FACTORY IMADOL LALITPUR aadeeremedies@gmail.com QA Manager: PRASHANT BASNET

1. INPLANTTRAININGATAADEE
Submittedby
Neeraj Ojha
CIST College,NewBaneshwor
AffiliatedtoPokharaUniversity
To
PrashantBasnet
QA Manager
Aadee Remedies,Imadol,Lalitpur

2. Acknowledgement
I am extremelyindebtedtothe technical andnon-technical workersatAadee remedies.Ihadextremely
goodtime learningfromthem byfriendlyconversationsandexchanges. Atproduction,Iamespecially
thankful toSunandanPoudel andSujanKarki whobecame fastfriendsandhelpedme understandalot
aboutthe productiondepartmentinaveryshort time. Itwouldhave beenimpossible tolearnsomuch
insuch a small periodof time.
At QC, fast understandingwithAmitSinghhelpedalottocomprehendthe subtle dutiesof the QC
department. The QCstaffslike SujataDahal,KishorChaudhary, PriyankaBogati andPoudel helpedalot
while performingthe wateranalysisandtestsonMetronidazole.Withoutthe helpof these assistantsat
QC, itwouldhave beenimpossible tocomplete all the tests thatIwasassignedtoina shortdurationof
7 daysat QC.
Besides,I wouldliketoexpressmydeepandsincere gratitudeatSushantPokharel atthe Storage
Departmentalongwiththe non-technical assistantsoverthere.Theyhelpedme understandthe duties
and obligationsatstorage department.Theyshowedme how todosamplinganddispensingatthe
production.SushantPokharel gave me the theoretical understandingof the workthat needstobe done
at the Storage department.
RonashShresthaat QC and SandeshKhatri atR&D alsogave me quickrun at theirrespective
departmentonthe verylastday of internship.Iowe themalot fortheirsupport.
Last but no least,Iwouldlike toexpressmydeepgratitudeandthankstoPrakashBistwho referredme
to thiswonderful organizationandPrashantBasnetwho made mytime atAadee veryeducative andfull
of learningexperiences.

3. Abbreviations
BMR: Batch manufacturingrecord
BP: BritishPharmacopoeia
BPR: Batch packagingrecord
DMW: De-mineralizedwater
DT: Disintegrationtime
FBD: FluidizedBedDryer
FG/FP:FinishedGoods/FinishedProducts
GLP: Good laboratorypractice
GMP: Goodmanufacturingpractice
HDPE: High DensityPolyethylene
HEPA: Highefficiencyparticulateair
HPLC: Highperformance liquid chromatography
HVAC:Heatingventilationandairconditioning
IP: IndianPharmacopoeia
IP C: Inprocesscontrol
QC: QualityControl
QA: QualityAssurance
R&D: Researchand Development
IPQC:In ProcessQualityControl
DDA: Departmentof DrugAdministration

4. CERTIFICAFTION
Thisis to certifyhere thatNeeraj Ojhahassuccessfullycompletedthe in-planttraining/internshipat
Aadee RemediesPvtLimitedthatbeganonPoush4th
2078 and endedonMagh 4th
2078. Duringthis
period, Mr. OjhawasexposedtoProductiondepartment,QualityControl,Store department,Quality
Assurance and R&D.
Duringthisperiod,Mr. Ojha’sconductand behaviorwasfoundtobe extremelybonafide.He seemedto
enjoyworkingandlearningfromthe industrystaff alotthroughoutthis period. We wishhimbestinthe
future.
.........................
PrashantBasnet
Quality/PlantManager
...........................
AmitSingh
QC Officer
.............................
SunandanPoudel
Sr. ProductionOfficer
............................
SujanKarki
Jr. ProductionOfficer
............................
SandeshKhatri
R&D Officer

5. Table of Contents:
CompanyProfile Information
Objective of internship
Abbreviations
•Production
•QualityControl
•Store & Generator
•QA-R&D
•Summaryof processinvolvedinmanufacturingof aparticularproduct
•Water TreatmentPlant
EngineeringandUtility
AirCompressor
Generator
•Conclusion
Suggestion
References

6. 1. CompanyProfile Information:
Aadee remediespvt. Ltd.Isa pharmaceutical companyestablishedin23rd
Ashoj 2060 B.S.and startedits
operationfrom11th
Mangsir2071 B.S. fromImadol,Lalitpurfroman areawhichwas notreally
residentialatthattime.Atthismoment,the companyissurroundedbyseveral residential homes.
Companymostlydealswithdermatological,gynecological,PPIs,dentalandurological products.Santosh
Baral isthe actingmanagingdirectorat the headoffice andPrakashBistat Patan office.Thisindustry
has over40 employeesatthe Imadol locationatthismoment. PlantmanageratAadee isPrashant
Basnetcurrently.He’sbeencontributingtothe pharmaceutical industryforover7 yearsby workingin
pharmaceutical production,GMPrecommendeddocumentationinQA department,handling of
pharmaceutical machinerieslike RMG,FBD,AutomaticCapsule fillingmachine, ointmentmanufacturing
and fillingmachines, ointmentmanufacturingandfillingmachine,Drysyrupfillingline,LiquidfillingLine,
Autocoater,Conventionalcoatingandmuch more. He has expertknowledge onhandlingqualitycontrol
labequipments.Mr.BasnetobservesRegulatoryaffairsandformulationdevelopmentcloselyatAadee.
He alsohas beensupervisingall the technical departmentsintechnical matters.He alsohasbeen
individuallytalkingtoeachpersonnel ineverydepartmenttowardsthe efficientrealizationof
organizational goals.
QA officerslikeRonashShresthaof Sundarijalhave beenpreparingandmaintainingdocumentsright
fromthe stage of procuringraw materials.Theyare alsoinvolvedin processmonitoringateach
department.Ihada lotof opportunitytolearnaboutmedicinal chemistry,qualityassurance,
instrumentation,unitoperations,biotechnology,pharmaceutical management,researchmethodology,
biopharmaceuticsetcfromeachandeveryofficerlevel technical workersatAadee industrywithina

7. veryshort periodof time.These sortof momentespeciallyatQC withAmitSinghwere verymemorable
and informative.
Aadee isone of the fastestgrowingGMP certifiedpharmaceutical companylocatedinKumaripati-19,
Lalitpuralwayslookingforself driven,motivated,disciplinedandcreative teammemberswhetheritbe
as intern,employeesorpartners.
Highlysoldproductsof Aadee include PermethrinLotion5%, Halosol Gel,Halosol-Gointment,HalosolF
ointment, OroHeal Gel,Luly1% cream,Doxclin100 mg tablets,Domirab tabletsetc.
1.1 Objective of internship
General Objective:
To fulfill the internshiprequirementof PokharaUniversityBPharmcourse graduation
SpecificObjective:
 To findoutwhichsort of workat industrymightfitformy careerin future;
 To practicallyknowwhatI had learnedforover4 yearstheoreticallyatcollege;
 To knowand builtalliance withpeoplewhoare engagedinthe careerIam topursue inthe
future;

