GMP Checklist

Company Name:
Address
Phone Number:
Date:
Contact Person:
Title:
Phone Number:
Questions Response
1.1. GENERAL 3 2 1
1.1.1. General information
1.1.1.1. Is there evidence of registration of the ey persons responsible by the !egulatory
Authority"
1.1.1.2. Is the #ualified person responsible$ according to company%s organi&ation chart$ present
at the time of the inspection"
1.1.1.'. Is there evidence of a license to operate issued by the !egulatory Authority"
1.1.1.(. is there a complete separation bet)een beta*+actam ,penicillin -cephalosporin.$
hormones or cytoto/ic products or any ha&ard material )ith other area0 +ines in the
scope of inspection incase the line not for one of this products"
1
1.1.1.5. Is there a 12P related recalls from the maret in last 3 years"
1.1.2. Premises
1.1.3.1. Are there any sources of environmental contamination in the area surrounding the
building"
1.1.3.3. If 45674$ are protective measures undertaen"
1.1.3.'. Are there approved and up to date layouts for the area"
1.1.3.(. Are toilets located before change rooms"
1.1.3.8. Are there physically separated areas for each production step"
1.1.2.6. Is the flo) of personnel and materials sho)n such that they are unidirectional0 prevent
product contamination 0mi/ up"
1.1.3.9. Is there a distinct and separate area for )ashing
1.1.3.:. Do the flo) of cleaned e#uipment through the )ashing room don;t allo) re
contamination"
1.1.3.<. Is there pacaging area completely physically separated from processing area"
1.1.3.1=. Are drained e#uipped to prevent bac flo)"
1.1.3.11. Are the visible electrical installations maintained in good condition"
1.1.2.12. Does the company comply )ith the national legislation on fire control and prevention"
1.1.3.1'. Is )aste treatment program covering the entire factory"
1.1.3.1(. Is there a special lighting system in the sampling$ )eighing$ processing area in case
those photosensitive ra) materials are being handled"
1.1.3. Ancillary area
1.1.'.1. Are there 7>P;s for )ashing uniforms separately depending on the type of area ,sterile$
non sterile$ maintenance$ special products."
1.1.3.2. Is there a laundry area for uniforms )hich is separate from production areas"
1.1.'.'. If an outside laundry facility is used$ are personnel and the person responsible
instructed about the corresponding 7>P"
1.1.'.(. Is this outside laundry facility periodically audited 0 the audit recorded"
1.1.'.8. Is there a pure steam generator$ if necessary"
1.1.'.?. Is there a compressed air generator free of oil$ if necessary"
1.1.3.7. Is there an electricity generator for the maintenance of critical systems and processes to
be used in case of problems )ith the electricity supply occur"
1.1.'.:. I7 it connected to critical e#uipment as autoclave$ lyophili&er @etc"
1.1.'.<. Do its performance tested 0the time it starts )or after electricity drop is suitable"
2
1.2. VALIDAI!N
1.2.1. General aspects"
1.3.1.1. Is there a validation master plan"
1.3.1.3. Is there a validation and re*validation program$ and under the responsibility of #uality
assurance for approval and follo)*up of its activities"
1.3.1.'. Are critically important processes validated"
1.3.1.(. Are the validations performed and documented"
1.3.1.8. Is every important modification to the manufacturing process validated$ including any
change in e#uipment$ manufacturing area$ materials$ changes in ra) materials$ pacing
materials$ changes in critical support systems processes and methods that may affect
the #uality of the product or reproducibility of the process"
1.3.1.?. In case electronic data processing systems are used$ are these validated"
1.3.1.9. If the system automated is a safety bac*up ept"
1.3.1.:. Are safety pass)ords used for system access"
1.3.1.<. Are these pass)ords only assigned to authori&e personnel"
1.2.1.10. Are the validation studies performed according to pre*defined protocols 0there is a
report"
1.3.1.11. Are trend analyses performed to assess the need to re*validate in order to assure the
processes and procedures continued to obtain the desired results"
1.2.2. #LEANING
1.2.2.1. Is a validation performed to confirm maAor0 minor cleaning effectiveness"
1.3.3.3. Is the #uality of the )ater used in the final rinse of the same #uality of the )ater used in
production"
1.3.3.'. Does the Balidation Protocol include Cleaning 7>P;s to be used0 clearly defined
sampling points"
1.3.3.(. Is the )or of the >perating Personnel effectively supervised"
1.3.3.8. Cave acceptance limits been set according )orst case"
1.3.3.?. Are detergent residues )ithin limits"
1.3.3.9. Are there Balidation !ecords"
1.3.3.:. Is the Dinal Balidation !eport is supported by the signature of all those involved$ the
verification by Production and the signature of Euality Assurance"
1.3. $AER %&%E'
1.3.1. 16N6!A+
3
1.'.1.1. Is the source of )ater used in the company allo)ing suitable continuous supply"
1.'.1.3. Are the system schematics sho)n"
1.'.1.'. Does the company have potable$ purified )ater tans"
1.'.1.(. Is the cleaning and disinfecting record for cistern ,if present. 0 potable )ater tans
documented$ is it maintained in good condition"
1.'.1.8. Does the procedure include a Austifiable fre#uency and sampling points"
1.'.1.?. Is there a 7>P for sampling of all types of produced )ater"
1.'.1.9. Are physicochemical0 microbiological tests0$ ,endoto/in for FDI. tests of all types of
produced )ater recorded0analysis established by current editions of official pharmacopoeias"
1.'.1.:. Does it include identification of pathogenic micro organism"
1.'.1.<. Are the sampling points rotated to cover all points adAacent to treatment stages in the
station 0 all point of use"
1.'.1.1=. Is the fre#uency of sampling Austifiable 0validated"
1.'.1.11. Is the action limit of purified )ater is no more than 1== cfu - m+0 1= cfu - 1==m+ for
FDI"
1.'.1.13. Fhen the action limit is e/ceeded$ is an investigation al)ays undertaen to ensure
#uality of the batches of product made )ith that )ater according >>7 plan"
1.'.1.1'. Is the documentation sho)n"
1.'.1.1(. Is there a preventive maintenance program that includes the )ater system"
1.'.1.18. Is there an automatic system to prevent use of the )aterG if it is out of specifications if
not is there another system"
1.'.1.1?. If there is an automatic system$ is this checed to verify that it is functioning properly"
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1.'.1.19. Are gauges in the station calibrated"
1.'.1.1:. Is there a record for monitoring pressure difference"
1.'.1.1<. Are there dead legs in the )ater system"
1.'.1.3=. Is there a trend analysis"
1.3.2. P(RI)IED $AER
1.'.3.1. Is the system used to obtain purified )ater satisfiable"
1.'.3.3. Are there )ritten procedures for the operation of the system"
1.'.3.'. Is there a tan for purified )ater storageG is it of sanitary type material"
1.'.3.(. Is it having a hydrophobic vent filter"
1.'.3.8. Are records periodic integrity tests ept"
1.'.3.?. If purified )ater ept circulating"
1.'.3.9. Are the pipes and valves used to distribute purified )ater made of sanitary material"
1.'.3.:. Is there a record for the sanitation of purified )ater storage and distribution system"
1.'.3.<. In case of using u.v lamp is there a record of its )oring hours"
