Manufacture of Sterile Manufacture of Sterile and Non Sterile Productsand Non Sterile Products

K V GOPINATH M Pharm PhD CPhT

Hospital Pharmacist

Tirumala Tirupati Devasthanams

Andhra Pradesh

gopinath.karnam@gmail.com

Hospital Pharmacist- Hospital Pharmacist- Production servicesProduction services

• The competent hospital pharmacist The competent hospital pharmacist will manufacture preparations that will manufacture preparations that can be prepare more economically can be prepare more economically than they purchasedthan they purchased..

SterileSterileNon-sterileNon-sterileRadio pharmaceuticalsRadio pharmaceuticalsCytotoxicCytotoxicQuality controlQuality control

Manufacture of Sterile Manufacture of Sterile and Non Sterile Products and Non Sterile Products in Hospital - Advantagesin Hospital - Advantages

• It is most efficacious , better , It is most efficacious , better , and more economic product than and more economic product than purchasedpurchased

• Alcoholic preparations are Alcoholic preparations are economically preparedeconomically prepared

• Facilities for researchFacilities for research• To prepare commercial not To prepare commercial not

available preparationsavailable preparations

Policy making of Policy making of manufacturable itemsmanufacturable items

• Factors affecting make- or- buy Factors affecting make- or- buy decisiondecision

QualityQualityQuantityQuantityCost Cost PurityPurityServiceServiceDemandDemandPersonnel requirementPersonnel requirementEquipmentsEquipmentsSpaceSpace

Cost Sheet for an IV Cost Sheet for an IV productproduct

• Name of the Name of the productproduct

• TotalTotal production/Annuproduction/Annumm– Cost of raw Cost of raw

materialsmaterials– Direct wagesDirect wages– Direct expensesDirect expenses

ClosuresClosuresLabelsLabelsHangersHangers

• Over head costOver head cost– Estt. SalariesEstt. Salaries– Rentals& Rentals&

DepreciationDepreciation– Machines and its Machines and its

maintenance costmaintenance cost– Electricity and Electricity and

waterwater– Cost of Cost of

productionproduction– Printing, Printing,

stationery, postalstationery, postal– Qc, detergents, Qc, detergents,

chemicals etcchemicals etc

EOQ can be applied to EOQ can be applied to make decisionmake decision

EOQ=EOQ= 2 US2 US

IDID

Where UWhere U = Expected usage in units over = Expected usage in units over timetime

DD = Cost/unit= Cost/unit

I I = Inventory carrying charge as = Inventory carrying charge as a %a %

SS = Set up costs or purchase costs= Set up costs or purchase costs

Policy making of Policy making of manufacturable items - manufacturable items -

demanddemand

• Service – more assuredService – more assured

• Estimation of DemandEstimation of DemandJudgementalJudgemental

Extension of past historyExtension of past history

Casual models – regression analysisCasual models – regression analysis

Policy making of Policy making of manufacturable items- manufacturable items- Personnel requirementPersonnel requirement

• Usually nonprofessionals and professionalsUsually nonprofessionals and professionals• Operator should be neat, orderly,reliable , alert Operator should be neat, orderly,reliable , alert

and good manual dexterityand good manual dexterity• All employees should be good health and All employees should be good health and

periodic physical examinationperiodic physical examination• Sterile coveralls(spun polyethylene), hoods, Sterile coveralls(spun polyethylene), hoods,

face masks, shoe covers and sterile rubber face masks, shoe covers and sterile rubber glovesgloves

• Preparatory procedures- removing outside Preparatory procedures- removing outside street clothing, scrubbing the hands and armsstreet clothing, scrubbing the hands and arms

• Persons working in equipment wash rooms etc Persons working in equipment wash rooms etc – not required to meet the special requirements– not required to meet the special requirements

Manufacturing Manufacturing equipmentsequipments

• Water still and or demineralizerWater still and or demineralizer• Ampoule and vial washerAmpoule and vial washer• AutoclaveAutoclave• Ointment or colloid millOintment or colloid mill• Mixer tanks with electric agitatorsMixer tanks with electric agitators• Steam jacketed kettleSteam jacketed kettle• Filter press or automatic filter and Filter press or automatic filter and

siphonsiphon

Equipment for parenteral Equipment for parenteral solution laboratorysolution laboratory

• Storage equipment for Storage equipment for ampoules and vialsampoules and vials

• Ampoule washing and Ampoule washing and drying equipmentdrying equipment

• Dust proof storage Dust proof storage cabinetscabinets

• Leal testing equipmentLeal testing equipment• Labeling and packing Labeling and packing

benchesbenches• Cold storage & Cold storage &

refrigeratorrefrigerator• Water stillWater still• Mixing tanks, filter pressMixing tanks, filter press• AutoclaveAutoclave• Hot air sterilizerHot air sterilizer• Benches for filling and Benches for filling and

sealingsealing

• Laminar flow unitLaminar flow unit• Seitz filter, filter Seitz filter, filter

candlescandles• Inspection tableInspection table• Bottle racksBottle racks• BalanceBalance• Hot plateHot plate• Pump, suction and Pump, suction and

pressure with gaugepressure with gauge• Stool, adjustableStool, adjustable• Flask, glass various Flask, glass various

sizessizes• Tank, storage, for Tank, storage, for

distilled waterdistilled water

Ointments, Emulsions, Ointments, Emulsions, Lotions and suspensionsLotions and suspensions