8.  To knowthe work environmentof anindustrial pharmacy;
1.2 Time Frame:
I was at productionhouse fora week.AtQC,I wasactivelyengagedforoveraweek.Iwas scheduledat
Storehouse for3 days.Restof the time,Iwas at QA andR/D.
2 Production
Productiondepartmentinthe industrial pharmacyreferstothe manufacturingareawhere the mass
manufacturingof the productis done asper the methoddevelopedandtestedbyR&Dinassociation
withthe marketingdepartmentandQC.The marketingdepartmentwhichhasa separate establishment
comesup witha productthat the market isdemandinganddevelopsageneral outline of the product
details.Thatisforwardedtothe R&D departmentatindustry.R&Ddevelopsthe productaccordingly
performedstabilitytestswiththe helpof QCand aftera certainperiodof time registersforthe
manufacturinglicenseatDDA.Thisis done online inthe presentmomentsthrough
http://dams.dda.gov.np/login website.The documentsare submittedbyR&Donline andalsoinpaper
printform inperson.Afterapproval byDDA,manufacturinglicense isreceivedbythe companyforthe
productafter necessarydocumentsubmission.
R&D ordersnecessarypackagingmaterialsandlabelingfromcompaniesabroadinthe case of Nepal.
Afterall these primarytasksare completed,the mattergoestoproductiondepartmentforthe bulk
production of the firstfewbatchesunderthe directionof R&D officer. Thisprocessis repeatedby
productiondepartmentunderthe directionof productionofficerwiththe same method everytime the
productis neededagaininbulk.
At mytime inproduction,wetgranulationwasperformedforthe Locettabletsunderthe directionof
Sunandan Poudel andassistance of SujanKarki.Ihada chance to personallyassistthe non-technical
workersat productionduringthe granulation.Allthe process wasalsosupervisedbyPrashantBasnetof
QA.Afterthe sample granuleswere testedandpassedbyQC, the tabletcompressionwasperformedin
the same week. Duringthisperiod,the hardnesstest,friabilitytestanddissolutiontestswere
performedonthe sample tabletsmanytimes.The adjustmentswere alsomade onthe tablet
compressionmachine settings. Afterthe sampletabletsmetthe necessaryrequirementslike dissolution
time (lessthan15 minutes),friability(lessthan1) etc.,the tabletcompressionwasperformedinbulk.
On the firstday over80000 tabletswere producedbythe compressionmachine.Onthe nextday,
several lakhsof tabletswere produced. ThisiscalledIPQC,inprocessqualitycontrol.

9. Dispensingandsamplingwere alsobeingdone atproductionwhileIwasthere. Thiswasdone underthe
presence of QCperson,KishorChaudharyof Saptari inthiscase.The samplingof productslike
permethrinanddispensingof productslike menthol were doneinmypresence.Samplingisthe process
of takingoutsmall portionof productsthat are necessarytobe testedatthat period intime byQC.
Storage departmentdetermines whichproductsneedstobe sampledatthat periodintime depending
uponthe several factors. “Swabpass” isa term usedinthiscase. Thisisdone veryfrequently.
Dispensingisthe processof releasingthe productsnecessary forthe bulkproductionaccordingtothe
ordersreceivedbyotherdepartmentslike marketingandR&D.For the purpose of dispensing,the
machinesare firstcalibratedwiththe standards.Aftertheyare foundfitandOK,the necessaryproducts
are dispensedinappropriate containers.The containers andthe ladlesare properlywashedfirstwith
soap andthenwipedwithisopropylalcohol (IPA).
The dispensedproductsare thenkeptinthe quarantine section.Dispensingmachine isusedwhich
exchangingitemsbetweenstorage andthe production.Thismachine operateswith UV radiationthat
killsthe harmful bacteriainthe containersandpackagingif exposedforatleast30 secsunderUV.
RoomPressure difference ismaintainedverywell inthe productiondepartment.Everypersonis
requiredtowearapronand cap before enteringthe production.Differentslippersare assignedfor
productionareaand maskis necessary.
Tabletsare compressedsolidsubstanceseitherroundorcylindrical inshape containingcertain active
alongwithseveral excipientsmeanttocure certaindisease ormitigate certainmedical condition.
Creamsare semisoliddosage formscontainingdispersible anddispersionsystems.Theycontainmore
than 20% water or volatile componentsandtypically lessthan50% hydrocarbonor waxes.
Ointmentsare alsosemisoliddosageformsmeantespeciallyforapplicationonthe skin.Theycontainan
active substance meanttoact ona skinfora special purpose.Theyhave oilyorgreasyconsistencyand
appearstiff uponapplication.
Granulationisa processof convertingraw material particle intomore spherical anduniformstructure
that can be easilycompressedintotablets.Granulationisgenerallyof twotypes.WetandDry
granulations. Wettingagentorliquidisusedinwetgranulationwhile drygranulationisperformed
withoutanyliquid.
Wet granulationinvolvesthe size reductionof the particlesusingdifferentkindsof mills,sieving,
shifting,mixingetc.

10. Aftersieving
Mixingbefore samplingthe granules

11. Granulationroomand equipments
Fig.Granulationflowdiagram
2.1 Weighinganddispensing:

12. Excipientsindifferentcontainerswere weighedanddispensedinadust extractionhood.Thenthe
materialsare sentto a cubicfeetblender.
1. Pre-mixing:
Blenderisusedforthe pre-mixingpurpose.Then,itisdischargedintothe binsformilling.
2. Milling:
Millingismeantforsize reduction. There are several methodsthatcanbe appliedforthe size reduction
process.Material istransferredfromPKBlendertoa QuadroComil formilling.Itisusedtofeedother
excipientsand Pre-Mix.Then,the productisdischargedintothe drums.
3. Blending:
Blendingisdone withthe lubricant.Thisisthe laststepatthe granulationroombefore the beginningof
tabletcompressionatthe differentchamber.
4. TabletCompression:
Tabletcompressiontakesplace inaverycontainedenvironment.Itisa separate chamberat Aadee
Productiondepartmentawayfromthe granulationroom. The blendedproductisdispensedusingdrums
and isfedthroughthe hoppersat the top everyfew minutes.Followingcompression,tabletspass
throughthe dedusteranda metal detector. Rejectedtabletsare passedintothe reconcilatorforthe
disposal.Acceptable tabletsare collectedusingdrumsorhuge plasticbags.
Fewtabletsare testedinthe testingroomforfriability,weightvariation,hardnessetcbeforethe bulk
productionisbegun.
2.2 Process equipmentinclude the following:
1. QuadroComil:
It consistsof mill body,infeedchute,rotorshaft assemblywithimpellerandscreen.All the partsare
constructedof 316 stainless steel.Thisisahighqualityrustresistantsteel.
2. Blender:
All the productcontact surfacesare constructedof 316L stainlesssteel.All othercomponentsare
constructed of 304L stainlesssteel.A timercanvarythe blendingsequence time from0to 20 mins.
3. TabletPress:
The stationhas certaincapacity.It can prove over1 lakhtabletsinnotime.The pressis fullyautomated
withPCIPLCcontrol,recipe anddata loggingsystem.Powderisfedfromthe top.The tabletpresshas
upperand lowercamtracks, upperand lowerpunches,dyes, hydraulicpressforce control systemetc.
Thoroughmixingisdone firstsothat active isuniformlydistributedthroughoutthe mixture. Thisisthen
sievedthroughmeshesof differentsizes.Active iscarefullyhandledduringthisprocessthatnoloss

13. occurs. It isthengranulatedinthe planetarymixer.A tappinghammerisusedtopreventthe granules
fromremainingattachedtothe mixer. A solutionisprepared.Wettingisdone withthishelpof this
solution.Granulesare thendriedinadryerat over40 degree Celsiusof temperature.Glidantsand
lubricantsare thenaddedto the mixer.Final mixingisdone withthe helpof turbulamixer. The sampleis
giventothe QC for confirmation.If itisapproved,compressionisdone ata differentsectionwiththe
helpof tabletcompressor.Necessarytestsare performedatthissectionbeforebulkproductis
underway.
2.3 Tabletcoatingwasperformedthe verynextweekbutIwasshiftedforQCthen.
1. TabletCoating:
Tabletcoatingisa processof coveringupor designingof the outercoveringof the compressed
tabletsoas to increase itsappeal ormake itfeasible forthe consumer.Mostof the time,tablet
coatingmay be sugar coated,entericcoated,filmcoateddependinguponthe needorasper the
timing.
Sugar coatingisdone in orderfor the tablettobe appealingintermsof taste.Mostof the time,
childrendonotwant to consume tabletsdespite the necessity.However,whenthe same tablet
isdesignedwithsugarcoating,itappealstothemas doescandy.
Entericcoatingis done tomake the drughabitable tothe intestinal environment.The stomach
ph isacidicwhile the intestine phisalkaline.Entericcoatingisdone sothat drug issoluble inthe
alkaline environment.Entericcoatedtabletsshouldremainintactinthe gastricenvironmentat
leastfora couple of hours.
Filmcoatingisdone for the protectionfromexternal environmentorthe targeteddrugrelease
process.Thus,tabletcoatinghasvariousfunctionsdependinguponthe needof the moment.
Filmcoatingisdone to hide bitterness,make itsmoothsothatit can be easilyswallowedeg.
Paracetamol. Besidesthe one mentionedhere,there are variousothertypesof tabletcoating.
Variousadvancedequipmentslike coatingpansandothermachinesare usedforthe purpose of
tabletcoating.
2. Typesof tabletcoating:
 Entericcoating
 Gastric coating( Entericcoatingand Gastric coatingare termsveryinterchangeable.Dtof the
entericandgastric coatingtabletsshouldbe assuchthat the tabletwill remaininthe gastric
environmentatleastfor2 hrs. as mentionedearlier.)Thisisassuredinthe labbypreparinga
buffersolutionoutof HCLand examinedwhetherthe tabletswilldisintegrate inthe periodof
time.
 Filmcoating
 Sugar coating
 Compressioncoating
 Electrostaticcoating

14.  Dipcoating
 Vacuumfilmcoating
 MAIC, Magneticallyassistedimpactioncoating
 Electrostaticdrycoating
 Gelatincoating:Althoughgelatincoatingisdone mostlyinthe case of capsules,itissome times
alsoappliedinthe case of tablets.
3. Critical parametersof tabletcoating:
Critical parametersrefertothose parametersthatare setby pharmacopoeiafor the standard
productionof the pharmaceutical products.Inthe case of coatedtablets,the critical parameters
are as follows:
o Spray rate:Spray rate refersto the quantitysprayof the coatingmaterial perunittime.
Dependinguponthe thicknessof coatingsprayrate is adjusted.
o Inletairtemperature:Airtemperaturedeterminesthe qualityof tabletcoating.Inletair
temperature isincreasedordecreasedasperthe necessity.
o Pan speed:Pansare usedforthe purpose of coating of the tablets.Panspeedsare altered
accordingto the necessity.
o Relationbetweencoatingpanandspraygun: Distance betweenthe coatingpanandspraygun
determinesthe qualityof tabletcoating.So,itmustbe properlyadjusted.
4. Problemsintabletcoating:
 Blistering:Blisteringisaprocessinwhichthe coatedtabletshowsa particularnature of
sweating.Or,the tabletsburstoutof the blister.Thiscanbe overcome bypropercare during
the coatingprocess.Milddryingis recommendedinthissituation.
 Mottling:Thisisa processof the lossof colorof the tablet.Thismaybe due to interactionwith
the air particlesordue to reactive oxygenspecies,ROS.Toovercome this,properpackaging
mightbe done.Thisisa problemdue tothe lack of propercolor mixing.Toovercome this
problem,coloringagentshouldbe made intocolloid.
 Chipping:Thisisa processof slightbreakage of the tabletdue tofrictionduringthe packaging
process.Thiscan be overcome byproperlytestingforthe hardness,friability,dissolution,
disintegrationrate etc.andadjustingthe tabletcoatingmachine accordingly.Panshouldbe
filledwithsufficientamountof core tablets.Appropriatebaffle designsshouldbe used.Highfilm
strengthcoatingformulashouldbe used.Correct panspeedshouldbe recommended.Tablet
toolingshouldbe replaced.Propertabletshape shouldbe used.Optimumsprayrate shouldbe
used.Suspensionsolidlevel shouldbe increased.Hardnessof the filmshouldbe increasedby
increasingthe molecularweightof the coatingpolymer.
 Cratering:Thisisa processof formationof little craterlike structuresonthe surface of the
tablets.Crateringcanbe overcome bypropermixingof the raw materialsduringthe granulation
process.Sprayrate shouldbe decreased.Optimumdryingconditionshouldbe used.Viscosityof
the coatingsolutionshouldbe increased.
 Picking:
 Pitting:

15.  Blooming:Lowconcentrationorhighmolecularweightplasticizer isrecommendedinthis
situation.
 Blusing:Dryingairtemperature shouldbe decreasedinthiscircumstance.The use of HPMC,
Cellulose etcwiththe sorbital shouldbe avoidedinthissituation.
 Bridging:
 Capping:
 Erosion:
 Twinning:Tabletshape shouldbe changed.Lesstackycoatingformulasshouldbe used.
Appropriate tabletshape shouldbe used.Panspeedshouldbe increased.Atomizingspeed
shouldbe increased.Sprayrate shouldbe reduced.Optimumdryingconditionsshouldbe used.
 Peelingandfrosting:
 Orange peel:Milddryingconditionshouldbe used.Viscositysuspensioncoatingshouldbe used.
Atomizingairpressure shouldbe increased.The sprayrate shouldbe decreased.Betterspray
gunsshouldbe used.Viscosityof the coatingsuspensionshouldbe decreased.Gunshouldbe
adjustedtothe beddistance.
 Colorvariation:Colorvariationcanalsohappeninthe tabletcoatingprocess.Variationinthe
colorcan be overcome bypropertemperature,propercolorratioetc.
At a time,onlycouple of problemslistedabove appearsatthe productionhouse andtheyare tackled by
one or more methodsas explainedabove.Experiencedproductionmanagerscome upwith
extraordinarysolutionswhereasnovice personnel cannotdo so mostof the time.
Equipmentavailable atProduction:

16. TabletCompressionmachine(Upperpunch, lowerpunch,LowerandUpperCam track)

17. Digital weighingmachine

18. Computer/Internet

19. Sievesusedduringgranulation

21. Quarantine jarsand plasticbags
CleanRoomGarments
Each and everydepartmentincludingthe productionhaddifferentapronsforthe workingstaff,visitors
etc. These clotheswere regularlywashed. There werealsodisposablecapsandglovesatthe
production.Footwearsalsoclassifiedtobe usedoutside andinside.Wearingthe same slippersinside
and outside wasnotallowed.ThiswasfullyenforcedbyQA personnel visitingthe production.
On the otherhand,QC had separate thickglovesforuse at the sectioncontainingmuffle furnaceand
differentaprons formicrobiologysection.
AirlocksandChange-roomsincGMPfacility
No table of contents entriesfound.
3. QualityControl
QC isthe departmentwhere the analysisisdone.So,mostof the time,graduateswithatleastBPharm
degree are requiredtoworkat QC. For over7 days at QC, I wascontinuouslybusyinperforminganalysis
assignedtome by QC officerAmitSingh. Firstdaywasspentonperformingthe analysisof the water
qualitysuppliedbythe watersystematthe company. PH of the waterwastestedusingthe pH meter.
Conductivitywasmeasuredwiththe helpof anotherconductometer.Total dissolvedsolute TDSwas
determinedwiththe helpof anotherdevice. Acidityandalkalinityof the waterwascomparedwiththe
helpof litmus papers. Chloridetestwasdone.Afterthat,nitrate testonthe waterwasdone.Twotypes
of solutionswereprepared.Referencesolutionandtestsolution. Inthe referencetube,4.5ml of
distilledwaterwasmixedwith0.5ml of nitrite standardsolution of 2ppm. To thissame testtube,0.4ml
of potassiumchloridewasaddedalongwith0.1ml diphenylamine solutionalongwith5ml conc
sulphuricacid.Sulphuricacid,nitricacid etc. were keptinthe fume hood.Use of these acidswere done

22. withextracare inside the fume hood.The buretteswere thenwashedandplacedinthe washafter
some time.
Thissolutionwascomparedwiththe testsolutioninadifferenttesttube containing5ml of water(hot
solution). Itwaskeptat50 degree Celsiusfor15 minutes. Anyblue colorinthe testsolutionwasnot
more intense thaninreference solution.Thisprovedthe absenceof nitrates.
Afterthat presence of heavymetalsinthe waterwastestedfor.Tothe 100 ml of purifiedwatersample,
0.075 ml of 0.1 Mnitricacid was added.Then,itwasheateduntil the volume wasreducedto20 ml.
Reference solutionwaspreparedwith10ml of leadstandardsolution(1ppm) and 2 ml of reduced
solution.Blanksolutionwaspreparedwith10ml of distilledwaterand2 ml of reducedsolution.Test
solutionwasthenprepared bytaking12 ml of water.2 ml of buffersolutionwasthenaddedalongwith
1.2 ml of thioacetamidereagent.Theywerethenmixedandexaminedafter 2 minutes.Slightbrown
colorwas observedcomparedtothe blanksolution.Blankwasthencomparedwiththe reference
solution.Anybrowncolorinthe testsolutionwasnotmore intense thaninthe reference solution.
Afterthat,waterwas testedforthe oxidizable substance. To10 ml of sample,1 ml of dilute sulphuric
acid wasaddedalongwith0.01 ml of 0.02 M potassiumpermanganate.Itwasthenboiledfor5minutes.
Solutionremainedpink.Colorremained.Thisprovedthe presence of oxidizablesubstances.
Solutionswere preparedasperthe instructionsinthe volume IIof IndianPharmacopoeia.There were
twosectionscalledgeneral reagentsandchemical reagentsinthe volume twoof IPthatwere extremely
useful duringmytime atQC. Some of the codeslike 2.30.04 broughtusback to volume Ifor detailed
informationonthatmatter.I founditeasyto write downonmy notebookall the necessaryinstructions
firston the copy andthencontinue the experiment.
Similar,testswere performedfromthe verynext dayonsample active of Metronidazole(BatchnoMTZ-
0111877). Itwas a white/yellowcrystallinepowder.Samplewassparinglysolubleinwater.Itwas
sparinglysolubleinethanol.Itwasverysoluble inacetone.Itwasverysolubleindichloromethane.In
conclusion,itwasslightlysolubleinbothorganicandinorganicsolvents.

23. Afterthat identification of metronidazole wasdone withthe helpof IR.The powdersample wasplaced
on the FTIR surface and the graph producedmatchedwiththe standardalready presentinthe
computer.Similarly,whenexaminedinthe range 230 nm to 360 nm, a 0.001 % w/vsolutionin0.1 M
hydrochloricacidshowedanabsorptionmaximumatabout 277 nm anda minimumatabout240 nm,
absorbance at about277 nm,between0.365 and 0.395. On the otherhand, identificationwas
performedbyheating10 mg inthe waterbath with10 mg of Znpowder,1 ml of water and 0.25 ml of
2M hydrochloricacidfor 5 minutesandcooled.The solutiongave the reactionof primaryaromatic
amines. Anintense orange colorwasproducedasmentionedinthe pharmacopoeia.
QC officerAmitSinghguidedme withformulasforcreatingsolutionsof particularppm. These easilyset
formulasmade myworkat QC veryeasy.
InstrumentsmostfrequentlyusedatQC include HPLC,FTIR,pH meter,Dissolutionapparatus,
Disintegrationapparatus etc.Apparatusmostlyusedinclude testtube stand,bunsenburner,beakersof
differentsizes,RBflaskof differentsizes,testtubes,litmuspaper,weighingmachine etc.
3.1 Functionsof QC:
QC isone of the most importantdepartmentatthe pharmaceutical industry.QCperformsall the
analysisafterwhicheachdepartmentproceedswiththeirwork.QCperformsthe stabilitytesting upon
the formulationproducedbyR&D.OnlyafterthistestingcanR&D proceedwithobtainingthe necessary
license andregistrationforthe newproduct.QCperformsall the sample testsaccordingtowhichthe
storage departmentclassifiesthe products receivedorbeginsdispensingforthe productionof bulk
quantities.QCpersonisnecessarywhile samplinganddispensing.KishorChaudharydoesthisjobat
Aadee industryanddoesitwell. Moreover,QCperformsall the testsonthe packagingmaterial
accordingto the SOPdevelopedbythe companyandpassesordeniesthe packagingmaterial.So,QC
standsas the most crucial departmentatthe pharmaceutical industry.

24. QC has to performwateranalysisonthe dailybasis.Waterisusedalmosteverywhereinthe
pharmaceutical industryanditisvital thatit fallswithinthe limitdeterminedby the company.
QC alsoperformsthe documentationof eachandeveryanalysisthattake place atthe facility.Mostof
these documentsare preservedforatleast5 yearsand latershreddedordestroyedaccordingtothe
decisionof QA.Recently,documentsweredestroyedbyfire atAadee.Ittooka whole dayforseveral
staffsto helpthemdoso.
QC alsomanagesregularpest/insectcontrol.Mostof these are done on Fridayat the closingtime so
that the effectof insecticideiscompletedonSundaybythe office time.Insectslikecockroachesand
pestslike ratsare strictlypreventedtoenterpharmaceutical facilitiesformanyreasons.
3.2 Raw material analysisisone of the mostimportant functions of QC. Atthismomentintime,raw
materialsare notproducedinNepal.Mostof the activesare receivedfromnationslike IndiaandChina.
In thiscase,the raw material analysisbecomes vitallyimportant.Some of the time productsare sent
that have expirydate earlierthanexpected.Inthiscase,storage departmentregularlysendssamplesto
QC to make sure that the productsare properlyarranged.If QC doesnotapprove certainproduct,
storage departmentcategoriesitaccordinglysothatunapprovedmaterial doesnotgoforproduction.
AmitSinghledme to multipleSOPspreparedbythe companyforthe raw material analysis.Thiswere to
be strictlyfollowedbythe staff's performinganalysis.

25. Microbiologysection:
There wasa separate sectionatQC where the entrance wasstrictlyprohibitedexceptforthe analystin
essential cases.Thiswascalledmicrobiologylab.There wasseparate apronsandglovestoenterinto
thisdepartmenttoavoidcross-contamination.Thiswasthe place where organismcultureswere done.
There waslaminarhood,autoclave,petri-dishesetc.inthissection.
Althoughthere wasnoworkat this spotduringmystay at QC, it has responsibilitiesof performing
microbial tests,antibioticassaysandmicrobial contentof the environment.So,itwassegregatedasa
verysensitiveareaevenwithinthe QC.There wasa refrigeratorandincubatorinthissectionaswell.I
was instructedmanytimesnottoenterthissectionbythe QC officerandanalyststhere.
Besides,instrumentationsectionof the QCcontainedinstrumentslike weighingbalance,potentiometer,
hardnesstester,friabilitytester, potentiometer,disintegrationtestapparatus,tabletdissolution
apparatus,tabletdensitytestapparatus,digitalvernier caliper,flamephotometer,polarimeter,melting
pointtestapparatus,Karl Fischertitrator,UV visible spectrometer,FTIR,HPLCetc.
Chemical analysisroomof the QCcontainedwaterbath,fumeshood,magneticstirrer,sonicator,
separatingfunnel,pHmeter,centrifugemachine, vacuumpump,condenser,oven, muffle furnace,
several chemicalsetc.
Stabilitytestingchamberscontainedreal time andacceleratedstabilitytestingmachines.
5. Store Department
Thiswas where Ilearnedalot aboutabbreviationsusedatthe industrylike TR,RT date,difference
betweenPEG-400and PEG-4000 etc. SushantPokharel ledme tomultipleSOPsthatincluded
instructionsfordispensing,documentation,operationof BugZapperetc.
I was sentto productiondepartmentalongwithnon-technical workersof store forsamplingand
dispensingontwoseparate days.Inthiswas I wasable to observe inpersonthe operationsthatare
conductedduringthese sensitive procedures.

26. Raw materialswere classifiedatthe store as actives,excipientsandliquid/gelsinseparate columns.The
blisterpackagingwasstoredata separate room.The packaging's that requiredrefrigerationwere stored
inthe refrigerator.
Refrigeratedpackingmaterialsatthe store
There isa dispensingbox usingUV radiationconnectingthe dispensingboothof the production
departmentwiththe store department.Atleast30 secondsof exposure toUV in the dispensingbox
disinfectsmostof the microorganismspresentinthe packaging materials.
Dependinguponthe type of rawmaterial,theycome packagedindifferenttypesof jars,plasticbagsor
sacks.Some of the raw materialsmaybe borrowedorboughtfrom the nearestpharmaceutical
companyfor the promptuse in case orderingraw material fromabroad.One such case waspresent
while Iwasthere.FloridlaboratorylocatedinGyaneshworhadconfirmedthattheyhadsuchproducts
that Aadee neededatthat moment.

27. 5.1 Store room/Raw material classification
One whole sectioninthe store roomwasdedicatedtostoringORSraw materialsthatincludedsodium
chloride etc.ORSishighlydemandedinthe summerseasoncalled“JivanJal”inNepali. Thisisone of the
mostpopularproductsfor conditionssucha diarrhea,dehydrationetc.Thisproductisalsopopular
amongchildreninNepal.
Store room non-technical staffswere alsoactivelyinvolvedinhelpingQA officeratthe final packaging
section(secondarystore orfinishedgoodstore) byperformingchecksonthe final products,their
expirationdate,manufacturingdate onprimaryandsecondarypackagingmaterials.Theyalsohelped
count productsineach box to assure that theydonot containless,more ordamagedproducts.
QA officerslikeRonashShresthacame tothe final packagingroomforthispurpose on a dailybasis.

28. QC attachesgreenstickersinthe case of approvedproducts,theyattachredstickersinthe case the test
fails.Inthisway,the labellingwithdifferentcolorstickershelpsstore toquicklypickupthe materials
whenneededorsegregate thematthe store.Thistermsegregationiswidelyusedatthe store.
Differentsortsof drugswere handleddifferentlyatthe store:
a. Storedinthe refrigerator:ActiveslikeMupirocin,Bacitracin Zinc, PolymixinB-Sulphate,
Halobetasol,Butenafine HCLetc. were storedinthe refrigerator.
b. Protectedfromlight:Lightsensitive drugslikerabeprazole,Ilaprazole,Duloxeteine HCL,
Tretinoin,Mometasone, Hydroquinone,FerrousAscorbate,Lornoxicam, Leflunomide etc. were
protectedfromthe light.While samplingordispensing,theywere keptindark-blackcolored or
ambercoloredpolybags.If necessary,theywere packagedinaluminumfoils.
c. Protectfrommoisture:Drugslike rabeprazole sodium, Ilaprazole,Doxycycline,folicacidsetc
were protectedfromthe moisture. Theywere storedinadouble layeredpolybagsinawell
closedcontainer.Often,silicagel poucheswere placedbetweenpolybagsandcontainer.Silicais
a good absorberof moisture.
d. Materialswithpungentodoror eye irritation:Drugslike terbinafine,salicylicacid,miconazole
nitrate,Doxycyline Hyclate,Levocetrizine HCL, Mefenamicacid,Benzoyl peroxide etc.were
handledwithextracare usingpropermasksandsafetygoggles.
e. Volatile materials:VolatilematerialslikeCamphorandmenthol werestoredindouble layered
polybagsintightlyclosedcontainersatroomtemperature.
f. Active liquidswere handledwithpropergowningusingapron,gloves, goggles, andmask.They
were storedat roomtemperature inclosedcontainers.
g. Excipientsolidswere storedinclosedcontainers,storedincool anddryplaces.Theywere
protectedfrommoisture.Proper gowningwere usedduringthisprocess.
h. Moisture sensitivematerialslike carbomer940, carbomer980, HPMC 100, HPMC 15U were
storedindouble layeredpolybagsinwellclosedcontainers.Silicagel packswere placedin
betweenpolybagsandcontainerswhennecessary.

29. i. Materialsprovokingallergicreactionslike Chlorocresol,BHT,BHA were handledafterproper
gowning.Directcontactwitheye andskinwas avoided. If allergicreactionwasseen,
immediatelyfirstaidtreatmentwasperformedafterablutionwithwater.
j. Materialswithpungentodorandeye irritation like sodiumlauryl sulphateandsodium
metabisulfitewere handledwithpropergowning,glovesetc.
k. Excipientliquidswere handledinairtightcontainersatroomtemperature usingproper
gowning.
l. Volatile andinflammable materialslike IPA were handledusingaprons,glovesandmasks.
m. Liquidperfumes werehandledinairtightcontainersprotectingfromthe sunlightatcool place
preventingdirectcontactwitheyesandskin.
6. QualityAssurance Department
In thisway,all the departmentsare highlyinter-related.One cannotdowithoutthe other.So,the better
the relationshipbetweenthe departmentheads/officers,the effective the workwillbe. The internal
phone networks helpmake the communicationbetweendepartmentsquickandeasy.
QA includesQCplusall othersactivitiesconnectedtoit.Thus,QA is the headdepartmentasfar as the
industryisconcerned.Theydeal mostlywithdocumentingall the activitiesthattake place throughout
the companyincludingthe SOPs,checkspayable,recruitmentetc. QA hasa manager(PrashantBasnetat
Aadee) andQA officers(Ronash ShresthaatAadee).QA officersdealwiththe mostof the problemslike
ensuringthe finalizationof the bulkproductionandtake the matterto QA manageronlyif theydoubt
theirdecisionorcannotmake the final decision.
QA alsoexecutesthe final shreddingof mostof the documentsafter5 yearshave passed.QA isactively
engagedinsupervisingateverybulkproductionanddispensingatproductiondepartment. QA isthe
departmentthatensuresthe executionof GMPrulesat eachand everydepartmentbeginningwithQA
itself.Documentation,thatis,dowhatyou write andwrite whatyou dois strictlyenforcedbyQA
throughoutthe industry.Documentationsreceivedfromeachdepartmentare thoroughlyreviewedand
thensentfor processinginproperfile cabinet.
Some of the mostimportantfunctionsof the QA are as follows:
1. Batch release:Afterthe certainbatchisproduced,itis keptseparate fromothersat the final
goodsstore.It isthe dutyof QA officertoperformall the examination of the batchthat isbeing
released.Forthispurpose,QA officeralongwiththe store staffsexamineseachandevery
productfor the labelling,packagingandquantity.Marketretail price,MRP,issetso thatthe
productis not soldinthe marketby anymore at price more thanset bythe company.Any
personor pharmacythat sellsthe productat price higherthanMRP is liable tobe punishedby
lawif reported. Forthispurpose,the QA managerregularlysupervisesthroughoutall
departmentstoensure thatbatchrelease isperfectlydoneatall times.
2. Approval:
Approval of QA is requiredbyeachandeverydepartment.Approvalisthe greenlightfromQA togo
aheadwiththe processwhetheritbe bulkproduction,packagingorbatchrelease.Withoutthe QA

30. approval,none of the departmentsare allowedtotake onany endeavor. Inthisaspect,QA isthe
supreme controlleratthe industrylevel andthe QA manager isthe supreme.
QA directsthe creationof masterformulas.The R&D developedmasterformulaislegal atthe company
level onlyafteritisapprovedbythe QA.Master formulaare the most secretdocumentsatthe industry
level.Itisanintellectualpropertyof the company.Incase itis stolenbythe competition,theywillsteal
all the hard work,expenses,staffs andcostof materialsthatwere investedincreatingthatformulation.
So,QA ensuresthatapprovedmasterformulasare keptsecretandnot divulgedtoanypersonthan
those withofficerlevel authorityatthe company.
3. Self-inspection:
On the otherhand,QA officerperformsall the necessaryentriesintothe DDA portal
http://dams.dda.gov.np/ withthe authorizedIDjustlike R&Dfirstentersall the necessarydocuments
for productregistrationbefore submittingtheminthe paperforminperson.Similarly,QA officers
performall the necessaryself-inspectionthroughoutthe companyandsubmitnecessarydocuments
online beforethe inspection arrivesatthe companyinpersonand demandsnecessarydocumentation.
DDA doesnotrenewthe GMP certificate every twoyearsif the companydoesnotpassthe inspection.
4. Validation:
Aadee Remedieshasamulti-productsfacilityatImadol,Lalitpursite here inNepal.Thismanufacturing
facilityisdesignedasperthe GMP incompliance withDDA,Nepal. ValidationMasterPlanincludesall
the mattersrelatedtomaintainingGMPat the Imadol facility.Thesedocumentsandactivities include
Installation Qualification (IQ),OperationQualification(OQ), Performance Qualification(PQ),and
ComputerSystemValidation(CSV).
Validationisgenerallyof 3 types:
♦ Prospective validation:Itisthe validationthatisdone priortothe production of products.
♦ Retrospective validation:Itisthe validationdone afterthe productionof productsandexecution
of packagingactivities.
♦ Concurrentvalidation:Itreferstothe validationdone duringthe production,duringthe analysis
at QC, duringthe packagingor storingof the materialsatthe store.Concurrentvalidationisvery
vital forthe well beingof the companyona longterm.
Special ValidationPlansare developedbythe companyas andwhenrequiredasplanthe demandsof
the people,place andtime e.g. Cleaningvalidation.
Validationisaprocessthatensuresthe consistencyinthe all the thingsdone atthe company.It ensures
that whenthe same processisrepeatedagainandagain,the consistencyremainsinall activities
whetheritbe same staffsor not. In thismanner,the new staffscan alsofollow the same SOPaftermany
yearsand produce the exactsame result.Thisisthe kindof consistencythat GMP alsodemands. Thisis
a processthroughwhichQA savestime,personnel andmoney.Throughvalidation,the same documents
do nothave to be createdagain,eachnew staff doesnotneedto be trainedfromzeroand the process
or masterformuladoesnothave to be createdagainand again.The same validatedinstructionscanbe
followedbyanypersonnel andproduce the same exactresult.The basicideabehindsystematicand

31. scientificstudyinvalidationisduplication.Duplicationisthe principlethatmostof the modern
franchisesare basedonwhere the same processisrepeatedateachestablishmentproducingexactly
the same resultthussavingtime andmoney.Due to the principle of duplication,the product,personnel,
behaviorandprofitcan be estimatedaccuratelyateach franchise.
Thisis ensuredbyscientificstudytoensure thatsystem, equipmentorprocessmeetsorexceedsthe
expectationsof the design, isproperlybuilt,operatedormaintained,issuitable foritsintended
application,conformsto criteriasetbyGMP, will satisfythe regulatorybodies, andiscapable of
operatingconsistentlyorproduce productsof consistentquality.
In orderto ensure processvalidation,multiple observationsare done andmultiple repetitionof the
processesare done.Three repetitionsare generallystandardrequirementforsuchvalidations. Testing
and monitoringare alsorequiredforextendedperiodof time incontrolledenvironments.Inthisway,
validationsare performedtomake the duplication possible.
All the validationsare documented,signedanddated.Theymustbe endorsedbythe QualityUnitof the
organization inordertoput themintoeffect. Atleastthree approvingsignaturesare requiredforthese
documentstobe circulatedthroughoutthe company.These signaturesincludesignatureof QA
Manager, QC Officer,QA officeretc.
Many guidelinesincludingICHare studiedandfollowed duringvalidationprocess.Manyguidelinesare
examinedandthe mostfeasible one ischosenforthe particularvalidation. Processvalidationinvolves
the validationof all the SOPscreatedforeachdepartmentsothat the same SOP can be repeatedagain
and againproducingthe exactresultwhosoeverthe staff maybe.
Failinginvestigationsare recommendedtoQualityassurance forcorrective actionviaDeviation Report.
Utilityvalidationsare equallyimportant.Primaryutilitiesinvolve compressedairandpurifiedwater.
Secondaryutilitiesinvolve HVACetc.These are vital componentsof the industryastheyare essential to
be in operationona dailybasis.
6.1 Process Validation(PV)
PV is establishingdocumentedevidence,whichprovidesahighdegree of assurance thatprocess to
produce productA will alwaysconsistentlyandexactlyproduce the productA meetingitsproduct
specificationsandqualityparameters.
Analysisof datacollectedfrommonitoringwillestablishthe variabilityof processparametersfor
individualrunsandwill establish whetherornotthe equipmentandprocesscontrol are adequate to
assure ProductA specificationsare met. Finishedproductandinprocesstestdata can be of value in
processvalidation, particularlyinsituationswhere qualityattributesandvariabilitycanbe measured.
There are several risksthatmustbe containedtoperformperfectprocessvalidation.
Validationdocumentsare separatelyindexedandclassifiedinaspecial manner.
HeatingVentilationandAirConditioning(HVAC)/EngineeringandUtility
I was touredoutat HVACsectiononthe verylastday by QA officerRonashShrestha.HVACisa very
importantaspectat the industrial pharmacy.Itensuresthe heatingandairconditioningateach

32. departmentasperthe GMP requirementssothat productsproducedmeetthe standardsintermsof
quality,safety,efficacyandmanagement.
AHU-XXXservedthe BlendingRoom#1. AHU-XXXservedthe QC.Similarly AHUXXXserved tablet
compressionroom#1, #2, #3, corridor,staging, wash,and weighingrooms. Asseeninthe picture,other
servedthe warehouse area.
HVACsystemissetat certaintemperature andrelative humidity.Itissetat least12 air changes per
hour. Air handlingsunitsdigitallyadjustthemselvesaccordingtothe feedbacksreceivedfromthe
sensorsandtransmitters.
Pre-coolingcoil,secondcoolingcoil,aftercoolingcoil are some of the temperature maintainingsystems
presentin the HVAC.The maintainthe programmedsupplyof rightconditionairtoeachdepartment.
Supplyairwill be filteredusingterminal HEPA filter.Returnairandexhaustairfromthe room will be

33. filteredthroughterminal HEPA filter. Additional ambientairwill make upforthe total predeterminedair
volume.
AHU servesall othermanufacturingareaslike tabletcompressionroom#1,#2, #3, corridor,staging,
wash,and weighingrooms. A mainexhaustfanlocatedinthe mainareaof the roof will serve areas
requiringdirectexhaust.
Ronashalsoshowedme the watersupplyupstairsandwaterpurificationsystemdownstairs.The
industrial areawasnotpopulatedsomuchin the past butin the recentyears, it'sbeenpopulatedwith
several houses.
6.2 VALIDATION MASTER PLAN Template
PRODUCT X MANUFACTURING FACILITY
Table of Content Page
I. Introduction
II. Scope
III. Validation
IV. Facility Description
V. Process Description
VI. Utility Systems
VII. Process Equipment
VIII. Control System
IX. Responsibilities
X. Project Schedule
XI. Other GMP Programs

34. XII. Reference Documents
XIII. Terms & Definitions
XIV. Appendices
6.3 Management Review
Approved by Signature Date
VALIDATION MANAGER
FACILITY, UTILITY AND
EQUIPMENT QUALIFICATION
MANAGER
COMPUTER VALIDATION
MANAGER
PRODUCT TRANSFER,
PROCESS AND CLEANING
VALIDATION MANAGER
MANUFACTURING MANAGER
PROJECT MANAGER
PLANT ENGINEER
QUALITY ASSURANCE
MANAGER

35. 6.4 GENERAL VALIDATION SCHEDULE & RESPONSIBILITIES
Programme Responsibili
ty
Week
1 2 3 4 5 6 7 8 9 10
1 Establish
Scope
Plant
manager
2 Consult FDC Plant
manager
3 Establish
validation
master
plan(VMP)
Plant
manager
4 Calibrate
laboratory
instruments
QC
5 Validate
analytical
methods
QC
6 Appoint
external
contractor for
IQ & OQ
Plant
manager
7 Collect
document (on
facility,
utility,
systems etc.)
Engineering
8 Establish IQ
protocol
Engineering
*Concept
*Review &
approval
9 Establish OQ
protocol
Engineering
10 Establish PQ
protocol
Production
*Concept
*Review &
approval
11 Establish
validation
performance
QA
12 Training on
GMP, SOPs
& protocols
QA
13 Preparation of
list of
equipment &
instrument for
calibration
QC &
Production

36. 14 Perform
calibration
QA
Lab.
instruments
QC
Production
equipment
Production
15 Establish
SOP, Change
control
QA
16 Performance
of IQ
Engineering
Facility
Utility
Equipment
17 Revise IQ QA/Engineeri
ng
18 Performance
of OQ
Engineering
*Utility
*Equipment
19 Revise OQ Engineering
20 Performance
of PQ/Process
validation
Production
*Equipment/S
ystem-
placebo
21 Revise
PQ/Process
validation
Production
22 Prepare
validation
report
QA
23 Approval/Cer
tification
QA & plant
manag.
Prepare by:
Date:
Checked by:
Date
Authorized by:
Date
No:
Date:
Supersedes No:
For the testing,certificationandmaintenance of mostof the HVACsystemandotherheavy equipment,
engineers fromthe respectivecompaniesfollow upatthe companyor are soughtout.

37. Each SOP iscreatedaccordingto the companystandardsandis providedtothe new internsornewly
hiredpersonnel fortrainingpurposes.Trainedemployeesare strictlyrequiredto follow the SOPaswell.
Trainingprogrammesare oftenorganizedfornew employees.Trainingsare obligatoryforthe new
employeesbefore theybegintheirtask.There are variousreasonstodoso. Equipmentusedfor
calibrationare tracedback to National Institute of MeteorologyandCalibration.
Calibrationisanotherimportantaspectof QA.CalibrationSOPsare createdforthispurpose.
6.5 QualityRiskManagement
Riskmanagementisaveryimportantaspectat QA. There are variouswaysof assessingrisk atdifferent
departments. Hazardidentificationinnecessarytopreventrisksorprepare forthe upcomingdisaster.
Industryisa verysensitive place where littlecarelessnessmightmeanlossof lifeproperty. Therefore,
risksmustbe identifiedandmanaged.Riskmanagementtoolsinclude failuremode andeffectanalysis,
faulttree analysis,fishbonediagram,CAPA etc.
6.7 Corrective andPreventive Action(CAPA)
Corrective actionsare those actionsperformedafterthe problemarises.Preventive actionis already
predictingthe future problemsandtakingactiontoavoidthembefore the problemarises.Thisisthe
majorduty of QA officeratan industry.Inthe case of preventive action,riskisprimarily identified.
Corrective actionsare reactive affairs thustheyare alwaysinferiortothe preventive actionsthatare
proactivelydone.
Example canbe the case of pestcontrol.Eitherwe can waituntil the rats and mice damage ourproducts
at final goodsstore and call the pestcontrol agency.Or, we can regularly schedulesprayingof
insecticidesandpesticidesonaregularbasis. Thispreventive actionistakenatAadee everyfew weeks.
Thisway the organizationcantake proactive stance ineach and everysituationratherthanwaitforthe
problemtoarise.Preventactionsinlongtermprove tobe cost effective andtime savingthancorrective
actions.
Initiationof CAPA includesalistof activitiesstrictlytobe followedbythe groupof personnel involved.It
includessubmissionof source documentby departmentheadtoQA,makinga decision, assigningthe
source documentnumber,fillingupthe CAPA form, sendingthe CAPA form,forwardingthe form,
assigninganidentificationcode consistingof departmentcode,serial numberandlastdigitof calendar
year.
Similarly,closure andverificationof the CAPA involvesalistof procedurestobe followedstrictly. They
include certifyingthe documentaftercompletionof actions,verifyingthe completionand
implementationwithsupportingdocuments,maintainingthe recordof documents,submittingthe
documentsbyQA personthe managementcommitteeduringregularmeetings,verificationandreview
by the managementandmakingthemavailableuponapproval bythe executivecommittee only.
6.8 ProductRecall and Withdrawal
Productrecall and withdrawal referstothe removingorpullingbackof a batch or all the batchesof a
certainproductdue to company report of qualityof productsor DDA notice whetheritbe throughDDA
examinationorcustomercomplaint.