1.'.3.1=. In the case of chemical sanitation$ or o&one treatment are there residues testing
record"
1.'.3.11. In the case that filters e/ist$ are there filter sanitation records"
1.'.3.13. Are the filter replacement records sho)n"
1.'.3.1'. If the )ater that feeds the system is chlorinated$ is there a system to remove the
chlorine"
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1.'.3.1(. In case of presence of carbon filter is there a record of saniti&ation of it )ith validated
fre#uency"
1.'.3.18. In case ionic e/change resins used$ is there a 7>P that considers the criteria to follo)
for the regeneration of resins and the fre#uency of regeneration"
1.'.3.1?. Are records ept"

1.'.3.19. If a reverse osmosis system is used$ is there a record for system saniti&ation )ith
satisfiable fre#uency"
1.'.3.1:. In case that chemical sani&atation is undertaen$ are saniti&ing agent residues
investigated0 Are records ept"
1.3.3. $AER )!R IN*E#I!N
1.'.'.1. Is distillation system is used to get Fater for InAection"
1.'.'.3. Is there a storage tan for the Fater used for inAection"
1.'.'.'. Is the tan made of sanitary material"
1.'.'.(. Does it have a hydrophobic vent absolute filter"
1.'.'.8. Are periodic integrity tests records ept"
1.'.'.?. Are pipes used in the distribution of Fater for InAection up to the point of use"
1.'.'.9. Are pipes made of sanitary material"
1.'.'.:. If there any type of heat e/changer are there guarantees that the heat e/changer is not a
source of contamination"
1.'.'.<. Is the )ater maintained circulating at 9=*:= HC"
1.'.'.1=. Is there a system to guarantee that temp maintained 9=*:=HC"
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1.3.+. VALIDAI!N"
1.'.(.1. Cave the )ater system installation been #ualified" Is a protocol and report been
produced"
1.'.(.3. Is pipes 0tans been passivated"
1.'.(.'. Cave the system operation #ualification been produced" is protocol and report been
produced"
1.'.(.(. Are there daily sampling records for every pretreatment 0treatment point and usage
point for a period of 3 to ( )ees in phase one validation"
1.'.(.8. Are there daily sampling records for every pretreatment0treatment point and usage
point for a period of ( to 8 )ees after Phase 1 for phase t)o validation"
1.'.(.?. Are the reports summari&ing the results of phases 1 and 3 of the validation available"
1.'.(.9. Are the )eely sampling records available of every usage point for a one*year period
continuously in phase three validation"
1.'.(.:. Is the validation summary report for phase three validation available" Is the result of
these records sho) the system is under control"
1.'.(.<. Is 7ampling point rotation program included in the performance #ualification
protocol0 report"
1.'.(.1=. Is Physical*chemical and microbiological analysis programme 0system release
parameter produced in it"
1.'.(.11. Are the cleaning and sanitation procedures and fre#uencies been defined in it"
1.'.(.13. Are 7>Ps have been initiated during the validation phase"
1.'.(.1'. Is any deviation from the designed criteria in #ualifications 0validation investigated
0action is taen0invetigation recorded in the report"
1.+. %!RAGE AREA
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1.+.1. %amplin, area
1.(.1.1. Is there a physically separated area for sampling"
1.(.1.3. Does the sampling area have sanitary finishes"
1.(.1.'. Does the sampling area has +AD unit "
1.(.1.(. Does it have change room"
1.(.1.8. Is there a 7>P for the cleaning of the sampling area"
1.(.1.?. Is there a place to eep the sampling utensils in an orderly fashion to protect it from
contamination"
1.(.1.9. Is there a )ashing area$ )hich is separated$ for the sampling utensils"
1.(.1.:. Incase no )ashing room for sampling areaG is there a 7>P for the handlig0storage of
those sampling utensils to their )ashing area"
1.(.1.<. Is there a 7>P for the incoming of ra) materials to sample and their transfer to the
#uarantine area after sampling"
1.+.2. $ei,-in, Area
1.(.3.1. Is there a physically separated )eighing area"
1.(.3.3. Is there a 7>P for the cleaning of the )eighing area"
1.(.3.'. Are the area have +AD unit"
1.(.3.(. Is there an area for the cleaning and sanitation of the containers"
1.(.3.8. Is there a ventilation system in the room )ith pressure differentials$ and the ra)
materials handled )ith controlled temperature$ humidity$ and air filtration$ if re#uired"
1.(.3.?. Does it have change room"
1.(.3.9. If orders )hich are already dispensed are not transferred to the plant immediately$ is
there a place or system that prevents mi/*ups"
1.(.3.:. Is there a 7>P for cleaning the tools-utensils 0 containers used in )eighing and-or
measuring"
1.(.3.<. Is there an area for )ashing the tools-utensils 0 containers used in )eighing and-or
measuring"
1.(.3.1=. Are these tools-utensils0 containers ept clean and labeled in a safe place"
1.(.3.11. Are the scales calibrated periodically$ is there arecord"
1.(.3.13. Are there records that scales checed on a defined scheduled basis"
1.(.3.1'. Is protective e#uipment used )hen necessary"
1.(.3.1(. Are the materials$ after being )eighed or measured$ immediately labeled in order to
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prevent mi/*ups"
1.(.3.18. >n the label$ does it state: Name or code and batch of the item $ Name or code of the
product to )hich the item is destined $ Product Iatch number$ Euantity that )as
)eighed or measured$ 7ignature and date of the )orer )ho carried out the operation $
7ignature and date of )eight verification"
1.(.3.1?. Is there a 7>P that describes all the operations of this sector-area"
1.+.3. $are-ouse
1.(.'.1. Is there a receiving area"
1.(.'.3. Is the receipt of materials documented and recorded"
1.(.'.'. Is a visual inspection done at receipt$ to verify damages or integrity of seal and
containers$ )hich could affect product #uality"
1.(.'.(. Is each received container labeled upon receipt0 label attached to the container body
and not to its removable parts"
1.(.'.8. Does the label contain the follo)ing information: Item name and code 7upplier name
7upplier%s lot number $ Total Number of 2anufacture date $ 6/piry date $ Internal lot
number $ 7pecial storage conditions $ Test Date $ !etest date "
1.(.'.?. Are the premises of ade#uate si&e according to the needs of the company"
1.(.'.9. Is the #uarantine0 release area properly identified"
1.(.'.:. Do the storage environmental conditions ,including lighting$ temperature and
humidity. comply )ith the established storage re#uirements"
1.(.'.<. Are there records for the temperature$ humidity"
1.(.'.1=. Are there temperature records for the cold room if present"
1.(.'.11. Is there an alert system to indicate deviations from the established temperature in the
cold room"
1.(.'.13. Is there a 7>P to handle such deviations"
1.(.'.1'. Are necessary precautions undertaen for the pacaging of finished products that
re#uire cold chain"
1.(.'.1(. Are the scales calibrated0 checed on a scheduled basis"
1.(.'.18. Are there areas physically separated or systems in place to prevent mi/*ups of different
materials and products"
1.(.'.1?. Are there procedures for all the operations of this area receipt of goods$ movement of
containers$ load conditions$ dispatches$ etc".
1.(.'.19. Is there 7toc control system of materials and products"
1.(.'.1:. Are the DID> -D6D> follo)ed for the use of starting materials"
9
1.(.'.1<. Iefore release by #uality control$ are all items and finished products properly identified
as such and maintained in #uarantine$ either physically or by a system"
1.(.'.3=. Are reAected materials properly identified and stored separately in restricted areas"
1.(.'.31. Is there procedure for materials destruction"
1.(.'.33. Are shelves and-or platforms separated from floors and )alls to allo) cleaning"
1.(.'.3'. Is there a 7>P0record for cleaning )are house"
1.(.'.3(. Are pacages and containers )ith items ,drums$ $ bo/es$ etc.. ade#uately closed"
1.(.'.38. Is there an area )hich is secure or )ith restricted access )hich is used to store labels"
1.(.'.3?. Are all outdated printed materials destroyed"
1.(.'.39. Fithin the storage room$ are there distinct areas )hich are physically separated and
)ith restricted access for psychotropic and narcotic substances"
1.(.'.3:. Is there a 7>P dealing )ith spills of corrosive or to/ic and active substances"
1.(.'.3<. Are there areas specific for the storage of flammable and e/plosive Products $is its
temperature 0humidity record comply )ith the stated on the drums"
1.(.'.'=. Is there an area for Dinished Product !elease"
1.4.3.31. Is there a suitable fire fighting system )ith record of regular chec on it"
1.+.+. Ro.ent / pest control
1.(.(.1. Is there control for rodent 0 insects"
1.(.(.3. Is there a map0 monitoring record for the rodent and pest control"
1.4.5. Returne.0 Recall Pro.uct
1.(.8.1. Is there an area that is physically separated and has restricted access for the storage of
returned or recalled products until their fate is determined"
1.(.8.3. Are the products properly identified as such"
1.(.8.'. Are all actions and decision taen recorded"
1.1. D!#('ENAI!N
1.1.1. 'aster formula
1.8.1.1. Is there an updated master formula for each product and si&e of lot to be manufactured"
Do the Technical Director and-or Euality Control-Assurance Director authori&e all
master formulas"
1.8.1.3. If it is necessary to modify the master formula$ are there )ritten procedures on ho) to
do this"
1.8.1.'. Is authori&ation from the Cealth Authority e/pected before undertaing the change"
1.8.1.(. Do all products have a master formula containing Product name$ code and product
10
number"
1.8.1.8. Do all products have a master formula containing Description of pharmaceutical
dosage form$ concentration and-or strength of the active ingredients$ Product shelf life"
1.8.1.?. Do all products have a master formula containing Theoretical intermediate yield and
theoretical final yields )ith their correspondent limits"
1.8.1.9. Indication of the areas in )hich each one of the process steps occur and e#uipment
used"
1.8.1.:. Do all products have a master formula containing Names and signatures of the
#ualified people involved in the issuance$ revie)$ and approval ,at least t)o."
1.8.1.<. Do all products have a master formula containing detailed instructions of the steps to
follo) for each stage of the process"
1.8.1.1=. Do all products have a master formula containing Instructions concerning controls
during the process$ of intermediate products and operational variations$ indicating
specifications"
1.8.1.11. Do all products have a master formula containing In the master formula$ are there
references to the 7>Ps related to different stages of manufacturing$ e#uipment
operation$ etc. )hen they correspond"
1.8.1.13. Do all products have a master formula containing 7pecial precautions that should be
taen during the different stages of the process due to the characteristics of the starting
materials handled and e#uipment"
1.8.1.1'. Do all products have a master formula containing The standards for the storage of the
intermediate or buls$ including the container$ the labeling and any other storage
condition )hen the product re#uires it"
1.8.1.1(. Do all products have a master formula containing Dormula revie) date"
1.8.1.18. Do all products have a master formula containing Dorms for record eeping of product
specifications during manufacture process ,)eight$ hardness$ friability$ closure of
capsules$ disintegration$ viscosity$ etc.. performed by production and #uality control"
1.8.1.1?. Is a production order issued for each batch of processed product"
1.1.2. 2atc- process recor.
1.8.3.1. Does the batch process record contain the Product name$ Issue date$ Iatch number$
6/piry date of finished product"
1.8.3.3. Does the batch process record contain the list of ra) materials involved ,including the
ones that are used up during processing. )ith their code numbers$ lot$ and-or analysis$
theoretical and real #uantities utili&ed for each of them"
11
1.8.3.'. If it is necessary to adAust the concentration of ra) materials$ is the modification signed
by a #ualified person"
1.8.3.(. Are the labels of the ra) materials separated$ attached"
1.8.3.8. Is the detailed description of each one of the steps included in the processed lot record"
1.8.3.?. Are the areas and e#uipment-lines released recorded"
1.8.3.9. Is the date$ the starting and ending time of every step recorded"
1.8.3.:. Are the values of operational deviations to be controlled during process ,6/.:
temperature$ pC$ times$ agitation speeds$ etc.. recorded and the acceptance limit
indicated"
1.8.3.<. If there are process deviations )ith regard to the master formula$ are they recorded"
1.8.3.1=. Fhenever there is an IPC in some step of the process$ are they recorded"
1.8.3.11. Are the real yields of the intermediate and end stage recorded"
1.8.3.13. Are the yields )ithin the acceptable limits"
1.8.3.1'. In case of a deviation$ is the cause of the deviation investigated according to the 7>P 0
the findings documented"
1.8.3.1(. Are the signatures- initials of the people )ho carry out the different operations and of
those )ho supervise them recorded"
1.8.3.18. It is verified that the data that should appear on the batch process record are completed
at the time in )hich each action is undertaen during the process"
1.8.3.1?. Are reprocessing and re)oring previously authori&ed by Control-Euality Assurance 0
done in accordance )ith a 7>P"
1.5.2.17. After the manufacture process is ended$ is all the documentation that is part of the
batch record$ including the certificate of analysis of the Dinished Product$ filed"
1.5.2.18. Is the file maintained for at least one year after the 6/piry date of the lot"
1.1.3. 2atc- pac3a,in, recor.
1.8.'.1. Is a pacaging order for every batch or part batch processed issued"
1.8.'.3. Is the release of areas and e#uipment- lines recorded"
1.8.'.'. Does the batch pacaging record contain the name of the product$ the batch number$
the e/piry date of the finished product and the #uantity of bul product to be paced$ as
)ell as the batch number and the planned #uantity of the finished product that )ill be
obtained$ the #uantity actually obtained$ and the reconciliation"
1.8.'.(. Does the batch pacaging record contain the date ,s. and time,s. of the pacaging
operations"
1.8.'.8. Does the batch pacaging record contain the initials of the operators of each one of the
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different steps"
1.8.'.?. Does the batch pacaging record contain the controls undertaen )ith the outcome of
verifying the identity and conforming to the pacaging instructions$ including the
results of the inprocess controls"
1.8.'.9. Does the batch pacaging record contain Details of the pacaging operations carried
out$ including references to e#uipment and the pacaging lines used$ cleaning records"
1.8.'.:. Does the batch pacaging record contain if necessary$ the instructions for eeping the
product unpacaged or a record of returning product that has not been pacaged to the
storage areas"
1.8.'.<. Does the batch pacaging record contain )henever possible$ samples of the printed
pacaging materials used$ including samples bearing the batch number$ e/piry date
signed"
1.8.'.1=. Does the batch pacaging record contain Notes on any special problems$ including
details of any deviation from the pacaging instructions$ )ith )ritten authori&ation by
the #ualified person responsible"
1.8.'.11. Does the batch pacaging record contain the #uantities and reference numbers or
identification of all the printed pacaging materials and bul product issued$ used$
destroyed or returned to stoc and the #uantities of product obtained to permit an
ade#uate reconciliation"
1.8.'.13. Are the reprocessing and re)oring of products controlled in a 7>P for deviations"
1.8.'.1'. After the pacaging process is ended$ is all the documentation that is part of the batch
pacaging record$ including the analytical protocol of the Dinished Product$ filed"
1.1.+. General .ocumentation
1.8.(.1. Dor each procedure$ are the purpose$ scope$ references$ issuing0 effective date and
responsibilities clearly defined"
1.8.(.3. Is there the detailed and precise description$ in order of the routine operations"
1.8.(.'. Are the procedures available$ current"
1.8.(.(. Are the signatures of the personnel that issue$ revie)$ and approve the document
indicated"
1.8.(.8. Are the records indicated )ithin the procedures available"
1.8.(.?. Does the use of correction fluid or eraser remain clearly prohibited in the
documentation"
1.8.(.9. If there are amendments-changes$ are the date and signature recorded"
1.8.(.:. Is there a 7>P for the handling of changes and deviations"
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1.4. N!N5%ERILE PR!D(#%
1.4.1. Area"
1.?.1.1. Are there ade#uate changing stages before entering the areas"
1.?.1.3. Is there )ritten instruction )ith that"
1.?.1.'. Are changing rooms having the same class as the area they lead to"
1.?.1.(. Are the change rooms designed )ith air locs"
1.6.1.5. Is a bench of sanitary conditions available6
1.?.1.?. Is the area for )ashing )ith a supply of purified )ater 0filtered air"
1.?.1.9. Is a validity period established for cleaned obAects"
1.?.1.:. Are personnel responsible for clean toilets 0there tools different from )ho clean
manufacturing area"
1.?.1.<. Are there gauges to detect pressure differentials" Is there a record"
1.?.1.1=. Are the )alls$ floors and ceiling surfaces smooth and easy to clean"
1.?.1.11. Are fi/ed pipes identified and do they indicate the direction of flo)$ )henever
necessary"
1.?.1.13. If ra) materials or the handled products )hich re#uire it$ are the temperature and
relative humidity measured and recorded"
1.?.1.1'. Is the IPC room )ith calibrated needed instruments"
1.?.1.1(. Is the area cleaned$ as per established !e#uirements in the cleaning 7>P" Is it
documented"
1.4.2. E7uipment
1.?.3.1. Are the materials used in the construction of the e#uipment$ non reactive )ith the
active ingredients handled"
1.?.3.3. Are the labels adhered to the containers$ e#uipment$ and other au/iliary elements of
production and areas unambiguous 0indicate its condition"
1.?.3.'. Are the records of use and maintenance of e#uipment ept"
1.?.3.(. Are the instruments correctly labeled indicating the validity of calibration"
1.?.3.8. Is the e#uipment not in use identified as such and removed from the production areas
according to the 7>P"
1.?.3.?. Are all the containers$ e#uipment and au/iliary elements cleaned after their use$ is it
documented"
1.?.3.9. Dor fluid bed dryers: is there a set of sleeves for each product$ or is there a cleaning
validation process that guarantees no cross*contamination"
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1.?.3.:. Are the integrity$ measurements$ and identity of the punches confirmed" Are records
ept"
1.?.3.<. Is the access to them restricted"
1.?.3.1=. Is the air inAected in the coating e#uipment filtered" Is it included in the preventive
maintenance plan"
1.?.3.11. Are the filters used in filtration of li#uid disposable" Are the changes recorded"
1.4.3. !peration
1.?.'.1. Is there a confirmation that only one product processed in each processing room"
1.?.'.3. Do personnel in production carry out the verification of the )eight of the ra) materials
used in the manufacturing of each lot"
1.?.'.'. Are the parameters of the drying operations measured and recorded"
1.?.'.(. Is there assurance that the drying ovens do not receive lots of different products or
different lots from a single product at the same time"
1.?.'.8. Is the transfer of semi manufactured-buls products bet)een one step of the process
and another carried out in a manner to prevent their contamination"
1.?.'.?. Is there confirmation that the suspensions and-or emulsions are maintained uniform
throughout the bottling process"
1.6.3.7. Do bottles receive some type of cleaning 0on line )ith before filling"
1.?.'.:. In the case of the automatic system$ are discarded units )hich are returned to the line$
previously inspected and approved by authori&ed personnel"
1.?.'.<. Are process controls performed at each production step"
1.4.+. Vali.ation
1.?.(.1. Is installation of e#uipment been #ualification ,IE." Is protocols 0report produced"
1.?.(.3. Is operation of e#uipment been #ualification ,>E." Is protocols 0report produced"
1.?.(.'. Is performance of e#uipment been #ualification ,PE." Is protocols 0report produced"
1.?.(.(. Is any deviation in the report of #ualification investigated 0action is taen"
1.8. %ERILE PR!D(#%
1.8.1. Premises9 Area Desi,n An. Layout"
1.9.1.1. Does the design of the areas$ grade A and I$ permit a visual vie) of all the operations
from the outside"
1.9.1.3. Is the preparation environment )here a solution is subAect to terminal sterili&ation a
grade D at least"
1.9.1.'. Are sterile products that are to be terminally sterili&ed$ filled in a )orstation )ith
15
laminar airflo) grade A surrounded by class C area"
1.9.1.(. Are products that are sterili&ed by filtration$ is the preparation of the solution in closed
tans carried out in a grade D environment at least"
1.9.1.8. Are products that are sterili&ed by filtrationG is the preparation of the solution in opened
tans carried out in a grade C environment"
1.9.1.?. Are sterile filtered products$ after the sterili&ing filtration process is the product
handled and filled under local grade A conditions )ithin a grade I or C bacground
environment"
1.9.1.9. Is the )hole manufacturing process of products prepared )ith aseptic ra) materials$
carried out under local grade A )ithin a grade I environment"
1.9.1.:. Are the )all surfaces$ floors$ doors and ceilings smooth and impervious$ minimi&ing
the shedding and the accumulation of particles and microorganisms"
1.9.1.<. Are they easy to clean and maintain sanitary"
1.9.1.1=. Are the pipes$ lighting fi/tures$ points of ventilation and other services designed in
such a )ay to permit their easy cleaning and sanitation"
1.9.1.11. Are pipes of dangerous li#uids or gases identified and indicate the direction of flo)$
)henever necessary"
1.7.2. #-an,in, Rooms"
1.9.3.1. Are there ade#uate changing stages before entering the sterile areas"
1.9.3.3. Is the entry of the personnel into the clean rooms )ith )atches$ Ae)elry$ or cosmetics
prohibited"
1.9.3.'. Is there )ritten instruction )ith that"
1.9.3.(. Are there change rooms e/clusive for the controlled environment areas"
1.9.3.8. Are changing rooms having the same class as the area they lead to"
1.9.3.?. Are the change rooms designed )ith air locs0 interlocing"
1.9.3.9. If no is there any type of alarm to prevent opening of more than one door in a time"
1.9.3.:. Is a bench of sanitary conditions available"
1.9.3.<. If no is there any alternative measure to separate the dirty &one from the clean one"
1.8.3. %terile Go:nin,"
1.9.'.1. Is there an area for the conditioning of the clothes for use in the controlled
environments after its sterili&ation"
1.9.'.3. Is there a validity period for the go)n after sterili&ation"
1.9.'.'. Is the clothing used appropriate for the areas and tass that are carried out"
1.9.'.(. Are the uniforms used for )or in aseptic areas$ clean$ in good condition and sterili&ed
16
prior to their use"
1.9.'.8. Is there validity time period established for the sterili&ation of the uniforms"
1.9.'.?. Are protection elements utili&ed for the operations that re#uire them"
1.9.'.9. If no does this compromise product #uality"
1.9.'.:. Is there an e/clusive laundry for the sterile area separated from laundry of other
department"
1.9.'.<. Are the gloves free of lubricants"
1.8.+. $as-in, Area
1.9.(.1. Is there an area or sector for the )ashing of containers and-or tools"
1.9.(.3. Is label attached to cleaned obAects sho)ing its status"
1.9.(.'. Is a validity period established for cleaned obAects"
1.7.5. Ampoules an. Vial $as-in, Area:
1.9.8.1. Is there a separate area for the )ashing and for the depyrogenation of empty bottles and
ampoules"
1.9.8.3. Is the operation of )ashing of empty bottles and ampoules done at the least in a grade
D area"
1.9.8.'. Do the cleaning machines of empty bottles and ampoules use )ater for inAection$ for at
least the last rinse"
1.9.8.(. Do the compressed air used in these )ashing machines ade#uately filtered"
1.9.8.8. Are depyrogenation ovens used are validated"
1.9.8.?. Are depyrogenation tunnels used are validated"
1.9.8.9. Are depyrogenation cycles validated"
1.9.8.:. Are depyrogenation cycles recorded"
1.7.6. #leanin,9 %aniti;ation an. <y,iene:
1.9.?.1. Are the materials and e#uipment sterili&ed and their containers saniti&ed"
1.9.?.3. Are there instructions in the 7>P for the cleaning and disinfection of every area"
1.9.?.'. Is the area cleaned$ )ithin 3( hours after ending the process activities"
1.9.?.(. Is a validity period established for area cleaning"
1.9.?.8. Are records for cleaning ept"
1.9.?.?. Is there 7>P of disinfection sho)ing sho) type$ conc0 contact time of disinfectants
used" is there a record"
1.9.?.9. Is there 7>P 0 record for disinfectant preparation and sterili&ation"
17
1.9.?.:. Are disinfectant used in alternative basis to prevent resistant strains"
1.9.?.<. Are containers for )aste collection identified as such"
1.9.?.1=. Are the materials used in containers construction compatible )ith the active ingredients
handled"
1.8.8. E7uipments"
1.9.9.1. Does the location of the e#uipment facilitate their cleaning$ as )ell as$ the cleaning of
the area in )hich are found"
1.9.9.3. Do the cleaning procedure validated"
1.9.9.'. Is there a log boo for every e#uipment usage"
1.9.9.(. Are there calibration records of the e#uipment-instruments available"
1.9.9.8. Is the unused e#uipment removed from the production areas"
1.9.9.?. Is the e#uipment in repair identified as such"
1.9.9.9. Are all e#uipment and au/iliary elements cleaned after their use"
1.9.9.:. Is a validity period for the cleaning of the e#uipment established"
1.9.9.<. Are all the hoses$ tubes and pipes used in the transfer of fluids identified"
1.9.9.1=. Fhen they are not dedicated$ is the cleaning validated"
1.9.9.11. Are the connections and valves used of sanitary conditions"
1.8.=. !perations
1.9.:.1. Are there flo) charts sho)ing the production steps and identify critical points"
1.9.:.3. Are process controls undertaen at the different steps of production"
1.9.:.'. Are records ept"
1.9.:.(. Is there ade#uate control on ma/imum number of personnel present in clean and
aseptic area"
1.9.:.8. If sterili&ing filtration systems utili&ed is the integrity of the filters confirmed before
filtration"
1.9.:.?. If the filters used are not disposable$ is their usage period established$are the
sterili&ation number recorded" ,N>. of sterili&ation cycles."
1.9.:.9. Are the changes recorded"
1.9.:.:. Are the filters dedicated by active ra) material"
1.9.:.<. Is the integrity of the filters confirmed after filtration"
1.9.:.1=. Are records ept"
1.9.:.11. Dor each product$ is the ma/imum time bet)een the starting of the preparation of a
solution and its sterili&ation or filtration through absolute filters established"
18
1.9.:.13. Are gases used to purge solutions ade#uately filtered"
1.9.:.1'. Is the batch sterili&ation in more than one cycle$ Is it divided to different identified lots
for sterility testing"
1.9.:.1(. Are records of time$ temperature$ and-or pressure of the autoclave and depyrogenation
oven maintained"
1.9.:.18. Are records of sterili&ation and depyrogenation of the container for the filtrate product
reception available"
1.9.:.1?. Is the transfer of intermediate-buls bet)een one step and another carried out in a
manner )hich prevents their contamination"
1.9.:.19. Is the ma/imum time elapsed bet)een the filtration and the product filling determined
for products )ithout terminal sterili&ation"
1.9.:.1:. Are mi/*ups avoided bet)een the sterile and non*sterile material"
1.9.:.1<. Is clean steam used in the sterili&ation cycles monitored to assure suitable #uality"
1.9.:.3=. Is a validation program for moist heat sterili&ation cycles performed and recorded"
1.9.:.31. Are indicators used at each cycle of sterili&ation"
1.9.:.33. Are records ept"
1.9.:.3'. Is the product 1==J visually inspected"
1.9.:.3(. Incase inspected by operators do they a record for periodical medical e/amination "
1.8.>. 'aterials an. #omponents"
1.9.<.1. Do they enter to the aseptic area by air loc"
1.9.<.3. Is there a validity time period established for the sterili&ation of components$ containers
of products in bul and other e#uipment"
1.9.<.'. Do the sterili&ed material and components transferred in a manner to prevent its
contamination or cross contamination"
1.9.<.(. Do lea test is done for ampoules"
1.8.1?. Aseptic Process Vali.ation"
1.9.1=.1. Is media fill conducted )ith culture medium$ in the )oring conditions$ at least on a
semiannual fre#uency"
1.9.1=.3. Are these tests carried out in such a)ay to most accurately reproduce the normal
)oring conditions in the area"
1.9.1=.'. Are they carried out in a minimum of '?== units"
1.9.1=.(. Are there records of these tests"
1.9.1=.8. Are the causes of any detected contamination investigated"
19
1.9.1=.?. Are there records of this investigation"
1.9.1=.9. Are there records of the corrective actions taen in those cases"
1.=. Q(ALI& #!NR!L
1.=.1. La@oratory e7uipment
1.:.1.1. Does the Euality Control laboratory carry out its o)n Physicochemical$
2icrobiological$ and Iiological controls"
1.:.1.3. Is a clearly defined flo) of samples and documentation established"
1.:.1.'. Are the physicochemical and microbiological controls sector physically separated"
1.:.1.(. Are the physicochemical and microbiological controls sector physically separated from
the production"
1.:.1.8. Is the Euality Control Department responsible for approving or reAecting the ra)
materials$ pacaging materials$ intermediate products$ and finished products"
1.:.1.?. Are the installations and the e#uipment as appropriate )ith the type of manufacture 0
active ingredients handled"
1.:.1.9. Is there a defined area for the )ashing and conditioning of materials e/clusively
destined for the physicochemical laboratory"
1.:.1.:. Are there safety installations such as sho)er$ eye )asher$ fire e/tinguisher$ and
protection elements"
1.:.1.<. Is there the necessary e#uipment for the analytical controls re#uired for the material 0
products"
1.=.2. %ta@ility
1.:.3.1. Does stability study program include a complete description of the product studied"
1.:.3.3. Does stability study program include the controlled parameters and validated analytical
methods that demonstrate the stability of the product in concordance )ith the
established specifications"
1.8.2.3. Does stability study program include a sufficient number of lots ,no less than three."
1.:.3.(. Does stability study program include timetable of the analytical tests to carry out for
every product"
1.:.3.8. Does stability study program include the accelerated 0real time stability"
1.:.3.?. Does stability study program include sufficient #uantities of samples in order to fulfill
)ith the program"
1.:.3.9. Is there a summary and obtained data including the evaluations and study conclusions"
1.:.3.:. I7 there a record of monitoring of the mareted products that maes it possible to
confirm that$ if the conditions of storage are met$ the product maintains its #uality
20
during its validity period"
1.=.3. Vali.ation
1.:.'.1. Does the Balidation 2aster Plan include the Euality Control laboratory"
1.:.'.3. Does the laboratory have e#uipment #ualification protocol0report"
1.:.'.'. If there is deviation in the #ualification is it investigated 0corrective action taen" is
that recorded "
1.:.'.(. Is there a validation program for those analytical methods not published by
internationally recogni&ed pharmacopoeias"
1.:.'.8. Are there documents supporting compliance )ith this procedure"
1.:.'.?. Are analytical methods verified )hen despite being coded by internationally
recogni&ed pharmacopoeias$ these are performed differently to the coding"
1.=.+. %amplin, proce.ure
1.:.(.1. Are there 7>Ps )ith the detailed description for the sampling of !a) materials$
Pacaging materials$ intermediate$ finished product"
1.:.(.3. Are there sampling plan for ra)$pacging$intermediate 0finished product "
1.:.(.'. Are all incoming pacaging materials$ )ithout e/ception$ sampled by Euality Control
in accordance )ith the established standard0 sampling plan"
1.:.(.(. Are the sampling elements duly stored and labeled"
1.:.(.8. Is there a )ritten procedure for the cleaning$ use$ and conservation of the sampling
eleme
1.=.1. Analytical met-o.
1.:.8.1. Are the analytical methods utili&ed authori&ed by the one responsible of Euality
Control"
1.:.8.3. Are there specifications for !a) materials$ Pacaging materials$ Intermediate$
finished$"
1.:.8.'. Are there records that Euality control checs if each manufactured lot meets the
established specifications"
1.:.8.(. Is there 7>P for out of specification"
1.:.8.8. Are there records of this investigation 0action taen"
1.:.8.?. Do the records of the tests contain 7ample identification$ Date$ Name of the analyst$
Identification of the reference standard$ Parameters and conditions that correspond"
1.:.8.9. Do the analysts have a serial logboo in )hich are recorded the laboratory results"
1.:.8.:. Are the calculations dated and signed by the analyst"
1.:.8.<. If there are observed modifications of data$ is the amendment carried out dated and
21
signed"
1.:.8.1=. Does the amendment mae possible to visuali&e the original datum"
1.:.8.11. In the records of the analyses$ it is indicated: Name of the analy&ed material$ +ot
number $ Analysis number $>btained results $ Date $ Ktili&ed methods and
specifications $ 7igns- initials of the people )ho carried out the test $ 7ign-initials of
the person that verified the tests and calculations "
1.=.4. Retaine. samples
1.:.?.1. Are samples of retention of the active ra) materials and finished products$ in enough
#uantity to carry out all the tests by duplicate$ ept in accordance to a 7>P"
1.:.?.3. Are the retention samples of finished products ept until a year after the e/piry date of
the product"
1.:.?.'. Are the samples of retention of ra) materials ept until a year after the e/piry date of
the last lot of product prepared )ith them"
1.=.8. Reference stan.ar.
1.:.9.1. Are there standards and reference materials"
1.:.9.3. Is a record of the primary standards ept"
1.:.9.'. Is a record of the secondary standards ept"
1.:.9.(. Is a record of the reference materials ept"
1.:.9.8. Does the company have primary standards$ coded by Pharmacopoeias or internationally
recogni&ed agencies$ for each active ingredient"
1.:.9.?. Do all the secondary standards and reference materials have current analytical
certificate"
1.:.9.9. Are there 7>Ps for the preparation$ use and conservation of standards and reference
materials"
1.:.9.:. Are those procedures fulfilled"
1.:.9.<. Are the records sho)n"
1.:.9.1=. Does the company have impurities and related substances standards$ officials or non*
officials$ especially for those considered to/ic"
1.=.=. Rea,ents
1.:.:.1. Are the reagents correctly labeled"
1.:.:.3. Are volumetric solutions used"
1.:.:.'. Is there a standard operating procedure for the preparation$ use$ and conservation of
volumetric solutions"
22
1.:.:.(. Is there log boo for the preparations of the reagent preparation include Name of the
analyst$ Name of the reagent$ Calculations$ Date of the preparation 0 e/piration"
1.:.:.8. Do every container of analytical solution have a label )here there is indicated: Name
of the solution Concentration * standardi&ation factor Preparation date$ !esponsible$
!etest date$ e/pired date$ 7torage conditions$ 7afety category$ !eference to the 7>P"
1.:.:.?. Are the unstable reagents labeled )ith reception date$ opening date and 6/piry date"
1.=.>. 'icro@iolo,y la@oratory
1.:.<.1. Does the company have separated areas for sterility test and other microbiological
controls "
1.8.9.2. Is there any change room before entering the microbiology laboratory"
1.8.9.3. Is there any change room before entering the areas for sterility test"
1.8.9.4. Is there sop for the cleaning 0 disinfectant of the change room"
1.:.<.8. Are there proper areas and laminar flo) for carry out the sterility tests"
1.:.<.?. Are the filters of the laminar flo) periodically checed"
1.8.9.7. Are the materials$ culture media and reagents )ithin the validity period"
1.:.<.:. Are the dehydrated culture media stored in the conditions of humidity and temperature
indicated by the manufacturer"
1.:.<.<. Are the parameters of every sterili&ation cycle of culture
1.:.<.1=. Is there separated +AD cabinet to perform gro)th promotion test"
1.:.<.11. Is the gro)th promotion test carried out )henever ne) lots of culture media are
utili&ed"
1.:.<.13. Is negative control test done in accordance )ith every sterility test"
1.:.<.1'. Is a standard operating procedure for the preparation of culture media"
1.:.<.1(. Are there microbial reference strains"
1.:.<.18. If there are reference strains$ are they certified by an internationally recogni&ed
agency"
1.:.<.1?. Is there a record of identification and use of strains"
1.:.<.19. Are sterility tests carried out"
1.:.<.1:. Dor sterility tests$ are coded methods utili&ed"
1.:.<.1<. If the lot fails the sterility test$ is it follo) >>7 "
1.:.<.3=. Are antibiotic potency assays carried out"
1.:.<.31. Does the company have areas or sectors assigned for the sample Preparation"
1.:.<.33. Does the company have areas or sectors assigned for the )ashing and Conditioning of
23
materials"
1.:.<.3'. Does the company have areas or sectors assigned for the preparation of culture media"
1.:.<.3(. Does microbiology sector have e#uipment for bacterial decontamination"
1.:.<.38. Is there a procedure for the handling and disposal of chemical and microbial )aste"
1.:.<.3?. Does the procedure indicate that should not be permitted the accumulation of discarded
materials"
1.:.<.39. Does Euality control carries out environmental microbiological controls"
1.:.<.3:. Are there records"
1.:.<.3<. Are tests of bacterial endoto/ins carried out in ra) materials and goods declared as
pyrogen*free by the supplier$ to be used in the inAection manufacture"
1.:.<.'=. Are tests of pyrogens or bacterial endoto/ins carried out in the finished products for
inAection"
1.:.<.'1. Is an official method utili&ed for bacterial endoto/in control"
1.:.<.'3. Is the method validated"
1.=.1?. Animal -ouse
1.:.1=.1. Are pyrogen tests carried out in animals"
1.:.1=.3. If 45674 Does the company has its animal house or uses a contracted animal house"
1.:.1=.'. In any of both cases$ does animal house fulfills )ith the current regulations on animal
operation and management"
1.:.1=.(. If the company have animal house$ is this separated from the other installations )ith
separate ACK"
1.>. Q(ALI& A%%(RAN#E
1.>.1. General
1.<.1.1. Is there in the company a #uality assurance system"
1.<.1.3. If the documentation is carried out through electronic data processing methods does the
company ept a reserve copy of the documentation"
1.<.1.'. Is the admission of ne) data or modifying of the e/isting data in the computer system
done only by the people authori&ed"
1.<.1.(. Is a record of the data modifications and-or elimination ept"
1.<.1.8. Are the records of lots electronically filed protected"
1.<.1.?. Is there a program of control of the 7>Ps"
1.<.1.9. Does Euality assurance is responsible of release of every batch is that indicated in a
7>P "
24
1.<.1.:. If in the revie) of the production records are detected bypasses of the established
procedures$ is #uality assurance responsible for ensuring a complete investigation of
the bypasses and that the final conclusions are Austified"
1.<.1.<. If a lot does not meet specifications$ does the investigation is e/tended to other lots of
the same product and of other products that could have had some relation )ith the
defect or the discrepancy"
1.<.1.1=. Does the company ept originals of all procedures and records of distribution of the
authori&ed copies"
1.<.1.11. If a procedure is modified$ is there a system by )hich the accidental use of a previous
version is prevented"
1.<.1.13. I7 there a 7>P for change control" is it fullfield"
1.<.1.1'. Is there a 7>P for annual product revie)" Is that DK+DI+6D"
1.9.1.14. Is there a 7>P for corrective 0preventive action"
1.>.2. PreAentatiAe maintenance/ cali@ration pro,ram

1.<.3.1. Is there a program for preventive maintenance for all the e#uipment$ premises $utilities"
1.<.3.3. Are there records that sho)n preventive maintenance program compliance"
1.<.3.'. Is there a program of e#uipment calibration"
1.<.3.(. In the e#uipment calibration program is indicated$ )hich operations are performed
internally and )hich by contracted services"
1.<.3.8. Is the fre#uency of calibration indicated in the e#uipment calibration program"
1.<.3.?. Are records of calibration of each e#uipment that sho)n program Compliance"
1.<.3.9. Are there )ritten procedures to perform the calibration of each e#uipment"
1.<.3.:. Is the e#uipment correctly labeled indicating the calibration validity"
1.<.3.<. In case of internal calibrations$ does the laboratory have certified standards"
1.<.3.1=. Are the corresponding certificates sho)n"
1.>.3. Q(ALI& A(DI%0 %EL)5IN%PE#I!N%
1.<.'.1. Are #uality self*inspections and-or audits carried out"
1.<.'.3. Is Euality assurance responsible for the coordination of #uality self*inspections and-or
audits"
1.<.'.'. Are the self*inspections-audits carried out )ith a pre*established plan"
1.<.'.(. Are the necessary corrective taen )ith in the time limit specified"
1.<.'.8. Do the )ritten instructions of #uality self*inspection- audits include the entire factory"
1.<.'.?. Are the !esults of previous self*inspections and adopted corrective measures
25
documented"
1.<.'.9. Does the report issued once finished the self*inspection contain the !esults of the self*
inspection"
1.<.'.:. Does the report issued once finished the self*inspection contain evaluation and
conclusions"
1.<.'.<. Does the report issued once finished the self*inspection contain corrective measures
recommended"
1.<.'.1=. Is the monitoring of the corrective measures carried out"
1.>.+. %(PPLIER% Q(ALI)I#AI!N
1.<.(.1. Is there a record of approved suppliers available for the areas that re#uire it"
1.<.(.3. Is there a program for evaluation and audits to suppliers"
1.<.(.'. Is it fulfilled"
1.>.1. RE#ALL
1.<.8.1. Is there A sop to recall products from the local and international maret$ if necessary"
1.<.8.3. Is there a responsible person ,independent from the mareting department. designated
by or in accordance )ith the #ualified person responsible for the coordination and
e/ecution of the recall procedure"
1.<.8.'. Is Euality control-Euality assurance-!egulatory Affairs notified of undertaen recall
operations"
1.<.8.(. Does the procedure indicate the mandatory re#uirement of notifying the Cealth
Authority immediately in the event that the cause is for health reasons"
1.<.8.8. In the case of having distributed products to other countries$ is the Cealth Authority of
the recipient country and the recipient of these products informed immediately"
1.<.8.?. Are distribution records available for a prompt recall of products from the maret"
1.<.8.9. Is there a classification of recall"
1.<.8.:. Is there an updated list of contact persons of the distributors"
1.>.4. #!'PLAIN
1.<.?.1. Is Euality assurance responsible for coordinating the reception and the monitoring of
the received complain"
1.<.?.3. Is there a responsible person assigned"
1.<.?.'. Are there )ritten procedures for the reception and investigation of the complain"
1.<.?.(. Is record of the complain ept"
1.<.?.8. If necessary$ is analytical control made"
26
1.<.?.?. Do the decisions 0corrective action made concerning the complaints remain
documented$ in the lot records"
1.1?. PA#BAGING"
1.1?.1. >P6!ATI>N:
1.1=.1.1. Is the mi/*up of different products or different lots of same product avoided by having
physical separation among the pacaging lines"
1.1=.1.3. Do all finished products have a printed batch number and an e/piry date on their
primary container"
1.1=.1.'. Is the printed information resistant to fading or erasing"
1.1=.1.(. If automatic machines are used to control dimensions$ )eights$ labels$ prospects$ bar
code$ etc.$ is their proper performance verified"
1.1=.1.8. If the revie)-verification of product done visually$ Is there a changeover of staff"
1.1=.1.?. If it is done automatically is it challenged for its performance "
1.1=.1.9. Are conditions of lighting and contrast for the revie)-verification controlled"
1.10.1.8. Are the containers that contain the already inspected material labeled as such"
1.1=.1.<. Are the right batch number and e/piry date confirmed by authori&ed personnel"
1.1=.1.1=. Are precautions taen on dispensing labels to prevent mi/*ups"
1.1?.2. D>CK26NT7:
1.1=.3.1. Does the company have pacaging orders )ith A full list of all pacaging material
re#uired for a normal si&e batch$ including #uantities$ si&es and types$ )ith the lot
number$ code or reference number related to specifications for every pacaging
material"
1.1=.3.3. Does the company have pacaging orders )ith Details concerning process control )ith
instructions for the sampling and acceptable limits"
1.1=.3.'. Is there a 7>P available for the process of the return of unused non*coded printed
material to the )arehouse"
1.11. <VA# %&%E'
1.11.1. 16N6!A+
1.11.1.1. Do they have an air supply filtered by C6PA terminal filter in the areas grade A$ I and
C"
1.11.1.3. Is the filters efficiency is ade#uate for such classes"
1.11.1.'. Do grade D areas have high efficiency filters"
27
1.11.1.(. Is the filters efficiency is ade#uate for such classes"
1.11.1.8. In the areas of controlled environment ,grade I$ C and D.$ is the number of air
Changes by hour is sufficient for such areas"
1.11.1.?. Are the integrity and the sealing of the filters confirmed"
1.11.1.9. Is there a 7>P for the revie) and changing of filters"
1.11.1.:. Are there records"
1.11.1.<. Do the areas have instruments )ith current calibration$ )hich mae it possible to
confirm a cascade of pressure differential"
1.11.1.1=. Are there records"
1.11.1.11. Do the air flo) patterns prevent contamination"
1.11.1.13. Is there an alarm system that indicates a deviation in the air supply to the aseptic areas"
1.11.1.1'. Is there a 7>P for ho) to proceed in the event that this occurs"
1.11.1.1(. Is there a measure in place to avoid a conveyor belt going from a grade I area to one of
lo)er air #uality"
1.11.1.18. Are the actual results complying )ith the designed criteria"
1.11.1.1?. Are there air locs bet)een different classes"
1.11.1.19. Is there a reasonable upgrading of area cleanliness from blac$ grey$ clean area"
1.11.1.1:. Are the toilets air not returned or mi/ed )ith production air"
1.11.1.1<. Is there ventilation )ith ade#uate temperature$ humidity$ and air filtration$ if the ra)
materials and-or handled products re#uire it"
1.11.1.3=. Are the temperature and relative humidity measured and recorded"
1.11.1.31. Are pressure differential values in the different areas measured and recorded"
1.11.1.33. Are records ept"
1.11.1.3'. Are particulate counts conducted in the controlled environments"
1.11.1.3(. Are records ept"
1.11.1.38. Is the fre#uency for performing the test in different classes suitable"
1.11.1.3?. Are microbiological controls conducted in the controlled environments"
1.11.1.39. Are records ept"
1.11.1.3:. Is the fre#uency for performing the test in different classes suitable"
1.11.1.3<. Are air conditioning and-or ventilation systems for each area in accordance )ith the
operation to be carried out"
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1.11.2. Vali.ation:
1.11.3.1. Is the system installation has been #ualified 0 a protocol )ith a report has been
produced"
1.11.3.3. Is the system operation has been #ualified 0a protocol )ith a report has been
produced"
1.11.3.'. Is the system performance has been #ualified 0a protocol )ith a report has been
produced"
1.11.3.(. Does D>P test done in the performance #ualification"
1.11.3.8. Is the air velocity in grade A has been measured"
1.11.3.?. Is a preventive maintenance program has been produced from the #ualification"
1.11.3.9. Is any deviation during #ualification investigated 0a corrective action taen to close
the case"
1.12. PER%!NNEL
1.12.1. General
1.13.1.1. Is there an updated organi&ation chart of the company"
1.13.1.3. Is there a description of the responsibilities and functions of production and #uality
control personnel"
1.13.1.'. Are the responsibilities of production and #uality control personnel independent of
each other"
1.12.2. rainin,
1.13.3.1. Is there a program for on Aob training 0 12P$ including specific training appropriate to
the duties assigned to them"
1.13.3.3. Is there a program for refreshment training on 12P$ including specific training
appropriate to the duties assigned to them"
1.13.3.'. Are the training records for the personnel in charge of cleaning$ if in*house personnel$
sho)n"
1.13.3.(. Is the >perating Personnel trained by Euality Control on sampling methods ,s)abs$
29
piece of fabric$ rinsing$ placebo."
1.13.3.8. Is there documented evaluation for the training"
1.12.3. Go:nin,
1.13.'.1. Are the personnel using the appropriate uniform for the specified area"
1.13.'.3. Is there a 7>P dealing )ith the use of proper clothing for other persons )ho enter
production areas ,technical service-maintenance$ cleaning personnel$ #uality control
inspectors$ #uality assurance inspectors$ and visitors."
1.12.+. 'e.ical c-ec3
1.13.(.1. Are the personnel re#uired to undergo a medical e/amination prior to being employed"
1.13.(.3. Is there a procedure to prevent any person )ho has an apparent illness from entering
areas in )hich they may adversely affect the #uality of the product or affect their o)n
health"
1.13.(.'. Are fre#uent ophthalmologic e/aminations conducted on the )orers in charge of the
revie)-verification"
30