+e" #he descri tion of the nonconformity that has been acce ted& and of re airs& shall be recorded to denote the actual condition" 3e aired or re$or4ed roducts shall be re-ins ected in accordance $ith the 1uality lan or documented rocedures" !rticle 144" 0anufacturers shall ensure that nonconformin% roducts are acce ted by concession only if re%ulatory re1uirements are met" #he identity of the erson(s) authori6in% the concession shall be recorded" @f roducts need to be re$or4ed& manufacturers shall document the re$or4 in a $or4 instruction that has under%one the same authori6ation and a ro+al rocedure as the ori%inal $or4 instruction" Prior to authori6ation and a ro+al& a determination of any ad+erse effect of the re$or4 u on the roduct shall be made and documented" /ha ter 15 /orrecti+e and Pre+enti+e !ction !rticle 145" 0anufacturers shall establish in $ritin% and maintain rocedures for im lementin% correcti+e and re+enti+e actions" !ny correcti+e or re+enti+e action ta4en to eliminate the causes of actual or otential nonconformities shall be to a de%ree a ro riate to the ma%nitude of roblems and commensurate $ith the ris4s encountered" 0anufacturers shall im lement and record any chan%es to the documented rocedures resultin% from correcti+e and re+enti+e actions"
7,

0anufacturers shall establish in $ritin% and maintain a feedbac4 system to ro+ide early $arnin% of 1uality roblems and for in ut into correcti+e and re+enti+e action systems" 0anufacturers shall %ain e. erience throu%h monitorin% of ostroduction hase feedbac4 data* the re+ie$ of this e. erience shall form art of the feedbac4 system" 0anufacturers shall maintain records of all customer com laint in+esti%ations" -hen the in+esti%ation determines that the acti+ities at remote remises contributed to the customer com laint& rele+ant information shall be communicated bet$een the manufacturer and the remote remises" @f any customer com laint is not follo$ed by correcti+e and re+enti+e action& the reason shall be recorded" 0anufacturers shall establish re ortin% rocedures %o+ernin% notification of the central com etent health authority $hen in8uries in+ol+in% medical de+ices occur" 0anufacturers shall establish& document and maintain rocedures for the issue of ad+isory notices for medical de+ices" #hese rocedures shall be ca able of bein% im lemented at any time" !rticle 147" follo$in%: #he rocedures for correcti+e action shall include the

(1) #he effecti+e handlin% of customer com laints and re orts of roduct nonconformities* (2) @n+esti%ation of the causes of nonconformities relatin% to roduct& rocess and 1uality system& and recordin% the results of the in+esti%ation*
74

(,) <etermination of the correcti+e action needed to eliminate the cause of nonconformities* (4) ! lication of controls to ensure that correcti+e action is ta4en and that it is effecti+e" !rticle 14'" follo$in%: #he rocedures for re+enti+e action shall include the

(1) #he use of a ro riate sources of information such as rocess and $or4 o erations $hich affect roduct 1uality& concessions& audit results& 1uality records& ser+ice re orts and customer com laints to detect& analy6e and eliminate otential causes of nonconformities* (2) <etermination of the ste s needed to deal $ith any roblems re1uirin% re+enti+e action* (,) @nitiation of re+enti+e action and a that it is effecti+e* lication of controls to ensure

(4) Ensurin% that rele+ant information on actions ta4en is submitted for mana%ement re+ie$" /ha ter 17 ;andlin%& Stora%e& Pac4a%in%& Preser+ation and <eli+ery 0anufacturers shall establish in $ritin% and maintain rocedures for handlin%& stora%e& ac4a%in%& reser+ation and deli+ery of roducts" 0anufacturers shall establish in $ritin% and maintain rocedures %o+ernin% medical de+ice shelf life or s ecial stora%e conditions" Said conditions shall be controlled and recorded" @f a ro riate& s ecial arran%ements shall be established& documented and maintained for the control of used roducts in order to re+ent contamination of other roducts& the manufacturin% en+ironment or ersonnel" !rticle 14:" 0anufacturers shall carry out handlin%& stora%e& ac4a%in%& reser+ation& and deli+ery of roducts in accordance $ith the follo$in% rules:
75