• Mixing tanksMixing tanks• Kettle, steam, gas or Kettle, steam, gas or

electricityelectricity• Mixer, power drivenMixer, power driven• Storage tanks or potsStorage tanks or pots• Colloid mill/emulsifierColloid mill/emulsifier• Tripple roller millTripple roller mill• Liquid filling Liquid filling

equipmentequipment• Jar or tube filling Jar or tube filling

equip,equip,

• Syrups, Elixirs and Syrups, Elixirs and solutionssolutions Mixing & storage Mixing & storage

tankstanks Portable mixerPortable mixer Vacuum or gravity Vacuum or gravity

filterfilter Water still or Water still or

deionizerdeionizer Filter pressFilter press

Manufacturing Manufacturing equipmentsequipments

• Tablets and capsulesTablets and capsules Tablet machine,Tablet machine, DisintegratorDisintegrator Powder mixerPowder mixer Mass mixerMass mixer GranulatorGranulator OvensOvens Coating panCoating pan PolishingPolishing GranulatorGranulator Heater and exhaust Heater and exhaust

systemsystem Mixing and blending Mixing and blending

equipmentequipment Capsule filling unitsCapsule filling units Capsule countersCapsule counters

• Equipment for Equipment for repackingrepacking Washing machineWashing machine Plastic siphonPlastic siphon Corks, assortedCorks, assorted BottlesBottles Tablet and capsule Tablet and capsule

counting machinescounting machines Labeling machinesLabeling machines Stainless scoops and Stainless scoops and

vesselsvessels Weighing and Weighing and

measuring measuring equipmentequipment

Filling equipmentFilling equipment

Manufacturing recordsManufacturing records• Master Formula RecordMaster Formula Record (4 x 6 inches)– (4 x 6 inches)–

Prepared, endorsed and dated by a competent Prepared, endorsed and dated by a competent responsible individualresponsible individual Name of the product , a description of the dosage Name of the product , a description of the dosage

form and its strengthform and its strength Completed list of ingredients and codesCompleted list of ingredients and codes Quantity by weight or volume of each ingredientsQuantity by weight or volume of each ingredients Standards of each ingredients used in the productStandards of each ingredients used in the product An appropriate statement concerning any calculated An appropriate statement concerning any calculated

excess of an ingredientexcess of an ingredient Appropriate statements of theoretic yield at various Appropriate statements of theoretic yield at various

stagesstages Manufacturing and control instructions, specifications, Manufacturing and control instructions, specifications,

precautions and special notations to be followedprecautions and special notations to be followed Description of the container, closures, labeling, Description of the container, closures, labeling,

packagingpackaging

Batch Reproduction Batch Reproduction RecordRecord

• It contain accurate reproduction of the It contain accurate reproduction of the manufacturing formula, production and manufacturing formula, production and product specifications from the correct product specifications from the correct master formula master formula

• Formula and directions are copied onto a Formula and directions are copied onto a working formula sheet and scrutinized by working formula sheet and scrutinized by another individualanother individual

• Used for checking quantities of ingredients, Used for checking quantities of ingredients, procedures and time required for completion procedures and time required for completion and other informationand other information

• Once completed, assign a control number, Once completed, assign a control number, filed for future referencefiled for future reference

Floor plan of a sterile Floor plan of a sterile products area with its products area with its

serviceservice • Ref. FigRef. Fig• Clean up area – walls coated with Clean up area – walls coated with

epoxy and vinyl polymeric film epoxy and vinyl polymeric film coatingcoating

• Preparation areaPreparation area• Aseptic areaAseptic area• Quarantine areaQuarantine area• Finishing and packaging areaFinishing and packaging area

Considerations in Considerations in development of formulaedevelopment of formulae

• VehicleVehicle• Additives-Additives-

StabilizersStabilizers Buffering agentsBuffering agents AntioxidantsAntioxidants PreservativesPreservatives Tonicity contributorsTonicity contributors Wetting agentsWetting agents Suspending and Suspending and

emulgentsemulgents

• QC testsQC tests Sterility testingSterility testing Pyrogen testingPyrogen testing Clarity testingClarity testing Leaker testingLeaker testing

Manufacturing of sterile Manufacturing of sterile preparationspreparations

• Aseptic AdmixtureAseptic Admixture –following activities –following activitiesMaintain master production recordsMaintain master production recordsInitiate/update admixture profile/recordInitiate/update admixture profile/recordPrepare labels and worksheetsPrepare labels and worksheetsAssemble and record drugs, labels and Assemble and record drugs, labels and

ordersordersPrepare clean air environment and cleanup Prepare clean air environment and cleanup

of personnelof personnelDrug additionDrug additionMaintain aseptic techniqueMaintain aseptic techniqueAssemble, label, record and verify productionAssemble, label, record and verify productionClean up activitiesClean up activitiesIV additive communicationIV additive communication

Non-Sterile FormulationsNon-Sterile Formulations

•PrepackPrepackMaintain master production Maintain master production recordsrecords

Enter information on prepacking Enter information on prepacking recordrecord

Obtain bulk drug item from storageObtain bulk drug item from storagePrepare the labelPrepare the labelVerify the labelVerify the labelPrepackingPrepackingInspect and verify prepacked drugsInspect and verify prepacked drugsClean upClean up

Non-Sterile Formulations Non-Sterile Formulations – II– II

Extemporaneous Extemporaneous CompoundingCompounding• Maintain master production recordsMaintain master production records

• Completed batch record sheetCompleted batch record sheet• Obtain necessary supplies from storageObtain necessary supplies from storage• Prepare labelsPrepare labels• Prepare equipment and containersPrepare equipment and containers• CompoundingCompounding• Package productPackage product• Inspect and verify final productInspect and verify final product• Clean –upClean –up• Product compounding informationProduct compounding information