38. Thisis a veryexpensive andreputationharmingsituationforeachandeverypharmaceutical company.
So,everythingisdone bythe companypriorto launchingproductinthe marketto preventproduct
recall andwithdrawal.Aadee inlast8years doesnothave more than 1 productrecalled.
For thisreason,R&D placesthe productat acceleratedstabilitytestingmachineforatleast3 months
and performsreal time stabilityafterthe productisproducedinbulk. Anyproblemsseeninthese
stabilitytastingsare seriouslytakenandmightevencause companytopull downall the relatedbatches
fromthe market.
Productrecall may be done forvariousreasonslike packagingissues,wronglabel,toxicityreports,
ineffectiveness,tabletbreakageetc.
6.9 Equipmentqualification(EQ)
Qualificationandvalidationare synonymoustermsusedatthe industry. Itallowsthe trainees,technical
and non-technical workersthe executionof installation,operationalandperformance protocols. EQ
allowsproperoperationof all the equipmentandconsistentproductof qualityproducts.
Equipmentqualificationisdone byassemblingthe validationteam, determiningthe intendeduser
requirements,conductingriskassessment, conductinginstallationandoperational qualification,along
withrequalificationreview.
In Asia,the vendorvalidationisusuallydoneonthe material while inEurope,vendorqualificationis
done inproduction.Inthisway,differentregionsmighthave differentaspectinwhichtheyvalidate.
Some of the machinesthat needequipmentqualificationinclude blisterpackagingproducingmachine,
semi-solidproducingmachine,compressionmachineetc.AtAadee,all of these belongtothe production
house.
6.10 ICH guidelines
Althoughall guidelinesare reviewedandstudiedat Aadee,ICHguidelinesare primarilyfollowedbyQA
officers.ICHguidelinesare primarilymade byfew countrieslikeJapan,USA,Germanyetc.These
guidelinesare strictlyfollowedinthesenations.ICHguidelinesstrictlyenforce certainprinciples similar
to GMP meantto maintainquality,safety,effectivenessandmanagement.
R&D(Summaryof the processinvolvedinmanufacturingof aparticularproduct)
Formulationof aproduct as directedbythe marketingdepartmentisdone byR&D bystudyingresearch
articlesandlookingforperfectcombinationinthe differentpharmacopoeias.Afterthis,atthe R&D lab,
the product iscreatedina small quantityandsenttoQC for acceleratedstabilitytesting.Aftersome
time,usually3months,the productis examinedandif found tofulfillthe requirements,the
manufacturinglicenseapplicationatDDA issubmitted.Productlicense isreceivedif the applicationis
approved.

39. Necessarypackagingmaterialswithlabellingeg tubesorblistersare thenorderedfromthe companies
inIndia.Afterthe necessarypackagingarrivesatthe firm, the productdepartmentiscommandedto
start manufacturingproductunderthe watchof R&D chief.The same processisduplicatedforbulk
productioninthe future.
6.11 Water TreatmentPlant
EWT, EffluentwatertreatmentishighlypromotedbyDDA as perthe GMP requirementtopreventthe
industrial waterreachingthe residential areasandharmingthe ecosystem.Thus,wateristreatedinside
the industry territoryandisconvertedbythe plantintonon-toxicwaterbefore leavingthe industrial
area.

40. Water receivedviatankerpassesthroughtheseseriesof systemsandare processedwell tomake it
usable forthe industrial purpose asseeninthe picture. WaterTreatmentPlantruns 24 hoursat Aadee.I
had an opportunitytoviewthe systemalongwiththe tankupstairs.
6.12 Chiller
Chillerisamachine thatmaintainsthe necessaryrefrigerationirrespective of the weatherconditions.
DuringwinterwhenHVAC cannotmaintainthe necessaryconditions,chillerdoesitswork. Vapor
compressionchillersmove the refrigerantaroundthe systembyusingelectricity.Vaporabsorption
chillersmove the refrigerantaroundthe systembyusingheatenergy.
ChillersatAadee workin conjunction withHVACsystem asshowsinthe diagram.

41. 6.13 Air Compressor
It isa device thatconvertsairintopotential energystoredinpressurizedair.Itforcesmore andmore
intostorage tank thuscontributingtoair pressure increment.
Compressorsare similartopumpsas theybothcan compressthe fluidthusincreasingitspressureand
make it flowthroughthe pipe.
6.14 Generator
Generatorisan essence ata nationlike Nepal where the electricitysupplyisnotdurable andload
sheddingisaregularoccurrence.Inthis situation,if we onlydependuponthe electricitysuppliedby
Nepal ElectricityAuthority,Lalitpur,thenthe pharmaceutical industrywill goindisorder.Thus,forthe
constantsupplyof electricityirrespectiveof powerline supplyespeciallyatHVACsystemandwater
treatmentsystem,generatorisof vital importance.
Generatorautomaticallystoresthe electricityandsuppliesittothe circuitwithoutbreakduringthe
poweroutage.
7. Conclusion
My internshipatAadee wasmeanttofulfill the requirementsof PokharaUniversityforgraduation.
However,Ihadan opportunitytolearnalot onhand aboutthe fieldIwasgoingto be involvedinthe
future.Ihad a chance in personto know a lotmore aboutindustrythanthe industrial tourfrom college
to Chitwanbasedpharmaceutical industries.
At QC,I had a chance to performanalysisindividuallythanatcollege wheredue tolimitedresourcesand
a large group itwas not feasibletodoeach processbymyself.Ihadwonderful co-operationfrom staff
at Aadee.Theypouredoutthere knowledge tome more thanI wascapable of grasping.
Overall,Ihada wonderful timeatAadee.
8. Suggestions:

42. I thinkAadee shouldencourageeachandeverypersonnel atitsfacilitytotake CAPA ona regularbasis.
In thisway,the staff will alsofeel asense of ownershipatthe place theyare working.Theymighteven
come up withcorrective andpreventive actionsthatare far superiorthanthose comingfromofficersat
higherpositions.Suggestionsboxesmightbe placedatsome place inside the companywhere suchstaffs
or eventhe visitorscan place theirideas.Administrationmightsave millionsof rupeeswithasingle good
ideacomingfroman individualthatjustpassedbythe company.
I likedhowQCofficerscheduledtasksforeachassistant/analysteverymorningandletthemenjoyspare
time if theyfinishedtheirtaskonhand.If the same processwouldbe duplicatedateachdepartment,
the productivityof the organizationwouldrise greatly.
Similarly,duringmystayat the company,it wasSujata Dahal’sbirthdayandAmitSingh’sfirst
anniversaryatAadee.If there wasa departmentora personassignedtocelebrate eachstaff’simportant
day,theywouldfeel abelongingtothe organizationandworkharderon theirtasks.Thissort of culture
was notseenat Aadee where eachpersonwastreatedlike aperson. Employee'sloyaltycouldbe earned
inthissort of behavior.
9. References:
RemingtonThe Science andPractice of Pharmacy
ICH Guidelines
https://www.pharmaguideline.com/2010/12/qualification-of-systems-and-equipment.html
Granulationstatespicture reference
http://www.pharmatips.in/Articles/Production/Granulation-Particle-Bonding-Mechanism-Process.aspx
CAPA
https://www.pharmaguideline.com/2011/07/corrective-and-preventive-actions-capa.html