(1) ;andlin%: methods of handlin% deterioration shall be used"

roducts that

re+ent dama%e or

(2) Stora%e: desi%nated stora%e areas or stoc4 rooms shall be used to re+ent dama%e or deterioration of roduct& endin% use or deli+ery* a ro riate methods for authori6in% recei t to and dis atch from said areas shall be sti ulated* the condition of roducts in stoc4 shall be assessed at a ro riate inter+als in order to detect deterioration" (,) Pac4a%in%: ac4in%& ac4a%in% and mar4in% rocesses (includin% materials used) shall be controlled to the e.tent necessary to ensure conformance to s ecified re1uirements* the identity of ersons $ho erform the final labelin% o eration for acti+e im lantable medical de+ices and im lantable medical de+ices shall be recorded" (4) Preser+ation: a ro riate methods for reser+ation and se%re%ation of roducts $hen said roducts are under the manufacturerAs control" (5) <eli+ery: arran%ements shall be made to rotect the 1uality of roducts after final ins ection and test* $here contractually s ecified& this rotection shall e.tend to include deli+ery to destination* the name and address of the shi in% ac4a%e consi%nee shall be included in the 1uality records for acti+e im lantable medical de+ices and im lantable medical de+ices" /ha ter 1' /ontrol of ?uality 3ecords !rticle 150" 0anufacturers shall establish in $ritin% and maintain rocedures for identification& collection& inde.in%& access& filin%& stora%e& maintenance and dis osition of 1uality records" ?uality records and their control shall conform to the follo$in% rules: (1) ?uality records shall be maintained to demonstrate conformance to s ecified re1uirements and the effecti+e o eration of the 1uality system" (2) Pertinent 1uality records from the subcontractor shall be an element of this data"

77

(,) 3etention times of 1uality records shall be clearly defined& and shall be at least e1ui+alent to the lifetime of the medical de+ice& but not less than t$o years from the date of dis atch from the manufacturer" (4) ?uality records shall be le%ible and shall be stored and retained in such a $ay that they are readily retrie+able in facilities that ro+ide a suitable en+ironment to re+ent dama%e& deterioration and loss" (5) -here a%reed contractually& 1uality records shall be made a+ailable for e+aluation by the customer for an a%reed eriod" !rticle 151" 0anufacturers shall establish and maintain a record for each batch of medical de+ices that ro+ides traceability and identifies the 1uantity manufactured and 1uantity a ro+ed for distribution" #he batch record referred to in the recedin% Para%ra h shall be +erified and authori6ed" /ha ter 19 @nternal ?uality !udits !rticle 152" 0anufacturers shall establish in $ritin% and maintain rocedures for lannin% and im lementin% internal 1uality audits to +erify $hether 1uality acti+ities and related results com ly $ith lanned arran%ements and to determine the effecti+eness of the 1uality system" !rticle 15," @nternal 1uality audits shall be scheduled by manufacturers on the basis of the status and im ortance of the acti+ity to be audited& and shall be carried out by ersonnel inde endent of those ha+in% direct res onsibility for the acti+ity bein% audited" #he results of the audits shall be recorded and brou%ht to the attention of the ersonnel ha+in% res onsibility in the area audited" #he mana%ement ersonnel res onsible for the area shall ta4e timely correcti+e action on the deficiencies found durin% the audit"

7'

Follo$-u acti+ities shall be carried out to +erify and record the im lementation and effecti+eness of the correcti+e action ta4en" /ha ter 1: #rainin% !rticle 154" 0anufacturers shall establish in $ritin% and maintain rocedures for identifyin% trainin% needs and ro+ide for the trainin% of all ersonnel erformin% acti+ities affectin% 1uality* ersonnel erformin% s ecific assi%ned tas4s shall be 1ualified on the basis of a ro riate education& trainin% or e. erience& as re1uired" ! ro riate records of the trainin% referred to in the recedin% Para%ra h shall be maintained" /ha ter 20 Ser+icin% -here ser+icin% is a s ecified re1uirement& the manufacturer shall establish in $ritin% and maintain rocedures for erformin%& +erifyin% and re ortin% that the ser+icin% meets the s ecified re1uirements" /ha ter 21 Statistical #echni1ues !rticle 157" 0anufacturers shall identify the need for statistical techni1ues re1uired for establishin%& controllin% and +erifyin% rocess ca ability and roduct characteristics" 0anufacturer shall establish in $ritin% and maintain rocedures to im lement and control the a lication of the statistical techni1ues referred to in the recedin% Para%ra h" Part 5 Su lementary Pro+isions

79

!rticle 15'" #his set of Standards shall come into force from the date of announcement"

7: